Liver Transplantation for Colorectal Liver Metastases: Current Management and Future Perspectives.

Patients with nonresectable liver metastases from colorectal cancer have few therapeutic options and a dismal prognosis. Although liver transplantation for this indication has historically a poor reputation, recent advances in the field of chemotherapy and immunosuppression have paved the way to revisit the concept. New data have shown promising results that need to be validated in several ongoing clinical trials. Since liver grafts represent a scarce resource, several new tools are being explored to expand the donor pool for this indication. The purpose of this review is to present all current available data and perspectives about liver transplantation for nonresectable liver metastases from colorectal cancer.

Adenoma detection with blue-water infusion colonoscopy: a randomized trial.

Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 - 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P < 0.001). Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known. CLINICAL TRIALS REGISTRATION: EudraCT 2012-A00548 - 35; NCT01937429.

Efficacy of EUS-guided hepaticogastrostomy in prolonging survival of patients with perihilar cholangiocarcinoma.

Background and Objectives: The background of this study was to evaluate the outcomes of perihilar cholangiocarcinoma (pCCA) patients treated with EUS-guided hepaticogastrostomy (EUS-HGS). Methods: All patients with pCCA who underwent EUS-HGS from 2010 to 2020 were analyzed. The primary outcome was clinical success; the secondary outcomes were technical success, adverse events (AEs), stent patency, and oncological outcomes. Cox proportional-hazards regression and Kaplan-Meier curves were analyzed to identify variables related to survival. Results: Thirty-four patients (50% females, 76 years old) were included; 24 (70.6%) presented with distant metastasis. Indications for EUS-HGS were ERCP failure (64.7%), duodenal stricture (23.5%), postsurgical anatomy (5.9%), and dilation limited to the left intrahepatic duct (5.9%). The technical success rate was 97.1%. The clinical success rate was 64.7%. Nine (26.5%) presented AEs, 2 fatal (bleeding and leakage). The overall survival was 91 (31-263) days. On multivariate analysis, EUS-HGS clinical success (Exp[b]: 0.23 [0.09-0.60]; P = 0.003) and chemotherapy (Exp[b]: 0.06 [0.02-0.23]; P < 0.001) were significantly associated with survival. The survival was longer in patients who achieved EUS-HGS clinical success (178[61-393] vs. 15[73-24] days; hazard ratio: 6.3; P < 0.001) and in those starting chemotherapy (324[178-439] vs. 31 [9-48]; hazard ratio: 1.2; P < 0.001). Conclusions: EUS-HGS is effective in pCCA patients despite a not negligible AE rate. Clinical success, potentially leading to jaundice resolution and chemotherapy start, significantly improves survival.

[Ano-rectal symptoms, related to Epstein-Barr Virus-Associated Burkitt's lymphoma in an immunocompetent patient]. / Manifestations anorectales, en rapport avec un lymphome de Burkitt associé au virus Epstein Barr, chez une malade immunocompétente.

We report the case of an immunocompetent 23-year-old Caucasian woman, with symptoms including rectal bleeding, tenesmus and epreint, 6 months after an anal sexual trauma. The rectal examination showed a hardened, inflammatory and painful anal margin, associated with stenosis of the anal canal, suggesting abscess. The neurological examination showed numbing of the chin. Pelvic MRI and CT scan confirmed a bulky posterior tissular pelvic mass more than 7 cm in diameter, infiltrating the rectum and the anal canal. Final diagnosis confirmed by biopsy performed during rectosigmoidoscopy was an Epstein-Barr Virus-Associated Burkitt's lymphoma. Chemotherapy resulted in rapid regression of the tumoral mass.

Differences in oxidative stress dependence between gastric adenocarcinoma subtypes.

AIM: To investigate the extent of oxidative stress in pre-neoplastic and neoplastic gastric mucosa in relation to their pathological criteria and histological subtypes. METHODS: A total of 104 gastric adenocarcinomas from 98 patients (88 infiltrative and 16 intraepithelial tumors) were assessed immunohistochemically for expression of iNOS and occurrence of nitrotyrosine (NTYR)-containing proteins and 8-hydroxy-2'-deoxyguanosine (8-OH-dG)-containing DNA, as markers of NO production and damages to protein and DNA. RESULTS: Tumor cells staining for iNOS, NTYR and 8-OH-dG were detected in 41%, 62% and 50% of infiltrative carcinoma, respectively. The three markers were shown for the first time in intraepithelial carcinoma. The expression of iNOS was significantly more frequent in tubular carcinoma (TC) compared to diffuse carcinoma (DC) (54% vs 18%; P = 0.008) or in polymorphous carcinoma (PolyC) (54% vs 21%; P = 0.04). NTYR staining was obviously more often found in TC than that in PolyC (72% vs 30%; P = 0.03). There was a tendency towards a higher rate of iNOS staining when distant metastasis (pM) was present. In infiltrative TC, the presence of oxidative stress markers was not significantly correlated with histological grade, density of inflammation, the depth of infiltration (pT), lymph nodes dissemination (pN) and pathological stages (pTNM). CONCLUSION: The iNOS-oxidative pathway may play an important role in TC, but moderately in PolyC and DC. DNA oxidation and protein nitration occur in the three subtypes. Based on the significant differences of NTYR levels, TC and PolyC appear as two distinct subtypes.

Preoperative radiotherapy for rectal adenocarcinoma: Which are strong prognostic factors?

PURPOSE: This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors. METHODS AND MATERIALS: Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen. RESULTS: The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p < 0.001) and cN stage (p < 0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p < 0.014) but not for uN (p < 0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p < 0.001 and p < 0.001, respectively). CONCLUSION: Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.

Impact of antireflux operation on columnar-lined esophagus.

BACKGROUND: The effect of antireflux operation on the natural history of columnar-lined esophagus (CLE) is not fully understood. The aim of this study was to assess a single center's experience and review the literature on the impact of antireflux operation on CLE without high-grade dysplasia. STUDY DESIGN: The medical records of 26 patients with CLE but without high-grade dysplasia who underwent antireflux operation in our unit were retrospectively analyzed at longterm followup with detailed endoscopic investigation. Thirteen patients presented with intestinal metaplasia (6 had short segments, and 1 had preoperative laser ablation) and 13 without intestinal metaplasia. For the group of 13 patients presenting with intestinal metaplasia, the mean endoscopic followup was 74.7 months (median 46 months). Three of six with short-segment lesion and two of seven with circumferential involvement had complete regression of intestinal metaplasia (one after laser therapy). None had progression to dysplasia or carcinoma. RESULTS: For the group of 13 patients without intestinal metaplasia, mean endoscopic followup was 43.9 months (median 28 months). One had complete regression of CLE, and none developed intestinal metaplasia during surveillance. CONCLUSIONS: Our study suggests that antireflux operation can alter the natural history of CLE, allowing disease stabilization in a substantial proportion of patients. After antireflux operation, total regression of CLE is possible, but in an unpredictable manner.

[Chemoembolization in hepatocellular carcinoma: multivariate analysis of survival prognostic factors after the first session]. / Chimio-embolisation des carcinomes hépatocellulaires: analyse multivariée des facteurs pronostiques de survie après la première séance.

AIM: The aim of the study was to determine whether simple routine parameters evaluating the first session of transarterial chemoembolization (variation in alfa-fetoprotein concentration, tumor lipiodol uptake, and post-embolization syndrome) can predict survival of patients treated for hepatocellular carcinoma. METHODS: Seventy-two patients treated with transarterial chemoembolization and evaluated one month after the first sessions with CT scan were included. Transarterial chemoembolization session included hepatic arteriography, lipiodol and doxorubicin (50 mg) emulsion injection, followed by gelatin sponge embolization. The following variables were studied in univariate and multivariate analysis: 6 recorded at the first session (age, cirrhosis etiology, Child-Pugh class, tumor number, largest lesion size, and alpha-fetoprotein concentration), and 5 recorded after the first session (variation in alfa-fetoprotein concentration, tumor lipiodol uptake, post-embolization syndrome, mean interval between each session, and associated treatment). RESULTS: Mean follow-up was 22.7 months (4-106). Mean survival was 30.4 months (95% CI: 23. 3-37.5). Actuarial survival at 1, 2, 3 and 5 years was respectively 65.5%, 44%, 29.5%, and 18%. The only independent prognostic factors in multivariate analysis were the Child Pugh class and the mean interval between sessions (P<0.001 and<0.01 respectively). None of our criteria evaluating the first TACE session significantly influenced survival. CONCLUSION: The 3 parameters (variation in alpha-fetoprotein concentration, tumor lipiodol uptake and post-embolization syndrome) after the first transarterial chemoembolization did not predict survival. They could not be used to determine which patient could benefit from repeated transarterial chemoembolization sessions.

[Squamous cell carcinoma of the celiac area. Report of a case and review of the literature]. / Carcinome épidermoïde primitif coeliaque.

Primary squamous cell carcinoma of the pancreas or of the stomach is rare and represents a controversial entity. The unusual case of a 50-year-old woman with a large squamous cell carcinoma located in the celiac area and involving liver, stomach and pancreas, is reported here. The patient underwent complete surgical resection. The microscopic diagnosis was well-differentiated squamous cell carcinoma without glandular structure. Following the procedure, search for another possible primary lesion (esophagus, anus, colon, lung, head and neck, pelvic floor) was performed. This search was negative. In this context, final diagnosis was primary gastric or pancreatic squamous cell carcinoma. Local recurrence located in the eso-jejunal anastomosis was discovered three years later. Subsequent radiation combined with chemotherapy was instituted, allowing complete remission. During the subsequent 27-month follow-up, no local or systemic recurrence was observed. Pathogenesis of gastric as well as pancreatic primary squamous cell carcinoma remains obscure and controversial. These tumors usually have a very poor prognosis with rapid vascular and lymphatic involvement. Nevertheless, favorable outcome seems possible, as exhibited in our patient.

Propensity score analysis confirms the independent effect of parenteral nutrition on the risk of central venous catheter-related bloodstream infection in oncological patients.

BACKGROUND & AIMS: Parenteral nutrition is known as a high-risk factor for central venous catheter-related bloodstream infection (CVC-RBSI) in cancer patients. Owing to ethical and technical problems, the studies in the literature have nonrandomized designs and are therefore often confounded by biases. We performed a propensity score analysis to estimate the effect of parenteral nutrition on CVC-RBSI in digestive cancer patients who underwent chemotherapy. METHODS: Data were collected prospectively. A logistic regression model was used to calculate a propensity score, which was the probability of receiving parenteral nutrition. Kaplan-Meier survival and Cox regression model were used to estimate the effect of the parenteral nutrition on CVC-RBSI after adjustment for the propensity score. RESULTS: Before the propensity score analysis, the differences between patients with (n = 113) and without (n = 312) parenteral nutrition were identified including: male gender, body weight, weight loss, performance status, location of primary cancer, FOLFIRI, and previous long-term corticotherapy. After propensity score stratification, all of the covariates were balanced within each stratum. After adjustment, patients with parenteral nutrition were at a higher risk for CVC-RBSI. CONCLUSION: By using the propensity score analysis, this study confirmed that parenteral nutrition was an independent risk factor for CVC-RBSI in digestive cancer patients.

Clinical performance of the carbohydrate-deficient transferrin (CDT) assay by the Sebia Capillarys2 system in case of cirrhosis. Interest of the Bio-Rad %CDT by HPLC test and Siemens N-Latex CDT kit as putative confirmatory methods.

BACKGROUND: The CDT assay used to detect chronic alcohol abuse is difficult with cirrhotic patients. This article describes the performances of several CDT assays in case of cirrhosis. The CDT-Capillarys assay by capillary zone electrophoresis was used for initial testing. Two additional methods were tested as putative confirmatory methods. METHODS: 110 patients with known hepatic status had their CDT measured by the Capillarys2 or alternative methods. Self-reported alcohol intake was used to assess the performances of CDT assays. RESULTS: Capillarys2 performance was lower in case of cirrhosis, many electropherograms displaying various abnormalities. We used the proper separation of the di- and tri-sialotransferrin peaks to select reliable profiles. This selection led to the classification of cirrhotic and non-cirrhotic patients in abusers and abstainers with similar performances. However, no interpretation was available for 54% of the cirrhotic patients and neither the BioRad %CDT by HPLC test, nor the Siemens N-Latex CDT kit was suitable as confirmatory methods for these samples. CONCLUSIONS: An attentive profile examination is required for the validation of Capillarys CDT results of cirrhotic patients. Reliability is significantly improved when samples with an improper separation are excluded. To date, no commercial test can confirm the excluded samples.

Totally implantable central venous access port infections in patients with digestive cancer: incidence and risk factors.

BACKGROUND: Central venous access port-related bloodstream infection (CVAP-BSI) is associated with morbidity and mortality in patients with cancer. This study examined the incidence rates and risk factors for CVAP-BSI in adult patients with digestive cancer. METHODS: This prospective observational cohort study was performed from 2007 to 2011 in 2 oncology units of a university hospital. Incidence rate was expressed as number of CVAP-BSI per 1,000 catheter-days. A Cox regression model was used to identify risk factors for CVAP-BSI. RESULTS: A total of 315 patients were included. CVAP-BSI occurred in 41 patients (13.0%). The overall incidence rate was 0.76/1,000 catheter-days. The rate was higher in patients with esophageal cancer (1.28. P = .05) and pancreatic cancer (1.24; P = .007). Risk factors independently associated with CVAP-BSI were World Health Organization performance status between 2 and 4, catheter utilization-days in the previous month, pancreatic cancer, and parenteral nutrition. Coagulase-negative Staphylococci and enterobacteria were the main microorganisms isolated. CONCLUSIONS: In adult patients with digestive cancer, pancreatic cancer, cumulative catheter utilization-days, World Health Organization performance status, and parenteral nutrition were identified as independent risk factors for CVAP-BSI. Patients with any of these risk factors could be candidates for preventive strategies.

Outcome of patients receiving chemotherapy for advanced biliary tract or gallbladder carcinoma.

PURPOSE: Patients with cholangiocarcinoma or gallbladder cancer have poor overall prognosis and their management is often complex. Currently, there is no standard chemotherapy for this disease, but several single agents and combinations have shown promising activity, most notably gemcitabine-based combinations. PATIENTS AND METHODS: We conducted a retrospective analysis of all cases of biliary tract cancer treated at two academic centers in Lyon, France: 127 cases were identified, 67 underwent primary surgery, 13 of which were deemed unresectable upon surgery and were treated medically; 60 patients received medical treatment only. Overall, 71 patients received chemotherapy for locally advanced or metastatic disease and are the subject of this report. RESULTS: The median age was 60.7 years, 47 (66%) patients were male and 55 (77%) patients had metastatic disease. Twenty-seven patients (38%) required biliary drainage before chemotherapy. Twenty-four patients received single-agent gemcitabine, 37 patients received gemcitabine-platinum combination and 10 patients received fluorouracil-based regimens. The response rates, median progression-free survival and overall survival times were 24%, 4.1, 7.5 months, respectively. There was a significant increase in the response rate with gemcitabine-platinum combinations compared with other regimens. Fluororuracil-based regimens provided lower response rates and shorter median progression-free survival and overall survival as compared with gemcitabine-based regimens (both single agents and combinations). CONCLUSION: Although retrospective, these data support the use of gemcitabine-containing regimens in patients with advanced biliary tract or gallbladder cancer. The benefit of adding oxaliplatin in this setting remains unclear.

Benefit of sustained virological response to combination therapy on graft survival of liver transplanted patients with recurrent chronic hepatitis C.

Recurrent hepatitis C infection is an important cause of progressive fibrosis, cirrhosis and graft loss after liver transplantation. Treatment for post-transplant recurrence results in sustained virological response (SVR) in up to 30% of cases. The aim of this study was to evaluate the impact of SVR on patients and graft survival. Thirty-four patients with an SVR to IFN-ribavirin were included. Forty-six nonresponders to the combination formed the control group. Follow-up data were recorded every 6 months and included HCV RNA, and the occurrence of clinical problems (cirrhosis, decompensation, hepatocellular carcinoma, death). A graft biopsy was performed every year. The mean follow-up duration was 52 months in responders and 57 months in nonresponders. Two patients died in each group of patients. Two patients with SVR developed late virological relapse. Fibrosis decreased in 38% of patients with SVR, remained stable in 44% and worsened in 18%. In contrast, fibrosis increased in the majority of nonresponder patients (74%, p<0.001). At the end of follow-up, no patient without cirrhosis at inclusion developed cirrhosis of the graft versus 9 among nonresponder patients (p=0.009). No difference in patient survival was observed in the two groups. In conclusion, this study shows that HCV eradication has a positive impact on graft survival.

Value of rectal ultrasound in predicting staging and outcome in patients with rectal adenocarcinoma.

PURPOSE: Transrectal ultrasonography is considered the best method to stage rectal cancer, and thus the need for preoperative radiotherapy. This retrospective study was designed to determine the prognostic value of uTN classification on survival of patients treated by preoperative radiotherapy and surgery. METHODS: A total of 218 patients with proven rectal adenocarcinoma were staged by transrectal ultrasonography before treatment. Transrectal ultrasonography reports were reviewed for TN classification, quality of examinations, and downstaging (pT < uT). RESULTS: Transrectal ultrasonography stages were as follows: uT1, n = 2; uT2, n = 61; uT3, n = 145; uT4, n = 10; uN0, n = 94; uN+, n = 124. After radiotherapy, based on operative specimen, lesions were staged as pT0, n = 27; pT1, n = 20; pT2, n = 60; pT3/4, n = 111; pN0, n = 160; pN+, n = 58; pM+, n = 10. Downstaging (measured as a reduction in TN level determined by transrectal ultrasonography and pathology of resected specimen) occurred in 42.6 percent for T and 38.1 percent for N. Five-year overall and disease-free survivals were 71.3 and 62.7 percent, respectively (median follow-up, 62 months). In univariate or multivariate analysis including parameters available before treatment, uT and age but not uN were statistically significant prognosis factor for overall survival. Patients with TN downstaging had significantly better overall survival. In multivariate analysis, including all parameters, only age, gender, pT, and pN+ status predicted poor outcome. CONCLUSIONS: In patients with rectal adenocarcinoma treated by preoperative radiotherapy, uT classification determined by transrectal ultrasonography before radiotherapy, pT and pN classification determined after radiotherapy, and tumor downstaging were predictors of survival contrary to uN. Only pTN classification, age, and gender were independent predictors in multivariate analysis.