How to deal with right hepatic artery coming from the superior mesenteric artery during minimally invasive pancreaticoduodenectomy: A systematic review

Background: Anatomical variations in the liver arterial supply are quite common and can affect the surgical strategy when performing a minimally invasive pancreaticoduodenectomy(MIPD). Their presence must be preemptively detected to avoid postoperative liver and biliary complications. Data sources: Following the PRISMA guidelines and the Cochrane protocol we conducted a systematic review on the management of an accessory or replaced right hepatic artery(RHA) arising from the superior mesenteric artery when performing an MIPD. Results: Five studies involving 118 patients were included. The most common reported management of the aberrant RHA was conservative(97.0%);however, patients undergoing aberrant RHA division without reconstruction did not develop liver or biliary complications. No differences in postoperative morbidity or long-term oncological related overall survival were reported in all the included studies when comparing MIPD in patients with standard anatomy to those with aberrant RHA. Conclusions: MIPD in patients with aberrant RHA is feasible without increase in morbidity and mortality. As preoperative strategy is crucial, we suggested planning an MIPD with an anomalous RHA focusing on preoperative vascular aberrancy assessment and different strategies to reduce the risk of liver ischemia.

Laparoscopic liver resection:Experience based guidelines

Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant(both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments(1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of lap-aroscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.

Lateral lymph node dissection for low rectal cancer: Is it necessary?

Rectal cancer constitutes a major public health issue.Total mesorectal excision has remained the gold standard treatment for mid and low rectal tumors since its introduction in the late 1980s.Removal of all lymph nodes located in the mesorectum has indeed improved pathological and oncological outcomes.However,when cancer spreads to the lateral lymph nodes(located along the iliac and obturator arteries)Western and Japanese practices differ.Where the Western guidelines consider this condition as an advanced form of the disease and use neoadjuvant radiochemotherapy liberally,the Japanese guidelines define it as a local disease and proceed to lateral lymph node dissection with or without neoadjuvant treatment.Herein,we review the current literature regarding both therapeutic strategies,with the aim of contributing to potential improvements in treatment and outcome for patients with low and mid rectal cancer.

Tropomyosin-related kinase B/brain derived-neurotrophicfactor signaling pathway as a potential therapeutic targetfor colorectal cancer

Colorectal cancer(CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor(EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B(Trk B), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of Trk B and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating Trk B-expressing CRC tumors.

Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model

AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.

Predictive factors for compliance with transanal irrigation for the treatment of defecation disorders

AIM To investigate compliance with transanal irrigation(TAI) one year after a training session and to identify predictive factors for compliance.METHODS The compliance of one hundred eight patients [87 women and 21 men; median age 55 years(range 18-83)] suffering from constipation or fecal incontinence(FI) was retrospectively assessed. The patients were trained in TAI over a four-year period at a single institution. They were classified as adopters if they continued using TAI for at least one year after beginning the treatment or as non-adopters if they stopped. Predictive factors of compliance with TAI were based on pretreatment assessments and trainingprogress. The outcomes of the entire cohort of patients who had been recruited for the TAI treatment were expressed in terms of intention-to-treat.RESULTS Forty-six of the 108(43%) trained patients continued to use TAI one year after their training session. The patients with FI had the best results, with 54.5% remaining compliant with TAI. Only one-third of the patients who complained of slow transit constipation or obstructed defecation syndrome continued TAI. There was an overall discontinuation rate of 57%. The most common reason for discontinuing TAI was the lack of efficacy(41%). However, 36% of the patients who discontinued TAI gave reasons independent of the efficacy of the treatment such as technical problems(catheter expulsion, rectal balloon bursting, instilled water leakage or retention, pain during irrigation, anal bleeding, anal fissure) while 23% said that there were too many constraints. Of the patients who reported discontinuing TAI, the only predictive factor was the progress of the training(OR = 4.9, 1.3-18.9, P = 0.02).CONCLUSION The progress of the training session was the only factor that predicted patient compliance with TAI.

Liver resection and metabolic disorders: An undescribed mechanism leading to postoperative mortality

AIM: To investigate the mechanism leading to perioperative mortality in patients undergoing major liver resection and presenting with metabolic disorders.

Combined radiologic and endoscopic treatment(using the “rendezvous technique”) of a biliary fistula following left hepatectomy

Despite the ongoing decrease in the frequency of complications after hepatectomy, biliary fistulas still occur and are associated with high morbidity and mortality rates. Here, we report on an unusual technique for managing biliary fistula following left hepatectomy in a patient in whom the right posterior segmental duct joined the left hepatic duct. The biliary fistula was treated with a combined radiologic and endoscopic procedure based on the "rendezvous technique". The clinical outcome was good, and reoperation was not required.

Adult human liver slice cultures:Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs

BACKGROUND Liver fibrosis can result in end-stage liver failure and death.AIM To examine human liver fibrogenesis and anti-fibrotic therapies,we evaluated the three dimensional ex vivo liver slice(LS)model.METHODS Fibrotic liver samples(F0 to F4 fibrosis stage according to the METAVIR score)were collected from patients after liver resection.Human liver slices(HLS)were cultivated for up to 21 days.Hepatitis C virus(HCV)infection,alcohol(ethanol stimulation)and steatosis(palmitate stimulation)were examined in fibrotic(F2 to F4)liver slices infected(or not)with HCV.F0-F1 HLS were used as controls.At day 0,either ursodeoxycholic acid(choleretic and hepatoprotective properties)and/or α-tocopherol(antioxidant properties)were added to standard of care on HLS and fibrotic liver slices,infected(or not)with HCV.Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzymelinked immunosorbent assay.RESULTS The cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs.Expression of the biomarkers of fibrosis and the progression to steatosis(estimated by triglycerides production)was increased with the addition of HCV and/or ethanol or palmitate.From day 15 of the follow-up studies,a significant decrease of both transforming growth factorβ-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures.CONCLUSION These results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver(viral,alcoholic,nonalcoholic steatohepatitis liver diseases)and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.

Quantitative analysis using ELISA of vascular endothelial growth factor and basic fibroblast growth factor in human colorectal cancer,liver metastasis of colorectal cancer and hepatocellular carcinoma

Angiogenesis consists of the sprouting of capillaries from pre-existing vessels. It is well-known that tumor growth is angiogenesis-dependent. Vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF） stimulated vascular endothelial cell proliferation and are involved in the neoplastic angiogenesis of several types of tumors including those of the intestinal tract. Authors usually investigated VEGF and using immunohistochemistry bFGF protein expressions or Western blotting and VEGF and bFGF transcripts using reverse transcriptase Dolymerase chain reaction （RT-PCR）.

Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients

AIM： To assess pre-orthotopic liver transplantation （OLT） factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma （HCC） recurrence and disease-free survival after liver transplantation （LT）.METHODS： Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence. RESULTS： Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were： presence of cirrhosis （P = 0.001）, etiology of liver disease （P = 0.03）, α fetoprotein level （〈 200, 200 to 2000, or 〉 2000; P 〈 0.0001）, y-GT activity （N, N to 2N or 〉 2N; P = 0.02）, the number of nodules （1, 2-3 or ≥ 4; P = 0.02）, maximal diameter of the largest nodule （〈 3 cm, 3 to 5 cm or 〉 5 cm; P 〈 0.0001）, the sum of the diameter of the nodules （〈 3 cm, 3 to 5 cm, 5 to 10 cm or 〉10 cm; P 〈 0.0001）, bilobar location （P = 0.01）, preoperative portal thrombosis （P 〈 0.0001）, peri-operative treatment of the tumor （P = 0.002） and chemoembolization （P = 0.03）, tumor differentiation （P = 0.01）, initial type of calcineurin inhibitor （P = 0.003）, the use of antilymphocyte antibodies （P = 0.02）, rejection episodes （P = 0.003） and period of LT （P 〈 0.0001）. By multivariate analysis, 6 variables were independently associated with HCC recurrence： maximal diameter of the largest nodule （P 〈 0.0001）, time of LT （P 〈 0.0001）, tumor differentiation （P 〈 0.0001）, use of anti-lymphocyte antibody （ATG） or anti-CD3 antibody （OKT3） （P = 0.005）, preoperative portal thrombosis （P = 0.06） and the number of nodules （P = 0.06）. CONCLUSION： This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation.

Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli(E. coli) using optical imaging.METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume(mm^3). Inflammation measuring myeloperoxidase(MPO) activity and reactive oxygen species production was monitored by a bioluminescent(BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay(ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells(HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitisCEABAC10 DSS models, which mimicked Crohn's disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume(P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group(P < 0.005). ELISA confirmed that MPO levels were significantly higher(1556 ± 313.6 vs 234.6 ± 121.6 ng/m L P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model(CEABAC10/DSS).CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand hostpathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.

Laparoscopic sleeve gastrectomy for morbid obesity

The incidence of obesity is steadily rising, and it has been estimated that 40% of the US population will be obese by the year 2025 if the current trend continues. In recent years there has been renewed interest in the surgical treatment of morbid obesity in concomitance with the epidemic of obesity. Bariatric surgery proved effective in providing weight loss of large magnitude, correction of comorbidities and excellent short-term and long-term outcomes, decreasing overall mortality and providing a marked survival advantage. The Laparoscopic Sleeve Gastrectomy (LSG) has increased in popularity and is currently very "trendy" among laparoscopic surgeons involved in bariatric surgery. As LSG proved to be effective in achieving considerable weight loss in the short-term, it has been proposed by some as a sole bariatric procedure. This editorial focuses on the particular advantages of LSG in the treatment of morbid obesity.

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

Alpha-fetoprotein(AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma(HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/m L could be an exclusion criterion, whereas values of < 15 ng/m L indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.

Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

AIM： Platelet-activating factor （PAF） is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF （the PAF precursor）, phospholipase A2 （PLA2, the enzymatic activity generating lyso-PAF）, acetylhydrolase activity （AHA, the PAF degrading enzyme） and PAF receptor （PAF-R） transcripts in cirrhotic liver and hepatocellular carcinoma （HCC）. METHODS： Twenty-nine patients with HCC were enrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. Lyso- PAF was assessed after its chemical acetylation into PAR AHA was determined by degradation of [^3H]-PAE PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR. RESULTS： Elevated amounts of PAF and PAF-R transcripts 1 （leukocyte-type） were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 （tissue-type） were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC. CONCLUSION： While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

Minimally invasive surgery for gastric cancer: A comparison between robotic, laparoscopic and open surgery

AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy(RG), laparoscopic gastrectomy(LG), open gastrectomy(OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.RESULTS The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients(RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery(P = 0.42) and stage of the disease(P = 0.16). Intraoperative blood loss was significantly lower in the LG(95.93 ± 119.22) and RG(117.91 ± 68.11) groups compared to the OG(127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG(27.78 ± 11.45), LG(24.58 ± 13.56) and OG(25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay(P < 0.0001). A similar complications rate was found(P = 0.13). The leakage rate was not different(P = 0.78) between groups.CONCLUSION Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.

Role of near-infrared fluorescence in colorectal surgery

Near-infrared fluorescence(NIRF)is a technique of augmented reality that,when applied in the operating theatre,allows the colorectal surgeon to visualize and assess bowel vascularization,to identify lymph nodes draining a cancer site and to identify ureters.Herein,we review the literature regarding NIRF in colorectal surgery.

Atrial embolism caused by portal vein embolization:Treatment by percutaneous withdrawal and stenting

Hepatectomy remains the only curative treatment for many primary and secondary liver cancers.Portal vein embolization(PVE) has been used to increase the volume of the future liver remnant and thus lower the risk of small-for-size syndrome and postoperative liver failure.This technique has proven its safety,with a low post-procedure morbidity rate.Here,we describe a very rare case in which a young patient suffered a glue embolism to the right atrial cavity following PVE in preparation for a major hepatectomy for colorectal metastasis.The foreign body was withdrawn from the heart with a femoral,percutaneous device and trapped against the wall of the femoral vein with a self-expanding metal stent.Our report shows that this previously unknown complication of PVE can be resolved without recourse to sternotomy and open heart surgery.

胰十二指肠切除术治疗十二指肠壁异位胰腺囊肿

Aim of the study- Cystic dystrophy in heterotopic pancreas (CDHP) is rare. The aim of this study was to evaluate the diagnosis, management, and follow-up of the CDHP. Patients and methods- Between August 1990 and March 2004, 12 patients with CDHP underwent a duodenopancreatectomy. The patients were retrospectively reviewed. Results- There were 11 men and 1 woman with a mean age of 42.4 years (range : 34- 54 years). Nine patients (75% ) were alcoholic and 8 patients had chronic pancreatitis. The diagnosis of CDHP was performed in 8 patients (66.6% ) after the preoperative workup. Seven patient had a medical treatment with octreotid and endoscopic cystic ponction (N = 3) or cystic fenestration (N = 1). Recurrence of pain was noted after a mean period of 5 months. Three patients had recurrent acute pancreatitis. Duodenopancreatectomy was performed in all cases. The mortality and morbidity rate were respectively 8.3% (N = 1) and 25% (N = 3). Mean follow-up was 64 months (ranges: 6- 158 months). One patient was seen 70 months later with epigastric pain and features of acute pancreatitis of the pancreatic stump due to anastomotic stenosis. The other patients were asymptomatic. Conclusions- Diagnosis of CDHP is difficult. After failure of medical treatment, duodenopancreatectomy can be proposed.

大便失禁患者生活质量(FIQL)量表法语版的有效性

Introduction-The aim of this multicenter study was to validate the French version of the fecal incontinence quality-of-life scale (FIQL scale) developed in the Unites States of America.Patients and methods-The FIQL scale has 29 items in four scales: lifestyle, coping/behavior, depression/self-perception and embarrassment. Each item is scored from 1 to 4, with poorest quality-of-life scored 1. An average is calculated for each scale. After linguistic validation of the questionnaire, the French version of the FIQL scale was tested twice, at day 0 and day 7, by 100 patients with fecal incontinence (FI). Construction validity, internal reliability, clinical validity and reproducibility were analysed. Results-Analysis of convergent validity of the French version of the FIQL scale showed very good correlation between items and the corresponding scale for lifestyle (0.50-0.79)and depression/self-percep-tion (0.44-0.74), good correlation for coping/behavior (0.31-0.70) and weak correlation for embarrassment (0.30-0.40). Valid discrimination was observed for 24 of the 29 items. Internal reliability was good for each scale (a Cronbach between 0.78 and 0.92). Scores determined with the FIQL scale were significantly correlated with Wexner FI scores, demonstrating the clinical validity of the instrument. Reproducibility, evaluated in patients whose FI was unchanged between day 0 and day 7, was good with intraclass correlation coefficients ranging from 0.80 (embarrassment) to 0.93 (lifestyle). Conclusions-The linguistic and psychometric evaluation demonstrated the validity of the French version of the FIQL scale. This standardized instrument is now available for clinical use in France for quality-of-life assessment in patients with FI.