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Data on Mesothelin expression in human normal and cancerous tissues is controversial. We employed immunohistochemistry on a tissue microarray from 599 pancreatic cancers and 12 large tissue sections of pancreatitis. Mesothelin expression was highest in pancreatic adenocarcinomas (89%) and adenocarcinomas of the ampulla Vateri (79%), infrequent in pancreatitis and absent in 6 acinus cell carcinomas and normal pancreas. Mesothelin expression was unrelated to pathological tumor stage, grade, metastasis, and tumor infiltrating CD8+ lymphocytes. In conclusion, pancreatic cancer may be ideally suited for putative anti-mesothelin therapies, and mesothelin may represent a suitable biomarker for pancreatic cancer diagnosis, especially on small biopsies.

BACKGROUND Immune checkpoint-inhibitors targeting the PD-1/PD-L1 system are FDA approved in microsatellite instable (MSI) or mismatch repair deficient (dMMR) colorectal cancer (CRC). PD-L1 expression is tightly linked to features connected to immune checkpoint inhibitor response, but studies on large subsets of cancers analyzing the correlation between different status of MSI/dMMR, tumor infiltrating lymphocytes and PD-L1 expression are still lacking. METHODS More than 1800 CRC were analyzed for PD-L1 by immunohistochemistry in a tissue microarray format. Data were compared to MMR, the number of intratumoral CD8+ cytotoxic T-cells, and adverse clinico-pathological parameters. Different cutoff levels for defining PD-L1 positivity in tumor cells (1%, 5%, 10%, and 50%) yielded comparable results. RESULTS At a cutoff level of 5%, PD-L1 positivity was seen in 5.1% of tumors. PD-L1 was more often positive in dMMR (18.6%) than in MMR proficient (pMMR) cancers (4.1%; p

Zusammenfassung Hintergrund In der Schwangerschaft diagnostizierte neuroendokrine Tumoren (NET) sind eine absolute Rarität. Die vorliegende Kasuistik beschreibt Diagnostik und Therapie eines im 2. Trimenon symptomatisch gewordenen metastasierten NET des Pankreas. Fallbeschreibung Eine 33-jährige Patientin stellte sich in der 19. Schwangerschaftswoche (SSW) mit persistierender Diarrhoe in der Notaufnahme vor. Laborchemisch fiel eine ausgeprägte Hyperkalzämie (3,53 mmol/l) auf. In der Bildgebung fand sich eine Raumforderung im Bereich des Pankreaskorpus/-schwanzes mit ausgedehnter Lebermetastasierung. Histologisch zeigte sich ein NET (G2, SSTR-positiv) mit einer paraneoplastischen Parathormon-related-Peptide-Sekretion als Ursache der Hyperkalzämie. Unter einer Therapie mit Octreotid normalisierte sich das Kalzium, die Diarrhoe sistierte. Nach Geburt eines gesunden Kindes (32. SSW per sectio) fand sich ein Progress; der Pankreastumor wurde komplett entfernt, die Leberfiliae so weit wie möglich. In einem postoperativen CT zeigten sich verbliebene metastasensuspekte Läsionen, eine palliative Therapie mit Lanreotid wurde eingeleitet. Darunter ist die Patientin seit einem Jahr symptomfrei, das Serumkalzium blieb normwertig. Das Kind entwickelte sich unauffällig. Diskussion Dieser ungewöhnliche Fall zeigt, dass es auch bei ausgedehnt metastasierten symptomatischen NETs in der Schwangerschaft weitreichende diagnostische und therapeutische Optionen geben kann, die in enger interdisziplinärer Zusammenarbeit unter sorgfältiger Risiko-Nutzen-Abwägung für Mutter und Kind eine Fortführung der Schwangerschaft erlauben.

Introduction: Mucin 5AC (MUC5AC) belongs to the family of secreted gel-forming mucins. It is physiologically expressed in some normal mucin producing epithelial cells but also in pancreatic, ovarian, and colon cancer cells. The role of MUC5AC expression in cancer is not fully understood. This study was designed to explore the role of MUC5AC for pancreatic cancer progression, its association to microsatellite instability, and its diagnostic utility. Methods: Mucin 5AC expression was studied immunohistochemically in a tissue microarray (TMA) from 532 pancreatic cancers, 61 cancers of the ampulla Vateri, six acinar cell carcinomas and 12 large sections of pancreatitis. Results: Mucin 5AC staining was interpretable in 476 of 599 (79%) arrayed cancers. Staining was completely absent in normal pancreas and pancreatitis, but frequent in pancreatic cancer. Membranous and cytoplasmic MUC5AC expression was most common in pancreatic adenocarcinomas (71% of 423), followed by carcinomas of the ampulla Vateri (43% of 47), and absent in six acinar cell carcinomas. Mucin 5AC expression was unrelated to tumor phenotype (tumor stage, tumor grade, lymph node, and distant metastasis), and microsatellite instability in ductal adenocarcinomas and carcinomas of the ampulla Vateri. Conclusion: Our study indicates that MUC5AC is an excellent biomarker for pancreatic cancer diagnosis, especially to support the sometimes-difficult diagnosis on small biopsies. Mucin 5AC expression is unrelated to pancreatic cancer aggressiveness.

The transmembrane channel protein DOG1 (Discovered on GIST1) is normally expressed in the gastrointestinal interstitial cells of Cajal and also in gastrointestinal stroma tumors arising from these cells. However, there is also evidence for a relevant role of DOG1 expression in colorectal cancers. This study was undertaken to search for associations between DOG1 expression and colon cancer phenotype and key molecular alterations.A tissue microarray containing samples from more than 1,800 colorectal cancer patients was analyzed by immunohistochemistry.DOG1 immunostaining was detected in 503 (30.2%) of 1,666 analyzable colorectal cancers and considered weak in 360 (21.6%), moderate in 78 (4.7%), and strong in 65 (3.9%). Strong DOG1 immunostaining was associated with advanced pT stage (p=0.0367) and nodal metastases (p=0.0145) but these associations were not retained in subgroups of 1,135 mismatch repair proficient and 86 mismatch repair deficient tumors. DOG1 positivity was significantly linked to several molecular tumor features including mismatch repair deficiency (p=0.0034), BRAF mutations (p0.0001), nuclear p53 accumulation (p=0.0157), and PD-L1 expression (p=0.0199) but unrelated to KRAS mutations and the density of tumor infiltrating CD8 positive lymphocytes.Elevated DOG1 expression is frequent in colorectal cancer and significantly linked to important molecular alterations. However, DOG1 overexpression is largely unrelated to histopathological parameters of cancer aggressiveness and may thus not serve as a prognostic parameter for this tumor entity.

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p p p

Background Microsatellite instability (MSI) has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in pancreatic cancer, but data on the possible extent of intratumoral heterogeneity are lacking. Methods To study MSI heterogeneity in pancreatic cancer, a tissue microarray (TMA) comprising 597 tumors was screened by immunohistochemistry with antibodies for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Results In six suspicious cases, large section immunohistochemistry and microsatellite analysis (Bethesda panel) resulted in the identification of 4 (0.8%) validated MSI cases out of 480 interpretable pancreatic ductal adenocarcinomas. MSI was absent in 55 adenocarcinomas of the ampulla of Vater and 7 acinar cell carcinomas. MMR deficiency always involved MSH6 loss, in three cases with additional loss of MSH2 expression. Three cancers were MSI-high and one case with isolated MSH6 loss was MSS in PCR analysis. The analysis of 44 cancer-containing tumor blocks revealed that the loss of MMR protein expression was always homogeneous in affected tumors. Automated digital image analysis of CD8 immunostaining demonstrated markedly higher CD8 + tumor infiltrating lymphocytes in tumors with (mean = 685, median = 626) than without (mean = 227; median = 124) MMR deficiency (p Conclusions Our data suggest that MSI occurs early in a small subset of ductal adenocarcinomas of the pancreas and that immunohistochemical MMR analysis on limited biopsy or cytology material may be sufficient to estimate MMR status of the entire cancer mass.

Objectives Information of the clinicopathological characteristics and outcome data of patients with adenosquamous carcinoma of the pancreas (ASCAP) remains limited. This study's aim is to describe the clinical, pathological, and molecular characteristics of 25 resected ASCAPs. Methods Of all 25 cases, patient characteristics, follow-up data, and pathological/immunohistological features were reviewed and analyzed. Results In this 3-institutional retrospective analysis of 562 pancreatic cancer patients, we identified 25 cases with histologically confirmed ASCAP (4.4%). Follow-up was available in 21 ASCAP and 50 pancreatic ductal adenocarcinoma control patients with a median overall survival of 8.2 and 21 months, respectively. Age, tumor size, localization in the tail, lymph node status, and resection margin seem to be the most significant factors of survival in our ASCAP cohort. In contrast to pancreatic ductal adenocarcinoma, positive expression of p63, keratins K5/14, and the epidermal growth factor receptor are a robust marker profile of these tumors. Conclusions Adenosquamous carcinoma of the pancreas comprises a group of neoplasms in which stage and adverse morphological features contribute to its bad prognosis. Further work must be pursued to improve detection and treatment options to reduce mortality. Specifically, differences in biology might become a target for the development of possible therapies.

An 81-year-old patient with significant cardiac comorbidities, a history of sigmoid resection 6 years ago, and iliac bypass surgery 19 years ago presented with mild hematochezia for the previous 3 days. While hemodynamically stable at first, he developed massive bleeding during preparation for colonoscopy and underwent a short course of cardiopulmonary resuscitation. Colonoscopy revealed no active bleeding but a protuberance of the colonic wall and a coagulation clot. In ultrasonography immediately after endoscopy, a large aneurysm was diagnosed and diagnosis of an iliaco-colonic fistula was assumed. CT scan demonstrated a large pseudoaneurysm of the distal anastomosis after iliaco-iliac bypass. With endovascular treatment, the original lumen of the iliac artery could be recanalized, and 2 covered stents were placed to cover both anastomosis of the prosthetic bypass leading to a complete shutdown of bypass perfusion. A double-barreled transversostoma was established to minimize contamination of the aneurysmal sac. Seven months after these procedures, the patient is well and free of infection.Though aorto- or iliaco-colonic fistula after aortic or iliac surgery are very rare, endoscopists should be aware of their possibility. A high index of clinical suspicion in patients with prior abdominal vascular bypass surgery should prompt rapid imaging studies, possibly before endoscopy. In critically ill patients, endovascular treatment may be a suitable alternative and result in a favorable outcome.Ein 81jähriger Patient mit erheblichen kardialen Begleiterkrankungen, Zustand nach Sigmaresektion vor 6 Jahren und einem iliakalen Bypass vor 19 Jahren stellte sich mit einer seit 3 Tagen bestehenden milden Hämatochezie vor. Der hämodynamisch zunächst stabile Patient entwickelte während der Koloskopie – Vorbereitung eine massive peranale Blutung und musste kurzzeitig kardiopulmonal reanimiert werden. Koloskopisch fand sich keine aktive Blutung, aber eine Vorwölbung der Darmwand und ein Koagel. In einer unmittelbar nach der Endoskopie durchgeführten Sonografie wurde ein großes Pseudoaneurysma gesehen und eine iliaco-colische Fistel vermutet. Die CT bestätigte ein großes Aneurysma der distalen Anastomose des iliaco-iliakalen Bypasses.Mittels endovaskulärer Therapie konnte das ursprüngliche Lumen der A. iliaca rekanalisiert werden. Beide Anastomosen des bypasses wurden mit 2 ummantelten Stents überbrückt, die Perfusion des Bypasses wurde dadurch ausgeschaltet. Um eine Kontamination des Aneurysmasacks zu minimieren wurde ein doppelläufiges Transversostoma angelegt. 7 Monate später geht es dem Patienten gut, es gibt keine Zeichen einer Infektion.Trotz der Seltenheit einer solchen Diagnose sollten sich Endoskopiker der Möglichkeit einer aorto- oder iliaco-colischen Fistel nach Aorten- oder Iliakalchirurgie bewußt sein. Auch geringgradigere Blutungen bei Patienten nach abdominellen Gefäßeingriffen sollten zu einer raschen Bildgebung führen, möglichst vor einer Endoskopie. Bei kritisch kranken Patienten kann eine endovaskuläre Therapie eine sinnvolle Alternative sein.