J.-M. Regimbeau

Transient receptor potential melastatin-related 7 channel is overexpressed in human pancreatic ductal adenocarcinomas and regulates human pancreatic cancer cell migration

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer with a tendency to invade surrounding healthy tissues, leading to a largely incurable disease. Despite many advances in modern medicine, there is still a lack of early biomarkers as well as efficient therapeutical strategies. The melastatin‐related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that is involved in maintaining Ca2+ and Mg2+ homeostasis. It has been recently reported to regulate cell differentiation, proliferation and migration. However, the role of TRPM7 in PDAC progression is far to be understood. In our study, we show that TRPM7 is 13‐fold overexpressed in cancer tissues compared to the healthy ones. Furthermore, TRPM7 staining is stronger in tumors with high grade, suggesting a correlation between TRPM7 expression and PDAC progression. Importantly, TRPM7 expression is inversely related to patient survival. In BxPC‐3 cell line, dialyzing the cytoplasm during the patch‐clamp whole‐cell recording with a 0‐Mg2+ solution activated a nonselective current with a strong outward rectification. This cation current is inhibited by intracellular Mg2+ and by TRPM7 silencing. The downregulation of TRPM7 by small interference RNA dramatically inhibited intracellular Mg2+ fluorescence and cell migration without affecting cell proliferation, suggesting that TRPM7 contributes to Mg2+ entry and cell migration. Moreover, external Mg2+ following TRPM7 silencing fully restored the cell migration. In summary, our results indicate that TRPM7 is involved in the BxPC‐3 cell migration via a Mg2+‐dependent mechanism and may be a potential biomarker of poor prognosis of PDAC.

Enterococci increase the morbidity and mortality associated with severe intra-abdominal infections in elderly patients hospitalized in the intensive care unit

OBJECTIVESnEnterococci may increase morbidity and mortality in elderly patients with intra-abdominal infections (IAIs) hospitalized in the intensive care unit (ICU).nnnPATIENTS AND METHODSnA single-centre, retrospective evaluation of an ICU database (1997-2007) of elderly ICU patients (≥75 years) with a severe IAI was performed. Demographics, severity scores, underlying diseases, microbiology and outcomes were recorded. Patients with enterococci isolated in peritoneal fluid (E+ group) were compared with those lacking enterococci in peritoneal fluid (E- group). Stepwise multivariate logistic regression was used to identify independent factors associated with mortality.nnnRESULTSnOne hundred and sixty patients were included (meanu200a±u200aSD age 82u200a±u200a5 years; nu200a=u200a72 in the E+ group). The E+ group was more severely ill than the E- group, with higher Simplified Acute Physiologic Score 2 (61u200a±u200a20 versus 48u200a±u200a16, Pu200a=u200a0.0001) and Sequential Organ Failure Assessment scores (8u200a±u200a3 versus 5u200a±u200a3, Pu200a=u200a0.0001), a greater postoperative infection rate (58.3% versus 34.1%, Pu200a=u200a0.01), a higher incidence of inappropriate empirical antimicrobial therapies (33.3% versus 19.3%, Pu200a=u200a0.04), a longer duration of mechanical ventilation (11.8u200a±u200a10.9 versus 7.8u200a±u200a10.2 days, Pu200a=u200a0.02) and greater vasopressor use (7.2u200a±u200a7.1 versus 3.3u200a±u200a4.1 days, Pu200a=u200a0.001). ICU mortality was higher in the E+ group than in the E- group (54.2% versus 38.6%, Pu200a=u200a0.05). In the multivariate analysis, E+ status was independently associated with mortality (odds ratio 2.24; 95% confidence interval 1.06-4.75; Pu200a=u200a0.03).nnnCONCLUSIONSnIn severely ill, elderly patients in the ICU for an IAI, the isolation of enterococci was associated with increased disease severity and morbidity and was an independent risk factor for mortality.

Sleeve gastrectomy: Technique and results

Sleeve gastrectomy (SG), sometimes also called longitudinal gastrectomy, is performedwith increasing frequency in the treatment of morbid obesity, second only to gastric bypass(GBP).SG is the natural offspring of other operations performed for morbid obesity, namely,calibrated vertical gastroplasty (CVG) (or Mason’s vertical banded gastroplasty), theMagenstrasse’s operation and Mill’s operation, mainly performed in the UK [1]. Hess andMarceau introduced the SG into the armamentarium of the bariatric surgeon in 1988 [2]as the restrictive part of the duodenal switch (DS). Gagner and Rogula [3] described thisoperation as the first of two stages of biliopancreatic diversion (BPD) with DS performed6 to 12 months later, in order to decrease the high mortality associated with this complexoperation in the super-obese. The SG was described as an isolated therapeutic modalityfor the first time in 1993 [1].As this procedure has been introduced only recently in bariatric surgery, the techniqueof SG has not yet been standardized in all its steps (the type of stapler, the size of thecalibration bougie, the size of the pouch, the type of staples, the number of firings as wellas whether or not to reinforce the staple line). This variability of technique, along withpoorselectionofcandidatesfortheprocedure(‘‘sweeteaters’’),arepossibleexplanationsfor the wide variations in outcome found in the different published series.Herein we describe the technique of SG, as performed in our unit since 2004 (230interventions—oral communication). Based on the literature and our midterm results wealso report the main complications and their management.

The current abdominoperineal resection: oncological problems and surgical modifications for low rectal cancer.

Abdominoperineal resection is the one of the oldest surgical procedures for rectal cancer. Outcome after abdominoperineal resection for rectal carcinoma is not as good as anterior resection as the risk of local recurrence is higher and survival is poorer. During abdominoperineal resection, the rate of rectal perforation is high and the circumferential margin is often involved. Recently the concept of cylindrical abdominoperineal resection has been reintroduced. It allows a large excision and the initial results are encouraging. The purpose of this article was to analyse the oncological results of abdominoperineal resection and to develop the potential technical modifications of the procedure.

Permissivity of Primary Human Hepatocytes and Different Hepatoma Cell Lines to Cell Culture Adapted Hepatitis C Virus

Significant progress has been made in Hepatitis C virus (HCV) culture since the JFH1 strain cloning. However, developing efficient and physiologically relevant culture systems for all viral genotypes remains an important goal. In this work, we aimed at producing a high titer JFH1 derived virus to test different hepatic cells’ permissivity. To this end, we performed successive infections and obtained a JFH1 derived virus reaching high titers. Six potential adaptive mutations were identified (I599V in E2, R1373Q and M1611T in NS3, S2364P and C2441S in NS5A and R2523K in NS5B) and the effect of these mutations on HCV replication and infectious particle production was investigated. This cell culture adapted virus enabled us to efficiently infect primary human hepatocytes, as demonstrated using the RFP-NLS-IPS reporter protein and intracellular HCV RNA quantification. However, the induction of a strong type III interferon response in these cells was responsible for HCV inhibition. The disruption of this innate immune response led to a strong infection enhancement and permitted the detection of viral protein expression by western blotting as well as progeny virus production. This cell culture adapted virus also enabled us to easily compare the permissivity of seven hepatoma cell lines. In particular, we demonstrated that HuH-7, HepG2-CD81, PLC/PRF/5 and Hep3B cells were permissive to HCV entry, replication and secretion even if the efficiency was very low in PLC/PRF/5 and Hep3B cells. In contrast, we did not observe any infection of SNU-182, SNU-398 and SNU-449 hepatoma cells. Using iodixanol density gradients, we also demonstrated that the density profiles of HCV particles produced by PLC/PRF/5 and Hep3B cells were different from that of HuH-7 and HepG2-CD81 derived virions. These results will help the development of a physiologically relevant culture system for HCV patient isolates.

Antibiotic therapy in acute calculous cholecystitis.

Acute calculous cholecystitis may progress in a variety of ways from mild cases treatable with (or even without) oral antibiotics to severe cases complicated by bile peritonitis that require emergency surgical or radiological intervention. A sample of bile should always be sent for microbial cultures to identify aerobic and anaerobic bacterial organisms. Empirically selected broad spectrum antibiotic therapy (with a defined duration, dosage and administration route) should be prescribed according to the severity of the cholecystitis, an associated history of recent antibiotic therapy, and local bacterial susceptibility patterns. As soon as causative organisms have been identified, antibiotic therapy should be adjusted to a narrower spectrum antimicrobial agent based on the specific micro-organism(s) and the results of sensitivity testing.

Non-hepatic gastrointestinal surgery in patients with cirrhosis

Gastrointestinal surgery is feasible in patients with Child A cirrhosis, but is associated with higher morbidity and mortality. Hernia repair, biliary and colonic surgery are the most frequently performed interventions in this context. Esophageal and pancreatic surgery are more controversial and less frequently performed. For patients with decompensated liver function (Child B or C patients), the indications for surgery should be discussed by a multi-specialty team including the hepatologist, anesthesiologist, surgeon; liver function should be optimized if possible. During emergency surgery, histologic diagnosis of cirrhosis should be confirmed by liver biopsy because the histologic diagnosis has therapeutic and prognostic implications. The management of patients with Child A cirrhosis without portal hypertension is little different from the management of patients without cirrhosis. However, the management of patients with Child B or C cirrhosis or with portal hypertension is more complex and requires an accurate assessment of the balance of benefit vs. risk for surgical intervention on a case-by-case basis.

Gastrointestinal bleeding complication of gastric fistula after sleeve gastrectomy: consider pseudoaneurysms

BackgroundGastric fistula (GF) is the most serious complication after longitudinal sleeve gastrectomy (LSG), with an incidence ranging from 0 to 5xa0%. In this context, concomitant upper gastrointestinal bleeding (UGIB) has never been described. Here, we describe our experience of this situation and suggest a procedure for the standardized management of this life-threatening complication.MethodsWe retrospectively analyzed all patients having been treated for post-LSG UGIB in our university medical center between November 2004 and February 2012. Data on GF and UGIB (time to onset, diagnosis and management) were assessed.ResultsForty patients were treated for post-LSG GF in our institution, 18 of whom (45xa0%) had been referred by tertiary centers. Four patients presented UGIB (10xa0%): two had undergone primary LSG, one had undergone simultaneous gastric band removal and LSG, and one had undergone repeat LSG. The median time interval between GF and UGIB was 15xa0days. The four cases of UGIB included three pseudoaneurysms (75xa0%, with two affecting the left gastric artery and one affecting the upper pole of the splenic artery) and one case of bleeding related to stent-induced gastric ulceration. Computed tomography enabled diagnosis of the pseudoaneurysm in all cases. Two of the four patients (50xa0%) were treated with selective embolization during arteriography, and two (50xa0%) were treated surgically with arterial ligation. One of the surgically treated patients died during follow-up.ConclusionsUGIB after LSG was investigated in the context of a postoperative GF and was found to have been caused by a pseudoaneurysm in 75xa0% of cases. When looking for a pseudoaneurysm, a primary angiography should be preferred to endoscopy allowing selective arterial embolization in hemodynamically stable patients, whereas surgery should be reserved for treatment failures or hemodynamically instability.

Management of the perineal wound after abdominoperineal resection

Although many options are available for the management of perineal wounds after abdominoperineal resection, ranging from direct closure to flap reconstruction, treatment remains challenging. A better understanding of the aims, drawbacks and progress in perineal wound management after abdominoperineal rectal resection can help the surgeon make better choices for each patient, but it is very difficult to propose a single, optimal, evidence-based procedure for the management of pelvic exenteration. Recent progress provided by the extralevator abdominoperineal resection technique and perforator flap concepts have changed our conception of reconstruction leading to the different technical options highlighted in this review.

Percutaneous, computed tomography-guided drainage of deep pelvic abscesses via a transgluteal approach: a report on 30 cases and a review of the literature.

AimPercutaneous drainage of abdominal and pelvic abscesses is a first-line alternative to surgery. Anterior and lateral approaches are limited by the presence of obstacles, such as the pelvic bones, bowel, bladder, and iliac vessels. The objective of this study was to assess the feasibility, safety, tolerability, and efficacy of a percutaneous, transgluteal approach by reviewing our clinical experience and the literature.Materials and methodsWe reviewed demographic, clinical and morphological data in the medical records of 30 patients having undergone percutaneous, computed tomography (CT)-guided, transgluteal drainage. In particular, we studied the duration of catheter drainage, the types of microorganisms in biological fluid cultures, complications related to procedures and the patient’s short-term treatment outcome.ResultsFrom January 2005 to October 2011, 345 patients underwent CT-guided percutaneous drainage of pelvis abscesses in our institution. A transgluteal approach was adopted in 30 cases (10 women and 20 men; mean age: 52.6 [range 14–88]). The fluid collections were related to post-operative complications in 26 patients (86.7xa0%) and inflammatory or infectious intra-abdominal disease in the remaining 4 patients (acute diverticulitis: nxa0=xa02; appendicitis: nxa0=xa01; Crohn’s disease: nxa0=xa01) (13.3xa0%). The mean duration of drainage was 8.7xa0days (range 3–33). Laboratory cultures were positive in 27 patients (90xa0%) and Escherichia coli was the most frequently present microorganism (in 77.8xa0% of the positive samples). A transpiriformis approach (nxa0=xa05) was more frequently associated with immediate procedural pain (nxa0=xa03). No major complications were observed, either during or after the transgluteal procedure. Drainage was successful in 29 patients (96.7xa0%). One patient died from massive, acute cerebral stroke 14xa0days after drainage.ConclusionWhen an anterior approach is unfeasible, transgluteal, percutaneous, CT-guided drainage is a safe, well tolerated and effective procedure. Major complications are rare. This type of drainage is an alternative to surgery for the treatment of deep pelvic abscesses (especially for post-surgical collections).