PD-L1 expression in the microenvironment and the response to checkpoint inhibitors in head and neck squamous cell carcinoma.

In head and neck squamous cell carcinoma (HNSCC), data from studies using checkpoint-inhibiting antibodies that target programmed death 1 (PD-1) or its ligand the programmed death ligand 1 (PD-L1) demonstrated outstanding clinical activity. Translational investigations also suggested some correlations between therapeutic response and PD-L1 expression in tumor tissue. We comprehensively summarize results that have evaluated PD-L1 expression in HNSCC. We discuss flaws and strength of current PD-1/PD-L1 detection, quantification methods and the evaluation of PD-L1 as a prognostic and theragnostic biomarker. Understanding tumor microenvironment may help understanding resistance to checkpoint inhibitors, designing clinical trials that can exploit drug combinations.

Morphological imaging and CT histogram analysis to differentiate pancreatic neuroendocrine tumor grade 3 from neuroendocrine carcinoma.

PURPOSE: To compare morphological imaging features and CT texture histogram parameters between grade 3 pancreatic neuroendocrine tumors (G3-NET) and neuroendocrine carcinomas (NEC). MATERIALS AND METHODS: Patients with pathologically proven G3-NET and NEC, according to the 2017 World Health Organization classification who had CT and MRI examinations between 2006-2017 were retrospectively included. CT and MRI examinations were reviewed by two radiologists in consensus and analyzed with respect to tumor size, enhancement patterns, hemorrhagic content, liver metastases and lymphadenopathies. Texture histogram analysis of tumors was performed on arterial and portal phase CT images. images. Morphological imaging features and CT texture histogram parameters of G3-NETs and NECs were compared. RESULTS: Thirty-seven patients (21 men, 16 women; mean age, 56±13 [SD] years [range: 28-82 years]) with 37 tumors (mean diameter, 60±46 [SD] mm) were included (CT available for all, MRI for 16/37, 43%). Twenty-three patients (23/37; 62%) had NEC and 14 patients (14/37; 38%) had G3-NET. NECs were larger than G3-NETs (mean, 70±51 [SD] mm [range: 18 - 196mm] vs. 42±24 [SD] mm [range: 8 - 94mm], respectively; P=0.039), with more tumor necrosis (75% vs. 33%, respectively; P=0.030) and lower attenuation on precontrast (30±4 [SD] HU [range: 25-39 HU] vs. 37±6 [SD] [range: 25-45 HU], respectively; P=0.002) and on portal venous phase CT images (75±18 [SD] HU [range: 43 - 108 HU] vs. 92±19 [SD] HU [range: 46 - 117 HU], respectively; P=0.014). Hemorrhagic content on MRI was only observed in NEC (P=0.007). The mean ADC value was lower in NEC ([1.1±0.1 (SD)]×10-3 mm2/s [range: (0.91 - 1.3)×10-3 mm2/s] vs. [1.4±0.2 (SD)]×10-3 mm2/s [range: (1.1 - 1.6)×10-3 mm2/s]; P=0.005). CT histogram analysis showed that NEC were more heterogeneous on portal venous phase images (Entropy-0: 4.7±0.2 [SD] [range: 4.2-5.1] vs. 4.5±0.4 [SD] [range: 3.7-4.9]; P=0.023). CONCLUSION: Pancreatic NECs are larger, more frequently hypoattenuating and more heterogeneous with hemorrhagic content than G3-NET on CT and MRI.

Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A.

Orexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting inflammation and ulcers that affect the colon and rectum mucosa and is known to be a significant risk factor for colon cancer development. Based on our recent studies showing that OX1R is aberrantly expressed in colon cancer, we wondered whether orexin-A could play a role in UC. Immunohistochemistry studies revealed that OX1R is highly expressed in the affected colonic epithelium of most UC patients, but not in the non-affected colonic mucosa. Injection of exogenous orexin-A specifically improved the inflammatory symptoms in the two colitis murine models. Conversely, injection of inactive orexin-A analog, OxB7-28 or OX1R specific antagonist SB-408124 did not have anti-inflammatory effect. Moreover, treatment with orexin-A in DSS-colitis induced OX1R-/- knockout mice did not have any protective effect. The orexin-A anti-inflammatory effect was due to the decreased expression of pro-inflammatory cytokines in immune cells and specifically in T-cells isolated from colonic mucosa. Moreover, orexin-A inhibited canonical NFκB activation in an immune cell line and in intestinal epithelial cell line. These results suggest that orexin-A might represent a promising alternative to current UC therapies.

Thymic function is a major determinant of onset of antibody-mediated rejection in heart transplantation.

Thymic function decreases progressively with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether thymic function was related to the onset of rejection. Twenty-eight antithymocyte globulin-treated heart transplant recipients were included. Patients diagnosed for an antibody-mediated rejection on endomyocardial biopsy had a higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects. Thymus volume and density, assessed by computed tomography in a subset of patients, was also higher in patients experiencing antibody-mediated rejection. We demonstrate that thymic function is a major determinant of onset of antibody-mediated rejection and question whether thymectomy could be a prophylactic strategy to prevent alloimmune humoral responses.

MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

Adenocarcinoma of the pancreas: Does prognosis depend on mode of lymph node invasion?

BACKGROUND: Lymph node (LN) invasion in pancreatic ductal adenocarcinoma (PDAC) is the most important prognostic factor after surgical resection. The mechanisms of LN invasion include lymphatic spreading and/or direct extension from the main tumor. However, few studies have assessed the impact of these different patterns of invasion on prognosis. PATIENTS AND METHODS: Pathologic reports of pancreatic resections for PDAC from 1997 to 2007 were retrospectively analyzed. The mode of LN invasion was defined as follows: standard lymphatic metastases (S), contiguous from the main tumor (C) and standard with extracapsular invasion (EI). Clinical outcomes were compared according to the mode of invasion and the number of invaded LN. RESULTS: 306 patients were reviewed. Median age at resection was 61 years (range, 34-81). Eighty seven patients were N- (28.9%) and 214 were N+ (71.1%). Of the N+ patients, 195 (91.1%) were S+, 35 (16.3%) were C+, and 24 (12.3% of the S+ patients) were EI+. Median survival in N+ patients was lower than in N- patients (29 vs. 57 months, p < 0.001). In patients without standard involvement, C+ patients (n = 19) had worse survival than C- patients (n = 47) (34 vs. 57 months, p = 0.037). In S+ patients, C status was correlated with prognosis when the number of LN S+ was <2 (p = 0.07). EI status had no influence on prognosis. On multivariate analysis, only perineural invasion (p = 0.02) and LN ratio (p = 0.042) were independent prognostic factors. CONCLUSION: Direct invasion of LN by the tumor is predictive of reduced survival, but has little impact compared to standard LN involvement and perineural invasion.

Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells.

OBJECTIVES: In obesity, while hyperleptinemia highly correlates with excess fat mass, the status of gastric leptin remains unknown. Here, we investigated the expression of leptin in stomach biopsies of obese humans and analyzed the temporal changes of gastric leptin expression in response to diet-induced obesity and its impact on 5-hydroxytryptamine (5HT)-producing cells. METHODS: Enterochromaffin (EC) cells and expression of leptin, PAX4 (critical factor for EC specification), tryptophane hydroxylase-1 (TPH1, the peripheral rate-limiting enzyme for 5HT) and 5HT were examined by immunofluorescence, quantitative real-time PCR, radioimmunoassay, respectively, in stomach and duodenum biopsies from 19 obese and 14 normo-weighed individuals, and in mucosa scrapings from C57Bl6/J diet-induced obese mice, leptin-deficient ob/ob mice and intestine-specific leptin receptor isoform B-deficient mice. RESULTS: Gastric mucosa of obese subjects displays an increased expression of leptin (LEP mRNA by fivefold and protein by twofold, P<0.01), TPH1 ((1.75-2.73, 95% confidence interval (CI)) vs (0.38-0.67, 95% CI); P<0.01) and PAX4 ((1.33-2.11, 95%CI) vs (0.62-0.81, 95% CI); P<0.01) as compared with normo-weighed individuals. In diet-induced obese mice, the overexpressions of gastric leptin, antral Pax4, Tph1 and increased EC cell number occurred before the onset of obesity and hyperleptinemia (reflect of adipocyte leptin production). In addition, leptin deficiency was associated with reduced Pax4 mRNA, whereas oral leptin treatment enhanced both Tph1 and Pax4 mRNA. Finally, mice with an intestine-specific deletion of leptin signaling exhibit significant decrease in duodenal mucosa 5HT content. CONCLUSIONS: These data demonstrate that gastric leptin is upregulated in obese individuals. RESULTS from high-fat diet mice showed that overexpression of gastric leptin that is linked to gut '5HT pathway' occurred before the onset of obesity and expansion of fat mass. This may be relevant in the pathophysiology of obesity.

FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3.

Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide-platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide-platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide-platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide-platinum combination, 19 (49%; 12 women, median age 53 (29-78) years) received the FOLFIRI regimen with a median number of 6 (1-16) courses. Six patients (31%) had at least one episode of grades 3-4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide-platinum combination. These results should be confirmed in a future prospective study.

TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study.

BACKGROUND: Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms. METHODS: The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. RESULTS: Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk groups (with stage I as the reference; stage II hazard ratio [HR] of death = 16.23, 95% confidence interval [CI] = 2.14 to 123, P = .007; stage III HR of death = 51.81, 95% CI = 7.11 to 377, P < .001; and stage IV HR of death = 160, 95% CI = 22.30 to 1143, P < .001). However, the UICC/AJCC/WHO 2010 TNM staging system compressed the disease into three differently populated classes, with most patients in stage I, and with the patients being equally distributed into stages II-III (statistically similar) and IV (with stage I as the reference; stage II HR of death = 9.57, 95% CI = 4.62 to 19.88, P < .001; stage III HR of death = 9.32, 95% CI = 3.69 to 23.53, P = .94; and stage IV HR of death = 30.84, 95% CI = 15.62 to 60.87, P < .001). Multivariable modeling indicated curative surgery, TNM staging, and grading were effective predictors of death, and grading was the second most effective independent predictor of survival in the absence of staging information. Though both TNM staging systems were independent predictors of survival, the UICC/AJCC/WHO 2010 TNM stages showed very large 95% confidence intervals for each stage, indicating an inaccurate predictive ability. CONCLUSION: Our data suggest the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system and supports its use in clinical practice.

Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.

BACKGROUND: Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS: A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-ß receptor, CXCR4, and LKB1. RESULTS: High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002). CONCLUSIONS: CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.

Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of digestive endocrine carcinomas.

The prognosis remains ill-defined in patients with liver metastases of well-differentiated (WD) digestive endocrine carcinomas (DEC) with high Ki-67 index. The objectives of this study were to determine whether Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with DEC, and whether chemotherapy commonly used in patients with poorly differentiated (PD) carcinomas might be applied to those with high Ki-67 index but well-differentiated DEC. Sixty-three patients with DEC metastatic to the liver were retrospectively studied and divided into three prognostic groups. Group 1 comprised patients with well-differentiated carcinomas and Ki-67 index<15% (n=28), group 2 comprised those with well-differentiated carcinomas and Ki-67 index≥15% (n=17), and group 3 comprised those with poorly differentiated carcinomas (n=18). Therapeutic strategy was decided in accordance to guidelines, and tumoral response rate was assessed by computed tomography scan (RECIST). Prognostic factors were determined by uni/multivariate analysis. The 5-year survival rates were 89, 36, and 6% in groups 1, 2, and 3 respectively (P<0.001). Multivariate analysis showed that Ki-67 index≥15%, poor tumor differentiation, and large liver tumor burden were independent predictors of poorer survival. Disease control rates after etoposide-cisplatin were 50 and 53% in groups 2 and 3 respectively (NS). In conclusion, Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of DEC. Patients with well-differentiated carcinomas with high Ki-67 index (≥15%) have intermediate prognosis and a similar response rate to the etoposide-cisplatin combination as those with poorly differentiated carcinomas.

Clinical and imaging follow-up after exhaustive liver resection of endocrine metastases: a 15-year monocentric experience.

Liver metastases are common in gastroenteropancreatic neuroendocrine tumors and significantly impair survival. Hepatic resection is the only potential curative treatment. The records of 41 consecutive patients undergoing exhaustive resection of liver-only endocrine metastases and followed between 1992 and 2006 were reviewed. Patient's outcome and diagnostic accuracy of somatostatin receptor scintigraphy (SRS) and morphological imaging (MI) for detection of recurrences during post-operative follow-up were assessed. All identified primary had been resected. MI studies including abdominal computed tomography (CT) and/or liver magnetic resonance imaging and thoracic CT if indicated were performed every 6 months; SRS timing was decided by referring clinician. Tumor recurrences were confirmed by pathology or subsequent imaging studies. The results of 136 MI and SRS examinations performed within a 30-day interval from each other were retrospectively compared. Median post-operative follow-up was 51 months (7-165). Recurrences developed in 32 patients (78%), mainly in the liver (n=24) after a median of 19 months (2-79). Five-year overall and disease-free survival rates were 79 and 3% respectively. For recurrence detection, sensitivity, specificity, and accuracy were 89, 94, and 91% for SRS, 68, 91, and 74% for MI respectively. In 11 out of 32 patients (34%), abdominal or extra-abdominal metastases were detected 15.5 months earlier by SRS than MI. In conclusion, despite exhaustive liver surgery for endocrine metastases, hepatic or extra-hepatic recurrences are frequent and develop early. SRS is highly accurate for the detection of recurrences during post-operative follow-up and permitted early diagnosis in one third of patients; therapeutic implications of this early diagnosis remain to be determined.

[Desmoplastic small round cell tumour of the pancreas with breast metastasis]. / Tumeur desmoplastique à petites cellules rondes du pancréas avec métastase mammaire.

Desmoplastic small round cell tumour (DSRCT) is a very rare, highly aggressive neoplasm. Most cases have been reported in adolescent and young male patients. These tumours occur mainly in the peritoneal cavity, with peritoneal and lymphatic dissemination. Their histologic features are unspecific and immunohistochemistry and cytogenetic or biomolecular techniques are required for their diagnosis. Involvement of the pancreas is exceptional and is difficult to differentiate from other pancreatic primary tumours. We report here the case of a 49-year-old woman who had a DSRCT of the pancreas with metastasis to the breast. She died within one year after the diagnosis despite an aggressive surgical strategy.

Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas.

The NF2 gene product, merlin/schwannomin, is a cytoskeleton organizer with unique growth-inhibiting activity in specific cell types. A narrow spectrum of tumors is associated with NF2 deficiency, mainly schwannomas and meningiomas, suggesting cell-specific mechanisms of growth control. We have investigated merlin function in mouse Schwann cells (SCs). We found that merlin regulates contact inhibition of proliferation by limiting the delivery of several growth factor receptors at the plasma membrane of primary SCs. Notably, upon cell-to-cell contact, merlin downregulates the membrane levels of ErbB2 and ErbB3, thus inhibiting the activity of the downstream mitogenic signaling pathways protein kinase B and mitogen-activated protein kinase. Consequently, loss of merlin activity is associated with elevated levels of ErbB receptors in primary SCs. We also observed accumulation of growth factor receptors such as ErbB2 and 3, insulin-like growth factor 1 receptor and platelet-derived growth factor receptor in peripheral nerves of Nf2-mutant mice and in human NF2 schwannomas, suggesting that this mechanism could play an important role in tumorigenesis.

[Limited pancreatic resections for intraductal papillary mucinous neoplasm]. / Résections limitées du pancréas pour tumeur intracanalaire papillaire et mucineuse non invasive.

INTRODUCTION: For non-invasive intraductal papillary and mucinous neoplasm (IPMN) with limited extent, pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) seem excessive due to the risk of pancreatic insufficiency. Enucleation (EN) or medial pancreatectomy (MP) are not commonly performed for IPMN. The aim of this study was to evaluate the feasibility and results of EN and MP for non-invasive IPMN. PATIENTS AND METHODS: Of 249 patients with IPMN, we attempted a limited resection in 50 (20%) EN (n=31) or MP (n=20) with routine intra-operative frozen section pathology. One attempted EN was converted to MP. Indications for surgery were pain/pancreatitis (44%), suspicion of main duct involvement (28%), mural nodules in branch duct (14%), branch duct>30 mm (8%) or suspicion of mucinous cystadenoma (6%). Follow-up clinical assessment and MRI were performed on a yearly basis. RESULTS: Of the 31 attempted enucleations, 5 (13%) were immediately converted (4 PD, 1 MP) due to technical reasons (n=3) or due to findings on frozen section (n=2). At definitive pathological examination (accuracy of frozen sectioning=98%), branch ducts were involved by mild (n=21), moderate (n=7) or high grade dysplasia (n=2). One patient underwent a double EN. Of 20 attempted medial pancreatectomies, 8 (40%) required additional segmental resection due to significant IPMN lesions at pancreatic margins; 3 of the additional resection margins were tumor-free, and 5 were involved by IPMN (4 conversions to PD or DP, one contra-indication to PD). Overall, 49 pancreatic margins were analyzed by frozen sectioning with 98% accuracy. Resected specimens of 16 MP showed involvement by mild (n=7), moderate (n=7) or high grade dysplasia (n=2). There was no postoperative mortality. Median length of stay was 21 and 30 days respectively after EN and MP. Pancreatic fistula rate was 54% and 81% respectively after EN and MP. Three patients underwent early re-operation for hemorrhage. Overall median follow-up was 24 months (3-121). All patients are alive, 2 patients (5%) have presented with recurrent pain and 4 have developed tumor recurrence on imaging follow-up (4/33=12%). Two patients (5%) developed de novo diabetes (one after EN combined with DP) and a third patient developed worsening of pre-existing diabetes plus exocrine insufficiency. No patient had surgery for recurrence. CONCLUSIONS: EN and MP are feasible for non-invasive IPMN. Their significant early morbidity is counterbalanced by low rates of both long-term functional disorders and tumor recurrence.

Cystic dystrophy in gastric heterotopic pancreas complicated by intracystic hemorrhage and fistulisation in the stomach - a pediatric case.

CONTEXT: Cystic dystrophy of the digestive wall, a rare but well-known complication of heterotopic pancreas when it is located in the duodenum, has been mainly described in adult series. Cystic dystrophy of the heterotopic pancreas within the gastric wall has been reported in only six adult cases. To our knowledge, no pediatric case has been described. CASE REPORT: We report a 15-year-old boy surgically treated for cystic dystrophy located in the antrum, complicated by an intracystic hemorrhage and fistulisation into the stomach. CONCLUSION: The diagnosis of heterotopic pancreas must be considered in case of submucosal cystic-gastric lesions, even in pediatric cases. Although the surgical approach is not systematic, it is recommended when cystic dystrophy is symptomatic (e.g., occlusion or hemorrhage).

[Verner-Morrison syndrome revealing a ganglioneuroblastoma in an adult]. / Syndrome de Verner-Morrison révélant un ganglioneuroblastome chez un adulte.

Most vasoactive intestinal peptide (VIP)-producing tumours are from epithelial origin. Tumours derived from the sympathetic nervous system can produce VIP as well. We report here the case of a Verner-Morrison syndrome in a 40-year-old woman revealing a metastatic ganglioneuroblastoma. The diarrhea resolved after the resection of primary tumour and liver metastases. Neuroblastic tumours occur extremely rarely in adults. Thus, the management of these tumours is poorly defined in adults.

A new mRNA splice variant coding for the human EP3-I receptor isoform.

The cellular localization of prostaglandin E2 receptors (EP) and their corresponding transcripts were investigated in human gastric and vascular tissues. A strong staining of the EP3 receptor on the gastric glands, mucous cells, media of the mammary and pulmonary arteries was observed by immunohistochemistry. We identified a new mRNA splice variant of the EP3 gene in human gastric fundic mucosa, mammary artery and pulmonary vessels. This EP3-Ic transcript contains exons 1, 2, 3, 5 and 6 of the EP3 gene and should be translated in the EP3-I isoform. In addition, the EP3-Ib, EP3-II, EP3-III, EP3-IV and EP3-e mRNAs were detected in these tissues.