Symptomatic Pancreaticojejunal Anastomotic Stricture After Pancreaticoduodenectomy Managed by Longitudinal Pancreaticogastrostomy: A Report of Two Cases.

Symptomatic pancreaticojejunal anastomotic stricture is a rare complication following pancreaticoduodenectomy. Literature for the management of pancreaticojejunal anastomotic strictures is limited. Revision of pancreaticojejunostomy anastomosis, endoscopic dilation, stenting of pancreaticojejunal stricture, and modified Puestow procedure have all been described with variable outcomes. We present a report of two patients who developed symptomatic pancreaticojejunal anastomotic stricture following a pancreaticoduodenectomy, managed by longitudinal pancreaticogastrostomy with no complications, and resolution of symptoms with an average follow-up interval of 45 months.

Rare Case of a Transverse Colon Schwannoma.

Schwannomas are tumors comprised of schwann cells of the peripheral nervous system and infrequently present in the gastrointestinal tract. Transverse colon schwannomas are an even more rare subtype of gastrointestinal schwannomas. This study presents the case of a transverse colon schwannoma, in addition to presenting a literature review.

Transdiaphragmatic-pericardial Hernia: Case Report of an Unusual Condition Managed by Utilization of a Robotic Surgical System.

Transdiaphragmatic hernia via the central tendon in the pericardium is a rare entity. Most often, these hernias are acquired and related to the iatrogenic creation of a transdiaphragmatic-pericardial defect. We would like to present a case of a 62-year-old male who presented with acute chest pain and was diagnosed to have a transdiaphragmatic-pericardial hernia on computed tomography. He has a history of cardiac intervention via an abdominal approach 12 years earlier. A segment of jejunum was found strangulated in the defect. We used DaVinci Xi® (Intuitive Surgical, Sunnyvale, CA) robot and were able to successfully reduce the hernia, repair the defect, and resect a short segment of jejunum which was non-viable. The utilization of a minimally invasive approach may be feasible, and the use of a robotic surgical system may enhance the surgeon's ability to repair the defect.

A Case Report of a Ventral Hernia Containing a Liver Cyst in a Patient with Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited renal disorder and the fourth most common cause of end-stage renal disease. ADPKD is a systemic disease with multiple extrarenal manifestations, including cystic involvement of other organs, such as the liver and pancreas, and connective tissue abnormalities. The prevalence of hernias is higher in patients with ADPKD. It has been hypothesized that these hernias are the result of abnormal extracellular matrix production and/or increased intra-abdominal pressure from the cyst burden. We present a case of a 56-year-old female with polycystic kidney disease who was admitted for an incarcerated ventral hernia. The patient presented with obstructive symptoms concerning for bowel impingement. The patient underwent operative management, and during the procedure, an incarcerated liver cyst was identified in the hernia sac. This was successfully reduced, and the hernia was repaired with mesh.

The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.

Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways.

Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.

TGF-ß Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-ß) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-ß inhibition using the anti-TGF-ß antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-ß inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.