Combined Bile Duct and Pancreatic Duct Injuries during Distal Gastrectomy for Obstructing Peptic Ulcer Disease

A combination of bile and pancreatic duct injuries is very rare. Anomalous ductal anatomy, distorting duodenal fibrosis, and pancreatic atrophy predispose to this untoward complication during performance of distal gastrectomy for benign peptic stricture. The technical challenges posed by this complication and experience gained by managing it are shared.

Immune Checkpoint Inhibitor-Associated Diabetes Mellitus: A Single-Institution Experience

<b>OBJECTIVE</b> <p>To characterize immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in a single-institution case series. </p> <p><b>DESIGN AND METHODS</b></p> <p>Retrospective chart review of 18 patients with new-onset ICI-DM following anti-PD-1/anti-PD-L1 therapy for advanced carcinomas.</p> <p><b>RESULTS</b></p> <p>9/18 patients had diabetic ketoacidosis (median glucose: 27.92mmol/L; median glucose before presentation: 6.35mmol/L). Median C-peptide at ICI-DM diagnosis was low, and declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56-12.23). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically.</p> <p><b>CONCLUSIONS</b></p> <p>ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may <a>occur both earlier following PD-L1 blockade compared to PD-1 inhibition </a>and in those who have positive GAD65 autoantibodies.</p>

Immune Checkpoint Inhibitor-Associated Diabetes Mellitus: A Single-Institution Experience

<b>OBJECTIVE</b> <p>To characterize immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in a single-institution case series. </p> <p><b>DESIGN AND METHODS</b></p> <p>Retrospective chart review of 18 patients with new-onset ICI-DM following anti-PD-1/anti-PD-L1 therapy for advanced carcinomas.</p> <p><b>RESULTS</b></p> <p>9/18 patients had diabetic ketoacidosis (median glucose: 27.92mmol/L; median glucose before presentation: 6.35mmol/L). Median C-peptide at ICI-DM diagnosis was low, and declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56-12.23). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically.</p> <p><b>CONCLUSIONS</b></p> <p>ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may <a>occur both earlier following PD-L1 blockade compared to PD-1 inhibition </a>and in those who have positive GAD65 autoantibodies.</p>

Pirfenidone Alleviates Features of Well-Established Chronic Pancreatitis in Mouse Models

Introduction/Objective Chronic pancreatitis (CP) is a fibro-inflammatory disease of pancreas with no targeted therapy and is considered irreversible. Antifibrotic agent pirfenidone is FDA approved for idiopathic pulmonary fibrosis. However, exact molecular mechanism of its action is not clear. The aim of this study was to evaluate pirfenidone as a therapeutic agent for CP. Methods Caerulein-CP was induced in C57BL/6 mice by caerulein injections (50ug/kgx7, i.p., hourly x twice weekly x10 weeks). At 11 weeks, animals were randomized and assigned to either saline or pirfenidone group (400 mg/kg/d by oral gavage for 5 weeks). Mice were euthanized at 17 weeks. L-arginine induced CP was induced by i.p. injections of L-arginine (4.5g/kg x2 hourly, once a week x 4) and treatment was started after 5 weeks of start. Mice were sacrificed at early time-points after starting treatment. Single-cell suspension of pancreata were used for flow- cytometry. Pancreatic atrophy, histology, fibrosis and cytokine mRNA profile were evaluated. In vitro studies were done on stellate cells. Results The treated caerulein-CP mice had improvement in pancreas/mouse weight ratio, (7.03±0.41 vs. 4.75±0.28; p&lt;0.0001). Histology scores and fibrosis markers were reduced. Pancreatic atrophy and histology scores showed significant improvement by day 14 of treatment in L-arginine CP. Flow cytometry showed that by day 7 of treatment there was significant reduction in macrophage infiltration (1.09 ± 0.18 % vs 3.26 ± 0.4 %; p&lt;0.001) and pro-fibrotic M2 macrophage markers [IL-4 (1.5 ± 0.1 % vs 2.8 ± 0.2%; p=0.007)], while M1 marker (MHC II) did not change. mRNA levels of pro-inflammatory and pro-fibrotic cytokines decreased, and of anti-inflammatory cytokines increased. In vitro study on stellate cells showed reduction in mRNA levels of pro-fibrotic and pro-inflammatory cytokines as well as fibrosis markers in treatment group. Conclusion Pirfenidone ameliorates well-established CP in mouse models by altering immune cells.