Preoperative nutrition forseverely malnourished patients in digestive surgery: A retrospective study.

INTRODUCTION: Malnutrition increases postoperative morbidity and mortality. The objective of this study was to evaluate preoperative refeeding in malnourished patients at risk of refeeding syndrome (RS). METHODOLOGY: A retrospective study, conducted between June 2016 and January 2017, reported to the CNIL, compared two groups of malnourished patients: a group of refeeding patients (RP) and a group of non-refeeding patients (NRP). The inclusion criteria were weight loss of more than 10% or albuminemia less than 35g/L and RS risk factor. The primary endpoint was postoperative morbidity. The secondary endpoints were weight change and serum albumin over 6 months. RESULTS: Seventy-three patients (30 RP and 43 NRP) were included. At the time of initial management, median weight loss was 18% [1-71], while albuminemia was 26g/L [13-40] in the RP group and 32.5g/L [32-48] in the NRP group (P=0.01). The overall postoperative morbidity rate was 88% (83% RP versus 90% NRP, P=0.47), and there was no significant difference between the 2 groups. The rate of anastomotic complications was 4% for RP versus 26% for NRP (P=0.03) after exclusion of liver surgery. Medium-term weight loss tended to be greater in RP (P=0.7). Nutritional support was continued until the third postoperative month in 13% of RPs vs. no NRPs (P=0.0002). CONCLUSION: After preoperative renutrition, we did not observe a decrease in morbidity but rather a decrease in the rate of anastomotic complications in favor of the RP group. This study underscores the middle-term importance of nutritional management in view of preserving the benefits of preoperative renutrition.

Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

INTRODUCTION: During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. METHODS: Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. RESULTS: Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. CONCLUSIONS: Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort.

BACKGROUND: Ampullary carcinoma (AC) is a relatively rare entity often managed as a biliopancreatic carcinoma. AC has a better prognosis than peri ampullary tumors after resection, but more than a third of patients relapse. Factors predictive of recurrence are controversial, mainly because the relevant studies are very small or also included non AC tumors. There are no guidelines on the use of adjuvant or neoadjuvant chemotherapy. The aim of this study was to identify prognostic factors for recurrence after AC resection in a large multicentric cohort, and to establish a simple, practical, predictive score for recurrence in order to guide multidisciplinary decisions. METHODS: We included 152 consecutive patients who underwent Whipple's pancreaticoduodenectomy for ampullary carcinoma from January 2000 to December 2010 in 10 gastrointestinal oncology departments. RESULTS: The estimated overall 5-year disease-free survival rate (DFS) was 47.1%. In multivariate analysis, age≥ 75 years at diagnosis (p < 0.0001), poor general condition (p = 0.01), poorly (p = 0.005) or moderately differentiated tumors (p = 0.01) and TNM stage IIb or III (p = 0.05) were associated with poor DFS. Based on this multivariate analysis, we developed a prognostic score with three levels of risk: DFS at 5 years was 73.5% in the low-risk group and 20.1% in the high-risk group. CONCLUSION: This simple score based on age, general condition, tumor differentiation and TNM stage can classify patients into subgroups with different risks of recurrence and could help with therapeutic decisionmaking.

Elective subtotal colectomy with ileosigmoid anastomosis for colon cancer preserves bowel function and quality of life.

AIM: We report on our experience of elective subtotal colectomy and ileosigmoid anastomosis for colon cancer with focus on postoperative results, function and quality of life. METHOD: Between 1998 and 2011, 106 consecutive patients with colonic malignancy underwent this procedure electively. Function and quality of life (EORTC QLQ-C30) were evaluated retrospectively with questionnaires sent to all patients free of recurrence. RESULTS: There were 62 men and 44 women (mean age 63 years). Postoperative mortality and morbidity rates were 1.9 and 26.4%, respectively. Persistent ileus was the main early complication (16%). After a mean follow-up of 67 ± 36 months, 50 (78.1) out of 64 patients have been evaluated for function and quality of life. The mean number of bowel movements per 24 h was 3 ± 2 and significantly lower when the length of the remaining sigmoid colon was more than 15 cm (P = 0.049). Compared with a European reference population for EORTC QLQ-C30 results, our patients had significantly more diarrhoea (26 vs 3, P = 0.0002) but less pain (10 vs 25, P < 0.0001) and better global quality of life (77 vs 62, P < 0.0001). CONCLUSION: Elective subtotal colectomy for colon cancer is safe and associated with good function and quality of life. Ileosigmoid anastomosis should be discussed when extended colectomy is required, providing the rectosigmoid junction and its vascular supply can be oncologically preserved. For tumours located in the transverse colon or at the splenic flexure, this procedure may be the best surgical option.

Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.

BACKGROUND: Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS: A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-ß receptor, CXCR4, and LKB1. RESULTS: High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002). CONCLUSIONS: CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.

Liver preservation with SCOT 15 solution decreases posttransplantation cholestasis compared with University of Wisconsin solution: a retrospective study.

BACKGROUND: SCOT 15 is a new solution to preserve abdominal organs for transplantation. Its principal characteristic is the use of polyethylene glycol. Herein We report our experience using SCOT 15 compared with the reference University of Wisconsin (UW) solution for hepatic transplantation. METHODS: We compared 2 groups: SCOT 15 (n = 33; 2009-2010) versus UW (n = 34; 2008-2010), which were paired for cold and warm ischemic times, donor ages, and graft weights. Endpoints were biologic tests in the first 2 months after the operation. A linear mixed model was used to evaluate longitudinal changes and influences of each solution. RESULTS: No primary failure was observed. At postoperative day 0, transaminase values were higher in the SCOT 15 than in the UW group: aspartate transaminase: 2,435 ± 399 vs 589 ± 83 IU/L (P < .01); alanine transaminase: ALT: 1,207 ± 191 vs 484 ± 64 IU/L (P < .05), then returned to low levels in both groups. From day 0 to 8, coagulation factors reached normal values; there was no difference between the 2 groups. Total bilirubin decreased similarly in the 2 groups. However, from the second postoperative week (W1) to W8, the SCOT 15 group showed a slow decrease in the mean values of gamma-glutamyltranspeptidase (gGT) from 233 ± 125 to 130 ± 161 IU/L, which were significantly lower than those in the UW group, where the gGT remained around 300 IU/L (P < .01). The End-Stage Liver Disease, Child-Pugh, or United Network for Organ Sharing scores, primary liver diseases, hepatitic C virus status, arterial or biliary complications, and male/female ratio, which was different in the 2 groups, did not statistically influence these results. CONCLUSIONS: The main effect of cold storage of human liver using SCOT 15 compared with UW solution was to decrease cholestasis following transplantation.

Perioperative management of combined heart-liver transplantation in patients with cirrhosis, renal insufficiency, or pulmonary hypertension.

UNLABELLED: STATING THE MAIN PROBLEM: Only few reports have detailed perioperative management and outcome of combined heart and liver transplantation (CHLT), and none describe the long-term renal function. METHODS: Three patients presented clinical signs of cardiomyopathy with reduced ejection fraction and proven cirrhosis with evidence of portal hypertension. Two of them presented renal failure, and the other pulmonary hypertension. After cardiac transplantation and closure of the sternum, liver transplantation was performed using systematically venovenous double-limb (portal and caval) bypass. RESULTS: Mean cold ischemic time for heart and liver was 2 h 46 min and 12 h 47 min, respectively. Intraoperative hemodynamics remained grossly stable during surgery. Mean transfusions were 12 red blood cell packs. All three patients received anti-R-Il2 antibodies at post-operative day 1 and 4. Mean plasma creatinine concentration was 90 ± 8 µmol/L one yr post-CHLT, vs 160 ± 62 µmol/L pre-CHLT. All three patients are alive with functional grafts after a mean follow-up of 26 months (12-38). CONCLUSION: CHLT could be performed safely through two consecutive and independent usual procedures. Perioperative hemodynamic stability, minimal blood loss, and routine splanchnic decompression are probably major determinants of a favorable outcome and good long-term renal function.

[Hepatotoxicity of metastatic colorectal cancer chemotherapy: systematic review]. / Toxicité hépatique de la chimiothérapie du cancer colorectal métastatique: revue de la littérature.

AIM: Hepatic toxicity of chemotherapy for colorectal cancer and its complications after hepatic metastasis surgery are unclear. Studies reporting hepatic lesions after chemotherapy for colorectal cancer and published before July 2009 have been identified by searching the Medline database. Data concerning these hepatic lesions and outcome after surgery are resumed in this review. RESULTS: Studies concerning the link between hepatic steatosis and chemotherapy have contradictory results but steatosis is clearly associated to an increase of postoperative morbidity. Steatohepatitis, especially due to irinotecan, is associated with increased postoperative mortality. Sinusoidal obstruction syndrome, a severe form of vascular hepatic lesion, associated to oxaliplatin, seems to be linked with an increase of postoperative morbidity, but not mortality. Bevacizumab would not increase, when used in combination with oxaliplatin, the rate of postoperative complications. Some studies suggest a decrease of vascular hepatic lesions when bevacizumab is administered with chemotherapy. The literature concerning hepatic toxicity of anti-EGF-R antibody is freak. CONCLUSION: The fact that irinotecan may be linked to an increased risk of hepatic failure and postoperative death, which is not the case of oxaliplatine, must be taken in consideration in the choice of the preoperative chemotherapy before resection of hepatic metastasis of colorectal cancer.

Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab.

BACKGROUND: Recent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases. METHODS: Expressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested. RESULTS: Among 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036). CONCLUSION: Biomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.

Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue.

BACKGROUND: The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3(+)CD25(+)CD4(+) regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumours. In this descriptive study, we analysed blood and tissue regulatory T cell populations in patients with CRC. METHODS: Blood and tissue regulatory Foxp3(+) T cells from 40 patients with CRC were compared to regulatory Foxp3(+) T cells from normal colonic tissue and from blood of 26 healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3(+) T cell populations. Correlations were sought with the tumour stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3(+) T cells was assessed by their effect on CD4(+)CD25(-) T cell proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells. RESULTS: We found a significant increase of CD8(+)CD25(+)Foxp3(+) cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased cytoxic T lymphocyte-associated antigen-4, glucocorticoid-induced tumour necrosis factor-related protein, and transforming growth factor (TGF)beta1 expression compared to T8reg from normal autologous colonic tissue. Moreover, T8reg were able to suppress CD4(+)CD25(-) T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGF beta 1 synergistically induced the generation of CD8(+)CD25(+)Foxp3(+) T cells ex vivo. CONCLUSIONS: We have identified a new regulatory T cell population (CD8(+)Foxp3(+)) in colorectal tumours. After isolation from cancer tissue these CD8(+)Foxp3(+) cells demonstrated strong immunosuppressive properties in vitro. These data suggest that these cells may contribute to tumoral immune escape and disease progression.

[Lymphoepithelial cyst of the pancreas: a new case report]. / Le kyste lymphoépithélial du pancréas : à propos d'un nouveau cas.

We report the case of a lymphoepithelial cyst of the pancreas discovered by chance on imaging in a 54-year old man. CT-scan showed a 10 cm hypodense multilocular cystic tumor of the pancreatic isthmus. Fine-needle aspiration did not provide further information. Due to the lack of preoperative diagnosis and mostly because it was not known if the cyst was malignant or benign, the patient underwent a cephalic duodenopancreatectomy. Lymphoepithelial cyst of the pancreas is a rare benign lesion which is difficult to diagnose before surgery. Histologically, the cyst wall is lined by mature keratinizing squamous epithelium and a distinct surrounding lymphoid tissue layer. The cysts are filled with keratin plugs that are not always visualized on imaging. Cytological and histological analysis of fine-needle aspiration material if the sample material is sufficient may help avoid extensive surgery.

Sonographic preoperative assessment of liver volume before major liver resection.

OBJECTIVE: The use of ultrasonography is widespread for both the diagnosis and treatment of liver tumors. However, the measurement of liver volume by ultrasonography is not commonly done. We report an original method of liver volumetry using ultrasonography and an investigation into the usefulness of ultrasonography in this context. METHODS: The data for 50 patients undergoing various types of major hepatectomy were collected. We preoperatively measured liver volume using ultrasonography, dividing the liver into three main compartments according to precise anatomical landmarks, and then made comparisons with the volume of the actual specimen after hepatectomy, for all of the study participants. RESULTS: Total volume correlation between the two groups was good (r = 0.916, P < 0.001). However, the correlation was weaker in cases of right hepatectomy compared with other types of hepatectomy. CONCLUSION: This study demonstrates the possibility of doing liver volumetry using an ultrasound device. Further investigation to establish the reliability of this easily available and noninvasive approach is needed.

[Late complications of a skin oesophagoplasty realized 45 years before: an historical case]. / Complications tardives d'une oesophagoplastie cutanée, réalisée 45 ans plus tôt.

We report the case of a patient operated for the late complications of a skin-lined tube reconstruction of the esophagus performed 45 years ago. We recall the historical interest of this method for total esophageal reconstruction and emphasize the fact that it can still be a solution of last resort when intestinal tubes are no longer available.