Increased SLC38A4 Amino Acid Transporter Expression in Human Pancreatic α-Cells After Glucagon Receptor Inhibition.

Plasma amino acids and their transporters constitute an important part of the feedback loop between the liver and pancreatic α-cell function, and glucagon regulates hepatic amino acid turnover. Disruption of hepatic glucagon receptor action activates the loop and results in high plasma amino acids and hypersecretion of glucagon associated with α-cell hyperplasia. In the present study, we report a technique to rescue implanted human pancreatic islets from the mouse kidney capsule.

Colorectal Neuroendocrine Neoplasms: Areas of Unmet Need.

The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges.

pT but not pN stage of the 8th TNM classification significantly improves prognostication in pancreatic ductal adenocarcinoma.

The UICC TNM (tumour-node-metastasis) staging system for pancreatic ductal adenocarcinoma (PDAC) has been a matter of debate over decades because survival prediction based on T stages was weak and unreliable. To improve staging, the recently published 8th TNM edition (2016) introduced a conceptually completely changed strictly size-based T staging system and a refined N stage for PDAC. To investigate the clinical value of the novel TNM classification, we compared the prognostic impact of pT and pN stage between the 7th and 8th edition in two well-characterised independent German PDAC cohorts from different decades, including a total number of 523 patients.

Multiple small "imaging" branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?

Most screening programs for familial pancreatic cancer are currently based on endoscopic ultrasonography and/or magnetic resonance imaging (MRI). Cystic lesions, especially those suspicious for small intraductal pancreatic mucinous neoplasms (IPMNs) of the branch ducts, can be visualized in up to 40 % of individuals at risk, but their pathological importance in the setting of FPC is yet not well established. Individuals at risk from a prospective screening program for familial pancreatic cancer with small "imaging" IPMNs of the branch-duct type (BD-IPMN) who underwent pancreatic resection were analysed regarding clinico-pathological data and the locations of pancreatic lesions.

Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer.

Background: New therapeutic options for metastatic pancreatic cancer are urgently needed. In pancreatic cancer, overexpression of the epidermal growth factor receptor 2 (HER2) has been reported in up to 45%. This multicentre phase II study investigated the efficacy and toxicity of the HER2 antibody trastuzumab combined with capecitabine in the patients with pancreatic cancer and HER2 overexpression.

Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey.

Objective: The objective of this study was to clarify the clinical and pathophysiological characteristics of autoimmune pancreatitis (AIP) and its subtypes (lymphoplasmacytic sclerosing pancreatitis [LPSP] and idiopathic duct-centric pancreatitis [IDCP]) seen around the world.

Methods: An international multicenter survey of AIP was conducted in 15 institutes from 8 countries. We compared clinical and pathologic profiles of AIP (n = 731) and the clinical profiles of LPSP (n = 204) and IDCP (n = 64) patients.

Histopathologic and clinical subtypes of autoimmune pancreatitis: the honolulu consensus document.

Autoimmune pancreatitis (AIP) has been extensively reported from Japan, Europe and the USA. While the descriptions of AIP from Japan have predominantly been based on the presence of a distinct clinical phenotype, reports from Europe and the USA describe at least 2 histopathologic patterns in patients diagnosed with AIP, namely lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) or granulocytic epithelial lesion- positive pancreatitis. While the 2 entities share common histopathologic features (periductal lymphoplasmacytic infiltration and peculiar periductal fibrosis), expert pathologists can accurately distinguish them on the basis of other unique histopathologic features.

Histopathologic and clinical subtypes of autoimmune pancreatitis: the Honolulu consensus document.

Autoimmune pancreatitis (AIP) has been extensively reported from Japan, Europe, and the United States. Whereas the descriptions of AIP from Japan have predominantly been based on the presence of a distinct clinical phenotype, reports from Europe and the United States describe at least 2 histopathologic patterns in patients' condition currently diagnosed as AIP, viz, lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct centric pancreatitis (IDCP) or granulocyte epithelial lesion (GEL)-positive pancreatitis. Although the 2 entities share common histopathologic features (periductal lymphoplasmacytic infiltration and peculiar periductal fibrosis), expert pathologists can accurately distinguish them based on other unique histopathologic features.

The German NET-registry: an audit on the diagnosis and therapy of neuroendocrine tumors.

Aims: Clinical experience with neuroendocrine tumors (NETs) is difficult to acquire because they are rare and heterogeneous. The impact of guidelines on the care for NETs is not known. The German NET Registry compiled information for Germany pertaining to three questions: who provides care for NET patients; does the care comply with proposed guidelines, and are the results comparable to those described in the literature?

Patients And Methods: Between 2004 and 2007 data on 1,263 patients from 21 centers were compiled in a dedicated database.

Histopathologic features and microsatellite instability of cancers of the papilla of vater and their precursor lesions.

The prevalence and development of microsatellite instability (MSI) and underlying mismatch repair (MMR) deficiency in the carcinogenesis of adenocarcinomas of the papilla of Vater and their precursor lesions are not well established. We analyzed 120 ampullary adenomas (31 pure adenomas and 89 carcinoma-associated adenomas) and 170 pure adenocarcinomas for MSI, immunohistochemical expression of MMR proteins and specific histopathologic features. The most common histologic subtype was intestinal (46.

WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors.

Background: It is difficult to predict the biologic behavior of pancreatic endocrine tumors in absence of metastases or invasion into adjacent organs. The World Health Organization (WHO) has proposed in 2004 size, angioinvasion, mitotic activity, and MIB1 proliferation index as prognostic criteria. Our aim was to test retrospectively the predictive value of these 2004 WHO criteria and of CK19, CD99, COX2, and p27 immunohistochemistry in a large series of patients with long-term follow-up.

Chromoendoscopy is a valuable tool for screening of high-risk patients with head and neck cancer for early detection of esophageal cancer.

Background: The incidence of esophageal cancer is markedly increased in patients with head and neck cancer, and the presence of esophageal cancer is associated with reduced survival rates.

Aims: We investigated whether the results of screening for esophageal cancer in patients with head and neck cancer using chromoendoscopy would change the treatment of such patients.

Patients: 87 patients with head and neck cancer and known alcohol or nicotine abuse were screened for esophageal cancer.

'Enjoy Thinking, Even if It Is Hard Work': an interview with Professor Gunther Kloeppel. [Interview by Martín E. Fernández-Zapico].

Professor Gunther Kloeppel is a distinguished pancreatic pathologist, recognized the world over for his enormous contribution to the understanding of the pathogenesis of different pancreatic diseases. In the current article, Prof. Kloeppel, a role model for establishing a productive academic career, gives advice to junior investigators starting in the field of pancreatic research.

Resistance mechanisms of gastrointestinal cancers: why does conventional chemotherapy fail?

Background: Gastrointestinal cancers belong to the most important causes of cancer death in the Western world. Because cure can be achieved only by complete surgical removal of the tumor, and most patients have metastasis at the time point of diagnosis, the majority of patients receive chemotherapy.

Discussion: Indications for chemotherapy are either the prevention of recurrence after tumor resection (neoadjuvant or adjuvant) or palliative treatment if the tumor is already widespread at diagnosis.

Protective effects of cholestyramine on liver cirrhosis induced by carbon tetrachloride in the rat.

The influence of cholestyramine and chenodeoxycholic acid on the induction of liver cirrhosis by carbon tetrachloride was investigated in the Wistar rat. The addition of 1.3% cholestyramine to the diet of the experimental animals inhibited to a large extent the induction of cirrhosis.