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1. Zheng LD, Tong QS, Tang ST, Du ZY, Liu Y, Jiang GS, Cai JB: Expression and clinical significance of heparanase in neuroblastoma. World J Pediatr; 2009 Aug;5(3):206-10
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  • [Title] Expression and clinical significance of heparanase in neuroblastoma.
  • BACKGROUND: Previous studies indicate that heparanase (HPA), an endoglycosidase involved in tumor angiogenesis and metastasis, is up-regulated in a variety of malignancies.
  • However, the expression of HPA in neuroblastoma (NB), one of the most common extra cranial solid tumors in children, remains unknown.
  • This study was undertaken to explore the expression and clinical significance of HPA in NB.
  • METHODS: Immunohistochemical staining was applied to detect the expression of HPA in 42 cases of NB.
  • The relationships among HPA expression, international neuroblastoma staging system (INSS) stages, histopathological classification, and postoperative survival of the NB patients were analyzed.
  • RESULTS: The expression rate of HPA in NB was 61.9% (26/42), mainly in the cytoplasm of neuroblastoma cells.
  • The expression rates of stage 1-2, stage 3-4 and stage 4S were 35.7%, 80.0% and 62.5%, respectively.
  • The differences between stage 1-2 and stage 3-4 were significant (P<0.01).
  • The expression of HPA was significantly higher in the NB cases that had one of the histopathological factors: age more than 1 year (P<0.01), poorer differentiation (P<0.01), and higher mitosis karyorrhexis index (P<0.01).
  • The survival time of HPA-negative patients was significantly longer than that of HPA-positive patients (P<0.05).
  • CONCLUSION: Although these results indicate that heparanase might be correlated with development and progression of NB, a larger series of patients with a longer follow-up are probably needed to strengthen its role in assessment of NB prognosis.
  • [MeSH-major] Adrenal Gland Neoplasms / enzymology. Glucuronidase / metabolism. Neuroblastoma / enzymology
  • [MeSH-minor] Child. Child, Preschool. Disease Progression. Female. Humans. Immunohistochemistry. Infant. Male. Mediastinal Neoplasms / enzymology. Retroperitoneal Neoplasms / enzymology

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  • (PMID = 19693465.001).
  • [ISSN] 1708-8569
  • [Journal-full-title] World journal of pediatrics : WJP
  • [ISO-abbreviation] World J Pediatr
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Switzerland
  • [Chemical-registry-number] EC 3.2.1.- / heparanase; EC 3.2.1.31 / Glucuronidase
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2. Libè R, Groussin L, Tissier F, Elie C, René-Corail F, Fratticci A, Jullian E, Beck-Peccoz P, Bertagna X, Gicquel C, Bertherat J: Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity. Clin Cancer Res; 2007 Feb 1;13(3):844-50
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  • [Title] Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity.
  • PURPOSE: Allelic losses [loss of heterozygosity (LOH)] at the 17p13 locus are frequent (85%) in adrenocortical cancers.
  • The tumor suppressor gene TP53 is located at 17p13.
  • The aim of the study was to determine the frequency of TP53 somatic inactivating mutations in adrenocortical tumors with 17p13 LOH and their clinico-biological correlations.
  • EXPERIMENTAL DESIGN: TP53 somatic mutations, intragenic LOH (VNTR1 marker), and p53 overexpression were studied in 36 adrenocortical tumors with 17p13 LOH determined by Southern blot.
  • RESULTS: TP53 mutations were detected in 33% of the tumors, and VNTR1 LOH was present in 44% of the cases and did not always correlate with the presence of a TP53 mutation.
  • Only the TP53-mutant tumors exhibit a strong nuclear immunoreactivity.
  • TP53-mutant tumors were significantly larger than wild-type TP53 tumors (median tumor weight: 640 versus 185 g; P=0.02), were associated with a more advanced stage of tumor progression (MacFarlane stage IV; P=0.01), and had a shorter disease-free survival (P=0.03).
  • CONCLUSIONS: The finding that only a minority of adrenocortical tumors with 17p13 LOH had either a VNTR1 LOH or a TP53 mutation indicates that TP53 might not be the only or major tumor suppressor gene at 17p13 involved in adrenocortical cancer progression.
  • We suggest that a genetic instability of the 17p13 region, occurring early in adrenocortical cancer development, involves various genes located in this region.
  • TP53 might be only one of them, and its alteration by the occurrence of inactivating mutation is associated with the development of more aggressive tumors.
  • [MeSH-major] Adrenal Cortex Neoplasms / genetics. Chromosomes, Human, Pair 17. Genes, p53. Loss of Heterozygosity. Minisatellite Repeats / genetics. Mutation
  • [MeSH-minor] Adult. Alleles. Disease Progression. Female. Humans. Immunohistochemistry. Male. Middle Aged. RNA, Neoplasm / chemistry

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  • (PMID = 17289876.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / RNA, Neoplasm
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3. Wu XR, Zhu MH, Zhang ZD: [Expression of KAI1/CD82 in neuroblastoma and its correlation to prognosis]. Ai Zheng; 2005 Jul;24(7):885-9
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  • [Title] [Expression of KAI1/CD82 in neuroblastoma and its correlation to prognosis].
  • BACKGROUND & OBJECTIVE: KAI1/CD82 was recently detected as a tumor metastasis suppressor gene.
  • Its silencing contributes to progression and infiltration of some tumors.
  • Our study was designed to investigate the expression of KAI1/CD82 in neuroblastoma, and explore its correlation to clinicopathologic characteristics and prognosis of patients with neuroblastoma.
  • METHODS: The EnVision immunohistochemistry was used to detect the expression of KAI1/CD82 in 90 specimens of neuroblastoma (28 specimens of ganglioneuroblastoma and 62 specimens of neuroblastoma).
  • Clinical data and follow-up data of the 90 patients were analyzed.
  • RESULTS: Positive rate of KAI1/CD82 was significantly higher in ganglioneuroblastoma than in neuroblastoma (39.3% vs. 14.5%, P=0.014).
  • Its expression was negatively correlated to clinical stage of neuroblastoma (P=0.003).
  • CONCLUSIONS: The change of KAI1/CD82 expression is an early event in tumorigenesis of neuroblastoma.
  • Its down-regulation may be considered as a potential indicator to judge the differentiation and metastasis of neuroblastoma, which can serve as one of the combined indexes to clinical assessment of prognosis.
  • [MeSH-major] Adrenal Gland Neoplasms / metabolism. Antigens, CD82 / metabolism. Ganglioneuroblastoma / metabolism. Neuroblastoma / metabolism. Peritoneal Neoplasms / metabolism
  • [MeSH-minor] Biomarkers, Tumor. Child. Child, Preschool. Female. Follow-Up Studies. Humans. Infant. Lymphatic Metastasis. Lymphatic Vessels / metabolism. Male. Mediastinal Neoplasms / metabolism. Mediastinal Neoplasms / pathology. Neoplasm Staging. Prognosis. Survival Rate

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  • (PMID = 16004821.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antigens, CD82; 0 / Biomarkers, Tumor
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4. Nuver J, Smit AJ, Wolffenbuttel BH, Sluiter WJ, Hoekstra HJ, Sleijfer DT, Gietema JA: The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol; 2005 Jun 1;23(16):3718-25
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  • [Title] The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer.
  • PURPOSE: The metabolic syndrome may be an important risk factor for cardiovascular disease in long-term survivors of testicular cancer (TC).
  • We investigated the associations between hormone levels and the metabolic syndrome in these men.
  • PATIENTS AND METHODS: We included TC patients cured by orchidectomy and cisplatin-based chemotherapy, stage I TC patients after orchidectomy only, and healthy men of comparable age.
  • Presence of the metabolic syndrome was determined using guidelines from the National Cholesterol Education Program Adult Treatment Panel III.
  • Thyroid-stimulating hormone, follicle-stimulating hormone (FSH), inhibin B, luteinizing hormone (LH), total testosterone, sex-hormone-binding globulin, free testosterone, estradiol, dehydroepiandrosterone sulfate, and insulin-like growth factor 1 were determined in blood.
  • Cortisol metabolite excretion was measured in urine.
  • RESULTS: Eighty-six chemotherapy patients (median follow-up, 7 years) were compared with 44 stage I patients and 47 controls.
  • LH and FSH were higher, and inhibin B and total and free testosterone were lower in chemotherapy patients than controls.
  • Adrenal and thyroid hormone production were unaffected.
  • Chemotherapy patients with the metabolic syndrome (n = 22; 26%) had a higher body mass index (BMI) pretreatment, a larger BMI increase during follow-up, lower total testosterone, and higher urinary cortisol metabolite excretion than those patients without the metabolic syndrome.
  • BMI and insulin were associated with the metabolic syndrome, while total testosterone and urinary cortisol metabolite excretion were associated with BMI.
  • CONCLUSION: We found gonadal dysfunction, but normal adrenal and thyroid function.
  • Through its association with BMI, testosterone may play a role in the development of the metabolic syndrome in long-term TC survivors.
  • [MeSH-major] Follicle Stimulating Hormone / blood. Luteinizing Hormone / blood. Metabolic Syndrome X / blood. Sex Hormone-Binding Globulin / metabolism. Testicular Neoplasms / blood. Testosterone / blood
  • [MeSH-minor] Adult. Aged. Humans. Male. Middle Aged. Survivors. Time Factors

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  • [CommentIn] J Clin Oncol. 2005 Jun 1;23(16):3663-5 [15738543.001]
  • (PMID = 15738540.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Sex Hormone-Binding Globulin; 3XMK78S47O / Testosterone; 9002-67-9 / Luteinizing Hormone; 9002-68-0 / Follicle Stimulating Hormone
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5. Kasperlik-Zaluska AA, Cichocki A: Clinical role of determination of plasma mitotane and its metabolites levels in patients with adrenal cancer: results of a long-term follow-up. J Exp Ther Oncol; 2005;5(2):125-32
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  • [Title] Clinical role of determination of plasma mitotane and its metabolites levels in patients with adrenal cancer: results of a long-term follow-up.
  • Our study aimed at evaluation of the relations between the plasma levels of mitotane (o,p'-DDD) and its metabolites, o,p'-DDA and o,p'-DDE, and the efficacy of Mitotane therapy during a long-term follow-up.
  • Eighteen patients, aged 11 to 70 years, were included to the study.
  • Metastatic or regional stage was diagnosed in 15 patients, while localized disease in three patients.
  • Mitotane has been administered in daily doses of 3.0 to 10.0 g in metastatic and regional stages, and 1.5 to 4.0 g in the localized disease, simultaneously with hydrocortisone, prednisolone and fludrocortisone.
  • Mitotane and its metabolites were determined by a high-pressure liquid chromatographic method.
  • The plasma o,p'-DDD level exceeding 44 _M/L, considered as curative one, was reached in nine cases.
  • The o,p'-DDA/o,p'-DDD ratio rose significantly mainly in the first 1-3 months of therapy.
  • The o,p'-DDE levels rose slowly, reaching higher values in long-term therapy, over 12 months of mitotane administration.
  • In the group of patients with regional or metastatic stage, both the o,p'-DDE levels and the o,p'-DDE/o,p'-DDD ratios were higher in the survivors than in non-survivors.
  • The results of our study suggest that the plasma concentrations of o,p'-DDE were more closely related to clinical improvement or remission than the o,p'-DDD levels.
  • [MeSH-major] Adrenal Gland Neoplasms / drug therapy. Antineoplastic Agents, Hormonal / blood. Mitotane / analogs & derivatives. Mitotane / blood
  • [MeSH-minor] Adolescent. Adult. Aged. Child. Female. Follow-Up Studies. Humans. Male. Middle Aged

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  • (PMID = 16471038.001).
  • [ISSN] 1359-4117
  • [Journal-full-title] Journal of experimental therapeutics & oncology
  • [ISO-abbreviation] J. Exp. Ther. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Hormonal; 34113-46-7 / 2,2-(2-chlorophenyl-4'-chlorophenyl)acetic acid; 3424-82-6 / 2,2-(2-chlorophenyl-4'-chlorophenyl)-1,1-dichloroethene; 78E4J5IB5J / Mitotane
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6. Eloubeidi MA, Cerfolio RJ, Chen VK, Desmond R, Syed S, Ojha B: Endoscopic ultrasound-guided fine needle aspiration of mediastinal lymph node in patients with suspected lung cancer after positron emission tomography and computed tomography scans. Ann Thorac Surg; 2005 Jan;79(1):263-8
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  • [Title] Endoscopic ultrasound-guided fine needle aspiration of mediastinal lymph node in patients with suspected lung cancer after positron emission tomography and computed tomography scans.
  • BACKGROUND: The treatment of patients with non-small cell lung cancer (NSCLC) depends on the stage.
  • Positron emission and computed tomography (CT) scans can identify suspicious lymph nodes that require biopsy.
  • We prospectively evaluated the yield and accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in sampling mediastinal lymph nodes and compared its accuracy to that of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and CT in staging NSCLC.
  • METHODS: A consecutive series of patients with suspicious nodes on PET or CT scan in the posterior mediastinal lymph node stations (#5, 7, 8, or 9) were prospectively evaluated by EUS-FNA.
  • The reference standard included thoracotomy with complete lymphadenectomy in patients with lung cancer or if EUS-FNA was benign, repeat clinical imaging, or long-term follow-up.
  • RESULTS: There were 104 patients (63 men) with 125 lesions (117 lymph nodes, 8 left adrenal glands) who underwent EUS-FNA.
  • The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA were 92.5%, 100%, 100%, 94%, and 97%, respectively.
  • EUS-FNA was more accurate and had a higher positive predictive value than the PET or CT (p < 0.001) scan in confirming cancer in the posterior mediastinal lymph nodes.
  • EUS-FNA documented metastatic cancer to the left adrenal in all 4 patients with advanced disease.
  • No deaths resulted from EUS-FNA.
  • One patient experienced self-limited stridor.
  • CONCLUSIONS: EUS-FNA is a safe, accurate, and minimally invasive technique that improves the staging of patients with NSCLC.
  • It is more accurate and has a higher predictive value than either the PET scan or CT scan for posterior mediastinal lymph nodes.
  • [MeSH-major] Biopsy, Fine-Needle. Carcinoma, Non-Small-Cell Lung / secondary. Esophagoscopy. Lung Neoplasms / pathology. Lymphatic Diseases / pathology. Lymphatic Metastasis / pathology. Neoplasm Staging / methods. Positron-Emission Tomography. Tomography, X-Ray Computed. Ultrasonography, Interventional
  • [MeSH-minor] Aged. Breast Neoplasms / pathology. Carcinoma / pathology. Carcinoma / radiography. Carcinoma / radionuclide imaging. Carcinoma / secondary. Carcinoma / ultrasonography. Colonic Neoplasms / pathology. Endometrial Neoplasms / pathology. Female. Fluorodeoxyglucose F18. Granuloma / diagnosis. Histiocytosis / complications. Histiocytosis / diagnosis. Histoplasmosis / complications. Histoplasmosis / diagnosis. Humans. Kidney Neoplasms / pathology. Lung Diseases / complications. Lymphoma / pathology. Lymphoma / radiography. Lymphoma / radionuclide imaging. Lymphoma / ultrasonography. Male. Mediastinum. Middle Aged. Predictive Value of Tests. Prospective Studies. Radiopharmaceuticals. Sarcoidosis / complications. Sarcoidosis / diagnosis. Silicosis / complications. Silicosis / diagnosis. Urinary Bladder Neoplasms / pathology


7. Hirano H, Yoshida T, Sakamoto T, Yoshimura H, Fukuoka M, Tachibana S, Saito H, Ohkubo E, Nakasho K, Nishigami T: Pulmonary pleomorphic carcinoma producing hCG. Pathol Int; 2007 Oct;57(10):698-702
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  • [Title] Pulmonary pleomorphic carcinoma producing hCG.
  • An 80-year-old woman with a pleomorphic carcinoma (PC) producing hCG was admitted to Nippon Steel Hirohata Hospital because of an abnormal shadow on CT seen during a follow-up examination after surgery for breast cancer.
  • A right upper lobectomy was performed due to rapid growth of the shadow 3 months later.
  • Macroscopically the tumor was a 4.8 x 4.0 cm well-circumscribed grayish-white mass.
  • On histology the tumor consisted mostly of intermingled spindle and polygonal cells, while evidence of poorly differentiated adenocarcinoma was seen in a few areas.
  • A diagnosis of PC was made due to hCG expression in approximately 20% of the spindle and polygonal cells on immunohistology.
  • Six months after the operation metastasis to the liver and adrenal gland was seen on CT.
  • The patient died due to metastases 1 year after the operation, even though the patient had been at stage 1B at the time of the operation and appropriate chemotherapy had been given.
  • PC patients with immunohistochemical hCG expression have elevated risk of local recurrence and metastasis.
  • [MeSH-major] Adenocarcinoma / metabolism. Biomarkers, Tumor / metabolism. Carcinoma, Non-Small-Cell Lung / metabolism. Carcinosarcoma / metabolism. Chorionic Gonadotropin / metabolism. Lung Neoplasms / metabolism
  • [MeSH-minor] Aged, 80 and over. Combined Modality Therapy. Fatal Outcome. Female. Humans. Radiography, Thoracic. Tomography, X-Ray Computed

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  • (PMID = 17803660.001).
  • [ISSN] 1320-5463
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Chorionic Gonadotropin
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8. Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A: Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World J Surg; 2006 May;30(5):872-8
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  • [Title] Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress?
  • BACKGROUND: Adrenocortical carcinoma (ACC), a rare and aggressive malignancy, accounts for up to 14% of adrenal incidentalomas.
  • The only chance of cure for ACC is diagnosis at an early stage; therefore, a main indication for adrenalectomy in patients with adrenal incidentaloma has been the potential risk of ACC.
  • Recent studies suggest that this has led to earlier stage of ACC at diagnosis, more curative operations, and better survival.
  • METHODS: We analyzed data on ACC from The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.
  • Four equal time quartiles (1973-1979, 1980-1986, 1987-1993, and 1994-2000) were compared for changes in demographics, pathology, treatment, and cause-specific mortality.
  • RESULTS: The average age was 51.2 years (range: 1-97), and 45.9% of patients were men.
  • The average tumor size was 12 cm (range: 2-36 cm), and only 4.2% were < or = 6 cm.
  • Most (88%) patients had surgical resection of their tumor, and external beam radiotherapy was used in only 12% of patients.
  • Between the time quartiles compared (as well as annually), there was no significant difference at presentation in age at diagnosis, sex, race/ethnicity, tumor size, tumor grade, the frequency of distant metastasis, and overall TNM stage.
  • Low tumor grade, lower stage of ACC, later time quartile, and surgical resection were associated with a lower cause-specific mortality by univariate analysis (P < or = 0.002) and by multivariate analysis (P < or = 0.031).
  • CONCLUSIONS: Although adrenal incidentalomas have become a common indication for adrenalectomy, this has not resulted in patients with ACC being diagnosed earlier or treated at a lower stage of disease at the national level.
  • The most important predictors of survival in these patients are tumor grade, tumor stage, and surgical resection.
  • [MeSH-major] Adrenal Cortex Neoplasms / surgery. Adrenalectomy. Adrenocortical Carcinoma / surgery
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Child. Child, Preschool. Cohort Studies. Female. Humans. Infant. Male. Middle Aged. Neoplasm Staging. Radiotherapy, Adjuvant. Retrospective Studies. SEER Program. Treatment Outcome. United States / epidemiology

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  • (PMID = 16680602.001).
  • [ISSN] 0364-2313
  • [Journal-full-title] World journal of surgery
  • [ISO-abbreviation] World J Surg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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9. Groussin L, Bonardel G, Silvéra S, Tissier F, Coste J, Abiven G, Libé R, Bienvenu M, Alberini JL, Salenave S, Bouchard P, Bertherat J, Dousset B, Legmann P, Richard B, Foehrenbach H, Bertagna X, Tenenbaum F: 18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated patients. J Clin Endocrinol Metab; 2009 May;94(5):1713-22
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  • [Title] 18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated patients.
  • CONTEXT: Most adrenal incidentalomas are nonfunctioning adrenocortical adenomas (ACAs).
  • Adrenocortical carcinomas (ACCs) are rare but should be recognized at an early stage.
  • OBJECTIVE: The objective of the study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) to predict malignancy in patients without a previous history of cancer.
  • DESIGN: This was a prospective, multicenter study from 2001 to 2006.
  • SETTING: The study was conducted at a network of seven university hospitals in Paris.
  • PATIENTS: Seventy-seven patients were included.
  • All underwent surgery because of hypersecretory and/or growing benign lesions (n = 18), obvious ACCs (n = 21), or radiologically indeterminate lesions (n = 38).
  • MAIN OUTCOME MEASURE: The degree of (18)F-FDG PET uptake [maximum standardized uptake value (maxSUV)] was related to the pathological findings serving as a reference, and its diagnostic value was compared with that of computerized tomography (CT) scan.
  • RESULTS: Pathology eventually diagnosed 43 ACAs, 22 ACCs, and 12 nonadrenocortical lesions.
  • Using a cutoff value above 1.45 for adrenal to liver maxSUV ratio, the sensitivity and specificity to distinguish ACAs from ACCs were, respectively, 1.00 (95% confidence interval 0.85-1.00) and 0.88 (95% confidence interval 0.75-0.96).
  • Among the 38 indeterminate lesions at CT scan, we could analyze a subgroup of 16 adrenocortical tumors with high unenhanced density (>10 HU) and an inappropriate washout: (18)F-FDG PET correctly predicted the benignity in 13 of 15 ACAs.
  • CONCLUSIONS: In a multidisciplinary team approach, (18)F-FDG PET helps to manage suspicious CT scan lesions.
  • An adrenal to liver maxSUV ratio less than 1.45 is highly predictive of a benign lesion.
  • [MeSH-major] Adrenal Cortex Neoplasms / radionuclide imaging. Adrenal Cortex Neoplasms / surgery. Fluorodeoxyglucose F18
  • [MeSH-minor] Adult. Aged. Blood Glucose / metabolism. Diabetes Complications / radionuclide imaging. Female. Hormones / blood. Humans. Image Processing, Computer-Assisted. Male. Middle Aged. Paris. Positron-Emission Tomography. Preoperative Care. Prospective Studies. Tomography, X-Ray Computed


10. Abiven G, Coste J, Groussin L, Anract P, Tissier F, Legmann P, Dousset B, Bertagna X, Bertherat J: Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients. J Clin Endocrinol Metab; 2006 Jul;91(7):2650-5
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  • [Title] Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients.
  • CONTEXT: Adrenocortical carcinomas (ACC) are rare tumors with a poor prognosis.
  • Few reports concerning large and homogeneous series are available.
  • OBJECTIVE: We aimed to determine the clinical characteristics and outcome of ACC and to identify prognostic factors.
  • DESIGN AND SETTING: This study is a descriptive and multivariate analysis of a cohort from a single endocrinology center.
  • PATIENTS: A total of 202 consecutive patients with ACC were studied.
  • RESULTS: The sex ratio (female to male) was 2.7.
  • Mean age at diagnosis was 44 +/- 16 yr (range, 11-88 yr).
  • We found that 154 patients (76%) had hypersecreting tumors [mostly cortisol and androgens (47%), cortisol alone (27%), or androgens alone (6%)] and 43 patients (21%) had metastases at diagnosis.
  • At initial staging or during follow-up, 85 patients (42%) had liver metastases, 79 patients (39%) had lung metastases, and 20 patients had bone metastases (10%).
  • The survival rate was 37% at 5 yr.
  • Multivariate analysis identified the following independent prognostic factors associated with shorter survival: older age at diagnosis [hazard ratio (HR), 1.03; P < 0.0001], initial MacFarlane extension stages 3 (HR, 4.42; P = 0.005) and 4 (HR, 7.93; P < 0.0001), and cortisol hypersecretion (HR, 3.90; P < 0.0001).
  • Treatment with 1,1-dichlorodiphenildichloroethane (o,p'DDD) in the 3 months after surgery increased the survival rate of patients with cortisol-secreting tumors (HR, 0.40; P = 0.04).
  • CONCLUSION: This study highlights the better prognosis of ACC diagnosed at a noninvasive local stage, the particularly poor prognosis of patients with cortisol-secreting tumors, and the beneficial effect of o,p'DDD therapy in this subgroup of patients.
  • [MeSH-major] Adrenal Cortex Neoplasms / secretion. Hydrocortisone / secretion
  • [MeSH-minor] Adult. Analysis of Variance. Androgens / secretion. Antineoplastic Agents, Hormonal / therapeutic use. Bone Neoplasms / secondary. Chemotherapy, Adjuvant. Female. Humans. Liver Neoplasms / secondary. Lung Neoplasms / secondary. Male. Middle Aged. Mitotane / therapeutic use. Neoplasm Staging. Prognosis. Survival Rate

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  • (PMID = 16670169.001).
  • [ISSN] 0021-972X
  • [Journal-full-title] The Journal of clinical endocrinology and metabolism
  • [ISO-abbreviation] J. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Androgens; 0 / Antineoplastic Agents, Hormonal; 78E4J5IB5J / Mitotane; WI4X0X7BPJ / Hydrocortisone
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11. Zini L, Capitanio U, Jeldres C, Lughezzani G, Sun M, Shariat SF, Isbarn H, Arjane P, Widmer H, Perrotte P, Graefen M, Montorsi F, Karakiewicz PI: External validation of a nomogram predicting mortality in patients with adrenocortical carcinoma. BJU Int; 2009 Dec;104(11):1661-7
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  • [Title] External validation of a nomogram predicting mortality in patients with adrenocortical carcinoma.
  • OBJECTIVE: To develop nomograms predicting cancer-specific and all-cause mortality in patients managed with either surgery or no surgery for adrenocortical carcinoma (ACC).
  • PATIENTS AND METHODS: The models were developed in 205 patients with ACC and externally validated using 207 other patients with ACC, identified in the 1973-2004 Surveillance, Epidemiology and End Results database.
  • The predictors comprised age, gender, race, stage and surgery status.
  • Nomograms based on Cox regression model-derived coefficients were used for predicting the cancer-specific and all-cause mortality, and were tested using area under the receiver operating characteristics (ROC) curve.
  • RESULTS: In cancer-specific analyses, the median survival of patients within the development cohort was 26 months, vs 71 months in the external validation cohort (P < 0.001).
  • In overall survival analyses, the median values were 21 vs 32 months for, respectively, the development and the external validation cohort (P < 0.001).
  • Three variables (age, stage and surgical status) were included in the nomograms predicting cancer-specific and all-cause mortality.
  • In the external validation cohort, the nomograms achieved between 72 and 80% accuracy for prediction of cancer-specific or all-cause mortality at 1-5 years after either surgery or diagnosis of ACC for non-surgical patients.
  • CONCLUSION: Our models are the first standardized and individualized prognostic tools for patients with ACC.
  • Their accuracy was confirmed within a large external population-based cohort of patients with ACC.
  • [MeSH-major] Adrenal Cortex Neoplasms / mortality. Adrenocortical Carcinoma / mortality. Nomograms
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Cause of Death. Epidemiologic Methods. Female. Humans. Male. Middle Aged. Prognosis. Young Adult

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  • (PMID = 19493261.001).
  • [ISSN] 1464-410X
  • [Journal-full-title] BJU international
  • [ISO-abbreviation] BJU Int.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Validation Studies
  • [Publication-country] England
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12. Kim YS, Kim N, Kim SY, Cho KS, Park MJ, Choi SH, Lim SH, Yim JY, Cho KR, Kim CH, Kim DH, Kim SS, Kim JH, Choi BI, Jung HC, Song IS, Shin CS, Cho SH, Oh BH: Extracolonic findings in an asymptomatic screening population undergoing intravenous contrast-enhanced computed tomography colonography. J Gastroenterol Hepatol; 2008 Jul;23(7 Pt 2):e49-57
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  • [Title] Extracolonic findings in an asymptomatic screening population undergoing intravenous contrast-enhanced computed tomography colonography.
  • BACKGROUND AND AIM: The purpose of this study was to evaluate extracolonic findings that could be encountered with computed tomography colonography (CTC) using intravenous (IV) contrast material in an asymptomatic screening population.
  • METHODS: Intravenous contrast medium-enhanced CTC was performed in 2230 asymptomatic adults (mean age, 57.5 years).
  • Axial images were prospectively examined for extracolonic lesions.
  • These findings were classified into three categories: potentially important findings, likely unimportant findings, and clinically unimportant findings.
  • Potentially important extracolonic findings were defined as those which required immediate further diagnostic studies and treatment.
  • Clinical and radiologic follow up, missed lesions and clinical outcomes were assessed using medical records (mean duration of follow up, 1.6 years).
  • RESULTS: A total of 115 new potentially important findings in 5.2% of subjects (115/2230) were found.
  • Subsequent medical or surgical intervention was performed in 2.0% (45/2230).
  • New extracolonic cancer was detected in 0.5% (12/2230), and the majority of them (83.3%) were not metastasized.
  • Computed tomography colonography missed eight potentially important extracolonic findings in eight subjects (0.4%, 8/2230): 0.8-cm early-stage prostatic cancer, six adrenal mass and one intraductal papillary mucinous tumor.
  • There were no severe life-threatening complications related to contrast medium.
  • CONCLUSION: Intravenous contrast-enhanced CTC could safely detect asymptomatic early-stage extracolonic malignant diseases without an unreasonable number of additional work-ups, thus reducing their morbidity or mortality.
  • [MeSH-major] Colon / radiography. Colorectal Neoplasms / radiography. Contrast Media / administration & dosage. Mass Screening / methods. Neoplasms / radiography. Tomography, X-Ray Computed
  • [MeSH-minor] Adrenal Glands / radiography. Aged. Aged, 80 and over. Biliary Tract / radiography. Blood Vessels / pathology. Cost-Benefit Analysis. Early Diagnosis. Esophagus / radiography. Female. Humans. Injections, Intravenous. Kidney / radiography. Liver / radiography. Lung / radiography. Male. Medical Records. Middle Aged. Pancreas / radiography. Predictive Value of Tests. Prospective Studies. Stomach / radiography. Time Factors. Urogenital System / pathology


13. Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, Sanders D, Thomas DG, Doherty G, Hammer G: Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res; 2009 Jan 15;15(2):668-76
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  • [Title] Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling.
  • PURPOSE: Our understanding of adrenocortical carcinoma (ACC) has improved considerably, yet many unanswered questions remain.
  • For instance, can molecular subtypes of ACC be identified?
  • If so, what is their underlying pathogenetic basis and do they possess clinical significance?
  • EXPERIMENTAL DESIGN: We did a whole genome gene expression study of a large cohort of adrenocortical tissues annotated with clinicopathologic data.
  • Using Affymetrix Human Genome U133 Plus 2.0 oligonucleotide arrays, transcriptional profiles were generated for 10 normal adrenal cortices (NC), 22 adrenocortical adenomas (ACA), and 33 ACCs.
  • RESULTS: The overall classification of adrenocortical tumors was recapitulated using principal component analysis of the entire data set.
  • The NC and ACA cohorts showed little intragroup variation, whereas the ACC cohort revealed much greater variation in gene expression.
  • A robust list of 2,875 differentially expressed genes in ACC compared with both NC and ACA was generated and used in functional enrichment analysis to find pathways and attributes of biological significance.
  • Cluster analysis of the ACCs revealed two subtypes that reflected tumor proliferation, as measured by mitotic counts and cell cycle genes.
  • Kaplan-Meier analysis of these ACC clusters showed a significant difference in survival (P < 0.020).
  • Multivariate Cox modeling using stage, mitotic rate, and gene expression data as measured by the first principal component for ACC samples showed that gene expression data contains significant independent prognostic information (P < 0.017).
  • CONCLUSIONS: This study lays the foundation for the molecular classification and prognostication of adrenocortical tumors and also provides a rich source of potential diagnostic and prognostic markers.

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  • (PMID = 19147773.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA046592-209023; United States / NCI NIH HHS / CA / CA046592-219023; United States / NCI NIH HHS / CA / P30 CA046592; United States / NCI NIH HHS / CA / 5 P30 CA46592; United States / NCI NIH HHS / CA / CA046592-199023; United States / NCI NIH HHS / CA / P30 CA046592-219023; United States / NCI NIH HHS / CA / P30 CA046592-199023; United States / NCI NIH HHS / CA / P30 CA046592-209023
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cyclin E
  • [Other-IDs] NLM/ NIHMS78831; NLM/ PMC2629378
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14. Rabban JT, Barnes M, Chen LM, Powell CB, Crawford B, Zaloudek CJ: Ovarian pathology in risk-reducing salpingo-oophorectomies from women with BRCA mutations, emphasizing the differential diagnosis of occult primary and metastatic carcinoma. Am J Surg Pathol; 2009 Aug;33(8):1125-36
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  • [Title] Ovarian pathology in risk-reducing salpingo-oophorectomies from women with BRCA mutations, emphasizing the differential diagnosis of occult primary and metastatic carcinoma.
  • Risk-reducing salpingo-oophorectomy (RRSO) is an effective prophylactic procedure for women with mutations in BRCA1 or BRCA2 genes, both of which confer an increased lifetime risk for ovarian, tubal, peritoneal, and breast cancer.
  • In addition to lowering this risk, RRSO also offers the opportunity to detect occult early-stage fallopian tube or ovarian carcinoma.
  • The differential diagnosis of occult tubal/ovarian cancer includes a spectrum of benign tubal and ovarian alterations and also occult metastatic breast cancer, although only rare cases of the latter have been reported in RRSO.
  • Neoadjuvant breast cancer chemotherapy may contribute to diagnostic difficulty due to treatment-induced cytologic alterations.
  • With the aim of elucidating features which may help with differential diagnosis, this study reports the incidence and pathologic features of benign ovarian alterations, benign ovarian tumors, and occult primary and metastatic malignancies in prophylactic oophorectomies from 108 women with a BRCA mutation and from 35 women with other strong risk factors for hereditary breast/ovarian carcinoma.
  • We direct particular emphasis on morphologic features of primary ovarian lesions that may mimic occult metastatic breast cancer.
  • We also evaluate histologic alterations due to neoadjuvant breast cancer chemotherapy in the ovary and fallopian tube of patients who received such treatment immediately preceding RRSO.
  • Comparison is made to ovarian metastases of breast cancer in our hospital-based population of breast cancer patients, none of whom underwent RRSO.
  • Overall, 69% of RRSO patients had a personal history of breast cancer.
  • Neoadjuvant breast cancer chemotherapy was administered in 15%.
  • Occult primary carcinoma occurred in 7 (6.5%) BRCA patients (5 in fallopian tube, 1 in fallopian tube and ovary, 1 in ovary).
  • Ovarian metastasis of breast cancer occurred in 1 (1%) BRCA patient undergoing RRSO and in up to a similar proportion (0.8%) of the hospital-based population of breast cancer patients.
  • The metastasis in the RRSO patient was clinically occult, unilateral, 0.2 cm, and demonstrated mild atypia without mitoses.
  • Abundant foamy, vacuolated cytoplasm due to neoadjuvant chemotherapy exposure was notable.
  • In contrast, ovarian metastases in the non-RRSO population were all clinically detected, bilateral, large, and exhibited well-developed malignant cytologic features.
  • None of the normal cell types in the ovary or tube demonstrated any cytologic alterations in RRSO patients who received neoadjuvant chemotherapy.
  • The main morphologic mimics of metastasis with superimposed chemotherapy-induced alterations in RRSO were stromal hyperthecosis (n=8), nodular hyperthecosis (n=2), adrenal rests (n=3), hilus cell nodules (n=43), and hilus cell hyperplasia (n=4).
  • Occult primary ovarian carcinoma was reliably distinguished from ovarian metastases of breast cancer by WT-1+, p53+, mammaglobin-, GCDPF-immunoprofile.
  • These results demonstrate that evaluation of RRSO specimens requires awareness of a spectrum of ovarian lesions which may mimic occult primary or metastatic carcinoma; awareness of the masquerading effects of neoadjuvant chemotherapy; and awareness of the potential morphologic differences between occult metastatic breast cancer in RRSO and non-RRSO specimens.
  • [MeSH-major] Genes, BRCA1. Genes, BRCA2. Ovarian Neoplasms / genetics. Ovarian Neoplasms / pathology. Ovarian Neoplasms / prevention & control
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Breast Neoplasms / drug therapy. Diagnosis, Differential. Fallopian Tubes / surgery. Female. Genetic Predisposition to Disease. Humans. Mutation. Neoplasms, Multiple Primary / genetics. Neoplasms, Multiple Primary / pathology. Neoplasms, Multiple Primary / prevention & control. Ovariectomy. Ovary / drug effects. Ovary / pathology. Risk Factors


15. Ohta S, Lai EW, Morris JC, Bakan DA, Klaunberg B, Cleary S, Powers JF, Tischler AS, Abu-Asab M, Schimel D, Pacak K: MicroCT for high-resolution imaging of ectopic pheochromocytoma tumors in the liver of nude mice. Int J Cancer; 2006 Nov 1;119(9):2236-41
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  • [Title] MicroCT for high-resolution imaging of ectopic pheochromocytoma tumors in the liver of nude mice.
  • Successful outcomes for patients with cancer often depend on the early detection of tumor and the prompt initiation of active therapy.
  • Despite major advances in the treatment of many cancers, early-stage lesions often go undetected due to the suboptimal resolution of current anatomical and functional imaging modalities.
  • This limitation also applies to preclinical animal tumor models that are crucial for the evaluation and development of new therapeutic approaches to cancer.
  • We report a new mouse model of metastatic pheochromocytoma, generated using tail vein injection of the mouse pheochromocytoma cell (MPC) line that reproducibly generated multiple liver tumors in the animals.
  • Furthermore, we show that in vivo microCT imaging enhanced using a hepatobiliary-specific contrast agent, glyceryl-2-oleyl-1,3-di-7-(3-amino-2,4,6-triiodophenyl)-heptanoate (DHOG), detected tumors as small as 0.35 mm as early as 4 weeks after the injection of the tumor cells.
  • This model may be useful for in vivo studies of tumor biology and for development of new strategies to treat metastatic pheochromocytoma.

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  • (PMID = 16841334.001).
  • [ISSN] 0020-7136
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] ENG
  • [Grant] United States / NINDS NIH HHS / NS / R01 NS037685; United States / Intramural NIH HHS / / Z99 CA999999; United States / NINDS NIH HHS / NS / R01 NS 37685
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Contrast Media
  • [Other-IDs] NLM/ NIHMS43416; NLM/ PMC2288741
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16. Russo P, Synder M, Vickers A, Kondagunta V, Motzer R: Cytoreductive nephrectomy and nephrectomy/complete metastasectomy for metastatic renal cancer. ScientificWorldJournal; 2007;7:768-78
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  • [Title] Cytoreductive nephrectomy and nephrectomy/complete metastasectomy for metastatic renal cancer.
  • The objective of this study was to determine our institutional experience with cytoreductive nephrectomy alone or in conjunction with nephrectomy complete metastasectomy.
  • Between July 1989 and September 2003, we queried our department's renal tumor database for patients undergoing cytoreductive nephrectomy alone or in conjunction with complete metastasectomy.
  • Clinical and pathological factors analyzed included primary tumor size, stage and histological subtype, age, gender, Karnofsky Performance Status (KPS) prior to nephrectomy, number and location of metastatic sites, and the presence or absence of any systemic therapy.
  • Preoperative laboratory values analyzed included hemoglobin (HGB), calcium (CA), albumin (ALB), lactose dehydrogenase (LDH), alkaline phosphatase (ALP), and corrected calcium.
  • Corrected calcium was defined as follows: corrected calcium = total calcium-0.707*(albumin-3.4).
  • During this time frame,1628 patients underwent nephrectomy (partial or radical) for renal masses, 91 (5.6%) of whom had metastatic disease.
  • In this group, 71% of patients were male, 88% of patients had a KPS of 80% or greater, and 92% had conventional clear cell histology.
  • Sixty-four percent of patients had a single site of metastatic disease, with lung the most common, followed by bone, adrenal, brain, and liver.
  • Sixty-one patients (67%) had nephrectomy with removal of all metastatic sites (nephrectomy/complete metastasectomy) and 30 (33%) had cytoreductive nephrectomy alone.
  • Median survival for patients undergoing nephrectomy/complete metastasectomy was 30 months.
  • Median survival for patients undergoing cytoreductive nephrectomy alone was 12 months.
  • Perioperative complications occurred in 13% of patients and four patients died within 30 days of their operation.
  • For patients with metastatic renal cell carcinoma, surgical resection of the primary tumor alone (cytoreductive nephrectomy) or in conjunction with metastasectomy can be accomplished with acceptable perioperative morbidity and mortality.
  • This surgical experience provides a contemporary foundation as new targeted therapeutic agents are integrated into the neoadjuvant or adjuvant treatment of locally advanced and metastatic renal cancer.
  • [MeSH-major] Kidney Neoplasms / mortality. Kidney Neoplasms / surgery. Neoplasm Metastasis / prevention & control. Nephrectomy / mortality. Risk Assessment / methods
  • [MeSH-minor] Aged. Female. Humans. Male. Middle Aged. New York / epidemiology. Outcome Assessment (Health Care). Prevalence. Retrospective Studies. Risk Factors. Treatment Outcome


17. Dubois SG, London WB, Zhang Y, Matthay KK, Monclair T, Ambros PF, Cohn SL, Pearson A, Diller L: Lung metastases in neuroblastoma at initial diagnosis: A report from the International Neuroblastoma Risk Group (INRG) project. Pediatr Blood Cancer; 2008 Nov;51(5):589-92
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  • [Title] Lung metastases in neuroblastoma at initial diagnosis: A report from the International Neuroblastoma Risk Group (INRG) project.
  • BACKGROUND: Neuroblastoma is the most common extracranial pediatric solid cancer.
  • Lung metastasis is rarely detected in children with newly diagnosed neuroblastoma.
  • We aimed to describe the incidence, clinical characteristics, and outcome of patients with lung metastasis at initial diagnosis using a large international database.
  • PROCEDURE: The subset of patients from the International Neuroblastoma Risk Group database with INSS stage 4 neuroblastoma and known data regarding lung metastasis at diagnosis was selected for analysis.
  • Clinical and biological characteristics were compared between patients with and without lung metastasis.
  • Survival for patients with and without lung metastasis was estimated by Kaplan-Meier methods.
  • Cox proportional hazards methods were used to determine the independent prognostic value of lung metastasis at diagnosis.
  • RESULTS: Of the 2,808 patients with INSS stage 4 neuroblastoma diagnosed between 1990 and 2002, 100 patients (3.6%) were reported to have lung metastasis at diagnosis.
  • Lung metastasis was more common among patients with MYCN amplified tumors, adrenal primary tumors, or elevated lactate dehydrogenase (LDH) levels (P < 0.02 in each case).
  • Five-year overall survival +/- standard error for patients with lung metastasis was 34.5% +/- 6.8% compared to 44.7% +/- 1.3% for patients without lung metastasis (P = 0.0002).
  • However, in multivariable analysis, the presence of lung metastasis was not independently predictive of outcome.
  • CONCLUSIONS: Lung metastasis at initial diagnosis of neuroblastoma is associated with MYCN amplification and elevated LDH levels.
  • Although lung metastasis at diagnosis was not independently predictive of outcome in this analysis, it remains a useful prognostic marker of unfavorable outcome.

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  • [Copyright] (c) 2008 Wiley-Liss, Inc.
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  • (PMID = 18649370.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / U10 CA098543; None / None / / U10 CA098543-07; United States / NCI NIH HHS / CA / U10 CA098543-07
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / MYCN protein, human; 0 / Nuclear Proteins; 0 / Oncogene Proteins; EC 1.1.1.27 / L-Lactate Dehydrogenase
  • [Other-IDs] NLM/ NIHMS123413; NLM/ PMC2746936
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18. Kuczyk M, Wegener G, Jonas U: The therapeutic value of adrenalectomy in case of solitary metastatic spread originating from primary renal cell cancer. Eur Urol; 2005 Aug;48(2):252-7
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  • [Title] The therapeutic value of adrenalectomy in case of solitary metastatic spread originating from primary renal cell cancer.
  • INTRODUCTION: Solitary adrenal metastases occur in about 1.2-10% of renal cell cancer patients.
  • Since the vast majority of intraadrenal lesions can be detected preoperatively, we and others have recently recommended to renounce a routine adrenalectomy during surgery of renal cell cancer.
  • However, the impact of adrenalectomy on the patients' clinical prognosis in case of a solitary metastatic lesion within the adrenal gland remains an issue of controversial discussion.
  • Whereas some authors suggest adrenalectomy as a potentially curative treatment option in these cases, others compare its clinical value with that of a mere lymphadenectomy.
  • PATIENTS AND METHOD: Between 1981 and 2000, 648 patients (440 males and 208 females) underwent nephrectomy in combination with adrenalectomy in our clinic for the diagnosis of renal cell cancer.
  • The median age at first diagnosis was 59 (range 33-84) and 60 (range 20-85) years for male and female patients, respectively.
  • The median postoperative follow - up was 2.4 years (0.2-18 years).
  • According to the TNM - classification system (2003) tumor stages were classified as follows: T1, 228 pat. (37%); T2, 70 pat. (11%); T3, 287 pat. (46%); T4, 37 pat. (6%).
  • In total, 339 patients revealed regional lymph node or distant metastases at the time of the surgical treatment.
  • Although metastases of the adrenal gland were diagnosed in 48 patients, solitary intraadrenal metastases without further systemic spread were observed in only 13 cases.
  • Several patients' and tumor characteristics (age, tumor stage and size, the presence of regional lymph node metastases, the presence of metastatic lesions at different organ sites as well as the detection of solitary intraadrenal metastases) were correlated with the patients' overall survival by univariate and multivariate statistical analysis (logistic Cox regression analysis).
  • RESULTS: The median long - term survival was 4.8 years for the entire cohort of patients investigated.
  • The median long - term survival was 13.8 years and 11.7 years for patients with no evidence of metastatic spread as well as for patients with a solitary intraadrenal metastatic lesion, respectively.
  • Accordingly, the long - term survival rates at 5 and 10 years after surgery were 66%/50% and 51%/51% for patients with no evidence of metastatic spread or isolated intraadrenal metastases.
  • This difference was not statistically significant.
  • In contrast, for patients revealing lymph node or distant metastases at other organ sites, the median long - term survival was significantly decreased (lymph node metastases: 0.7 years; distant metastases: 1.2 years).
  • DISCUSSION: For patients with a solitary intraadrenal metastatic lesion, adrenalectomy is a potentially curative treatment option.
  • The observation that the long - term survival of the latter patients is comparable to that of patients with organ - confined disease might suggest the establishment of a separate TNM - category for patients revealing a solitary metastasis within the adrenal gland and no hint at further systemic metastatic spread.
  • [MeSH-major] Adrenal Gland Neoplasms / secondary. Adrenal Gland Neoplasms / surgery. Adrenalectomy. Carcinoma, Renal Cell / secondary. Carcinoma, Renal Cell / surgery. Kidney Neoplasms / pathology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Nephrectomy. Proportional Hazards Models. Survival Rate. Treatment Outcome


19. Leboulleux S, Deandreis D, Al Ghuzlan A, Aupérin A, Goéré D, Dromain C, Elias D, Caillou B, Travagli JP, De Baere T, Lumbroso J, Young J, Schlumberger M, Baudin E: Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis? Eur J Endocrinol; 2010 Jun;162(6):1147-53
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  • [Title] Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis?
  • CONTEXT: Peritoneal carcinomatosis (PC) is a rare site of distant metastases in patients with adrenocortical cancer (ACC).
  • One preliminary study suggests an increased risk of PC after laparoscopic adrenalectomy (LA) for ACC.
  • OBJECTIVE: The objective of the study was to search for risk factors of PC including surgical approach.
  • DESIGN: This was a retrospective cohort study conducted in an institutional practice.
  • PATIENTS: Sixty-four consecutive patients with ACC seen at our institution between 2003 and 2009 were included.
  • Mean tumor size was 132 mm.
  • Patients had stage I disease in 2 cases, stage II disease in 32 cases, stage III disease in 7 cases, stage IV disease in 21 cases, and unknown stage disease in 2 cases.
  • Surgery was open in 58 cases and laparoscopic in 6 cases.
  • MAIN OUTCOME: The main outcome was the risk factors of PC.
  • RESULTS: PC occurred in 18 (28%) patients.
  • It was present at initial diagnosis in three cases and occurred during follow-up in 15 cases.
  • The only risk factor of PC occurring during follow-up was the surgical approach with a 4-year rate of PC of 67% (95% confidence interval (CI), 30-90%) for LA and 27% (95% CI, 15-44%) for open adrenalectomy (P=0.016).
  • Neither tumor size, stage, functional status, completeness of surgery, nor plasma level of op'DDD was associated with the occurrence of PC.
  • CONCLUSION: We found an increased risk of PC after LA for ACC.
  • Whether this is related to an inappropriate surgical approach or to insufficient experience in ACC surgery should be clarified by a prospective program.

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  • (PMID = 20348273.001).
  • [ISSN] 1479-683X
  • [Journal-full-title] European journal of endocrinology
  • [ISO-abbreviation] Eur. J. Endocrinol.
  • [Language] ENG
  • [Publication-type] Journal Article
  • [Publication-country] England
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20. Fassnacht M, Johanssen S, Quinkler M, Bucsky P, Willenberg HS, Beuschlein F, Terzolo M, Mueller HH, Hahner S, Allolio B, German Adrenocortical Carcinoma Registry Group, European Network for the Study of Adrenal Tumors: Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification. Cancer; 2009 Jan 15;115(2):243-50
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  • [Title] Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification.
  • BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, and it was only in 2004 that the International Union Against Cancer (UICC) defined TNM criteria and published the first staging classification.
  • However, to date, the prognostic value of the proposed classification has not been evaluated.
  • METHODS: The German ACC Registry comprising 492 patients was searched for patients who were diagnosed between 1986 and 2007 with detailed information on primary diagnosis and a minimum follow-up of 6 months.
  • Patients were assigned to UICC tumor stage, and disease-specific survival (DSS) was assessed.
  • In addition, the contribution of potential risk factors for DSS was evaluated.
  • RESULTS: In total, 416 patients with a mean follow-up of 36 months met the inclusion criteria (stage I, n=23 patients; stage II, n=176 patients; stage III, n=67 patients; stage IV, n=150 patients).
  • Kaplan-Meier analysis revealed a stage-dependent DSS.
  • However, DSS in patients with stage II ACC did not differ significantly from DSS in patients with stage III ACC (hazard ratio, 1.38; 95% confidence interval, 0.89-2.16).
  • Furthermore, patients who had stage IV ACC without distant metastases had an improved DSS compared with patients who had metastatic disease (P=.004).
  • An analysis of different potential risk factors for defining stage III ACC revealed important roles in DSS for tumor infiltration in surrounding tissue, venous tumor thrombus (VTT), and positive lymph nodes; whereas tumor invasion in adjacent organs carried a prognosis similar to that of infiltration in surrounding tissue only.
  • CONCLUSIONS: The 2004 UICC staging classification for ACC has significant limitations.
  • On the basis of the current analysis, a revised classification with superior prognostic accuracy is proposed (the European Network for the Study of Adrenal Tumors classification).
  • In this system, stage III ACC is defined by the presence of positive lymph nodes, infiltration of surrounding tissue, or VTT; and stage IV ACC is restricted to patients with distant metastasis.
  • [MeSH-major] Adrenocortical Carcinoma / pathology. Neoplasm Staging / classification
  • [MeSH-minor] Humans. Lymphatic Metastasis. Neoplasm Invasiveness. Neoplasm Metastasis. Prognosis. Risk Factors

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  • [Copyright] Copyright (c) 2009 American Cancer Society.
  • [CommentIn] Cancer. 2009 Dec 15;115(24):5847; author reply 5848 [19827149.001]
  • (PMID = 19025987.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Investigator] Allolio B; Behrend M; Bucsky P; Brauckhoff M; Fasanacht M; Fottner C; Haaf M; Hahner S; Johanssen S; Koschker AC; Langer P; Laubner K; Linden T; Maeder U; Morcos M; Oelkers W; Quinkler M; Reincke M; Reisch N; Saeger W; Weismann D; Willenberg HS; Wortmann S; Baudin E; Bertherat J; Beuschlein F; Mannelli M; Terzolo M
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21. Grubbs EG, Callender GG, Xing Y, Perrier ND, Evans DB, Phan AT, Lee JE: Recurrence of adrenal cortical carcinoma following resection: surgery alone can achieve results equal to surgery plus mitotane. Ann Surg Oncol; 2010 Jan;17(1):263-70
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  • [Title] Recurrence of adrenal cortical carcinoma following resection: surgery alone can achieve results equal to surgery plus mitotane.
  • BACKGROUND: A recent nonrandomized interinstitutional study reported that adjuvant mitotane following surgery for adrenocortical carcinoma (ACC) was associated with decreased recurrence.
  • Because of the limitations of this study, we investigated the influences of surgery and adjuvant mitotane in a large series of ACC patients evaluated and treated at a single referral center.
  • STUDY DESIGN: Retrospective evaluation of patients followed at a single institution after surgery for ACC.
  • RESULTS: 218 patients with ACC underwent primary resection either at the index institution [surgery index (SI), n = 28] or an outside institution [surgery outside (SO), n = 190] and had a median follow-up of 88 months.
  • SI patients had a superior disease-free survival compared with SO patients (median 25 versus 12 months, P = 0.003), and SI patients also had a superior overall survival compared with SO patients (median not reached versus 44 months, P = 0.02).
  • Factors predicting increased risk of recurrence on multivariate analysis were surgery at an outside institution [hazard ratio (HR) 2.56, 95% confidence interval (CI) 1.44-4.53, P = 0.001] and no treatment with adjuvant mitotane (HR 1.95, 95% CI 1.06-3.59, P = 0.03), and those predicting a poorer survival were advanced stage at presentation (P = 0.01) and surgery at an outside institution (HR 2.62, 95% CI 1.31-5.25, P = 0.007).
  • CONCLUSIONS: The recurrence rate of the index group (50%) in the current series, the overwhelming majority of whom did not receive adjuvant mitotane, is indistinguishable from that reported for those who received adjuvant mitotane (49%) in the recent interinstitutional report, emphasizing the importance of completeness of initial surgery in the management of patients with ACC.
  • [MeSH-major] Adrenal Cortex Neoplasms / surgery. Adrenocortical Carcinoma / surgery. Antineoplastic Agents, Hormonal / therapeutic use. Mitotane / therapeutic use. Neoplasm Recurrence, Local / diagnosis
  • [MeSH-minor] Adolescent. Adult. Aged. Chemotherapy, Adjuvant. Child. Child, Preschool. Combined Modality Therapy. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Staging. Retrospective Studies. Survival Rate. Treatment Outcome. Young Adult

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  • (PMID = 19851811.001).
  • [ISSN] 1534-4681
  • [Journal-full-title] Annals of surgical oncology
  • [ISO-abbreviation] Ann. Surg. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P30 CA016672
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Hormonal; 78E4J5IB5J / Mitotane
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22. Ahlborn GJ, Nelson GM, Grindstaff RD, Waalkes MP, Diwan BA, Allen JW, Kitchin KT, Preston RJ, Hernandez-Zavala A, Adair B, Thomas DJ, Delker DA: Impact of life stage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice. Toxicology; 2009 Aug 3;262(2):106-13
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  • [Title] Impact of life stage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.
  • Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver.
  • Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumors in mice exposed to 85 ppm (approximately 8 mg/kg) inorganic arsenic during gestation.
  • To further characterize age susceptibility to arsenic carcinogenesis we administered 85 ppm inorganic arsenic in drinking water to C3H mice during gestation, prior to pubescence and post-pubescence to compare proliferative lesion and tumor outcomes over a one-year exposure period.
  • Inorganic arsenic significantly increased the incidence of hyperplasia in urinary bladder (48%) and oviduct (36%) in female mice exposed prior to pubescence (beginning on postnatal day 21 and extending through one year) compared to control mice (19 and 5%, respectively).
  • Arsenic also increased the incidence of hyperplasia in urinary bladder (28%) of female mice continuously exposed to arsenic (beginning on gestation day 8 and extending though one year) compared to gestation only exposed mice (0%).
  • In contrast, inorganic arsenic significantly decreased the incidence of tumors in liver (0%) and adrenal glands (0%) of male mice continuously exposed from gestation through one year, as compared to levels in control (30 and 65%, respectively) and gestation only (33 and 55%, respectively) exposed mice.
  • Together, these results suggest that continuous inorganic arsenic exposure at 85 ppm from gestation through one year increases the incidence and severity of urogenital proliferative lesions in female mice and decreases the incidence of liver and adrenal tumors in male mice.
  • The paradoxical nature of these effects may be related to altered lipid metabolism, the effective dose in each target organ, and/or the shorter one-year observational period.
  • [MeSH-major] Adrenal Gland Neoplasms / chemically induced. Arsenites / toxicity. Carcinogens / toxicity. Liver Neoplasms / chemically induced. Oviducts / drug effects. Sodium Compounds / toxicity. Urinary Bladder / drug effects
  • [MeSH-minor] Administration, Oral. Animals. Drug Administration Schedule. Female. Hyperplasia / chemically induced. Male. Maternal Exposure. Maternal-Fetal Exchange. Mice. Mice, Inbred C3H. Pregnancy. Prenatal Exposure Delayed Effects. Time Factors. Water Supply

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  • (PMID = 19450653.001).
  • [ISSN] 1879-3185
  • [Journal-full-title] Toxicology
  • [ISO-abbreviation] Toxicology
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / / Z01 BC005488-22; United States / Intramural NIH HHS / / Z01 BC005488-23
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Arsenites; 0 / Carcinogens; 0 / Sodium Compounds; 48OVY2OC72 / sodium arsenite
  • [Other-IDs] NLM/ NIHMS127111; NLM/ PMC3496158
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23. Fujino M, Shirato H, Onishi H, Kawamura H, Takayama K, Koto M, Onimaru R, Nagata Y, Hiraoka M: Characteristics of patients who developed radiation pneumonitis requiring steroid therapy after stereotactic irradiation for lung tumors. Cancer J; 2006 Jan-Feb;12(1):41-6
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  • [Title] Characteristics of patients who developed radiation pneumonitis requiring steroid therapy after stereotactic irradiation for lung tumors.
  • BACKGROUND: To find possible risk factors for symptomatic radiation pneumonitis (RP) after stereotactic irradiation (STI) for peripheral non-small cell lung cancer (NSCLC), pre-treatment pulmonary function test and dose volume statistics in patients who developed RP requiring steroid intake were retrospectively compared with statistics of those who did not develop RP.
  • MATERIALS AND METHODS: From 1996 to 2002, 156 patients with Stage I NSCLC received STI at 5 hospitals in Japan.
  • Of those patients, 12 were medicated with steroids for RP after treatment (RP group).
  • For comparison, 31 patients were randomly selected from the remaining 144 patients who received STI but did not receive steroids (control group).
  • RESULTS: There were no statistical differences in age, sex, tumor size, performance status, forced expiratory volume in 1 sec (FEV1.0%), or percent vital capacity (%VC) between patients medicated with steroids for RP and those who did not have RP and received no steroids.
  • V20 (%) was 7 to 18% (median 8%) in patients medicated with steroids for RP and 2 to 16% (median 7%) in those who did not have RP.
  • No difference was observed in V20, the biologically effectively dose (BED) at the periphery of the planning target volume, or the dose per fraction between the two groups.
  • CONCLUSIONS: Pre-treatment pulmonary function test (%VC, FEV1.0%), and dose volume statistics V20, total dose, BED, dose per fraction, peripheral dose) were not predictive of RP requiring steroid intake after STI for stage I NSCLC.
  • [MeSH-major] Carcinoma, Non-Small-Cell Lung / radiotherapy. Lung Neoplasms / radiotherapy. Radiation Pneumonitis / etiology. Radiotherapy, Computer-Assisted
  • [MeSH-minor] Adrenal Cortex Hormones / therapeutic use. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Predictive Value of Tests. Radiotherapy Dosage. Respiratory Function Tests. Retrospective Studies. Risk Factors. Stereotaxic Techniques

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  • [CommentIn] Cancer J. 2006 Jan-Feb;12(1):19-20 [16613657.001]
  • (PMID = 16613661.001).
  • [ISSN] 1528-9117
  • [Journal-full-title] Cancer journal (Sudbury, Mass.)
  • [ISO-abbreviation] Cancer J
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones
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24. Debevec L, Erzen J, Debeljak A, Crnjac A, Kovac V: Exploratory thoracotomy and its influence on the survival of patients with lung cancer. Wien Klin Wochenschr; 2006 Aug;118(15-16):479-84
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  • [Title] Exploratory thoracotomy and its influence on the survival of patients with lung cancer.
  • PURPOSE: To evaluate diagnostic procedures, reasons for exploratory thoracotomy (ET), causes of unresectability of lung cancer, possibility for reducing numbers of ETs, and the influence of ET on survival.
  • PATIENTS AND METHODS: Between 1990 and 1999, 1808 patients with lung cancer were operated on.
  • ET was performed in 165 (9.1%) of these cases.
  • In total, 131 ET patients were evaluable for analysis.
  • The clinical stages were: three patients in stage IA, 28 in IB, one in IIA, 35 in IIB, 50 in IIIA, 10 in IIIB (all due to invasion of the mediastinum), and four patients in IV (three with ipsilateral pulmonary and one with solitary suprarenal metastasis).
  • The control group for calculating survival difference consisted of 130 consecutive non-operated patients with comparable characteristics (age, sex, clinical stage, performance status, histology and comorbidity) who were diagnosed during the period 1996-1998.
  • RESULTS: The diagnostic procedure before ET comprised bronchoscopy in all patients, transthoracic needle biopsy in 13, cervical mediastinoscopy in nine, parasternal mediastinotomy in two and thoracoscopy in two, in all patients without proving unresectability.
  • A CT scan was performed in 118 patients indicating resectability in 33%, doubtful resectability in 64% and unresectability in 3%.
  • Clinical and surgical staging were equal in 3% of stage IIB patients, in 24% of stage IIIA, 100% of stage IIIB and 75% of patients in stage IV.
  • The 30-day operative mortality was 4.6%.
  • The reasons for ET were: diagnosis of preoperatively unverified tumor in one patient, necessity for pneumonectomy in the case of poor pulmonary function in 11 patients, and unresectability in 119 (due to invasion of the mediastinum in 98 patients, thoracic wall in three and vertebral body in one, and due to pleural metastases in 17 patients).
  • ET could have been avoided in 15 (11%) patients.
  • The median survival for both ET and control group patients was 11.1 months.
  • The survival difference was not statistically significant (p = 0.420).
  • CONCLUSION: ET could be partly avoided through a more accurate preoperative staging procedure.
  • It does not appear possible to avoid ET in patients with limited pulmonary reserve precluding a resection larger than that predicted, nor to avoid ET as a consequence of intraoperative complications.
  • Despite operative mortality, ET did not significantly influence the survival rate in the present study.
  • [MeSH-major] Lung Neoplasms / mortality. Thoracotomy
  • [MeSH-minor] Adrenal Gland Neoplasms / secondary. Adult. Aged. Aged, 80 and over. Chi-Square Distribution. Female. Humans. Lung / pathology. Male. Middle Aged. Neoplasm Invasiveness. Neoplasm Staging. Radiography, Thoracic. Survival Analysis. Tomography, X-Ray Computed

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  • [ISSN] 0043-5325
  • [Journal-full-title] Wiener klinische Wochenschrift
  • [ISO-abbreviation] Wien. Klin. Wochenschr.
  • [Language] eng
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article
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25. Lughezzani G, Sun M, Perrotte P, Jeldres C, Alasker A, Isbarn H, Budäus L, Shariat SF, Guazzoni G, Montorsi F, Karakiewicz PI: The European Network for the Study of Adrenal Tumors staging system is prognostically superior to the international union against cancer-staging system: a North American validation. Eur J Cancer; 2010 Mar;46(4):713-9
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  • [Title] The European Network for the Study of Adrenal Tumors staging system is prognostically superior to the international union against cancer-staging system: a North American validation.
  • BACKGROUND: A reclassification of the International Union Against Cancer (UICC) staging system for adrenocortical carcinoma (ACC) patients has recently been proposed by the European Network for the Study of Adrenal Tumors (ENSAT) to better discriminate between cancer-specific mortality (CSM) risk strata.
  • We formally tested the validity of the modified staging system in a large North American population-based cohort.
  • METHODS: Kaplan-Meier survival curves depicted CSM rates in the overall population and after stratification according to the 2004 UICC or the 2008 ENSAT-staging system.
  • Cox regression models addressing CSM tested the prognostic value of respectively the UICC or the ENSAT-staging system.
  • Harrell's concordance index quantified the accuracy of the standard versus the modified staging system.
  • RESULTS: In the overall population (n=573), the CSM-free survival rates at 1, 3, and 5 years were, respectively, 62.9%, 47.0%, and 38.1%.
  • No statistically significant differences in survival were recorded between 2004 UICC stages II and III patients (p=0.1).
  • Conversely, a statistically significant difference was observed between 2008 ENSAT stage II and stage III patients (p<0.001).
  • The 2008 ENSAT-staging system showed higher accuracy (83.0%) in predicting 3-year CSM rates, relative to the 2004 UICC-staging system (79.5%) (p<0.001).
  • CONCLUSION: Our study corroborates the superior accuracy of the ENSAT-staging system for ACC relative to the 2004 UICC-staging system.
  • In consequence, the 2008 ENSAT-staging system may warrant consideration in the next update of staging manuals.
  • [MeSH-major] Adrenal Gland Neoplasms / pathology. Adrenocortical Carcinoma / pathology. Neoplasm Staging / standards
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Epidemiologic Methods. Female. Humans. Lymphatic Metastasis. Male. Middle Aged. Prognosis. United States / epidemiology. Young Adult


26. Porpiglia F, Fiori C, Daffara F, Zaggia B, Bollito E, Volante M, Berruti A, Terzolo M: Retrospective evaluation of the outcome of open versus laparoscopic adrenalectomy for stage I and II adrenocortical cancer. Eur Urol; 2010 May;57(5):873-8
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  • [Title] Retrospective evaluation of the outcome of open versus laparoscopic adrenalectomy for stage I and II adrenocortical cancer.
  • BACKGROUND: Although there is consensus that laparoscopy is the standard of care for the resection of benign adrenal tumours, there is controversy regarding the role of laparoscopy for the resection of adrenocortical cancer (ACC).
  • OBJECTIVE: The aim of the present study was to review the ACC database of the San Luigi Hospital to compare the oncologic effectiveness of open adrenalectomy (OA) versus laparoscopic adrenalectomy (LA) in the treatment of patients with stage I and II ACC.
  • DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis involving 43 patients with stage I and II ACC who had undergone radical surgery.
  • INTERVENTION: The patients were stratified into two groups according to the surgical procedure.
  • The "open group" consisted of patients treated with OA; the "lap group" consisted of patients treated with LA.
  • MEASUREMENTS: Oncologic effectiveness of the procedures was tested comparing the recurrence-free survival of patients treated with OA versus LA.
  • Secondary outcome measures were differences in terms of type of recurrence and overall survival.
  • RESULTS AND LIMITATIONS: The open group consisted of 25 patients and the lap group of 18 patients.
  • The two groups were comparable in terms of demographic data.
  • The median follow-up was 38 mo in the open group and 30 mo in the lap group.
  • Recurrence rate was 64% in the open group and 50% in the lap group.
  • The median recurrence-free survival was 18 mo in the open group and 23 in the lap group (p=0.8).
  • No differences in terms of pattern of recurrences were recorded.
  • During follow-up, 28% of the open group patients and 5% of the lap group patients died.
  • No differences in terms of survival time were noted (p=0.3).
  • CONCLUSIONS: The present findings provide interesting evidence that OA and LA may be comparable in terms of recurrence-free survival for patients with stage I and II ACC when the principles of surgical oncology are respected.
  • [MeSH-major] Adrenal Cortex Neoplasms / pathology. Adrenal Cortex Neoplasms / surgery. Adrenalectomy / methods. Laparoscopy
  • [MeSH-minor] Adult. Aged. Female. Humans. Male. Middle Aged. Neoplasm Staging. Retrospective Studies. Treatment Outcome. Young Adult

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  • [Copyright] Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • (PMID = 20137850.001).
  • [ISSN] 1873-7560
  • [Journal-full-title] European urology
  • [ISO-abbreviation] Eur. Urol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Switzerland
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27. Landfried K, Bataille F, Rogler G, Brenmoehl J, Kosovac K, Wolff D, Hilgendorf I, Hahn J, Edinger M, Hoffmann P, Obermeier F, Schoelmerich J, Andreesen R, Holler E: Recipient NOD2/CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease. Clin Exp Immunol; 2010 Jan;159(1):87-92
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  • [Title] Recipient NOD2/CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease.
  • Nucleotide-binding oligomerization domain 2/caspase recruitment domain 15 (NOD2/CARD15) polymorphisms have been identified as risk factors of both Crohn's disease and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation.
  • However, the role of these receptors of innate immunity in the pathophysiology of gastrointestinal GVHD is still poorly defined.
  • Immunohistological features of intestinal GVHD were analysed in gastrointestinal biopsies from 58 patients obtained at the time of first onset of intestinal symptoms.
  • The observed changes were correlated with concomitant risk factors and the presence of polymorphisms within the pathogen recognition receptor gene NOD2/CARD15.
  • Intestinal GVHD was associated with a stage-dependent decrease in CD4 T cell infiltrates and an increase in CD8 T cells in the lamina propria; CD8 infiltrates correlated with extent of apoptosis and consecutive epithelial proliferation.
  • The presence of NOD2/CARD15 variants in the recipient was associated with a significant loss of CD4 T cells: in a semiquantitative analysis, the median CD4 score for patients with wild-type NOD2/CARD15 was 1.1 (range 3), but only 0.4 (range 2) for patients with variants (P = 0.002).
  • This observation was independent from severity of GVHD in multivariate analyses and could not be explained by the loss of forkhead box P3(+) T cells.
  • Our results suggest a loss of protective CD4 T cells in intestinal GVHD which is enhanced further by the presence of NOD2/CARD15 variants.
  • Our study might help to identify more selective therapeutic strategies in the future.
  • [MeSH-major] Cell Movement / immunology. Graft vs Host Disease / genetics. Graft vs Host Disease / immunology. Intestines / immunology. Nod2 Signaling Adaptor Protein / genetics. Peripheral Blood Stem Cell Transplantation. Polymorphism, Genetic / immunology
  • [MeSH-minor] Adrenal Cortex Hormones / pharmacology. Adrenal Cortex Hormones / therapeutic use. CD4-Positive T-Lymphocytes / immunology. CD4-Positive T-Lymphocytes / pathology. CD8-Positive T-Lymphocytes / immunology. CD8-Positive T-Lymphocytes / pathology. Cell Count. Forkhead Transcription Factors / metabolism. Humans. Immunosuppressive Agents / pharmacology. Immunosuppressive Agents / therapeutic use. Intestinal Mucosa / pathology. Middle Aged. Mucous Membrane / pathology. Neutrophils / pathology. Transplantation, Homologous / immunology

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  • (PMID = 19912254.001).
  • [ISSN] 1365-2249
  • [Journal-full-title] Clinical and experimental immunology
  • [ISO-abbreviation] Clin. Exp. Immunol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones; 0 / FOXP3 protein, human; 0 / Forkhead Transcription Factors; 0 / Immunosuppressive Agents; 0 / NOD2 protein, human; 0 / Nod2 Signaling Adaptor Protein
  • [Other-IDs] NLM/ PMC2802698
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28. Shen XC, Gu CX, Qiu YQ, Du CJ, Fu YB, Wu JJ: Estrogen receptor expression in adrenocortical carcinoma. J Zhejiang Univ Sci B; 2009 Jan;10(1):1-6
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  • [Title] Estrogen receptor expression in adrenocortical carcinoma.
  • OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare but highly malignant tumor, and its diagnosis is mostly delayed and prognosis is poor.
  • We report estrogen receptor (ER) expression in this tumor and our clinical experiences with 17 ACC cases.
  • METHODS: The data of the 17 patients (9 females and 8 males, age range from 16 to 69 years, mean age of 42.6 years) with ACC were reviewed, and symptoms, diagnostic procedures, treatment, and results of follow-up were evaluated.
  • Immunohistochemistry was used to detect ER expression in tumor samples from the 17 patients.
  • RESULTS: At the time of diagnosis, 4 tumors were classified as Stage I, 4 as Stage II, 3 as Stage III, and 6 as Stage IV.
  • Eight patients demonstrated positive nuclear immunostaining of ER.
  • The prognosis of patients with ER positive was significantly better (P<0.05) than that of patients with ER negative, with 1- and 5-year survival rates at 86% and 60% for ER-positive patients, and 38% and 0% for ER-negative patients, respectively.
  • CONCLUSION: ER-positivity may be one of the factors associated with a worse prognosis of ACC.
  • [MeSH-major] Adrenal Cortex Neoplasms / metabolism. Adrenal Cortex Neoplasms / mortality. Adrenocortical Carcinoma / metabolism. Adrenocortical Carcinoma / mortality. Biomarkers, Tumor / analysis. Neoplasm Proteins / analysis. Receptors, Estrogen / analysis
  • [MeSH-minor] Adolescent. Adult. Aged. China. Female. Humans. Incidence. Male. Middle Aged. Risk Assessment / methods. Risk Factors. Survival Analysis. Survival Rate. Young Adult

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  • (PMID = 19198016.001).
  • [ISSN] 1673-1581
  • [Journal-full-title] Journal of Zhejiang University. Science. B
  • [ISO-abbreviation] J Zhejiang Univ Sci B
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Neoplasm Proteins; 0 / Receptors, Estrogen
  • [Other-IDs] NLM/ PMC2613956
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29. McNutt DM, Holdsworth MT, Wong C, Hanrahan JD, Winter SS: Rasburicase for the management of tumor lysis syndrome in neonates. Ann Pharmacother; 2006 Jul-Aug;40(7-8):1445-50
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  • [Title] Rasburicase for the management of tumor lysis syndrome in neonates.
  • OBJECTIVE: To describe the management of tumor lysis syndrome (TLS) with rasburicase in 2 patients who presented with cancer within the first month of life and compare and contrast both cases with respect to their underlying renal physiology, management, and eventual outcome.
  • CASE SUMMARY: TLS developed in 2 neonates born at 38 weeks' gestational age; both were managed in part with rasburicase.
  • One patient was a 21-day-old infant who received 2 days of induction chemotherapy for the treatment of congenital Stage IV-S neuroblastoma.
  • With a single 0.2 mg/kg dose of rasburicase, the serum urate level normalized and the infant completed therapy without incident.
  • The second patient was a 4-day-old neonate with congenital precursor-B cell acute lymphoblastic leukemia who presented with spontaneous TLS complicated by renal dysfunction.
  • Despite several doses of intravenous rasburicase (2 doses of 0.1 mg/kg and 4 doses of 0.2 mg/kg), as well as aggressive supportive therapy, the infant died of complications arising from uncontrolled TLS.
  • DISCUSSION: Neonates may be at particular risk for TLS given their immature renal function and its predisposition toward metabolic derangements.
  • While rasburicase has the potential to provide a rapid reversal of TLS in this patient population, when TLS is complicated by pre-existing acute renal failure, additional interventions and alternative anti-tumor strategies may be necessary for a successful outcome.
  • When managing TLS in infancy, clinicians must consider the relative degree of renal immaturity and its predisposition toward metabolic derangements.
  • CONCLUSIONS: Rasburicase appears to be well tolerated and effective in lowering serum urate concentrations in the treatment of therapy-related TLS in neonates.
  • However, in instances of spontaneous TLS complicated by the normally low glomerular filtration rate in the newborn infant, the use of rasburicase and other supportive care measures may still be inadequate, warranting further study.
  • [MeSH-major] Tumor Lysis Syndrome / drug therapy. Urate Oxidase / therapeutic use
  • [MeSH-minor] Adrenal Gland Neoplasms / blood. Adrenal Gland Neoplasms / complications. Adrenal Gland Neoplasms / congenital. Adrenal Gland Neoplasms / drug therapy. Antineoplastic Agents / adverse effects. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Female. Humans. Infant, Newborn. Male. Neuroblastoma / blood. Neuroblastoma / complications. Neuroblastoma / congenital. Neuroblastoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood. Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Uric Acid / blood

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  • (PMID = 16868218.001).
  • [ISSN] 1060-0280
  • [Journal-full-title] The Annals of pharmacotherapy
  • [ISO-abbreviation] Ann Pharmacother
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 268B43MJ25 / Uric Acid; EC 1.7.3.3 / Urate Oxidase; EC 1.7.3.3. / rasburicase
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30. Tibaldi C, Vasile E, Bernardini I, Orlandini C, Andreuccetti M, Falcone A: Baseline elevated leukocyte count in peripheral blood is associated with poor survival in patients with advanced non-small cell lung cancer: a prognostic model. J Cancer Res Clin Oncol; 2008 Oct;134(10):1143-9
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  • [Title] Baseline elevated leukocyte count in peripheral blood is associated with poor survival in patients with advanced non-small cell lung cancer: a prognostic model.
  • PURPOSE: We aimed to investigate the prognostic significance of several baseline variables in stage IIIB-IV non-small cell lung cancer to create a model based on independent prognostic factors.
  • METHODS/RESULTS: A total of 320 patients were treated with last generation chemotherapy regimens.
  • The majority of patients received treatment with cisplatin + gemcitabine or gemcitabine alone if older than 70 years or with an ECOG performance status (PS) = 2.
  • Performance status of 2, squamous histology, number of metastatic sites >2, presence of bone, brain, liver and contralateral lung metastases and elevated leukocyte count in peripheral blood were all statistically significant prognostic factors in univariate analyses whereas the other tested variables (sex, stage, age, presence of adrenal gland and skin metastases) were not.
  • Subsequently, a multivariate Cox's regression analysis identified PS 2 (P < 0.001, hazard ratio 2.57), elevated leukocyte count (P < 0.001, hazard ratio 1.79), squamous histology (P = 0.005, hazard ratio 1.45) and presence of brain metastases (P = 0.035, hazard ratio 1.5) as independent prognostic factors for poor survival.
  • Patients were assigned to one of three risk groups according to the cumulative risk defined as the sum of simplified risk scores of the four independent prognostic factors.
  • Low-, intermediate- and high-risk patients achieved a median survival of 10.2 months (95% confidence interval (CI) 8.9-11.6), 5.1 months (95% CI 4.0-6.2) and 2.8 months (95% CI 0.5-5.2), respectively.
  • The high-risk group encompassed PS 2 patients with two or three adjunctive unfavourable independent prognostic factors.
  • CONCLUSIONS: Performance status, white blood cells count, histology and brain metastases resulted in our series prognostic factors of survival in NSCLC patients treated with chemotherapy at a multivariate analysis.
  • Leukocyte count resulted the stronger factor after performance status.
  • If prospectly validated, the proposed prognostic model could be useful to stratify performance status 2 patients in specific future trials.
  • [MeSH-major] Carcinoma, Non-Small-Cell Lung / immunology. Leukocyte Count. Lung Neoplasms / immunology
  • [MeSH-minor] Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Female. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Prognosis

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  • (PMID = 18347812.001).
  • [ISSN] 0171-5216
  • [Journal-full-title] Journal of cancer research and clinical oncology
  • [ISO-abbreviation] J. Cancer Res. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
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31. Lao XM, Chen DY, Zhang YQ, Xiang J, Guo RP, Lin XJ, Li JQ: Primary carcinosarcoma of the liver: clinicopathologic features of 5 cases and a review of the literature. Am J Surg Pathol; 2007 Jun;31(6):817-26
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  • [Title] Primary carcinosarcoma of the liver: clinicopathologic features of 5 cases and a review of the literature.
  • Carcinosarcoma of the liver is very rare worldwide.
  • The terminology and pathogenesis of hepatic carcinosarcoma remain controversial issues.
  • In this article, we studied the clinicopathologic features of 5 cases of hepatic carcinosarcomas (matching the World Health Organization definition), analyzed the clinical data, histologic and immunohistochemical (IHC) results, and discussed the terminology, pathologic differential diagnoses, pathogenesis, and prognosis.
  • The patients were 40 to 68 years old, and included 4 males and 1 female.
  • All patients were Hepatitis B surface antigen positive with para-tumorous cirrhosis.
  • The largest dimensions of the neoplasms ranged from 6.0 to 14.0 cm.
  • Satellite nodules, portal vein tumor thrombi, direct invasion into local tissues (right diaphragm, right adrenal gland, and gastric wall) as well as metastatic foci in lungs and abdominal lymph nodes were identified.
  • Pathologically, the neoplasms consisted of carcinomatous and sarcomatous components.
  • The carcinomatous components were exclusively conventional hepatocellular carcinomas in all 5 cases, whereas the sarcomatous components exhibited complex features.
  • Confirmed by IHC studies, the sarcomatous elements in different cases included rhabdomyosarcomas, malignant fibrous histiocytomas, fibrosarcoma, and poorly differentiated spindle cells without distinctive differentiation.
  • Furthermore, the sarcomatous elements in these 5 neoplasms stained negative for all the epithelial markers we applied for IHC staining, which support the pathologic diagnosis of carcinosarcoma rather than sarcomatoid carcinoma.
  • The presence of transitional zones between carcinomatous and sarcomatous components may support the transformation theory.
  • Four patients with palliative hepatectomy died within 6 months, whereas 1 patient is still alive 21 months after radical resection.
  • The poor prognosis of hepatic carcinosarcoma may be due to their highly invasive and metastatic features.
  • Radical resection of early stage hepatic carcinosarcoma may contribute to a relatively optimistic prognosis.
  • [MeSH-major] Carcinosarcoma / pathology. Liver Neoplasms / pathology
  • [MeSH-minor] Adult. Aged. Diagnosis, Differential. Female. Humans. Immunohistochemistry. Male. Middle Aged

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  • (PMID = 17527068.001).
  • [ISSN] 0147-5185
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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32. Ng VW, Ma RC, So WY, Choi KC, Kong AP, Cockram CS, Chow CC: Evaluation of functional and malignant adrenal incidentalomas. Arch Intern Med; 2010 Dec 13;170(22):2017-20
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  • [Title] Evaluation of functional and malignant adrenal incidentalomas.
  • BACKGROUND: Adrenal incidentalomas are adrenal masses discovered inadvertently.
  • We undertook this study to review the clinical characteristics of patients with adrenal incidentalomas who presented to a tertiary endocrine center in Hong Kong.
  • METHODS: Retrospective review of all 139 cases of adrenal incidentalomas that were referred to the Endocrine Centre of the Prince of Wales Hospital between June 1, 2000, and May 31, 2007.
  • We reviewed detailed patient history, physical examination findings, and symptoms and signs related to hormonal hypersecretion or malignant neoplasm and recorded clinical indications for performing diagnostic radiological imaging.
  • RESULTS: Sixty-one patients (43.9%) had nonfunctional benign adrenal adenomas, 52 (37.4%) had functional lesions, 15 (10.8%) had malignant adrenal lesions, and the remaining 11 (7.9%) had varying adrenal disease.
  • Among those with functional lesions, 27 (19.4%) had lesions that secreted excess cortisol; 12 (8.6%), lesions that secreted aldosterone; 12 (8.6%), lesions that secreted excess catecholamines; and 1 (0.7%), a lesion that demonstrated excess secretion of cortisol and aldosterone.
  • Only 5 of the 27 patients with cortisol-secreting adrenal incidentalomas had symptoms or signs of excess cortisol levels at presentation.
  • CONCLUSIONS: Adrenal incidentaloma is a commonly encountered clinical problem.
  • Functional or primary malignant adrenal incidentalomas can be detected at an earlier stage during hormonal and radiological evaluations, which provides an opportunity for further management.
  • [MeSH-major] Adrenal Gland Neoplasms / diagnosis. Adrenocortical Adenoma / diagnosis. Aldosterone / secretion. Catecholamines / secretion. Hydrocortisone / secretion
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Corticotropin-Releasing Hormone / blood. Early Detection of Cancer. Female. Hong Kong / epidemiology. Humans. Male. Middle Aged. Retrospective Studies

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  • (PMID = 21149760.001).
  • [ISSN] 1538-3679
  • [Journal-full-title] Archives of internal medicine
  • [ISO-abbreviation] Arch. Intern. Med.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Catecholamines; 4964P6T9RB / Aldosterone; 9015-71-8 / Corticotropin-Releasing Hormone; WI4X0X7BPJ / Hydrocortisone; Adrenal incidentaloma
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33. Miller BS, Gauger PG, Hammer GD, Giordano TJ, Doherty GM: Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade. Langenbecks Arch Surg; 2010 Sep;395(7):955-61
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  • [Title] Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade.
  • PURPOSE: Various staging systems for adrenocortical carcinoma (ACC) have been proposed.
  • We hypothesized that incorporating tumor grade into the current European Network for the Study of Adrenal Tumors (ENSAT) staging system would improve the ability to more accurately predict time to recurrence and death.
  • METHODS: A retrospective review of patients included in the University of Michigan ACC database from 2005 to 2009 was done; and stage, tumor grade, time to recurrence, and death were recorded and analyzed using the Cox regression and Kaplan-Meier survival curves.
  • RESULTS: Ninety one patients had complete information for inclusion.
  • The median follow-up was 24 months while the median time to recurrence was 4.1 months.
  • There were 28 deaths; overall, tumor grade showed a significant difference in time to tumor recurrence (p = 0.011) and time to death (p = 0.004).
  • Time to death among stage 2 patients separated into those with high- and low-grade tumors reached statistical significance (p = 0.05), and notable but not statistically significant differences were identified in all stages.
  • Based on tumor grade and survival curves, modifications to the current ENSAT staging system were made.
  • CONCLUSION: Tumor grade plays a significant role in the outcome of patients with ACC.
  • High-grade tumors are associated with shorter disease-free intervals and shorter overall survival.
  • The proposed modification of the ENSAT staging system allows for incorporation of tumor grade when predicting overall survival.
  • [MeSH-major] Adrenal Cortex Neoplasms / mortality. Adrenal Cortex Neoplasms / pathology. Adrenocortical Carcinoma / mortality. Adrenocortical Carcinoma / pathology. Neoplasm Recurrence, Local / mortality. Neoplasm Staging / trends
  • [MeSH-minor] Adolescent. Adrenalectomy / methods. Adult. Aged. Biopsy, Needle. Cohort Studies. Female. Follow-Up Studies. Forecasting. Humans. Immunohistochemistry. Kaplan-Meier Estimate. Male. Middle Aged. Proportional Hazards Models. Retrospective Studies. Risk Assessment. Sensitivity and Specificity. Statistics, Nonparametric. Survival Analysis. Time Factors. Treatment Outcome. Young Adult

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  • (PMID = 20694732.001).
  • [ISSN] 1435-2451
  • [Journal-full-title] Langenbeck's archives of surgery
  • [ISO-abbreviation] Langenbecks Arch Surg
  • [Language] eng
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34. Attard G, Reid AH, A'Hern R, Parker C, Oommen NB, Folkerd E, Messiou C, Molife LR, Maier G, Thompson E, Olmos D, Sinha R, Lee G, Dowsett M, Kaye SB, Dearnaley D, Kheoh T, Molina A, de Bono JS: Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol; 2009 Aug 10;27(23):3742-8
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  • [Title] Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer.
  • PURPOSE: It has been postulated that castration-resistant prostate cancer (CRPC) commonly remains hormone dependent.
  • Abiraterone acetate is a potent, selective, and orally available inhibitor of CYP17, the key enzyme in androgen and estrogen biosynthesis.
  • PATIENTS AND METHODS: This was a phase I/II study of abiraterone acetate in castrate, chemotherapy-naive CRPC patients (n = 54) with phase II expansion at 1,000 mg (n = 42) using a two-stage design to reject the null hypothesis if more than seven patients had a prostate-specific antigen (PSA) decline of > or = 50% (null hypothesis = 0.1; alternative hypothesis = 0.3; alpha = .05; beta = .14).
  • Computed tomography scans every 12 weeks and circulating tumor cell (CTC) enumeration were performed.
  • Prospective reversal of resistance at progression by adding dexamethasone 0.5 mg/d to suppress adrenocorticotropic hormone and upstream steroids was pursued.
  • RESULTS: A decline in PSA of > or = 50% was observed in 28 (67%) of 42 phase II patients, and declines of > or = 90% were observed in eight (19%) of 42 patients.
  • Independent radiologic evaluation reported partial responses (Response Evaluation Criteria in Solid Tumors) in nine (37.5%) of 24 phase II patients with measurable disease.
  • Decreases in CTC counts were also documented.
  • The median time to PSA progression (TTPP) on abiraterone acetate alone for all phase II patients was 225 days (95% CI, 162 to 287 days).
  • Exploratory analyses were performed on all 54 phase I/II patients; the addition of dexamethasone at disease progression reversed resistance in 33% of patients regardless of prior treatment with dexamethasone, and pretreatment serum androgen and estradiol levels were associated with a probability of > or = 50% PSA decline and TTPP on abiraterone acetate and dexamethasone.
  • CONCLUSION: CYP17 blockade by abiraterone acetate results in declines in PSA and CTC counts and radiologic responses, confirming that CRPC commonly remains hormone driven.
  • [MeSH-major] Androgen Antagonists / therapeutic use. Androstenols / therapeutic use. Antineoplastic Agents, Hormonal / therapeutic use. Drug Resistance, Neoplasm. Enzyme Inhibitors / therapeutic use. Neoplasms, Hormone-Dependent / drug therapy. Prostatic Neoplasms / drug therapy. Steroid 17-alpha-Hydroxylase / antagonists & inhibitors
  • [MeSH-minor] Adrenal Cortex Hormones / administration & dosage. Aged. Aged, 80 and over. Androstenes. Disease Progression. Drug Administration Schedule. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Prospective Studies. Prostate-Specific Antigen / blood. Testosterone / blood

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  • (PMID = 19470933.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United Kingdom / Cancer Research UK / / A7851; United Kingdom / Medical Research Council / / ; United Kingdom / Cancer Research UK / / ; United Kingdom / Department of Health / / C51/A7401; United Kingdom / Medical Research Council / / G0501019
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones; 0 / Androgen Antagonists; 0 / Androstenes; 0 / Androstenols; 0 / Antineoplastic Agents, Hormonal; 0 / Enzyme Inhibitors; 3XMK78S47O / Testosterone; EC 1.14.14.19 / Steroid 17-alpha-Hydroxylase; EC 3.4.21.77 / Prostate-Specific Antigen; G819A456D0 / abiraterone
  • [Other-IDs] NLM/ EMS28710; NLM/ PMC3535569
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35. Ohwada S, Izumi M, Tanahashi Y, Kawate S, Hamada K, Tsutsumi H, Horiguchi J, Koibuchi Y, Takahashi T, Yamada M: Combined liver and inferior vena cava resection for adrenocortical carcinoma. Surg Today; 2007;37(4):291-7
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  • [Title] Combined liver and inferior vena cava resection for adrenocortical carcinoma.
  • PURPOSE: Adrenocortical carcinoma (ACC) is a rare malignancy, usually diagnosed at an advanced stage when it has invaded or adhered to adjacent organs.
  • We report our experience of performing combined liver and inferior vena cava (IVC) resection for ACC.
  • METHODS: Six patients with clinical stage III (n = 4) or IV (n = 2) ACC underwent combined resection of the liver and IVC.
  • Two patients underwent extended right hepatectomy, and four underwent segmentectomy.
  • In four patients, the IVC was resected segmentally: it was replaced with expanded polytetrafluoroethylene (ePTFE) in three of these patients, and not reconstructed in one.
  • In two patients, the IVC was partially resected and closed directly.
  • RESULTS: Perioperative mortality was zero, and morbidity was 33.3%, with temporary liver failure in two patients and renal failure in one patient.
  • Recurrence was found within 8.1 months in three (50%) of the six patients.
  • The mean recurrence-free survival period was 20.1 +/- 7.7 months (95% confidence interval [CI]: 5.1-35.4), and the median survival time was 6.1 +/- 9.8 months (95% CI: 00-25.3).
  • The 5-year disease-free survival rate was 16.7%.
  • CONCLUSIONS: Patients with ACC involving both the liver and IVC are candidates for partial hepatectomy and segmental IVC resection.
  • Resection affords the possibility of negative margins, acceptable perioperative morbidity and mortality, and prolonged survival in some patients.
  • [MeSH-major] Adrenal Cortex Neoplasms / pathology. Adrenal Cortex Neoplasms / surgery. Adrenocortical Carcinoma / secondary. Adrenocortical Carcinoma / surgery. Liver Neoplasms / secondary. Liver Neoplasms / surgery. Vena Cava, Inferior / surgery
  • [MeSH-minor] Adult. Aged. Blood Vessel Prosthesis Implantation. Female. Hepatectomy. Humans. Male. Middle Aged. Neoplasm Invasiveness. Neoplasm Recurrence, Local. Neoplasm Staging. Polytetrafluoroethylene. Survival Rate

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  • (PMID = 17387560.001).
  • [ISSN] 0941-1291
  • [Journal-full-title] Surgery today
  • [ISO-abbreviation] Surg. Today
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 9002-84-0 / Polytetrafluoroethylene
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36. Fenske W, Völker HU, Adam P, Hahner S, Johanssen S, Wortmann S, Schmidt M, Morcos M, Müller-Hermelink HK, Allolio B, Fassnacht M: Glucose transporter GLUT1 expression is an stage-independent predictor of clinical outcome in adrenocortical carcinoma. Endocr Relat Cancer; 2009 Sep;16(3):919-28
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  • [Title] Glucose transporter GLUT1 expression is an stage-independent predictor of clinical outcome in adrenocortical carcinoma.
  • Owing to the rarity of adrenocortical carcinoma (ACC) no prognostic markers have been established beyond stage and resection status.
  • Accelerated glycolysis is a characteristic feature of cancer cells and in a variety of tumour entities key factors in glucose metabolism like glucose transporter 1 and 3 (GLUT1 and -3), transketolase like-1 enzyme (TKTL1) and pyruvate kinase type M2 (M2-PK) are overexpressed and of prognostic value.
  • Therefore, we investigated the role of these factors in ACC.
  • Immunohistochemical analysis was performed on tissue microarrays of paraffin-embedded tissue samples from 167 ACCs, 15 adrenal adenomas and 4 normal adrenal glands.
  • Expression was correlated with baseline parameters and clinical outcome.
  • GLUT1 and -3 were expressed in 33 and 17% of ACC samples respectively, but in none of the benign tumours or normal adrenals glands.
  • By contrast, TKTL1 and M2-PK were detectable in all benign tissues and the vast majority of ACCs.
  • GLUT1 expression was strongly associated with prognosis in univariate and multivariate analysis (P<0.01), whereas GLUT3, TKTL1 and M2-PK did not correlate with clinical outcome.
  • Patients with strong GLUT1 staining showed a considerably higher overall mortality (hazard ratio (HR) 6.34 (95% confidence interval 3.10-12.90) compared with patients with no GLUT1 staining.
  • When analysing patients in their early stages and advanced disease separately, similar results were obtained.
  • HR for survival was 5.31 (1.80-15.62) in patients with metastatic ACC and in patients after radical resection the HR for disease-free survival was 6.10 (2.16-16.94).
  • In conclusion, GLUT1 is a highly promising stage-independent, prognostic marker in ACC.
  • [MeSH-major] Adrenal Cortex Neoplasms / diagnosis. Adrenal Cortex Neoplasms / metabolism. Adrenocortical Carcinoma / diagnosis. Adrenocortical Carcinoma / metabolism. Glucose Transporter Type 1 / metabolism
  • [MeSH-minor] Adult. Aged. Biomarkers, Tumor / metabolism. Biomarkers, Tumor / physiology. Female. Glucose / metabolism. Humans. Male. Middle Aged. Neoplasm Staging. Prognosis

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  • (PMID = 19465749.001).
  • [ISSN] 1479-6821
  • [Journal-full-title] Endocrine-related cancer
  • [ISO-abbreviation] Endocr. Relat. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Glucose Transporter Type 1; 0 / SLC2A1 protein, human; IY9XDZ35W2 / Glucose
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37. Casey EM, Harb W, Bradford D, Bufill J, Nattam S, Patel J, Fisher W, Latz JE, Li X, Wu J, Hanna N: Randomized, double-blinded, multicenter, phase II study of pemetrexed, carboplatin, and bevacizumab with enzastaurin or placebo in chemonaïve patients with stage IIIB/IV non-small cell lung cancer: Hoosier Oncology Group LUN06-116. J Thorac Oncol; 2010 Nov;5(11):1815-20
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  • [Title] Randomized, double-blinded, multicenter, phase II study of pemetrexed, carboplatin, and bevacizumab with enzastaurin or placebo in chemonaïve patients with stage IIIB/IV non-small cell lung cancer: Hoosier Oncology Group LUN06-116.
  • INTRODUCTION: : Bevacizumab is approved in combination with chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC).
  • Preclinical data suggest that enzastaurin and bevacizumab may have complementary effects in inhibiting angiogenesis.
  • METHODS: : ELIGIBILITY CRITERIA: ≥18 years of age, chemonaïve, stage IIIB/IV nonsquamous NSCLC, and Eastern Cooperative Oncology Group performance status 0 to 1.
  • Patients were randomized to placebo or enzastaurin 500 mg orally daily (after a loading dose), plus pemetrexed 500 mg/m, carboplatin area under the curve 6, and bevacizumab 15 mg/kg, intravenously, every 21 days for four cycles.
  • Patients without progression received maintenance therapy with bevacizumab and placebo or enzastaurin.
  • The primary objective was progression-free survival (PFS).
  • Planned sample size was 90 patients, one-sided alpha of 0.20, with two interim analyses: one for safety and the second for futility, with a PFS hazard ratio of 0.8857.
  • RESULTS: : Forty patients were randomized.
  • No unique safety concerns were noted at the first interim analysis.
  • The early stopping rule for futility was met at the second interim analysis.
  • Median PFS was 3.5 months and 4.3 months (hazard ratio: 1.04, 95% confidence interval: 0.49-2.21), and response rates were 20% and 30% (p = 0.462) for enzastaurin and placebo, respectively.
  • Grade 3 or 4 toxicity was similar between the two arms.
  • Two patients died on study because of respiratory arrest and pulmonary embolism.
  • An additional patient died of sepsis secondary to a gastrointestinal perforation >30 days after study treatment discontinuation.
  • CONCLUSIONS: : Enzastaurin does not improve efficacy when combined with pemetrexed, carboplatin, and bevacizumab.
  • This combination does not warrant further study in NSCLC.
  • [MeSH-major] Adenocarcinoma / drug therapy. Adrenal Gland Neoplasms / drug therapy. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Neoplasms / drug therapy. Liver Neoplasms / drug therapy. Lung Neoplasms / drug therapy. Pleural Neoplasms / drug therapy
  • [MeSH-minor] Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Humanized. Bevacizumab. Carboplatin / administration & dosage. Double-Blind Method. Female. Glutamates / administration & dosage. Guanine / administration & dosage. Guanine / analogs & derivatives. Humans. Indoles / administration & dosage. Male. Middle Aged. Neoplasm Staging. Pemetrexed. Placebos. Survival Rate. Treatment Outcome


38. Yin ZH, Liu XY, Huang RL, Ren SP: Expression of TNF-alpha and VEGF in the esophagus of portal hypertensive rats. World J Gastroenterol; 2005 Feb 28;11(8):1232-6
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  • [Title] Expression of TNF-alpha and VEGF in the esophagus of portal hypertensive rats.
  • AIM: To investigate the expression of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in the development of esophageal varices in portal hypertensive rats.
  • METHODS: Thirty male Sprague-Dawley (SD) rats in the model group in which a two-stage ligation of portal vein plus ligation of the left adrenal vein was performed, were divided into three subgroups (M(7), M(14), and M(21)) in which the rats were kiued on the seventh day, the 14(th) d and the 21 d after the complete portal ligation.
  • Thirty male SD rats, which underwent the sham operation in the control group, were also separated into three subgroups (C(7), C(14) and C(21)) corresponding to the models.
  • The expression of TNF-alpha and VEGF in the esophagus of all the six subgroups of rats were measured with immunohistochemical SP technique.
  • RESULTS: The portal pressure in the three model subgroups was significantly higher than that in the corresponding control subgroups (23.82+/-1.83 vs 11.61+/-0.86 cmH(2)O, 20.90+/-3.27 vs 11.43+/-1.55 cmH(2)O and 20.68+/-2.27 vs 11.87+/-0.79 cmH(2)O respectively, P<0.01), as well as the number (9.3+/-1.6 vs 5.1+/-0.8, 11.1+/-0.8 vs 5.4+/-1.3 and 11.7+/-1.5 vs 5.2+/-1.1 respectively, P<0.01) and the total vascular area (78 972.6+/-3 527.8 vs 12 993.5+/-4 994.8 mum(2), 107 207.5+/-4 6461.4 vs 11 862.6+/-5 423.2 mum(2) and 110 241.4+/-49 262.2 vs 11 973.7+/-3 968.5 mum(2) respectively, P<0.01) of submucosal veins in esophagus.
  • Compared to the corresponding controls, the expression of TNF-alpha and VEGF in M(21) was significantly higher (2.23+/-0.30 vs 1.13+/-0.28 and 1.65+/-0.38 vs 0.56+/-0.30 for TNF-alpha and VEGF respectively, P<0.01), whereas there was no difference in M(7) (1.14+/-0.38 vs 1.06+/-0.27 and 0.67+/-0.35 vs 0.50+/-0.24 for TNF-alpha and VEGF respectively, P>0.05) and M(14) (1.20+/-0.25 vs 1.04+/-0.26 and 0.65+/-0.18 vs 0.53+/-0.25 for TNF-alpha and VEGF respectively, P>0.05).
  • And the expression of TNF-alpha and VEGF in M(21) was significantly higher than that in M(7) (2.23+/-0.30 vs 1.14+/-0.38 and 1.65+/-0.38 vs 0.67+/-0.35 for TNF-alpha and VEGF respectively, P<0.01) and M(14) (2.23+/-0.30 vs 1.20+/-0.25 and 1.65+/-0.38 vs 0.65+/-0.18 for TNF-alpha and VEGF respectively, P<0.01), but there was no difference between M(7) and M(14) (1.14+/-0.38 vs 1.20+/-0.25 and 0.67+/-0.35 vs 0.65+/-0.18 for TNF-alpha and VEGF respectively, P>0.05).
  • CONCLUSION: In the development of esophageal varices in portal hypertensive rats, increased TNF-alpha and VEGF may be not an early event, and probably play a role in weakening the esophageal wall and the rupture of esophageal varices.
  • [MeSH-major] Esophageal and Gastric Varices / metabolism. Esophagus / metabolism. Hypertension, Portal / metabolism. Tumor Necrosis Factor-alpha / metabolism. Vascular Endothelial Growth Factor A / metabolism
  • [MeSH-minor] Animals. Blood Pressure. Male. Mucous Membrane / blood supply. Mucous Membrane / metabolism. Rats. Rats, Sprague-Dawley. Rupture. Veins / pathology

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  • (PMID = 15754412.001).
  • [ISSN] 1007-9327
  • [Journal-full-title] World journal of gastroenterology
  • [ISO-abbreviation] World J. Gastroenterol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Tumor Necrosis Factor-alpha; 0 / Vascular Endothelial Growth Factor A
  • [Other-IDs] NLM/ PMC4250721
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39. Bodendorf MO, Haas V, Laberke HG, Blumenstock G, Wex P, Graeter T: Prognostic value and therapeutic consequences of vascular invasion in non-small cell lung carcinoma. Lung Cancer; 2009 Apr;64(1):71-8
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  • [Title] Prognostic value and therapeutic consequences of vascular invasion in non-small cell lung carcinoma.
  • The prognostic relevance of blood vessel invasion (BVI) in non-small cell lung carcinoma (NSCLC) remains controversial, as is the question of whether its finding should influence therapeutic decisions after an R0 resection.
  • One hundred and twelve cases of NSCLC were included in the study.
  • All had been treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy.
  • In all cases, lymphatic metastatic spread was at its earliest stage and only one regional lymph node was involved, 27.0+/-8.9 nodes per patient being examined histologically.
  • Most of the cases were pT2 (75.9%) and pN1 (81.3%), and all were MX/M0 and R0.
  • 62.5% were at stage IIB, 25.9% at stage IIIA, and 9.8% at stage IIA.
  • BVI was found in 45.5% of the tumors (V1), and 18.8% exhibited both lymphatic invasion and BVI (L1V1).
  • Local recurrence occurred in 10.7% of the patients, distant metastasis in 24.1%, and both forms of tumor progression simultaneously in a further 7.1%.
  • Thus 31.2% of the patients developed distant metastases by hematogenous spread (to the brain, bones, lung, adrenal, and liver, in descending order of frequency), mostly within two years of surgery.
  • Late metastasis is not typical of NSCLC.
  • Adenocarcinomas showed a strong tendency to be associated with a poorer prognosis than squamous cell carcinomas, probably because of their more frequent involvement of blood vessels.
  • Five-year survival (Kaplan-Meier method) was significantly lower in V1 cases (37.2%) than in V0 cases (56.0%; p = 0.0249).
  • Adjuvant mediastinal radiation in node-positive cases of NSCLC may prevent local recurrence but is unlikely to influence the development of distant metastases.
  • The histological detection of BVI is of prognostic relevance and should be considered for inclusion in the staging criteria and indications for adjuvant chemotherapy.
  • [MeSH-major] Carcinoma, Non-Small-Cell Lung / secondary. Lung Neoplasms / pathology. Neoplastic Cells, Circulating / pathology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Disease Progression. Female. Humans. Lymph Node Excision. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Invasiveness. Neoplasm Staging. Pneumonectomy. Prognosis. Survival Rate. Treatment Outcome

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  • (PMID = 18790545.001).
  • [ISSN] 0169-5002
  • [Journal-full-title] Lung cancer (Amsterdam, Netherlands)
  • [ISO-abbreviation] Lung Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Ireland
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40. Goel MC, Mohammadi Y, Sethi AS, Brown JA, Sundaram CP: Pathologic upstaging after laparoscopic radical nephrectomy. J Endourol; 2008 Oct;22(10):2257-61
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  • [Title] Pathologic upstaging after laparoscopic radical nephrectomy.
  • OBJECTIVE: Accurate tumor staging in renal cancer is critical for prognostic projections, follow-up schedules, clinical trials and potential systemic therapies.
  • We studied patients undergoing laparoscopic radical nephrectomy (LRN) to determine the extent of upstaging on histopathology evaluation and correlated the clinical and pathology staging to determine the factors responsible for upstaging.
  • PATIENTS AND METHODS: A retrospective review of patients undergoing LRN for renal cell cancer was performed.
  • Clinical staging was determined by CT/MRI scan and/or related preoperative work up (using AJCC TNM staging criteria).
  • Histopathology reports were studied in to determine the p-stage.
  • Lymph node (LN) status was evaluated with attention to number and positivity of LNs in the specimen.
  • Pathologic features that dictated upstaging were analyzed.
  • The factors responsible for pathologic upstaging were analyzed.
  • Statistical analysis was performed using JMP 5.0.12 software; comparisons were done using chi square or Fisher exact test.
  • RESULTS: One hundred twenty three patients qualified for the study; mean age was 62.14+/-13.6 years, M:F ratio was 60:63 and mean tumor size of 5.3+/-2.0 cm.
  • Clinical versus pathologic T stage distribution was T1a=41:37, T1b=43:31, T2=25:12, T3a=11:31, T3b=3:10 and T4=0:2.
  • A total 38/123 (31%) patients were upstaged following histopathology examination.
  • Upstaging was due to change in tumor size in 12, renal sinus fat involvement in 8, renal or adrenal vein involvement in 14, focal perirenal fat involvement in 6, and focal renal capsule penetration in 4 patients.
  • Fifty two patients had LNs in the specimen with 19 (16%) patients had 2 or more lymph nodes and 5 had positive LNs.
  • Mean tumor size was 5.3+/-2 cms at clinical, and 5.0+/-2.6 cms at pathology staging (P=NS).
  • 5 patients had LN metastasis detected with tumor size of 5.5, 5.6, 6.8, and 7.2 cms in diameter, and one patient with LN metastasis was T1a stage (3.2 cm).
  • Renal vein/inferior venal cava/adrenal vein was involved in 14 patients, adrenal was involved in 21 patients and renal sinus was involved in 19/123 patients.
  • CONCLUSIONS: Pathologic upstaging of malignant renal neoplasms occurred in about 31% of patients following LRN.
  • Down staging was less common and mean tumor size does not significantly change.


41. Balogova S, Huchet V, Kerrou K, Nataf V, Gutman F, Antoine M, Ruppert AM, Prignon A, Lavolée A, Montravers F, Mayaud C, Cadranel J, Talbot JN: Detection of bronchioloalveolar cancer by means of PET/CT and 18F-fluorocholine, and comparison with 18F-fluorodeoxyglucose. Nucl Med Commun; 2010 May;31(5):389-97
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  • [Title] Detection of bronchioloalveolar cancer by means of PET/CT and 18F-fluorocholine, and comparison with 18F-fluorodeoxyglucose.
  • AIM: Bronchioloalveolar (BAC) cancer is a source of false-negative F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) results.
  • A few studies reported better diagnostic performances with PET tracers of lipid metabolism, C-choline, or C-acetate, for the detection of well-differentiated adenocarcinoma or BAC.
  • F-fluorocholine (FCH) is a lipid analogue for PET imaging, with advantages in terms of logistics and image resolution.
  • We carried out this prospective pilot study to evaluate whether FCH PET/CT could detect lung cancer with a BAC component and could be more sensitive than FDG in this aim.
  • METHODS: Fifteen patients with a lung nodule or lesion suspected for BAC on CT and/or with a history of BAC had PET/CT 60-90 min after 5 MBq FDG/kg body mass and, on a separate day, 10-20 min after 4 MBq FCH/kg body mass.
  • The standard of truth was histology and a 6-month follow-up.
  • RESULTS: Nine patients (12 lesions) presented BAC or adenocarcinoma with BAC features, two patients presented adenocarcinoma without BAC features (five lesions) and four patients presented benign lesions (15 non-malignant sites).
  • For both FCH and FDG, patient-based sensitivity was 78% for detecting cancer with a BAC component and 82% for detecting malignancy.
  • Site-based sensitivity for detecting malignancy was 76 and 75% for detecting cancer with BAC features, for both radiopharmaceuticals.
  • Specificity was similar for FCH and FDG (site-based 93 vs. 81%, NS).
  • In these early-stage cancers, only one adrenal metastasis was observed that took up FCH and FDG.
  • CONCLUSION: In this population of patients with ground-glass opacities selected on CT suggestive of BAC or with a history of BAC and a recent lung anomaly on CT, FCH detected all malignant lesions with at least a 2.0 cm short axis.
  • However, FDG had similar performance.
  • [MeSH-major] Adenocarcinoma, Bronchiolo-Alveolar / radiography. Adenocarcinoma, Bronchiolo-Alveolar / radionuclide imaging. Choline / analogs & derivatives. Fluorodeoxyglucose F18. Positron-Emission Tomography / methods. Tomography, X-Ray Computed / methods
  • [MeSH-minor] Aged. Aged, 80 and over. Biological Transport. Female. Humans. Lung Neoplasms / metabolism. Lung Neoplasms / radiography. Lung Neoplasms / radionuclide imaging. Male. Middle Aged. Sensitivity and Specificity

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  • (PMID = 20145579.001).
  • [ISSN] 1473-5628
  • [Journal-full-title] Nuclear medicine communications
  • [ISO-abbreviation] Nucl Med Commun
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / fluorocholine; 0Z5B2CJX4D / Fluorodeoxyglucose F18; N91BDP6H0X / Choline
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42. Cheng Y, Li J, Martinka M, Li G: The expression of NAD(P)H:quinone oxidoreductase 1 is increased along with NF-kappaB p105/p50 in human cutaneous melanomas. Oncol Rep; 2010 Apr;23(4):973-9
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  • [Title] The expression of NAD(P)H:quinone oxidoreductase 1 is increased along with NF-kappaB p105/p50 in human cutaneous melanomas.
  • NAD(P)H:quinone oxidoreductase 1 (NQO1) is a key enzyme involved in metabolism of quinones and may perform multiple functions within the cell.
  • Recent studies demonstrated that NQO1 is overexpressed in many types of tumors, including the lung, ovary, adrenal gland, thyroid, liver, colon, breast, and pancreas.
  • To investigate whether NQO1 plays a role in melanoma pathogenesis, we used tissue microarray technology and immunohistochemistry to examine NQO1 expression in 56 dysplastic nevi and 93 primary melanoma biopsies.
  • Our data showed that NQO1 expression is significantly increased in primary melanomas compared with dysplastic nevi (P=0.015, chi2 test).
  • Our results also revealed that the increase of NQO1 was not associated with patient age, tumor thickness, ulceration, tumor site, American Joint Committee on Cancer (AJCC) stage, and 5-year patient survival.
  • Interestingly, we found that female patients had more NQO1 expression than male patients (P=0.022, chi2 test).
  • Furthermore, NQO1 expression level was significantly higher in superficial spreading melanomas compared with other tumor subtypes (P=0.020, chi2 test).
  • Moreover, we found that NQO1 expression is significantly correlated with the expression of NF-kappaB subunit p50 (P=0.032, chi2 test).
  • Our findings suggest that NQO1 may play an important role in the initiation stage of melanoma development.
  • [MeSH-major] Melanoma / metabolism. NAD(P)H Dehydrogenase (Quinone) / biosynthesis. NF-kappa B p50 Subunit / biosynthesis. Skin Neoplasms / metabolism
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Immunohistochemistry. Kaplan-Meier Estimate. Male. Middle Aged. Neoplasm Staging. Sex Factors. Tissue Array Analysis. Young Adult

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  • (PMID = 20204281.001).
  • [ISSN] 1791-2431
  • [Journal-full-title] Oncology reports
  • [ISO-abbreviation] Oncol. Rep.
  • [Language] eng
  • [Grant] Canada / Canadian Institutes of Health Research / / MOP-84559; Canada / Canadian Institutes of Health Research / / MOP-93810
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / NF-kappa B p50 Subunit; EC 1.6.5.2 / NAD(P)H Dehydrogenase (Quinone); EC 1.6.5.2 / NQO1 protein, human
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43. Uka K, Aikata H, Takaki S, Shirakawa H, Jeong SC, Yamashina K, Hiramatsu A, Kodama H, Takahashi S, Chayama K: Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World J Gastroenterol; 2007 Jan 21;13(3):414-20
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  • [Title] Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma.
  • AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients.
  • METHODS: After the diagnosis of HCC, all 995 consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period.
  • We assessed their clinical features, prognosis, and treatment strategies.
  • RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%).
  • The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively.
  • The median survival time was 4.9 mo (range, 0-37 mo).
  • Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure.
  • CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor.
  • With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases.
  • Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly, treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatic tumor stage (T0-T2), and are free of portal venous invasion may improve survival.
  • [MeSH-major] Carcinoma, Hepatocellular / diagnosis
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Cause of Death. Female. Humans. Liver Neoplasms / diagnosis. Liver Neoplasms / mortality. Liver Neoplasms / therapy. Male. Middle Aged. Neoplasm Metastasis / diagnosis. Neoplasm Metastasis / therapy. Prognosis. Retrospective Studies

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  • (PMID = 17230611.001).
  • [ISSN] 1007-9327
  • [Journal-full-title] World journal of gastroenterology
  • [ISO-abbreviation] World J. Gastroenterol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] China
  • [Other-IDs] NLM/ PMC4065897
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44. Miyazaki T, Tagawa T, Nakamura A, Yamasaki N, Hashizume S, Matsumoto K, Taguchi T, Morino S, Nagayasu T: [Surgical treatment for stage IV lung cancer]. Kyobu Geka; 2006 Jan;59(1):36-40
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  • [Title] [Surgical treatment for stage IV lung cancer].
  • OBJECTIVE: To find out the optimal surgical indication in stage IV lung cancer patients, we evaluated them retrospectively.
  • METHODS & RESULTS: From 1975 to 2005, 62 patients without multiple metastases were operated at our hospital.
  • The most common histological type was adenocarcinoma (67.7%).
  • The metastatic lesions were lung (33.9%), brain (24.2%), liver, bone, adrenal gland and so on.
  • The overall survival rate of stage IV lung cancer was 10.4% at 5-year.
  • Five-year survival for patients with lung or brain metastasis who had no lymph node metastasis were significantly more superior than those with lymph node metastasis (p=0.0389, 0.0021).
  • Four of 62 patients had 5-year survival.
  • Two were lung and the others were brain and adrenal gland metastasis without lymph node metastasis.
  • CONCLUSION: Stage IV lung cancer with lung or brain or adrenal gland metastasis without lymph node metastasis should be resected.
  • [MeSH-major] Lung Neoplasms / pathology. Lung Neoplasms / surgery
  • [MeSH-minor] Adenocarcinoma / mortality. Adenocarcinoma / surgery. Adult. Aged. Aged, 80 and over. Brain Neoplasms / mortality. Brain Neoplasms / secondary. Female. Humans. Male. Middle Aged. Neoplasm Staging / mortality. Retrospective Studies. Survival Analysis

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  • (PMID = 16440683.001).
  • [ISSN] 0021-5252
  • [Journal-full-title] Kyobu geka. The Japanese journal of thoracic surgery
  • [ISO-abbreviation] Kyobu Geka
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Japan
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45. Bedke J, Buse S, Pritsch M, Macher-Goeppinger S, Schirmacher P, Haferkamp A, Hohenfellner M: Perinephric and renal sinus fat infiltration in pT3a renal cell carcinoma: possible prognostic differences. BJU Int; 2009 May;103(10):1349-54
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  • [Title] Perinephric and renal sinus fat infiltration in pT3a renal cell carcinoma: possible prognostic differences.
  • OBJECTIVE: To evaluate the influence of perinephric (PN) and renal sinus (RS) fat infiltration on cancer-specific survival beyond other prognostic factors, as the Tumour-Node-Metastasis (TNM) classification system defines stage T3a renal cell carcinoma (RCC) as infiltration of perirenal fat and/or direct infiltration of the adrenal gland.
  • Perirenal fat invasion is differentiated into RS and PN fat infiltration, but not further classified for the prognosis.
  • PATIENTS AND METHODS: From 1990 to October 2007 106 patients with advanced RCC (T3a) were followed prospectively at one academic centre; all had a radical nephrectomy.
  • To identify prognostic effects of PN, RS or RS + PN fat infiltration, univariable and multivariable Cox proportional hazard regression models were applied, including lymph node status, metastases, presence of sarcomatoid features and tumour necrosis, Fuhrman's grade, Karnofsky performance status, and tumour size.
  • RESULTS: PN fat invasion alone was present in 58, RS in 21, and PN + RS in 27 patients.
  • The median follow-up was 2.9 years; 49 patients died from RCC.
  • In univariable and multivariable analyses RS fat infiltration was an unfavourable prognostic factor (adjusted hazard ratio, HR, 2.24, P = 0.019).
  • Univariable analysis of RS + PN fat infiltration showed the worst prognostic effect (HR 3.25, P < 0.001).
  • In multivariable analysis this combination was an independent prognostic factor (HR 2.75, P = 0.007), as was the presence of metastasis (HR 5.64, P < 0.001).
  • In this group of RS + PN fat infiltration the 5-year cancer-specific survival was 31%.
  • CONCLUSION: Univariable and multivariable analyses showed that the combination of RS and PN fat infiltration is an independent unfavourable prognostic marker.
  • We recommend that perirenal fat infiltration should be further differentiated into RS fat or PN infiltration in the TNM classification.
  • This will better stratify patient prognosis and might allow those in need of adjuvant therapy to be identified.
  • [MeSH-major] Adipose Tissue / pathology. Carcinoma, Renal Cell / pathology. Kidney Neoplasms / pathology. Nephrectomy / methods
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Epidemiologic Methods. Female. Humans. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Staging. Prognosis

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  • (PMID = 19076147.001).
  • [ISSN] 1464-410X
  • [Journal-full-title] BJU international
  • [ISO-abbreviation] BJU Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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46. Khorram-Manesh A, Ahlman H, Nilsson O, Friberg P, Odén A, Stenström G, Hansson G, Stenquist O, Wängberg B, Tisell LE, Jansson S: Long-term outcome of a large series of patients surgically treated for pheochromocytoma. J Intern Med; 2005 Jul;258(1):55-66
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  • [Title] Long-term outcome of a large series of patients surgically treated for pheochromocytoma.
  • OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997.
  • PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years.
  • DESIGN: Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long-term outcome after treatment.
  • SETTING: One referral centre for all patients from the western region of Sweden.
  • RESULTS: During an observation of 15 +/- 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001).
  • There was no intra- or post-operative mortality.
  • Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours.
  • Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes.
  • Besides older age at primary surgery, elevated urinary excretion of methoxy-catecholamines was the only observed risk factor for death (P = 0.02).
  • At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive.
  • However, pre- and post-operative hypertension did not influence the risk for death versus controls.
  • CONCLUSION: Pheochromocytoma/PG can be safely treated by surgery.
  • Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death.
  • We recommend life-long follow-up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases.
  • This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.
  • [MeSH-major] Adrenal Gland Neoplasms / surgery. Pheochromocytoma / surgery
  • [MeSH-minor] Adrenal Medulla / pathology. Adult. Aged. Blood Pressure / physiology. Female. Humans. Hyperplasia. Hypertension / complications. Male. Middle Aged. Neoplasm Invasiveness. Paraganglioma / mortality. Paraganglioma / pathology. Paraganglioma / surgery. Postoperative Period. Preoperative Care / methods. Receptors, Adrenergic, alpha / administration & dosage. Retrospective Studies. Survival Analysis. Treatment Outcome

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  • (PMID = 15953133.001).
  • [ISSN] 0954-6820
  • [Journal-full-title] Journal of internal medicine
  • [ISO-abbreviation] J. Intern. Med.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Receptors, Adrenergic, alpha
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47. Thompson RH, Leibovich BC, Cheville JC, Webster WS, Lohse CM, Kwon ED, Frank I, Zincke H, Blute ML: Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma? J Urol; 2005 Oct;174(4 Pt 1):1218-21
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  • [Title] Is renal sinus fat invasion the same as perinephric fat invasion for pT3a renal cell carcinoma?
  • PURPOSE: Perinephric and renal sinus fat invasion are classified as pT3a renal cell carcinoma (RCC) according to the 2002 American Joint Committee on Cancer.
  • We investigated the prognostic significance of each of these pathological features using a cohort of pT3a patients.
  • MATERIALS AND METHODS: Between 1970 and 2002, 205 patients without direct adrenal invasion underwent nephrectomy for pT3a clear cell RCC.
  • The associations of fat invasion with death from RCC were evaluated using Cox proportional hazards regression models.
  • RESULTS: Of the 162 patients with perinephric fat invasion and 43 patients with renal sinus fat invasion 95 (59%) and 31 (72%), respectively, died of RCC.
  • Patients with renal sinus fat invasion were 63% more likely to die of RCC compared with those with perinephric fat invasion (RR 1.63, 95% CI 1.09-2.46, p=0.018).
  • In addition, the risk of death persisted in multivariate analysis after adjusting for regional lymph nodes and distant metastases (RR 1.91, 95% CI 1.26-2.89, p=0.002) and after adjusting for the Mayo Clinic SSIGN (stage, size, grade and necrosis) score (RR 1.90, 95% CI 1.25-2.88, p=0.003).
  • CONCLUSIONS: Our results indicate that clear cell tumors invading the renal sinus fat are more aggressive than tumors with perinephric fat involvement.
  • We believe both of these features should be individually assessed during routine pathological examination.
  • External validation is needed before suggesting a change to the TNM staging system.
  • [MeSH-major] Carcinoma, Renal Cell / pathology. Kidney Neoplasms / pathology
  • [MeSH-minor] Adipose Tissue / pathology. Adrenal Glands / pathology. Aged. Female. Humans. Lymphatic Metastasis. Male. Middle Aged. Multivariate Analysis. Neoplasm Invasiveness. Neoplasm Staging. Prognosis

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  • [CommentIn] Adv Anat Pathol. 2007 Mar;14(2):63-8 [17471114.001]
  • (PMID = 16145373.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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48. Sharma S, Sharma MC, Johnson MH, Lou M, Thakar A, Sarkar C: Esthesioneuroblastoma - a clinicopathologic study and role of DNA topoisomerase alpha. Pathol Oncol Res; 2007;13(2):123-9
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  • [Title] Esthesioneuroblastoma - a clinicopathologic study and role of DNA topoisomerase alpha.
  • Esthesioneuroblastoma (ENB) differs from adrenal neuroblastomas in its histopathologic and biologic characteristics.
  • Hyams grading and Kadish staging have shown correlation with survival.
  • Scant data are available on proliferation indices and prognosis.
  • We retrospectively reviewed the clinicopathologic characteristics of ENB.
  • Both Kadish and UCLA staging systems were used.
  • Hyams grading was simplified into low and high grade.
  • DNA topoisomerase II alpha labeling index (T2alpha LI) was obtained in 8 cases using immunohistochemistry.
  • Of the 19 cases studied, 14 were males and 5 females.
  • Age range was 2 to 62 years (average 27 years).
  • The mass primarily involved the nose in 12 (63%) and paranasal sinuses in 7 cases (37%).
  • Patients presented with nose block in 19 (100%), epistaxis in 10 (53%), proptosis in 9 (47%) and loss of vision in 6 cases (32%).
  • Bony involvement was seen in 7 cases (37%), and intracranial spread in one case (5%).
  • Thirteen (68%) were low-grade tumors and 6 were (32%) high-grade.
  • There was no statistically significant difference between the low- and high-grade ENB in age (years) (p=0.2882), duration of symptoms (months) (p=0.5636), and either in the Kadish (p=0.5456) or the UCLA staging system (p=0.7771).
  • The difference in DNA topoisomerase alpha labeling index between the low- and highgrade ENB (medians: 10.4 and 22.3, respectively) was not statistically significant (p=0.0714), but it was suggestive of a positive association.
  • The results of this study should be interpreted with caution, because of the limited sample size.
  • Three cases recurred locally, one each stage A, B and C, but all low-grade.
  • This preliminary study suggests the need to combine a simplified histologic grading with accurate staging in a reasonable attempt to assess local progression in esthesioneuroblastoma.
  • Larger studies may clarify the role of T2alpha LI in improving histologic grading.
  • [MeSH-major] Antigens, Neoplasm / physiology. DNA Topoisomerases, Type II / physiology. DNA-Binding Proteins / physiology. Esthesioneuroblastoma, Olfactory / enzymology. Nasal Cavity / enzymology. Nose Neoplasms / enzymology
  • [MeSH-minor] Adolescent. Adult. Cell Proliferation. Female. Gene Expression Regulation, Enzymologic. Gene Expression Regulation, Neoplastic. Humans. Male. Middle Aged. Neoplasm Staging. Retrospective Studies

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  • (PMID = 17607373.001).
  • [ISSN] 1219-4956
  • [Journal-full-title] Pathology oncology research : POR
  • [ISO-abbreviation] Pathol. Oncol. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / DNA-Binding Proteins; EC 5.99.1.3 / DNA Topoisomerases, Type II; EC 5.99.1.3 / DNA topoisomerase II alpha
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49. Pan ZQ, Fang ZQ, Lu WL, Liang C, Wu ZH, Liu XM, Hou L, Zhang H, Zhuo SY, Liao MJ, Gao BF: [Differentially expressed genes in adrenal gland of H22 liver cancer mice with different syndromes and in different stages]. Zhong Xi Yi Jie He Xue Bao; 2008 Aug;6(8):843-51
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  • [Title] [Differentially expressed genes in adrenal gland of H22 liver cancer mice with different syndromes and in different stages].
  • OBJECTIVE: To reveal the characteristics of gene expression in adrenal gland of H22 tumor mice with typical syndromes and in different liver cancer stages.
  • METHODS: By the quantitative four diagnosis and syndrome differentiation methods and GeneChip Mouse Exon 1.0 ST Array, we observed adrenal gland gene expression in H22 tumor mice with pathogenic factor-toxin predominance syndrome and qi deficiency syndrome in the earlier stage, yang-qi deficiency syndrome in the intermediate stage, and qi-yin-yang deficiency syndrome in the advanced stage.
  • Genes highly expressed and remarkably different were analyzed in this study.
  • RESULTS: A total of seventy-three up-regulated coincident genes and twenty-six down-regulated coincident genes in different stages were investigated in the study.
  • Up-regulated coincident genes included Hp, C3, Anxa1, Procr, C2, Il4ra, Cd14, Ptprc, Cd52, C4b, Eno3, Xdh, Gpx3, and so on.
  • Down-regulated coincident genes included nervous system function-related genes such as Plp1, Mbp, Aldh1a1, Cck, Atn1, genes associated with electrolyte metabolism such as Aldh1a1 and Slc22a17, genes related to signal transduction such as Cxcr4, Spag5 and Stmn3, etc, and genes related to transcriptional control and protein biosynthesis such as Hspa1a, Dnajb1, Thra, Hhex and so on.
  • CONCLUSION: With the development of the tumorigenesis, the symptoms and signs and differentially expressed genes in adrenal gland of H22 tumor mice can be measured.
  • Up-regulated and down-regulated coincident genes may be the features of H22 tumor mice different from those of normal mice.
  • [MeSH-major] Adrenal Glands / metabolism. Diagnosis, Differential. Gene Expression Profiling. Liver Neoplasms, Experimental / genetics. Medicine, Chinese Traditional
  • [MeSH-minor] Animals. Gene Expression Regulation, Neoplastic. Male. Mice. Oligonucleotide Array Sequence Analysis. Random Allocation. Syndrome


50. Eisen T, Thatcher N, Leyvraz S, Miller WH Jr, Couture F, Lorigan P, Lüthi F, Small D, Tanovic A, O'Brien M: Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer. Lung Cancer; 2009 Apr;64(1):60-5
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  • [Title] Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.
  • OBJECTIVE: To evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.2mg/m(2) to patients with small cell lung cancer (SCLC) who relapsed or progressed after one line of chemotherapy.
  • PATIENTS AND METHODS: This was a multicenter, open-label, single-arm, exploratory, phase II clinical trial.
  • Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks.
  • Objective response rate (primary efficacy endpoint) was evaluated according to response evaluation criteria in solid tumors (RECIST).
  • The rate of stable disease (SD) lasting for at least 6 months and time-to-event variables were secondary endpoints of efficacy.
  • Toxicity was assessed using National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0.
  • RESULTS: Twenty pretreated SCLC patients (median age, 60 years) with extensive (n = 13) or limited-stage disease (n = 7) received a total of 24 treatment cycles (median, one cycle per patient; range, 1-2).
  • Objective tumor responses were not observed and only one of the 17 evaluable patients had SD.
  • With a median follow-up of 11.8 months, the progression-free survival and the median overall survival were 1.3 months and 4.8 months, respectively.
  • The most troubling or common toxicities were fatigue, muscle weakness, lymphopenia, anemia (no patients showed neutropenia), and asymptomatic, non-cumulative increase of transaminases levels and alkaline phosphatase.
  • CONCLUSION: This clinical trial shows that a cycle of 1h weekly i.v. infusion of plitidepsin (3.2mg/m(2)) was generally well tolerated other than fatigue and muscle weakness in patients with pretreated SCLC.
  • One patient died due to multi-organ failure.
  • The absence of antitumor activity found here precludes further studies of this plitidepsin schedule as second-line single-agent treatment of SCLC.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Depsipeptides / administration & dosage. Lung Neoplasms / drug therapy. Small Cell Lung Carcinoma / drug therapy
  • [MeSH-minor] Adrenal Gland Neoplasms / drug therapy. Adrenal Gland Neoplasms / secondary. Adult. Aged. Bone Neoplasms / drug therapy. Bone Neoplasms / secondary. Female. Humans. Infusions, Intravenous. Liver Neoplasms / drug therapy. Liver Neoplasms / secondary. Lymphatic Metastasis. Male. Maximum Tolerated Dose. Middle Aged. Neoplasm Staging. Prognosis. Salvage Therapy. Skin Neoplasms / drug therapy. Skin Neoplasms / secondary. Survival Rate. Treatment Outcome

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  • (PMID = 18692272.001).
  • [ISSN] 0169-5002
  • [Journal-full-title] Lung cancer (Amsterdam, Netherlands)
  • [ISO-abbreviation] Lung Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Depsipeptides; Y76ID234HW / aplidine
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51. Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A: Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med; 2007 Jun 7;356(23):2372-80
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Adjuvant mitotane treatment for adrenocortical carcinoma.
  • BACKGROUND: Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection.
  • Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial.
  • Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival.
  • METHODS: We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005.
  • Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery.
  • RESULTS: Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group.
  • Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared with 10 months in control group 1 and 25 months in control group 2).
  • Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively.
  • Multivariate analysis indicated that mitotane treatment had a significant advantage for recurrence-free survival.
  • Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients.
  • CONCLUSIONS: Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma.
  • [MeSH-major] Adrenal Cortex Neoplasms / drug therapy. Adrenocortical Carcinoma / drug therapy. Antineoplastic Agents, Hormonal / therapeutic use. Mitotane / therapeutic use
  • [MeSH-minor] Chemotherapy, Adjuvant. Humans. Multivariate Analysis. Neoplasm Recurrence, Local / epidemiology. Neoplasm Recurrence, Local / prevention & control. Retrospective Studies. Survival Analysis


52. Tsuchida Y, Miyauchi J, Kuroiwa M, Suzuki N, Sakamoto J, Suzuki M, Shitara T: Histologic survey of neuroblastomas after intensive induction chemotherapy. Pediatr Blood Cancer; 2005 Oct 15;45(5):656-62
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  • [Title] Histologic survey of neuroblastomas after intensive induction chemotherapy.
  • BACKGROUND: Histology after intensive induction chemotherapy is expected to become a beacon indicating when and how extensively radical surgery and lymph node dissection should be performed in advanced neuroblastoma.
  • A thorough histologic review of surgical specimens was undertaken.
  • PROCEDURE: All specimens from 34 patients who were pretreated intensively (> or =3 cycles) with recent chemotherapy were reviewed.
  • Thirty patients were >12 months of age with stage 3/4 disease, and 4 were <12 months of age but with MYCN-amplified stage 4 diseases.
  • After 3 to 7 cycles (mean, 4.3 cycles) of induction chemotherapy, patients underwent radical surgery of the primary tumor and lymph nodes in all retroperitoneal sections.
  • A single pathologist reviewed all of the specimens, and histologic chemotherapeutic effects were graded as: (+++), <1% viable tumor; (++), 1%-10% viable tumor; (+), 11%-50% viable tumor; (+/-), 51%-90% viable tumor; and (-), >91% viable tumor.
  • RESULTS: Grade (+++) effects were observed in 56% of patients treated with the new regimens, whereas grade (+++) was seen in only 20% treated with regimens before 1991.
  • Operation time and blood loss were 7 hr and 6 min (P = 0.087) and 646 ml (P = 0.064), respectively, in patients with >5 cycles (mean, 5.3 cycles) of chemotherapy, while they were 7 hr and 50 min and 1,168 ml, respectively, in those with approximately 3 cycles (mean, 3.2 cycles).
  • Histologically, metastases were found in the contralateral nodes beyond the aorta in 92% of those whose tumor originated on the left, and in 80% of those with tumors occurring on the right.
  • CONCLUSIONS: Five cycles of induction chemotherapy did not improve histologic chemotherapeutic effects, but helped to facilitate a shorter operation time and less blood loss than 3 cycles of chemotherapy.
  • Surgery after 5 cycles of (98)A(3) also appears to be easier to perform than that after 3 cycles of A(1)/new A(1).
  • Only 14% of the children treated before 1985 with the St. Jude protocols experienced grade (+++) chemotherapeutic effects, and 22% of the patients treated before 1991 with regimen A(1), or new A(1) of the Study Group of Japan showed grade (+++) effects, whereas 56% of the patients treated after 1991 with either regimen A(3) or (98)A(3) exhibited grade (+++) chemotherapeutic effects.
  • Histologic chemotherapeutic effects were roughly parallel with a good prognosis.
  • [MeSH-major] Abdominal Neoplasms / pathology. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Neuroblastoma / pathology
  • [MeSH-minor] Adrenal Gland Neoplasms / drug therapy. Adrenal Gland Neoplasms / pathology. Child. Child, Preschool. Humans. Infant. Lymphatic Metastasis

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  • (PMID = 15929130.001).
  • [ISSN] 1545-5009
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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53. Siemer S, Lehmann J, Loch A, Becker F, Stein U, Schneider G, Ziegler M, Stöckle M: Current TNM classification of renal cell carcinoma evaluated: revising stage T3a. J Urol; 2005 Jan;173(1):33-7
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  • [Title] Current TNM classification of renal cell carcinoma evaluated: revising stage T3a.
  • PURPOSE: : Recent studies of rare cases of pT3a renal cell carcinoma extending directly into the adrenal gland showed worse survival than in other pT3a cases and recategorization as stage pT4 was suggested.
  • We assessed the prognostic validity of a stage pT3a diagnosis based on perirenal fat infiltration.
  • MATERIALS AND METHODS: : The records of 1,794 patients with renal cell carcinoma who underwent surgical resection between 1975 and 2000 at our institution were analyzed retrospectively.
  • Focusing on pT3a tumors, as defined by perirenal fat infiltration, numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods with cancer specific survival as the primary end point.
  • RESULTS: : We identified 237 of 1,794 patients with perirenal fat infiltration, classified as having pT3a disease.
  • In patients with pT3a tumors tumor size was a significant parameter predicting survival.
  • The most significant cutoff value for tumor size in pT3a disease was 7 cm.
  • Patients with distant metastasis had a worse prognosis independent of T classification.
  • Therefore, to assess the prognostic value of the current T classification in regard to T3a tumors we excluded patients with tumor stage cM+ for further subgroup analysis.
  • Survival comparison of pT1 pNall, cM0 (744 of 1,794 cases) and pT3a pNall, cM0 7 cm or less (100 of 237) as well as pT2 pNall, cM0 (265 of 1,794) and pT3a pNall, cM0 greater than 7 cm (93 of 237) yielded similar results.
  • After splitting pT3a into a modified T1/T2 classification a significant difference in 5-year survival analysis for a modified T1/T2 stage was found (pT1 plus pT3a less than 7 cm 90% vs pT2 plus pT3a greater than 7 cm 73%, p <0.001).
  • Subsequently multivariate analysis in all 1,794 patients showed that modified T stage was an independent significant predictor of cancer specific survival.
  • CONCLUSIONS: : We suggest revising the current pT3a classification based on perirenal fat infiltration but rendering a modified pT1/pT2 classification, which resolves pT3a cases without the loss of prognostic validity.
  • Perirenal fat infiltration should not be used to assign T category.
  • Tumors directly infiltrating the adrenal gland should be reclassified as T4.
  • [MeSH-major] Carcinoma, Renal Cell / classification. Carcinoma, Renal Cell / pathology. Kidney Neoplasms / classification. Kidney Neoplasms / pathology
  • [MeSH-minor] Humans. Neoplasm Invasiveness. Neoplasm Staging. Nephrectomy. Prognosis. Retrospective Studies

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  • (PMID = 15592020.001).
  • [ISSN] 0022-5347
  • [Journal-full-title] The Journal of urology
  • [ISO-abbreviation] J. Urol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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54. Li J, Ma S, Kang S, Xie J, Sheng X, Luo R: [Evaluation on survival in locally advanced non-small cell lung cancer (NSCLC) for multimodality treatment with or without operation]. Zhongguo Fei Ai Za Zhi; 2005 Dec 20;8(6):535-7
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  • [Title] [Evaluation on survival in locally advanced non-small cell lung cancer (NSCLC) for multimodality treatment with or without operation].
  • BACKGROUND: It is uncertain that the effect of multimodality treatment with operation on survival for locally advanced non-small cell lung cancer (NSCLC).
  • The aim of this study is to evaluate the effect of multimodality treatment with or without operation on survival for locally advanced NSCLC.
  • METHODS: From May 1992 to May 1999, 114 patients with locally advanced NSCLC were divided into two arms.
  • Arm A (n=56): 39 cases were at stage IIIA, and 17 at stage IIIB; Median KPS was 80 (range from 70 to 90 ); Multimodality treatment program included operation, chemotherapy, radiotherapy and traditional Chinese herb medicine.
  • Of them, lobectomy plus mediastinal systematic lymph node dissection or lymph node sampling accounted for 49 cases, sleeve lobectomy plus mediastinal lymph node dissection for 5 cases, and pneumonectomy for 2 cases.
  • Preoperative or adjuvant chemotherapy regimens included MVP (mitomycin C, vindesine, cisplatin), NP (vinorelbine, cisplatin), TC (paclitaxel, carboplatin), GP (gemcitabine, cisplatin), which were repeated every 4 weeks for 4-6 cycles.
  • Total dose of radiotherapy for lesions in the lung or mediastinal field was 5000-6000cGy.
  • Arm B (n=58): 23 cases were at stage IIIA, and 35 at stage IIIB; Median KPS was 70 (range from 60 to 90); Treatment program was the same approximately as arm A except for no operation.
  • RESULTS: Arm A:.
  • (1) Metastatic locations in follow-up, in turn, showed as: lymph node, pleural-lung, bone, brain, liver, pericardium, skin and adrenal;.
  • (2) Median survival was 27 months, and 1-, 2- and 5-year survival rate was 82.1%, 60.7% and 25.0% respectively. Arm B:.
  • (1) Metastatic locations in follow-up, in turn, showed as: lymph node, pleural-lung, bone, brain, liver, pericardium, skin, adrenal, pancreatic and esophageal metastasis;.
  • (2) Median survival was 13 months, and 1-, 2- and 5-year survival rate was 53.4%, 31.0% and 1.7% respectively.
  • Median survival duration of Arm A was significantly superior to Arm B (P=0.0001).
  • There were significant differences in 1-, 2- and 5-year survival rate between the two groups (Chi-Square=9.4, P < 0.01; Chi-Square=8.9, P < 0.01;Chi-Square=11.5, P < 0.01).
  • CONCLUSIONS: Compared with non-operative multimodality treatment, operative multimodality treatment including lobectomy or pneumonectomy with mediastinal lymph node dissection can remarkably improve the survival in patients with locally advanced NSCLC.

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  • (PMID = 21208544.001).
  • [ISSN] 1009-3419
  • [Journal-full-title] Zhongguo fei ai za zhi = Chinese journal of lung cancer
  • [ISO-abbreviation] Zhongguo Fei Ai Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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