Improved Quality of Life Among Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation-Single Center Experience With Large Cohort of Patients.

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT. Two validated QoL surveys of the EORTC-QLQ-C30 and QLQ-PAN26-were administered in a prospective cohort of CP patients during pre-and post-operative scheduled visits. A total of 116 patients responded to the preoperative survey and were included in this study. The global health scale of QLQ-C30 was significantly improved after TPIAT when compared to baseline with delta scores of 24.26, 20.54, and 26.7 at 1, 2, and 3 years post-TPIAT (p < 0.001). The EORTC-PAN26 revealed significant improvements in symptom scales for pancreatic pain, bloating, digestive symptoms, taste, indigestion, weight loss, body image, and future worries. The comprehensive surveys in such a large cohort expands the QoL criterion in CP patients and indicates significant improvement in QoL post-TPIAT, further validating TPIAT as a treatment option for refractory CP.

Spleen-preserving total pancreatectomy and islet autotransplantation with complete preservation of the splenic arterial and venous supply does not impact islet yield and function.

BACKGROUND: Standard total pancreatectomy and islet autotransplantation (TPIAT) for chronic pancreatitis includes splenectomy, but TPIAT can be performed without splenectomy by full preservation of the blood supply to the spleen. METHODS: We compared the metabolic and clinical outcomes of patients who underwent TPIAT at our center between 2015 and 2021 with or without splenectomy. A total of 89 patients were included in the study, and 17 of them underwent spleen-preserving total pancreatectomy (SPTP). RESULTS: The two study groups had similar demographic and metabolic parameters. Short-term morbidity and long-term outcomes were similar. The operative time was significantly shorter with splenectomy: a median of 9.91 h (interquartile range [IQR] 8.89-10.83) compared to 10.78 h (IQR 10.2-11.6) for SPTP (P = 0.021). There was no difference between the groups in postoperative morbidity. Metabolic outcomes at 1 year were better in the SPTP group compared to the splenectomy group, with a median daily insulin requirement of 7 units (IQR 4-12) vs 15 units (IQR 7-26; P = 0.049) and a median C-peptide at 1 year of 0.65 (IQR 0.40-1.26) vs 1.00 (IQR 0.80-1.90; P = 0.63). The reduction in morphine milligram equivalents per day over time was significantly better in the SPTP group (P < 0.001), as was the decrease in pain score (P < 0.001). CONCLUSION: TPIAT with full arterial and venous preservation of the spleen had no adverse impact on islet yield or function. TPIAT can be safely and effectively performed with preservation of the spleen and the entire splenic artery and vein. The spleen should be preserved when feasible in every TPIAT surgery.

Circulating dipeptidyl peptidase-4 is independently associated with the presence and severity of NAFLD/NASH in individuals with and without obesity and metabolic disease.

INTRODUCTION: Dipeptidyl peptidase 4 (DPP4) levels are associated to metabolic and cardiovascular diseases in humans; initial evidence reported a relationship between DPP4 and chronic liver diseases. Aim of this study was to investigate hepatic and systemic DPP4 levels/activity in relation to NAFLD/NASH in individuals with and without metabolic disease. METHODS: We recruited fifty-two obese individuals undergoing bariatric surgery and intra-operative liver biopsy at Sapienza University, Rome, Italy. The association between DPP4 levels/activity and NAFLD was also evaluated in 126 non-obese individuals recruited in the same setting. RESULTS: NAFLD patients had significantly higher circulating DPP4 activity than no-NAFLD in both the obese and non-obese cohorts; plasma DPP4 activity and levels linearly correlated with steatosis grade and inflammation at the liver biopsy. Hepatic DPP4 mRNA was not associated to either its circulating levels/activity or NAFLD. In the multivariate logistic regression analysis on all the study participants (n = 178), higher circulating DPP4 activity was associated with NAFLD independently of potential confounders with OR (95% CI): 3.5 (1.2-10.21), p = 0.022. CONCLUSIONS: This study demonstrates the coexistence of increased plasma DPP4 levels and activity in NAFLD. Circulating DPP4 measurement may represent a novel cost-effective strategy for NAFLD/NASH risk stratification and a potential tool for monitoring disease's progression in established NAFLD.

Postoperative Outcomes Analysis After Pancreatic Duct Occlusion: A Safe Option to Treat the Pancreatic Stump After Pancreaticoduodenectomy in Low-Volume Centers.

Background: Surgical resection is the only possible choice of treatment in several pancreatic disorders that included periampullar neoplasms. The development of a postoperative pancreatic fistula (POPF) is the main complication. Despite three different surgical strategies that have been proposed-pancreatojejunostomy (PJ), pancreatogastrostomy (PG), and pancreatic duct occlusion (DO)-none of them has been clearly validated to be superior. The aim of this study was to analyse the postoperative outcomes after DO. Methods: We retrospectively reviewed 56 consecutive patients who underwent Whipple's procedure from January 2007 to December 2014 in a tertiary Hepatobiliary Surgery and Liver Transplant Unit. After pancreatic resection in open surgery, we performed DO of the Wirsung duct with Cyanoacrylate glue independently from the stump characteristics. The mean follow-up was 24.5 months. Results: In total, 29 (60.4%) were men and 19 were (39.6%) women with a mean age of 62.79 (SD ± 10.02) years. Surgical indications were in 95% of cases malignant diseases. The incidence of POPF after DO was 31 (64.5%): 10 (20.8%) patients had a Grade A fistula, 18 (37.5%) Grade B fistula, and 3 (6.2%) Grade C fistula. No statistical differences were demonstrated in the development of POPF according to pancreatic duct diameter groups (p = 0.2145). Nevertheless, the POPF rate was significantly higher in the soft pancreatic group (p = 0.0164). The mean operative time was 358.12 min (SD ± 77.03, range: 221-480 min). Hospital stay was significantly longer in patients who developed POPF (p < 0.001). According to the Clavien-Dindo (CD) classification, seven of 48 (14.58%) patients were classified as CD III-IV. At the last follow-up, 27 of the 31 (87%) patients were alive. Conclusions: Duct occlusion could be proposed as a safe alternative to pancreatic anastomosis especially in low-/medium-volume centers in selected cases at higher risk of clinically relevant POPF.

Myogenic oxidative imbalance interferes with antral motility in obese subjects.

BACKGROUND: Obesity is characterized by a systemic low-grade chronic inflammatory oxidative condition that affects vascular and cardiac smooth muscle relaxation. In human antrum, relaxation is mediated by vasoactive intestinal peptide (VIP) through cAMP and cGMP signaling pathways. A genome-wide association study has demonstrated an association between VIP and obesity. AIM: To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo. METHODS: Antral muscle strips and cells were isolated from surgical gastric samples from obese and normal weight subjects. Muscle contraction and relaxation, myogenic oxidative stress and inflammatory status were analyzed in vitro. Distal antral motility was evaluated in vivo by magnetic resonance imaging. RESULTS: Obese antral muscle cells showed an oxidative-inflammatory imbalance with overexpression of NLRP3 inflammasome, increased IL-1ß secretion and caspase1-activation, and reduced antioxidant capacity associated with a myogenic motor impairment of VIP-induced relaxation. The intracellular alterations were characterized by a decreased activation of the cAMP-signaling pathway and a decreased expression of eNOS. These in vitro alterations coincided with the hindering of antral motor activity observed in vivo. Apocynin treatment, counteracting oxidative stress, reverted alterations observed in obese antral muscle. CONCLUSION: Antral myogenic activity of obese subjects can be impaired by alterations of signaling pathways induced by oxidative stress.

Rectal Carcinoid Tumor With Liver Metastases Treated by Local Excision and Orthotopic Liver Transplant With Long-term Follow-up.

In patients affected by unresectable liver metastases from neuroendocrine tumor, liver transplant represents currently the only realistic chance for cure. The first attempt to establish selection criteria for liver transplant in patients affected by neuroendocrine tumor liver metastases was made by Mazzaferro and associates in 2007. We report the case of a 46-year-old man who came to our institution in 2006 with right upper quadrant abdominal pain. Diagnosis of rectal neuroendocrine tumor with bilobar liver nodules was made; the patient underwent transanal local resection. A liver biopsy confirmed the metastatic nature of the hepatic lesion, showing a low-grade neuroendocrine tumor (G1, proliferation index Ki-67 <2%). The patient underwent 2 sessions of transarterial chemoembolization that resulted in stable disease. Afterward, the patient underwent a liver transplant, using the piggyback technique without a venous-venous bypass. His postoperative course was uneventful. The patient has been disease-free for 3 years. Posttransplant treatment has played a key role in increasing the overall survival of the patient and assuring him a good quality of life. He died 9 years (102 mo) after liver transplant.