Survival outcome and prognostic factors after pancreatoduodenectomy for distal bile duct carcinoma: a retrospective multicenter study.

PURPOSE: Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma. METHODS: Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival. RESULTS: N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51-19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13-12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25-14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12-14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29-3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13-2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13-2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21-5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04-2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis. CONCLUSION: Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.

A Modified Switching Procedure from Temporary to Tunneled Central Venous Dialysis Catheters.

Background: Tunneled central venous catheters are commonly used for dialysis in patients without a functional permanent vascular access. In an emergent setting, a non-tunneled, temporary central venous catheter is often placed for immediate dialysis. The most critical step in the catheter insertion is venipuncture, which is often a major cause for longer intervention times and procedure-related adverse events. To avoid this critical step when placing a more permanent tunneled catheter, an exchange over a previously placed temporary one can be considered. In this paper, we present a modified switching approach with a separate access site. Methods: In this retrospective analysis of a prospective database, we examined whether this modified technique is non-inferior to a de novo application. Therefore, we included all 396 patients who received their first tunneled dialysis catheter at our site from March 2018 to March 2023. Out of these, 143 patients received the modified approach and 253 the standard de novo ultrasound-guided puncture and insertion. Then, the outcomes of the two groups, including adverse events and infections, were compared by nonparametric tests and multivariable logistic regression. Results: In both groups, the implantations were 100% successful. Catheter explantation due to infection according to CDC criteria was necessary in 18 cases, with no difference between the groups (5.0% vs. 4.4% p = 0.80). The infection rate per 100 days was 0.113 vs. 0.106 in the control group, with a comparable spectrum of bacteria. A total of 12 catheters (3 vs. 9) had to be removed due to a periinterventional complication. An early-onset infection was the reason in two cases (1.3%) in the study group and five in the control group (1.9%). A total misplacement of the catheter occurred in two cases only in the control group. After adjustment for potential confounders via multivariable logistic regression there was not a significant difference in the complication rate (adjusted odds ratio, aOR = 0.53, 95% CI = 0.14-2.03, p = 0.351) but an estimated decreased risk overall based on the average treatment effect of -1.7% in favor of the study group. Conclusions: The present study shows that a catheter exchange leads to no more infections than a de novo placement; hence, it is a feasible method. Moreover, misplacements and control chest X-rays to exclude pneumothorax after venipuncture were completely avoided by exchanging. This approach yields a much lower infection rate than previous reports: 1.3% compared to 2.7% in all existing aggregated studies. The presented approach seems to be superior to existing switching methods. Overall, an exchange can also help to preserve veins for future access, since the same jugular vein is used.

The impact of class I compression stockings on the peripheral microperfusion of the lower limb: A prospective pilot study.

OBJECTIVE: The use of medical compression stockings (MCS) in patients with peripheral arterial disease (PAD) and diabetes is the subject of an ongoing critical debate. While reducing leg edema of various origins by improving venous back flow, there is a concern about additional arterial flow obstruction when compression therapy is applied in pre-existing PAD. The aim of this study is to obtain further information on the use of class I MCS in patients with advanced PAD and to evaluate the framework conditions for a safe application. METHODS: The total collective (n = 55) of this prospective, clinical cohort study consisted of 24 patients with PAD Fontaine stage IIb and higher studied before revascularization, of whom 16 patients were examined again after revascularization, and 15 healthy participants included for reference. The microperfusion of the lower extremity of all participants was examined in a supine, elevated, and sitting position using the oxygen to see (O2C) method. RESULTS: The results indicate that leg positioning had the strongest influence on microcirculation (SO2 and flow: p = 0.0001), whereas MCS had no significant effect on the perfusion parameters (SO2: p = 0.9936; flow: p = 0.4967) and did not lead to a deterioration of values into critical ranges. CONCLUSION: Mild medical compression therapy appears to be feasible even in patients with advanced PAD. Larger studies are warranted to observe any long-term effects, in particular for the treatment of reperfusion edema after revascularization.

Disrupting the EMMPRIN (CD147)-cyclophilin A interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion.

OBJECTIVE: Inflammation and proteolysis crucially contribute to myocardial ischemia and reperfusion injury. The extracellular matrix metalloproteinase inducer EMMPRIN (CD147) and its ligand cyclophilin A (CyPA) may be involved in both processes. The aim of the study was to characterize the role of the CD147 and CyPA interplay in myocardial ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: Immunohistochemistry showed enhanced expression of CD147 and CyPA in myocardial sections from human autopsies of patients who had died from acute myocardial infarction and from mice at 24 hours after I/R. At 24 hours and 7 days after I/R, the infarct size was reduced in CD147(+/-) mice vs CD147(+/+) mice (C57Bl/6), in mice (C57Bl/6) treated with monoclonal antibody anti-CD147 vs control monoclonal antibody, and in CyPA(-/-) mice vs CyPA(+/+) mice (129S6/SvEv), all of which are associated with reduced monocyte and neutrophil recruitment at 24 hours and with a preserved systolic function at 7 days. The combination of CyPA(-/-) mice with anti-CD147 treatment did not yield further protection compared with either inhibition strategy alone. In vitro, treatment with CyPA induced monocyte chemotaxis in a CD147- and phosphatidylinositol 3-kinase-dependent manner and induced monocyte rolling and adhesion to endothelium (human umbilical vein endothelial cells) under flow in a CD147-dependent manner. CONCLUSION: CD147 and its ligand CyPA are inflammatory mediators after myocardial ischemia and reperfusion and represent potential targets to prevent myocardial I/R injury.

Implantation of a peritoneal dialysis catheter in patients with ESRD using local anesthesia and Remifentanil.

STUDY OBJECTIVE: The main objective of this study is to test the feasibility of the local anesthetic (LA) Mepivacaine 1% and sedation with Remifentanil as the primary anesthetic technique for the insertion of a peritoneal dialysis (PD) catheter, without the need to convert to general anesthesia. METHODS: We analyzed 27 consecutive end-stage renal disease (ESRD) patients who underwent the placement of a peritoneal catheter at our center between March 2015 and January 2019. The procedures were all performed by a general or vascular surgeon, and the postoperative care and follow-up were all conducted by the same peritoneal dialysis team. RESULTS: All of the 27 subjects successfully underwent the procedure without the need of conversion to general anesthesia. The catheter was deemed prone to usage in all patients and was found to be leak-proof in 100% of the patients. CONCLUSION: This study describes a safe and successful approach for insertion of a PD catheter by combined infiltration of the local anesthetic Mepivacaine 1% and sedation with Remifentanil. Hereby, ESRD patients can be treated without general anesthesia, while ensuring functionality of the PD catheter.

Redo Surgery After Duodenum-Preserving Pancreatic Head Resection for Chronic Pancreatitis: High Incidence in Long-Term Follow-up.

INTRODUCTION: Duodenum-preserving pancreatic head resection is a safe procedure with a more favorable short-term outcome compared to pancreaticoduodenectomy. However, some patients develop mechanical complications or suspicion of malignancy during follow-up and need reoperation years after primary surgery. Aim of this study was to evaluate incidence, techniques, and complication rates of redo operations. MATERIALS AND METHODS: We reviewed short- and long-term outcomes of 33 patients who underwent duodenum-preserving pancreatic head resection for chronic pancreatitis from 1997 to 2010 at our department from a prospective database. RESULTS: Short-term outcome after duodenum-preserving pancreatic head resection was comparable with previous data. Follow-up (mean 89 months) was achieved for 26 patients. Eight patients (30.1 %) needed a redo operation of which seven were performed. Indications were obstructive jaundice (four patients) and suspicion of cancer of pancreatic head (four patients; carcinoma confirmed in three patients). Mean interval between initial and redo operation was seven years for benign stenoses and 4 years for cancer. Three of seven operated patients needed revision. CONCLUSION: Need for redo operations after duodenum-preserving pancreatic head resection is high and these operations have high complication rates. In most cases, redo operations can be avoided by performing pancreaticoduodenectomy as initial operation.

Inhibition of glucose turnover by 3-bromopyruvate counteracts pancreatic cancer stem cell features and sensitizes cells to gemcitabine.

According to the cancer stem cell (CSC) hypothesis, the aggressive growth and early metastasis of pancreatic ductal adenocarcinoma (PDA) is due to the activity of CSCs, which are not targeted by current therapies. Otto Warburg suggested that the growth of cancer cells is driven by a high glucose metabolism. Here, we investigated whether glycolysis inhibition targets CSCs and thus may enhance therapeutic efficacy. Four established and 3 primary PDA cell lines, non-malignant cells, and 3 patient-tumor-derived CSC-enriched spheroidal cultures were analyzed by glucose turnover measurements, MTT and ATP assays, flow cytometry of ALDH1 activity and annexin positivity, colony and spheroid formation, western blotting, electrophoretic mobility shift assay, xenotransplantation, and immunohistochemistry. The effect of siRNA-mediated inhibition of LDH-A and LDH-B was also investigated. The PDA cells exhibited a high glucose metabolism, and glucose withdrawal or LDH inhibition by siRNA prevented growth and colony formation. Treatment with the anti-glycolytic agent 3-bromopyruvate almost completely blocked cell viability, self-renewal potential, NF-κB binding activity, and stem cell-related signaling and reverted gemcitabine resistance. 3-bromopyruvate was less effective in weakly malignant PDA cells and did not affect non-malignant cells, predicting minimal side effects. 3-bromopyruvate inhibited in vivo tumor engraftment and growth on chicken eggs and mice and enhanced the efficacy of gemcitabine by influencing the expression of markers of proliferation, apoptosis, self-renewal, and metastasis. Most importantly, primary CSC-enriched spheroidal cultures were eliminated by 3-bromopyruvate. These findings propose that CSCs may be specifically dependent on a high glucose turnover and suggest 3-bromopyruvate for therapeutic intervention.