Protracted immune disorders at one year after ICU discharge in patients with septic shock.

BACKGROUND: Sepsis is a leading cause of mortality and critical illness worldwide and is associated with an increased mortality rate in the months following hospital discharge. The occurrence of persistent or new organ dysfunction(s) after septic shock raises questions about the mechanisms involved in the post-sepsis status. The present study aimed to explore the immune profiles of patients one year after being discharged from the intensive care unit (ICU) following treatment for abdominal septic shock. METHODS: We conducted a prospective, single-center, observational study in the surgical ICU of a university hospital. Eighty-six consecutive patients admitted for septic shock of abdominal origin were included in this study. Fifteen different plasma biomarkers were measured at ICU admission, at ICU discharge and at one year after ICU discharge. Three different clusters of biomarkers were distinguished according to their functions, namely: (1) inflammatory response, (2) cell damage and apoptosis, (3) immunosuppression and resolution of inflammation. The primary objective was to characterize variations in the immune status of septic shock patients admitted to ICU up to one year after ICU discharge. The secondary objective was to evaluate the relationship between these biomarker variations and patient outcomes. RESULTS: At the onset of septic shock, we observed a cohesive pro-inflammatory profile and low levels of inflammation resolution markers. At ICU discharge, the immune status demonstrated decreased but persistent inflammation and increased immunosuppression, with elevated programmed cell death protein-1 (PD-1) levels, and a counterbalanced resolution process, with elevated levels of interleukin-10 (IL-10), resolvin D5 (RvD5), and IL-7. One year after hospital discharge, homeostasis was not completely restored with several markers of inflammation remaining elevated. Remarkably, IL-7 was persistently elevated, with levels comparable to those observed after ICU discharge, and PD-1, while lower, remained in the elevated abnormal range. CONCLUSIONS: In this study, protracted immune disturbances were observed one year after ICU discharge. The study results suggested the presence of long-lasting immune illness disorders following a long-term septic insult, indicating the need for long-term patient follow up after ICU discharge and questioning the use of immune intervention to restore immune homeostasis after abdominal septic shock.

Multidisciplinary management of gastrointestinal fibrotic stenosis in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease that can involve virtually any part of the gastrointestinal tract. CD complications are the main indications for surgery. A large proportion of these interventions are due to stricturing disease. Although immunosuppressive treatments have been used more frequently during the last 25 years, there is no significant decrease in the need for surgery in patients with CD. Unfortunately, surgery is not curative, as the disease ultimately reoccurs in a substantial subset of patients. To best identify the patients who will require a specific treatment and to plane the most appropriate therapeutic approach, it is important to precisely define the type, the size, and the location of CD stenosis. Diagnostic approaches aim to distinguish fibrotic from inflammatory strictures. Medical therapy is required for inflammatory stenosis. Mechanical treatments are required when fibrotic CD strictures are symptomatic. The choice between endoscopic balloon dilation, stricturoplasty, and laparoscopic or open surgery is based on the presence of perforating complications, the remaining length of small bowel, and the number and length of strictures. The non-hierarchical decision-making process for the treatment of fibrotic CD therefore requires multidisciplinary clinical rounds with radiologists, gastroenterologists, interventional endoscopists, and surgeons.

Local and systemic innate immune response to secondary human peritonitis.

INTRODUCTION: Our aim was to describe inflammatory cytokines response in the peritoneum and plasma of patients with peritonitis. We also tested the hypothesis that scenarios associated with worse outcome would result in different cytokine release patterns. Therefore, we compared cytokine responses according to the occurrence of septic shock, mortality, type of peritonitis and peritoneal microbiology. METHODS: Peritoneal and plasma cytokines (interleukin (IL) 1, tumor necrosis factor α (TNFα), IL-6, IL-10, and interferon γ (IFNγ)) were measured in 66 patients with secondary peritonitis. RESULTS: The concentration ratio between peritoneal fluid and plasma cytokines varied from 5 (2 to 21) (IFNγ) to 1310 (145 to 3888) (IL-1). There was no correlation between plasma and peritoneal fluid concentration of any cytokine. In the plasma, TNFα, IL-6, IFNγ and IL-10 were higher in patients with shock versus no shock and in nonsurvivors versus survivors (P ≤0.03). There was no differential plasma release for any cytokine between community-acquired and postoperative peritonitis. The presence of anaerobes or Enterococcus species in peritoneal fluid was associated with higher plasma TNFα: 50 (37 to 106) versus 38 (29 to 66) and 45 (36 to 87) versus 39 (27 to 67) pg/ml, respectively (P = 0.02). In the peritoneal compartment, occurrence of shock did not result in any difference in peritoneal cytokines. Peritoneal IL-10 was higher in patients who survived (1505 (450 to 3130) versus 102 (9 to 710) pg/ml; P = 0.04). The presence of anaerobes and Enterococcus species was associated with higher peritoneal IFNγ: 2 (1 to 6) versus 10 (5 to 28) and 7 (2 to 39) versus 2 (1 to 6), P = 0.01 and 0.05, respectively). CONCLUSIONS: Peritonitis triggers an acute systemic and peritoneal innate immune response with a simultaneous release of pro and anti-inflammatory cytokines. Higher levels of all cytokines were observed in the plasma of patients with the most severe conditions (shock, non-survivors), but this difference was not reflected in their peritoneal fluid. There was always a large gradient in cytokine concentration between peritoneal and plasma compartments highlighting the importance of compartmentalization of innate immune response in peritonitis.

Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Researchers have suggested that antibiotics could cure acute appendicitis. We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis. METHODS: In this open-label, non-inferiority, randomised trial, adult patients (aged 18-68 years) with uncomplicated acute appendicitis, as assessed by CT scan, were enrolled at six university hospitals in France. A computer-generated randomisation sequence was used to allocate patients randomly in a 1:1 ratio to receive amoxicillin plus clavulanic acid (3 g per day) for 8-15 days or emergency appendicectomy. The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10 percentage points. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT00135603. FINDINGS: Of 243 patients randomised, 123 were allocated to the antibiotic group and 120 to the appendicectomy group. Four were excluded from analysis because of early dropout before receiving the intervention, leaving 239 (antibiotic group, 120; appendicectomy group, 119) patients for intention-to-treat analysis. 30-day postintervention peritonitis was significantly more frequent in the antibiotic group (8%, n=9) than in the appendicectomy group (2%, n=2; treatment difference 5·8; 95% CI 0·3-12·1). In the appendicectomy group, despite CT-scan assessment, 21 (18%) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. In the antibiotic group, 14 (12% [7·1-18·6]) of 120 underwent an appendicectomy during the first 30 days and 30 (29% [21·4-38·9]) of 102 underwent appendicectomy between 1 month and 1 year, 26 of whom had acute appendicitis (recurrence rate 26%; 18·0-34·7). INTERPRETATION: Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis. Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment. FUNDING: French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.

No-incision (NOTES) versus single-incision (single-port) surgery for access to sites of peritoneal carcinomatosis: a back-to-back animal study.

BACKGROUND: Preoperative radiological diagnosis and evaluation of limited peritoneal carcinomatosis (PC) is suboptimal. Triangle laparoscopy is considered a noncarcinologic option due to the risk of tumoral spreading through the lateral ports into the abdominal wall muscles. Open surgery is therefore often needed to characterize PC. A minimally invasive approach would be progress. METHODS: We aimed to compare access rates to elective sites of PC using natural orifice transluminal endoscopic surgery (NOTES) with those using single-port laparoscopic surgery (SPLS). Sixteen acute experiments were performed in a live porcine model. Back-to-back NOTES and SPLS standardized peritoneoscopy were conducted in a cross-over design. Access rates to 11 elective sites of PC were considered as end points based on operators' consensus and necropsy verification. RESULTS: Access to the targets was successful in 89 % with NOTES and 80 % with SPLS (p = 0.27). NOTES and SPLS achieved a 100 % access rate to the diaphragmatic domes and paracolic gutters, to the splenic area, to the pelvic floor, and to the trigonal bladder (p > 0.99). Access rates of NOTES versus SPLS to other elective sites of PC were the following: mesentery root (94 % vs. 0 %, p < 0.001), inferior mesenteric vein origin (88 % vs. 0 %, p < 0.001), inferior vena cava (88 % vs. 75 %, p = 0.85), and hepatic pedicle (8 % vs. 100 %, p < 0.001). CONCLUSIONS: Both transgastric NOTES and SPLS provided quick and easy access to most elective sites of PC, except for the mesenteric vessel root (better achieved by NOTES) and the hepatic pedicle (better achieved by SPLS). Both techniques could be improved or combined to overcome their specific drawbacks.

Effect of variations in the amounts of P-glycoprotein (ABCB1), BCRP (ABCG2) and CYP3A4 along the human small intestine on PBPK models for predicting intestinal first pass.

It is difficult to predict the first-pass effect in the human intestine due to a lack of scaling factors for correlating in vitro and in vivo data. We have quantified cytochrome P450/3A4 (CYP3A4) and two ABC transporters, P-glycoprotein (P-gp, ABCB1) and the breast cancer resistant protein BCRP (ABCG2), throughout the human small intestine to determine the scaling factors for predicting clearance from intestinal microsomes and develop a physiologically based pharmacokinetic (PBPK) model. CYP3A4, P-gp and BCRP proteins were quantified by Western blotting and/or enzyme activities in small intestine samples from 19 donors, and mathematical trends of these expressions with intestinal localization were established. Microsome fractions were prepared and used to calculate the amount of microsomal protein per gram of intestine (MPPGI). Our results showed a trend in CYP3A4 expression decrease from the upper to the lower small intestine while P-gp expression is increasing. In contrast, BCRP expression did not vary significantly with position, but varied greatly between individuals. The MPPGI (mg microsomal protein per centimeter intestine) remained constant along the length of the small intestine, at about 1.55 mg/cm. Moreover, intrinsic clearance measured with specific CYP3A4 substrates (midazolam and an in-house Servier drug) and intestinal microsomes was well correlated with the amount of CYP3A4 (R(2) > 0.91, p < 0.01). In vivo data were more accurately predicted using PBPK models of blood concentrations of these two substrates based on the segmental distributions of these enzymes and MPPGI determined in this study. Thus, these mathematical trends can be used to predict drug absorption at different intestinal sites and their metabolism can be predicted with the MPPGI.

A laparoscopic approach to iterative ileocolonic resection for the recurrence of Crohn's disease.

BACKGROUND: Laparoscopy is a valuable approach to primary ileocecal resection for ileocolonic Crohn's disease (CD). This study aimed to evaluate the feasibility of using laparoscopy for reoperation in the case of ileocolonic CD recurrence and to determine the risk factors and consequences of conversion for these patients. METHODS: From 1998 to 2008, 57 patients underwent 62 reoperations for CD recurrence. Of these 62 reoperations, 29 were laparoscopic procedures (laparoscopy group [LG]). Preoperative and intraoperative characteristics and postoperative outcome were compared with those for 33 open procedures (open group [OG]). RESULTS: The preoperative characteristics were similar in the two groups. The number of intraoperative intestinal injuries was higher in the LG group (n = 5) than in the OG group (n = 0) (p = 0.01). The use of a temporary stoma (7/29 vs. 6/33; nonsignificant difference [NS]) and the mean operating time (215 + or - 70 vs. 226 + or - 107 min, NS) were similar in the two groups. The postoperative mortality was nil in both groups. The overall morbidity rate was 38% (11/29) in LG and 30% (10/33) in OG (NS). Severe complications (DINDO > or = 3) occurred for three of the 29 patients in LG (10%) compared with five of 33 patients in OG (15%) (NS). The median hospital stay was 9 days in both groups. The conversion rate was 31% (9/29). Univariate analysis showed that the risk factors for conversion were fistulizing disease (p = 0.02) and intraoperative intestinal injury (p < 0.001). The morbidity rate was not increased by the need for a conversion (7/20 for the nonconverted vs. 4/9 for the converted patients, NS). CONCLUSION: Laparoscopy for ileocolonic CD recurrence is challenging and complex. The morbidity rate was similar to that for the open approach, and the risk of small bowel injury associated with laparoscopy could possibly induce postoperative septic complications. However, the authors believe that laparoscopy can be recommended for selected patients with CD recurrence, especially patients with nonfistulizing disease.

Impact of complex Crohn's disease on the outcome of laparoscopic ileocecal resection: a comparative clinical study in 124 patients.

PURPOSE: This prospective study assessed the feasibility of laparoscopic ileocolonic resection for complex Crohn's disease, i.e., recurrence or complication from abscess and/or fistula, and compared postoperative outcomes in patients with and without complex Crohn's disease. METHODS: Between November 1998 and August 2007, 124 laparoscopic ileocolonic resections were attempted for Crohn's disease: 54 patients with complex Crohn's disease (group I) and 70 patients without complex Crohn's disease (group II). Postoperative mortality and morbidity were compared between group I and group II. RESULTS: Indications for surgery in group I included fistula (43 percent), abscess (30 percent), and recurrent disease after ileocolonic resection (27 percent). Complex Crohn's disease was significantly associated with increased mean (standard deviations) operative time [214 (13) vs. 191(53) minutes, P < 0.05), increased conversion rate to open procedure (37 percent vs. 14 percent, P < 0.01), and increased use of temporary stoma (39 percent vs. 9 percent, P < 0.001). No patients died. Overall postoperative morbidity was similar between both groups [17 percent vs. 17 percent, P = not significant (NS)], including major surgical postoperative complications (7 percent vs. 6 percent, P = NS). Mean (SD) hospital stay was not statistically different between both groups [8 (3) vs. 7 (3) days, P = NS]. CONCLUSIONS: This large comparative study suggested that laparoscopic ileocolonic resection for complex Crohn's disease was feasible and safe with good postoperative outcomes. In our experience, complex Crohn's disease does not appear as a contraindication to a laparoscopic approach.

Laparoscopic peritoneal lavage or primary anastomosis with defunctioning stoma for Hinchey 3 complicated diverticulitis: results of a comparative study.

PURPOSE: This study was designed to compare postoperative outcomes of laparoscopic peritoneal lavage and open primary anastomosis with defunctioning stoma in the management of Hinchey 3 diverticulitis. METHODS: From 1994 to 2006, 35 patients underwent laparoscopic peritoneal lavage for Hinchey 3 diverticulitis in three institutions. Data prospectively collected were compared with those of a retrospective series of 24 patients matched for Hinchey's classification and who underwent primary anastomosis with defunctioning stoma. RESULTS: There was no postoperative death. Postoperative morbidity was not different between the two groups. One patient in the laparoscopic peritoneal lavage group required a Hartmann's procedure because of a colonic fistula. One patient in the primary anastomosis with defunctioning stoma group underwent a reoperation for incisional dehiscence. The median hospital stay was lower in patients treated by laparoscopic peritoneal lavage (8 vs. 17 days, P < 0.0001). Twenty-five patients in the laparoscopic peritoneal lavage group underwent elective laparoscopic resection. One of them required conversion to laparotomy. All patients in the primary anastomosis with defunctioning stoma group have had their ileostomy closed. Cumulative surgical morbidity (16 vs. 37.5 percent, P = 0.0507) and hospital stay (14 vs. 23 days, P < 0.0001) were lower in the laparoscopic peritoneal lavage group. CONCLUSION: In the management of Hinchey 3 diverticulitis, laparoscopic peritoneal lavage does not result in excess morbidity or mortality, it reduces the length of hospital stay and avoids a stoma in most patients, and it is, therefore, a reasonable alternative to primary anastomosis with defunctioning stoma.

Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis.

INTRODUCTION: The risk factors associated with poor outcome in generalized peritonitis are still debated. Our aim was to analyze clinical and bacteriological factors associated with the occurrence of shock and mortality in patients with secondary generalized peritonitis. METHODS: This was a prospective observational study involving 180 consecutive patients with secondary generalized peritonitis (community-acquired and postoperative) at a single center. We recorded peri-operative occurrence of septic shock and 30-day survival rate and analyzed their associations with patients characteristics (age, gender, SAPS II, liver cirrhosis, cancer, origin of peritonitis), and microbiological/mycological data (peritoneal fluid, blood cultures). RESULTS: Frequency of septic shock was 41% and overall mortality rate was 19% in our cohort. Patients with septic shock had a mortality rate of 35%, versus 8% for patients without shock. Septic shock occurrence and mortality rate were not different between community-acquired and postoperative peritonitis. Age over 65, two or more microorganisms, or anaerobes in peritoneal fluid culture were independent risk factors of shock. In the subgroup of peritonitis with septic shock, biliary origin was independently associated with increased mortality. In addition, intraperitoneal yeasts and Enterococci were associated with septic shock in community-acquired peritonitis. Yeasts in the peritoneal fluid of postoperative peritonitis were also an independent risk factor of death in patients with septic shock. CONCLUSIONS: Unlike previous studies, we observed no difference in incidence of shock and prognosis between community-acquired and postoperative peritonitis. Our findings support the deleterious role of Enterococcus species and yeasts in peritoneal fluid, reinforcing the need for prospective trials evaluating systematic treatment against these microorganisms in patients with secondary peritonitis.

Laparoscopic subtotal colectomy for acute or severe colitis complicating inflammatory bowel disease: a case-matched study in 88 patients.

BACKGROUND: The aim of this study was to assess the morbidity of laparoscopic subtotal colectomy (STC) with or without anastomosis in patients with acute or severe colitis (SAC) complicating inflammatory bowel disease (IBD) who failed medical treatment. METHODS: Forty patients undergoing laparoscopic STC for SAC complicating IBD were identified and well-matched for age, gender, ASA score, and IBD severity at the time of colectomy (acute colitis vs steroid dependence only) with 48 patients undergoing open STC. RESULTS: There was no operative mortality. Mean (+/-SD) operative time was similar after laparoscopic and open STC (253 +/- 56 vs 231 +/- 75 min; NS). Two patients (5%) required conversion into laparotomy due to intensive adhesions (n = 1) and colonic fistula (n = 1). Overall morbidity and hospital stay was similar after laparoscopic STC and open STC (35% vs 56%) (9 +/- 3 vs 12 +/- 7 days) (P > .1) respectfully. After laparoscopic STC, 84% of the patients underwent restorative intestinal continuity (with either ileorectal or ileoanal anastomosis) through reoperative laparoscopy (n = 15) or elective incision at the site of previous stoma (n = 16). CONCLUSIONS: This case-matched study suggests that laparoscopic STC was as safe and effective as open STC for IBD patients with SAC. A laparoscopic STC allows restoration of intestinal continuity restoration (ie, ileal pouch anal or ileorectal anastomosis) through a laparoscopic approach or elective incision for the majority of the patients. For these reasons, laparoscopic approach represents the best approach for colitis-complicating IBD.

Adrenal response in patients with septic shock of abdominal origin: relationship to survival.

OBJECTIVE: To evaluate the prognostic value of adrenocortical response to corticotropin in septic shock patients operated on exclusively for an intra-abdominal source of infection. DESIGN AND SETTING: Prospective, observational, single-center study in a surgical intensive care unit of a university hospital PATIENTS: 118 consecutive septic shock patients undergoing laparotomy or drainage for intra-abdominal infection. MEASUREMENTS AND RESULTS: Baseline cortisol (t (0)) and cortisol response to corticotropin test (Delta) were measured during the first 24 h following onset of shock. The relationship between adrenal function test results and survival was analyzed as well as the effect of etomidate anesthesia. Cortisol plasma level at t (0) was higher in nonsurvivors than in survivors (33 +/- 23 vs. 25 +/- 14 microg/dl), but the response to corticotropin test did not differ between these two subgroups. ROC analysis showed threshold values for t (0) (32 microg/dl) and Delta (8 microg/dl) that best discriminated survivors from nonsurvivors in our population. We observed no difference in survival at the end of hospital stay using log rank test when patients were separated according to t (0), Delta, or both. In addition, adrenal function tests and survival did not differ in patients who received etomidate anesthesia (n = 69) during the surgical treatment of their abdominal sepsis. CONCLUSIONS: In this cohort of patients with abdominal septic shock baseline cortisol level and the response to corticotropin test did not discriminate survivors from nonsurvivors. No deleterious impact of etomidate anesthesia on adrenal function tests and survival was observed in these patients.

Incidence, risk factors, and complications of cholelithiasis in patients with home parenteral nutrition.

BACKGROUND: Previous studies showed high prevalence rates of cholelithiasis in patients with home parenteral nutrition (HPN). Our aim was to determine, in an HPN population, the incidence and risk factors for gallstones and sludge and their complications. STUDY DESIGN: Retrospective chart review was conducted in a tertiary care center. One hundred fifty-three consecutive patients who received HPN for longer than 2 months (range 2 to 204 months; median 15 months) between 1985 and 1997 were followed with ultrasonography. Kaplan-Meier curves and log-rank tests were calculated to assess risk factors for gallbladder lithiasis and complications. RESULTS: Thirty-four patients (22%) underwent cholecystectomy before HPN. Of the 119 remaining patients with gallbladder in situ, cholelithiasis appeared during HPN in 45 (38%). The probability of cholelithiasis developing during HPN was estimated to be 6.2%, 21.2%, and 38.7% at 6, 12, and 24 months, respectively. Biliary complications developed in eight patients (7%) during followup. Therapy consisted of endoscopic sphincterotomy (three patients) or operation (five patients) with uncomplicated outcomes except for one patient; no death was observed. Incidence rates of biliary complication during HPN were estimated to be 0.0%, 4.7%, and 10.1% at 6, 12, and 24 months, respectively. Nil or negligible ingesta was the only factor notably associated with incidence of cholelithiasis (p < 0.01) or biliary complications (p < 0.01). CONCLUSIONS: This first incidence study shows a high rate of cholelithiasis and a low rate of complications during HPN. Both events were notably related to nil or negligible ingesta.

Three-step ileal pouch-anal anastomosis under total laparoscopic approach for acute or severe colitis complicating inflammatory bowel disease.

BACKGROUND: A two- or three-step procedure is mandatory for restorative proctocolectomy in patients presenting with severe or acute colitis complicating inflammatory bowel disease (IBD). The aim of this study was to analyze the feasibility of a total laparoscopic approach for consecutive subtotal colectomy (STC) and secondary ileal pouch-anal anastomosis (IPAA). STUDY DESIGN: All patients underwent a three-step procedure that included first, a laparoscopic STC with ileostomy and sigmoidostomy; second, a laparoscopic proctectomy and IPAA, and third, closure of the temporary ileostomy. RESULTS: Eighteen consecutive patients (7 women and 11 men), with a mean age of 39+/-14 years (range 15 to 59 years) were included. Mean lengths of the procedures were 252+/-59 minutes for STC, and 286+/-46 minutes for IPAA, respectively. Two patients (11%) after laparoscopic IPAA required conversion into laparotomy. No patient died postoperatively. Four patients had reoperations after laparoscopic IPAA for intraperitoneal hemorrhage by laparotomy (n=2) and by a transanal approach for anastomotic leakage (n=2). The overall morbidity rate was 33% (12 of 36 procedures). Mean hospital stay was 8+/-2 days after STC, and 10+/-2 days after IPAA. After a mean follow up of 13 months, all patients underwent intestinal continuity restoration. CONCLUSIONS: Our study suggests that a total laparoscopic approach is feasible and safe in inflammatory bowel disease patients with acute or severe colitis, not only for STC but also for IPAA after STC, with no mortality and an acceptable morbidity rate.

[Expression of SERCA pumps during cell differentiation and tumorigenesis: application to colonic carcinogenesis]. / Expression des pompes calciques de type SERCA au cours de la différenciation cellulaire et de la tumorigenèse: application à la carcinogenèse colique.

Calcium homeostasis of the endoplasmic reticulum (ER) is involved in intracellular signaling pathways and is implicated in major cell functions such as cell growth, differentiation, protein synthesis and apoptosis. The accumulation of calcium in the ER is performed by specific sarco/endoplasmic reticulum calcium transport ATPases (SERCA iso-enzymes). The expression of biochemically distinct SERCA isoforms is cell type dependent and developmentally regulated. This review summarizes pertinent data about the modulation of the expression of SERCA enzymes during the differentiation of normal and tumor cells. These data support the implication of SERCA pumps and especially SERCA3 in the differentiation program of cancer and leukemia cells. During the multi-step process of colon carcinogenesis, the decrease of SERCA3 expression seems to be linked to enhanced APC/ss-catenin/TCF4 signaling and deficient Sp1-like factor-dependent transcription.

Transjugular intrahepatic portosystemic shunt as bridge-to-surgery in refractory gastric antral vascular ectasia.

Gastric antral vascular ectasia (GAVE) may cause gastrointestinal bleeding (GIB). The treatment of GAVE relies on endoscopic approaches such as electrocoagulation (argon plasma coagulation, laser therapy, heater probe therapy, radiofrequency ablation), cryotherapy, and band ligation. In refractory cases, antrectomy may be considered. In the event of an associated cirrhosis and portal hypertension, it has been suggested that antrectomy could be an option, provided the mortality risk isn't considered too great. We report the case of a 67-year-old cirrhotic patient who presented with GAVE related GIB, unresponsive to multiple endoscopic treatments. The patient had a good liver function (model for end-stage disease 10). After a multidisciplinary meeting, a transjugular intrahepatic portosystemic shunt (TIPS) procedure was performed, in order to treat the cirrhosis associated ascites. The outcome was successful. An antrectomy was then performed, with no recurrence of GIB and no transfusion need during three months of follow up. In this case, the TIPS procedure achieved a complete ascites regression, allowing a safer surgical treatment of the GAVE-related GIB.

Could immunosuppressive drugs reduce recurrence rate after second resection for Crohn disease?

BACKGROUND: The aim of this study was to assess the possible benefit of postoperative immunosuppressive drugs administration (ie, azathioprine, 6-mercaptopurine, or methotrexate) on long-term surgical recurrence rate after second anastomotic ileocolonic resection. METHODS: From 1984 to 2000, 26 patients with CD underwent second resection for ileocolonic anastomotic recurrence. There were 14 women and 12 men (mean age +/- SD: 34 +/- 9 years). Two groups of patients were compared according to the postoperative treatment: immunosuppressive (IS) drugs group was composed of 14 patients, and control group was composed of 12 patients receiving either salicylates (n = 5) or no treatment (n = 7). RESULTS: Clinical recurrence rate at 3 years was significantly lower in the IS group than in the control group (3/12, 25% vs 6/10, 60%; P < 0.05). Although not significant, after a mean follow-up of 80 +/- 46 months (extr. 17-178 months) after the second resection, clinical recurrence rate at follow-up was also lower in IS group (6/14, 43%) than in control group (9/12, 75%). The mean delay of recurrence was similar in both groups (27 +/- 13 months vs 28 +/- 21; NS). A third intestinal resection was performed less frequently in the IS group than in control group (2/14, 17% vs 7/12, 58%; P < 0.02). CONCLUSIONS: In patients treated with IS drugs, the rate of postoperative recurrence after second ileocolonic CD resection is lower than in untreated patients. Our results suggest that IS drugs should be evaluated prospectively for prevention of second postoperative CD recurrence.

Inflammatory cytokines, C reactive protein, and procalcitonin as early predictors of necrosis infection in acute necrotizing pancreatitis.

BACKGROUND: Infection of necrosis is a major risk factor in patients with acute pancreatitis. Systematic use of broad spectrum antibiotics has been recommended in these patients but may induce serious side effects. To better target patients in whom antibiotic prophylaxis could be beneficial, we evaluated whether early serum profiles of interleukin 6 (IL-6), tumor necrosis factor (TNF-alpha, C reactive protein (CRP) and procalcitonin (PCT) help to discriminate between patients who eventually develop infection of necrosis and those who do not. METHODS: Forty-eight patients with acute pancreatitis and a computed tomography (CT) severity index score of more than 3 were prospectively screened. They were then separated into infected and non-infected groups according to the occurrence of infected pancreatic necrosis. The severity of illness was assessed with Ranson's classification and Simplified Acute Physiologic Score II. Serum levels of IL-6, TNF-alpha, CRP, and PCT were measured during the first 3 days after admission. CT-guided fine needle aspiration of pancreatic necrosis was performed to prove infection when sepsis of abdominal origin was suspected. Using the methodology of receiver operating curves, we determined the presence of a threshold for markers that would be predictive of the development of infected necrosis. RESULTS: PCT and IL-6 were higher in the serum of patients who eventually developed infection of necrosis (P < 0.003 and < 0.04, respectively). No difference was noted between the 2 groups for TNF- alpha and CRP. The combination of IL-6 < 400 pg/l and PCT < 2 ng/L best identified patients who were not at risk for necrosis infection. The negative predictive value for these thresholds was 91%, whereas sensitivity and specificity were 75% and 84%. CONCLUSIONS: PCT and IL-6 serum levels were elevated very early in patients who eventually developed necrosis infection. A combination of PCT and IL-6 thresholds could be helpful in identifying a subgroup of patients in whom antibiotic prophylaxis is likely to be ineffective.