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Oncology AND MEN 1 [keywords]
- Extensive multiarterial resection attending total duodenopancreatectomy and adrenalectomy for MEN-1-associated neuroendocrine carcinomas. [Journal Article]
- World J Gastrointest Surg 2012 Oct 27; 4(10):238-45.
Pancreatic neuroendocrine tumors (PNTs) are relatively uncommon although these neoplasms have been noted to grow in occurrence in recent decades. Surgical removal of locally advanced PNTs involving major vessels and adjacent organs is warranted by reason of an appreciably more favorable prognosis as compared to exocrine pancreas cancer. We are reporting a case of successful multi-organ resection combined with a wide excision of the superior mesenteric, common, proper, left and right hepatic arteries (in the presence of the hepatomesenteric trunk variant of aberrant arterial anatomy) for multifocal PNTs in the setting of multiple neuroendocrine neoplasia type 1 syndrome. The procedure resulted in pain abolition, a significant improvement in the patient's life quality and allowed her to return to work. Follow-up computed tomography at 15 mo post-surgery showed no evidence of disease recurrence.
- The genetics of neuroendocrine tumors. [Journal Article]
- Semin Oncol 2013 Feb; 40(1):37-44.
Neuroendocrine tumors (NETs) present a wide spectrum of malignant diseases from rather benign to very malignant variants. The majority of these tumors are sporadic, but there are several familial (inherited) syndromes to consider, such as multiple endocrine neoplasia type 1 and type 2 (MEN-1 and MEN-2), von Hippel-Lindau syndrome (VHL), tuberosclerosis, and neurofibromatosis syndromes. The MEN-1 gene is mutated not only in MEN-1 families, but a recent study shows that more than 40% of sporadic pancreatic NETs (PNETs) harbor MEN-1 gene mutations. The same study reported that ATRX/DAXX genes are mutated in a significant number of tumors, as are genes encoding components of the mammalian target of rapamycin (mTOR) signal transduction pathway. These findings have implications for the new therapies that have been approved for the treatment of PNETs, such as the tyrosine kinase inhibitor sunitinib, as well the mTOR inhibitor everolimus. Small intestinal NETs show a less varied mutational pattern in that the majority of genetic alterations are found on chromosome 18. There seem to be no differences between the sporadic and the familiar type of small intestinal NETs (carcinoids). A wide range of genetic alterations have been described for the different subtypes of NETs, but the mechanisms underlying tumor development are essentially unknown except for MEN-2, in which an activating mutation of the RET proto-oncogene drives tumor progression and affords a direct genotype/phenotype correlation. Genome-wide screening of different types of NETs can now be performed for a reasonable price and is likely to generate new insights into the tumor biology and carcinogenesis in various subtypes of NETs.
- A case report of metastatic atypical thymic carcinoid with ectopic ACTH production: locoregional control after adaptive radiation treatment. [Case Reports, Journal Article]
- Tumori 2012 Nov; 98(6):172e-5e.
Thymic carcinoid is an extremely rare malignancy. This tumor is often associated with endocrine disorders such as Cushing's syndrome, multiple endocrine neoplasia type 1 and superior vena cava syndrome. We describe the case of a 44-year-old Italian woman with metastatic atypical thymic carcinoid secreting ectopic adrenocorticotropic hormone who was treated with adaptive radiation therapy with a curative dose schedule for a symptomatic mediastinal tumor. After 22 months, the patient was in good clinical condition, presenting stable disease without any evidence of local or systemic progression. To our knowledge there are no previously reported data regarding radical radiotherapy in the treatment of thymic carcinoids.
- [Surgery for pancreatic neuroendocrine tumors]. [English Abstract, Journal Article]
- Nihon Geka Gakkai Zasshi 2012 Nov; 113(6):502-6.
Approximately half of pancreatic neuroendocrine tumors (PNETs) are nonfunctioning, and insulinoma and gastrinoma are frequent forms of functioning tumors. The treatment of patients with PNETs should be based on the consideration that more than half are malignant except for insulinomas. Multiple endocrine neoplasia type 1 (MEN1) is often complicated with gastrinoma. Endoscopic ultrasound and somatostain receptor scintigraphy are useful in diagnosing PNETs, and the selective arterial secretagogue injection test is performed if necessary. WHO2010 is available as a histopathologic grading system of malignancy. Although surgical resection should first be considered as a treatment for PNETs, liver metastasis is a major factor hindering resection. In Japan, the choices of drugs to treat liver metastases are too few. In patients with MEN1 in whom PNETS are frequently multiple, we should perform procedures that preserve pancreatic function, although some patients may require total pancreatectomy for the complete resection of tumors. The indications for total pancreatectomy should be determined individually based on the tumor status and patient age.
- Treatment of multiple endocrine neoplasia 1/2 tumors: case report and review of the literature. [Case Reports, Journal Article, Review]
- Oncology 2013; 84(3):127-34.
Neuroendocrine tumors are uncommon tumors that are histopathologically and biologically heterogeneous and include the multiple endocrine neoplasia (MEN) 1 and 2 syndromes. The morbidity of MEN-1 and MEN-2 is often due to the symptomatology of the endocrine hormones produced, and the mortality mainly occurs from hepatic dysfunction incurred by liver metastases. At present, there is essentially no effective cure once the tumor has metastasized to the liver.We present a patient with progressive, metastatic MEN-1 with the classic '3 P's' triad of neuroendocrine tumor of the pancreas, parathyroid adenoma and a pituitary adenoma.After progression on high-dose Sandostatin LAR (60 mg/month) and multiple surgeries, the patient had a partial response (40% decrease) to a novel regimen of capecitabine and temozolomide (CAPTEM) and progression-free survival of 18 months. He had minor grade 1 toxicities and no grade 2, 3 or 4 toxicities.The history and treatment options for MEN-1/2 cancers are reviewed, as well as the data behind our novel regimen, CAPTEM.The CAPTEM regimen is a tolerable, safe, easy to administer oral regimen with possible efficacy for MEN-1 tumors.
- Does overweight influence the prognosis of renal cell carcinoma? Results of a multicenter study. [JOURNAL ARTICLE]
- Int J Urol 2012 Nov 26.
OBJECTIVES:To assess the impact of overweight on prognosis of renal cell carcinoma patients.
PATIENTS AND METHODS:A total of 2030 patients who underwent surgery for renal cell carcinoma from 1990 to 2011 in three University Medical Centers were included in this retrospective analysis. For all patients, height and weight measurements at the time of diagnosis were available for review. The median (mean) follow up was 56.6 months (66.0 months).
RESULTS:A low body mass index was significantly associated with poor tumor differentiation, histology, microscopic vascular invasion and metastatic disease at the time of diagnosis. A lower-than-average body surface area - stratified according to the European average for men (1.98 m(2) ) and women (1.74 m(2) ) - was significantly related to older age, poor tumor differentiation, the histological subtype and microscopic vascular invasion. In addition, a low visceral fat area calculated in a subgroup of 133 evaluable patients was associated with a higher risk of advanced disease (pT3-4 and/or N/M+) at diagnosis. The tumor-specific 5-year survival rate was 71.3, 78.7 and 80.1%, for patients with a body mass index of, <25, 25-30 and ≥30. Multivariate analysis confirmed body mass index as an independent prognostic factor.
CONCLUSION:Our findings suggest that overweight represents an independent prognostic factor in renal cell carcinoma patients. Further research should address the question of why obese people have a higher incidence of renal cell carcinoma, but at the same time a significantly better prognosis than other patients, particularly in the case of localized disease.
- Association of type-O blood with neuroendocrine tumors in multiple endocrine neoplasia type 1. [Journal Article, Research Support, N.I.H., Intramural]
- J Clin Endocrinol Metab 2013 Jan; 98(1):E109-14.
The ABO blood type system describes the expression of human blood group antigens found on both erythrocytes and normal tissue throughout the body. We recently reported an association between O blood type and the manifestation of pancreatic neuroendocrine tumors in a cohort of patients with Von Hippel-Lindau syndrome.The aim of the study was to determine whether there is an association of ABO blood type with the development of neuroendocrine tumors in patients with multiple endocrine neoplasia, type 1 (MEN-1).A retrospective analysis of 105 patients with MEN-1 was performed. Demographic, clinical, and biochemical data were analyzed by ABO blood type. Fisher's exact test was used to determine association between ABO blood type and manifestation of neuroendocrine tumor.Demographic and clinical characteristics were similar amongst blood type cohorts. We found an association between O blood type and the manifestation of a primary neuroendocrine tumor of the gastrointestinal tract, lung, pancreas, and thymus in patients with MEN-1 (P = 0.01). Sixteen of 17 (94%) metastatic tumors had type-O blood, compared to 32 of 43 (74%) with a benign tumor who had non-O blood type.Our findings suggest an association between O blood type and the manifestation of a primary neuroendocrine tumor in patients with MEN-1. Prospective clinical studies are warranted to see whether patient blood type status may be a useful addition to current screening and surveillance practices.
- Obesity is underestimated using body mass index and waist-hip ratio in long-term adult survivors of childhood cancer. [Journal Article]
- PLoS One 2012; 7(8):e43269.
Obesity, represented by high body mass index (BMI), is a major complication after treatment for childhood cancer. However, it has been shown that high total fat percentage and low lean body mass are more reliable predictors of cardiovascular morbidity. In this study longitudinal changes of BMI and body composition, as well as the value of BMI and waist-hip ratio representing obesity, were evaluated in adult childhood cancer survivors.Data from 410 survivors who had visited the late effects clinic twice were analyzed. Median follow-up time was 16 years (interquartile range 11-21) and time between visits was 3.2 years (2.9-3.6). BMI was measured and body composition was assessed by dual X-ray absorptiometry (DXA, Lunar Prodigy; available twice in 182 survivors). Data were compared with healthy Dutch references and calculated as standard deviation scores (SDS). BMI, waist-hip ratio and total fat percentage were evaluated cross-sectionally in 422 survivors, in who at least one DXA scan was assessed.BMI was significantly higher in women, without significant change over time. In men BMI changed significantly with time (ΔSDS = 0.19, P<0.001). Percentage fat was significantly higher than references in all survivors, with the highest SDS after cranial radiotherapy (CRT) (mean SDS 1.73 in men, 1.48 in women, P<0.001). Only in men, increase in total fat percentage was significantly higher than references (ΔSDS = 0.22, P<0.001). Using total fat percentage as the gold standard, 65% of female and 42% of male survivors were misclassified as non-obese using BMI. Misclassification of obesity using waist-hip ratio was 40% in women and 24% in men.Sixteen years after treatment for childhood cancer, the increase in BMI and total fat percentage was significantly greater than expected, especially after CRT. This is important as we could show that obesity was grossly underestimated using BMI and waist-hip ratio.
- Prognostic models to predict survival in non-small-cell lung cancer patients treated with first-line paclitaxel and carboplatin with or without bevacizumab. [Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural]
- J Thorac Oncol 2012 Sep; 7(9):1361-8.
To determine prognostic factors and build a model to predict 1-year overall survival (OS) and 6-month progression-free survival (PFS) in advanced non-small-cell lung cancer (NSCLC) patients treated with first-line paclitaxel and carboplatin with or without bevacizumab.We analyzed 26 pretreatment clinical variables in 850 NSCLC patients treated in the randomized Eastern Cooperative Oncology Group 4599 study. Univariate and multivariate analyses were performed to identify prognostic factors. Cox regression with 50% randomly sampled data was used to build nomograms with a prognostic score assigned to each factor. The model was validated with the remaining 50% of data.Eleven poor factors for OS (hazard ratio) were as follows: skin metastasis (4.49), body mass index less than 18.5 (2.09), increased serum lactate dehydrogenase (1.74), adrenal metastasis (1.52), performance status greater than 0 (1.45), low serum albumin (1.45), men (1.39), bone metastasis (1.39), large cell/not otherwise specified histology (1.29), mediastinal nodal metastasis (1.23), and treatment without bevacizumab (1.18). Seven poor factors for PFS were as follows: skin metastasis (3.13), treatment without bevacizumab (1.52), bone metastasis (1.41), liver metastasis (1.40), low serum albumin (1.39), performance status greater than 0 (1.21), and mediastinal nodal metastasis (1.14). Based on these factors, we built and validated two nomograms predicting 1-year OS and 6-month PFS.Using our proposed models, the probability of survival with first-line paclitaxel and carboplatin with or without bevacizumab in nonsquamous NSCLC patients can be estimated. These prognostic models provide a tool for research design and clinical decision making, such as patient stratification and therapy selection.
- MRP3 gene expression correlates with NRF2 mutations in lung squamous cell carcinomas. [Journal Article, Research Support, Non-U.S. Gov't]
- Mol Med Rep 2012 Oct; 6(4):705-8.
The expression of multidrug-resistant protein-3 (MRP3), a membrane-bound transporter, has been linked to drug resistance in non-small cell lung cancers (NSCLCs). Recently, we reported that NRF2 gene (NFE2L2) mutations are correlated with poor prognosis for lung squamous cell carcinomas. We hypothesized that tumor MRP3 expression may be correlated with the mutation status of upstream regulators, including NRF2, in NSCLC patients. MRP3 mRNA levels were analyzed by quantitative real-time polymerase chain reaction (qPCR) in 67 surgically-treated lung squamous cell cancer cases from the Nagoya City University Hospital and normalized by β-actin mRNA levels. Fourteen NRF2 mutation cases were included. The mean MRP3/β-actin mRNA levels did not differ according to age (≤65 vs. >65 years), Brinkman index (≤400 vs. >400) or the pathological stage of the lung squamous cell carcinoma. MRP3/β-actin mRNA levels were significantly higher in men (1.200±1.524) than in women (0.179±0.083; p=0.0036). In addition, the MRP3/β-actin mRNA levels were significantly higher in NRF2 mutants (2.598±2.373) than in wild-type NRF2 mutants (0.734±0.820; p=0.0002). These data support the hypothesis that the expression of MRP3 is induced by NRF2 activation in lung squamous cell cancers.