Search

BACKGROUND Primary duodenal gastrinomas are now recognized as a common etiology for patients with sporadic Zollinger Ellison Syndrome (ZES); however, the clinical and pathologic features of this condition and long-term outcome after operation are not well characterized.METHODS Between November 1982 and September 2000, 63 patients diagnosed with sporadic ZES underwent resection of a primary duodenal gastrinoma and regional nodal metastases with curative intent. Data from a prospectively maintained database were reviewed for clinical and pathologic parameters relating to primary tumor size, location, frequency of lymph node metastases, and disease-specific and disease-free survival.RESULTS There were 41 males and 22 females (mean age, 48.6 years). The majority of duodenal gastrinomas were in the first or second portions of the duodenum (83%). Tumor size ranged from 0.2 to 2.0 cm with 62% measuring less than 1.0 cm. Sixty percent of individuals had regional lymph node metastases identified primarily in proximity to the primary tumor. At a median 10-year follow-up, the overall disease-specific and disease-free survivals were 100% and 60%, respectively. Actuarial 10-year disease-free survival was significantly higher for patients without lymph node metastases versus those with lymph node metastases (78% versus 48%, P = 0.0137).CONCLUSIONS Duodenal gastrinomas in patients with sporadic ZES are frequently small, most commonly located in the proximal duodenum, and associated with regional lymph node metastases in 60%. Disease-free survival is lower for patients with regional lymph node metastases suggesting that a more systematic lymphadenectomy to extirpate occult disease may be indicated in this group. [ABSTRACT FROM AUTHOR]

During the progression of malignant peritoneal mesothelioma (MPeM), tumor nodules propagate diffusely within the abdomen and tumors are characterized by distinct phenotypic sub-types. Recent studies in solid organ cancers have shown that cancer stem cells (CSCs) play a pivotal role in the initiation and progression of tumors. However, it is not known whether tumorigenic stem cells exist and whether they promote tumor growth in MPeM. In this study, we developed and characterized a CSC model for MPeM using stably expandable tumorigenic stem cells derived from patient tumors. We found morphologically distinct populations of CSCs that divide asymmetrically or symmetrically in MPeM in vitro cell culture. The MPeM stem cells (MPeMSCs) express stem cell markers c-MYC, NES and VEGFR2 and in the presence of matrix components cells form colony spheres. MPeMSCs are multipotent, differentiate into neuronal, vascular and adipose progeny upon defined induction and the differentiating cells express lineage-specific markers such as TUBB3, an early neuronal marker; vWF, VEGFA, VEGFC and IL-8, endothelial markers; and PPARγ and FABP4, adipose markers. Xenotransplantation experiments using MPeMSCs demonstrated early tumor growth compared with parental cells. Limiting dilution experiments using MPeMSCs and endothelial lineage-induced cells derived from a single MPeMSC resulted in early tumor growth in the latter group indicating that endothelial differentiation of MPeMSCs is important for MPeM tumor initiation. Our observation that the MPeM tumors contain stem cells with tumorigenic potential has important implications for understanding the cells of origin and tumor progression in MPeM and hence targeting CSCs may be a useful strategy to inhibit malignant progression.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. To identify biologically relevant genes with prognostic and therapeutic significance in PDAC, we first performed the microarray gene-expression profiling in 45 matching pairs of tumor and adjacent non-tumor tissues from resected PDAC cases. We identified 36 genes that were associated with patient outcome and also differentially expressed in tumors as compared with adjacent non-tumor tissues in microarray analysis. Further evaluation in an independent validation cohort (N = 27) confirmed that DPEP1 (dipeptidase 1) expression was decreased (T:N ratio ∼0.1, P

Background: This study was designed to determine the clinical significance of preoperative thrombocytosis in patients with malignant peritoneal mesothelioma (MPM) undergoing operative cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). CRS and HIPEC have been associated with prolonged survival in patients with MPM and is the preferred treatment in select patients. However, patient selection criteria remain ill-defined for this operation that is also associated with significant morbidity and mortality. Preoperative thrombocytosis has been associated with poor outcomes in various malignancies but never studied in MPM., Methods: Between January 2006 and December 2015, 100 patients with high-grade epithelioid MPM were evaluated and selected for CRS and HIPEC at our center (M: 53, F: 47; mean age: 54 years [range 17-81 years]). We analyzed various patient and treatment related factors potentially associated with overall survival (OS)., Results: The median actuarial overall survival was 32.8 months; the actuarial 1-, 3-, 5-year survivals were 70, 49, and 36%, respectively. On multivariate analysis, suboptimal resection (CCR > 1), high tumor burden (PCI > 20), and elevated preoperative platelet count (>367,000/mm 3 ) were independently associated with shortened OS (P < 0.05). Median OS in patients with elevated versus normal platelet counts were 13 and 58 months, respectively (P < 0.001). Compared with patients with normal platelet counts, patients with elevated counts had significantly greater residual disease after operation (P = 0.008)., Conclusions: Elevated preoperative platelet count is independently associated with poor outcome. Notably, thrombocytosis reflects aggressive tumor biology and should be considered a factor in patient selection for CRS and HIPEC.

Objectives: Diffuse isolated liver metastases are the dominant mode of tumor progression in a number of cancers and present a major treatment challenge for oncologists. An experimental treatment, percutaneous hepatic perfusion (PHP), utilizes partial venovenous cardiopulmonary bypass to allow administration of high-dose chemotherapy directly and solely to the liver with filtration of chemotherapeutic agents from the blood prior to its return to the systemic circulation, thereby minimizing toxic systemic effects. The following case series describes the management of 5 patients with metastatic melanoma undergoing serial PHPs., Design: A single-center experience from a national multi-center random-assignment trial comparing PHP to best alternative care (BAC) in patients with diffuse melanoma liver metastases., Setting: A tertiary care hospital., Participants: Five patients with metastatic melanoma to the liver., Intervention: Five patients underwent a total of fifteen PHPs using a venovenous bypass circuit with hemofiltration, receiving hepatic intra-arterial melphalan, 3 mg/kg of ideal body weight, for 30 minutes with a total of 60 minutes of hemofiltration., Measurements and Main Results: Five patients tolerated the procedure well with transient hemodynamic and metabolic changes., Conclusions: In patients with diffuse isolated liver metastases, PHP is a safe and well-tolerated procedure that can be performed more than once and is associated with marked anti-tumor activity in some patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To explore associations between nonalcoholic fatty liver disease (NAFLD) and benign gastrointestinal and pancreato-biliary disorders., Methods: Patient demographics, diagnoses, and hospital outcomes from the 2010 Nationwide Inpatient Sample were analyzed. Chronic liver diseases were identified using International Classification of Diseases, the 9(th) Revision, Clinical Modification codes. Patients with NAFLD were compared to those with other chronic liver diseases for the endpoints of total hospital charges, disease severity, and hospital mortality. Multivariable stepwise logistic regression analyses to assess for the independent association of demographic, comorbidity, and diagnosis variables with the event of NAFLD (vs other chronic liver diseases) were also performed., Results: Of 7800441 discharge records, 32347 (0.4%) and 271049 (3.5%) included diagnoses of NAFLD and other chronic liver diseases, respectively. NAFLD patients were younger (average 52.3 years vs 55.3 years), more often female (58.8% vs 41.6%), less often black (9.6% vs 18.6%), and were from higher income areas (23.7% vs 17.7%) compared to counterparts with other chronic liver diseases (all P < 0.0001). Diabetes mellitus (43.4% vs 28.9%), hypertension (56.9% vs 47.6%), morbid obesity (36.9% vs 8.0%), dyslipidemia (37.9% vs 15.6%), and the metabolic syndrome (28.75% vs 8.8%) were all more common among NAFLD patients (all P < 0.0001). The average total hospital charge ($39607 vs $51665), disease severity scores, and intra-hospital mortality (0.9% vs 6.0%) were lower among NALFD patients compared to those with other chronic liver diseases (all P < 0.0001).Compared with other chronic liver diseases, NAFLD was significantly associated with diverticular disorders [OR = 4.26 (3.89-4.67)], inflammatory bowel diseases [OR = 3.64 (3.10-4.28)], gallstone related diseases [OR = 3.59 (3.40-3.79)], and benign pancreatitis [OR = 2.95 (2.79-3.12)] on multivariable logistic regression (all P < 0.0001) when the latter disorders were the principal diagnoses on hospital discharge. Similar relationships were observed when the latter disorders were associated diagnoses on hospital discharge., Conclusion: NAFLD is associated with diverticular, inflammatory bowel, gallstone, and benign pancreatitis disorders. Compared with other liver diseases, patients with NAFLD have lower hospital charges and mortality., (© 2013 Baishideng Publishing Group Co., Limited. All rights reserved.)

Background: High-grade appendiceal adenocarcinoma is a rare malignancy with propensity for peritoneal metastases (PM). The impact of neoadjuvant chemotherapy on operative cytoreduction (CRS) and intraperitoneal chemotherapy (HIPEC) and patient survival was reviewed., Methods: A total of 45 patients with PM from high-grade appendiceal adenocarcinoma were identified from a prospective database. All patients had laparotomy with intent to undergo CRS and HIPEC. Operative parameters, complications, and survival outcomes were analyzed., Results: Of the 45 patients (male: 27, female: 18; median age: 55 years), 26 received neoadjuvant chemotherapy ± bevacizumab. Of the 26, 15 (58 %) had a response based on improvement in imaging, biomarkers, or both and 9 (34 %) had stable disease. The median peritoneal cancer index (PCI) was 27. Also, 30 (67 %) had a completeness of cytoreduction score (CCR) of ≤1 and 37 (82 %) received HIPEC. There were no differences in PCI, CCR score, operative blood loss, or major organ resection between those who received or did not receive neoadjuvant chemotherapy. Operative time was significantly shorter in those who did not receive neoadjuvant chemotherapy. Major complications and length of hospital stay were similar between the groups. The median actuarial overall survival calculated from the date of initial therapeutic intervention was not different in those treated with or without neoadjuvant therapy., Conclusions: Neoadjuvant chemotherapy has marked clinical activity in patients with PM from high-grade appendiceal adenocarcinoma and does not adversely affect operative outcomes. These data support conducting a prospective clinical trial to define the role of neoadjuvant chemotherapy in this clinical setting.

Multiple endocrine neoplasia type 1 (MEN1), among all syndromes, causes tumors in the highest number of tissue types. Most of the tumors are hormone producing (e.g., parathyroid, enteropancreatic endocrine, anterior pituitary) but some are not (e.g., angiofibroma). MEN1 tumors are multiple for organ type, for regions of a discontinuous organ, and for subregions of a continuous organ. Cancer contributes to late mortality; there is no effective prevention or cure for MEN1 cancers. Morbidities are more frequent from benign than malignant tumor, and both are indicators for screening. Onset age is usually earlier in a tumor type of MEN1 than of nonhereditary cases. Broad trends contrast with those in nonneoplastic excess of hormones (e.g., persistent hyperinsulinemic hypoglycemia of infancy). Most germline or somatic mutations in the MEN1 gene predict truncation or absence of encoded menin. Similarly, 11q13 loss of heterozygosity in tumors predicts inactivation of the other MEN1 copy. MEN1 somatic mutation is prevalent in nonhereditary, MEN1-like tumor types. Compiled germline and somatic mutations show almost no genotype/phenotype relation. Normal menin is 67 kDa, widespread, and mainly nuclear. It may partner with junD, NF-kB, PEM, SMAD3, RPA2, FANCD2, NM23beta, nonmuscle myosin heavy chain II-A, GFAP, and/or vimentin. These partners have not clarified menin's pathways in normal or tumor tissues. Animal models have opened approaches to menin pathways. Local overexpression of menin in Drosophila reveals its interaction with the jun-kinase pathway. The Men1+/- mouse has robust MEN1; its most important difference from human MEN1 is marked hyperplasia of pancreatic islets, a tumor precursor stage.