Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

Donor characteristics and risk of hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: To date, studies assessing the risk of post-transplant hepatocellular carcinoma (HCC) recurrence have focused on tumour characteristics. This study investigated the impact of donor characteristics and graft quality on post-transplant HCC recurrence. METHODS: Using the Scientific Registry of Transplant Recipients patients with HCC who received a liver transplant between 2004 and 2011 were included, and post-transplant HCC recurrence was assessed. A multivariable competing risk regression model was fitted, adjusting for confounders such as recipient sex, age, tumour volume, α-fetoprotein, time on the waiting list and transplant centre. RESULTS: A total of 9724 liver transplant recipients were included. Patients receiving a graft procured from a donor older than 60 years (adjusted hazard ratio (HR) 1.38, 95 per cent c.i. 1.10 to 1.73; P = 0.006), a donor with a history of diabetes (adjusted HR 1.43, 1.11 to 1.83; P = 0.006) and a donor with a body mass index of 35 kg/m(2) or more (adjusted HR 1.36, 1.04 to 1.77; P = 0.023) had an increased rate of post-transplant HCC recurrence. In 3007 patients with documented steatosis, severe graft steatosis (more than 60 per cent) was also linked to an increased risk of recurrence (adjusted HR 1.65, 1.03 to 2.64; P = 0.037). Recipients of organs from donation after cardiac death donors with prolonged warm ischaemia had higher recurrence rates (adjusted HR 4.26, 1.20 to 15.1; P = 0.025). CONCLUSION: Donor-related factors such as donor age, body mass index, diabetes and steatosis are associated with an increased rate of HCC recurrence after liver transplantation.

Surgical management of patients with colorectal cancer and simultaneous liver and lung metastases.

BACKGROUND: The management of patients with colorectal cancer and simultaneously diagnosed liver and lung metastases (SLLM) remains controversial. METHODS: The LiverMetSurvey registry was interrogated for patients treated between 2000 and 2012 to assess outcomes after resection of SLLM, and the factors associated with survival. SLLM was defined as liver and lung metastases diagnosed 3 months or less apart. Survival was compared between patients with resected isolated liver metastases (group 1, control), those with resected liver and lung metastases (group 2), and patients with resected liver metastases and unresected (or unresectable) lung metastases (group 3). An Akaike test was used to select variables for assessment of survival adjusted for confounding variables. RESULTS: Group 1 (isolated liver metastases, hepatic resection alone) included 9185 patients, group 2 (resection of liver and lung metastases) 149 patients, and group 3 (resection of liver metastases, no resection of lung metastases) 285 patients. Ten variables differed significantly between groups and seven were included in the model for adjusted survival (age, number of liver metastases, synchronicity of liver metastases with primary tumour, carcinoembryonic antigen level, node status of the primary tumour, initial resectability of liver metastases and inclusion in group 3). Adjusted overall 5-year survival was similar for groups 1 and 2 (51·5 and 44·5 per cent respectively), but worse for group 3 (14·3 per cent) (P = 0·001). CONCLUSION: Patients who had resection of liver and lung metastases had similar overall survival to those who had undergone removal of isolated liver metastases.

Liver resection in patients with eight or more colorectal liver metastases.

BACKGROUND: Patients with large numbers of colorectal liver metastases (CRLMs) are potential candidates for resection, but the benefit from surgery is unclear. METHODS: Patients undergoing resection for CRLMs between 1998 and 2012 in two high-volume liver surgery centres were categorized according to the number of CRLMs: between one and seven (group 1) and eight or more (group 2). Overall (OS) and recurrence-free (RFS) survival were compared between the groups. Multivariable analysis was performed to identify adverse prognostic factors. RESULTS: A total of 849 patients were analysed: 743 in group 1 and 106 in group 2. The perioperative mortality rate (90 days) was 0.4 per cent (all group 1). Median follow-up was 37.4 months. Group 1 had higher 5-year OS (44.2 versus 20.1 per cent; P < 0.001) and RFS (28.7 versus 13.6 per cent; P < 0.001) rates. OS and RFS in group 2 were similar for patients with eight to ten, 11-15 or more than 15 metastases (48, 40 and 18 patients respectively). In group 2, multivariable analysis identified three preoperative adverse prognostic factors: extrahepatic disease (P = 0.010), no response to chemotherapy (P = 0.023) and primary rectal cancer (P = 0.039). Patients with two or more risk factors had very poor outcomes (median OS and RFS 16.9 and 2.5 months; 5-year OS zero); patients in group 2 with no risk factors had similar survival to those in group 1 (5-year OS rate 44 versus 44.2 per cent). CONCLUSION: Liver resection is safe in selected patients with eight or more metastases, and offers reasonable 5-year survival independent of the number of metastases. However, eight or more metastases combined with at least two adverse prognostic factors is associated with very poor survival, and surgery may not be beneficial.

Toward a better liver graft allocation that accounts for candidates with and without hepatocellular carcinoma.

In some countries where the Model for End-Stage Liver Disease (MELD) score is used for graft allocation, selected patients with hepatocellular carcinoma (HCC) receive a fixed number of exception points at listing, and increasing priority on the list by accruing additional exception points at regular time intervals. This system originally aimed at balancing the risks of HCC patients of developing contraindications and of non-HCC patients of dying before transplantation, is not ideal because it appears to offer an advantage to HCC patients, regardless of tumor characteristics and response to loco-regional treatment. Scores modulated by HCC characteristics have been proposed. They are based on a more refined estimate of the risk of pretransplant drop-out or of the posttransplant transplant benefit expressed as the life-years gained for each graft. This review describes the newly proposed systems, and discusses their advantages and drawbacks. We believe that the current exception points allocation should be revised and that drop-out-equivalent or transplant benefit-equivalent models should be studied further. As with all policy changes, these should be done under close monitoring that allows subsequent revisions.

Systematic review and meta-analysis of the effect of perioperative steroids on ischaemia-reperfusion injury and surgical stress response in patients undergoing liver resection.

BACKGROUND: Several therapeutic strategies, such as ischaemic preconditioning, intermittent or selective pedicle clamping and pharmacological interventions, have been explored to reduce morbidity caused by hepatic ischaemia-reperfusion injury and the surgical stress response. The role of steroids in this setting remains controversial. METHODS: A comprehensive literature search in MEDLINE, Embase and the Cochrane Register of Clinical Trials (CENTRAL) was conducted (1966 onwards), identifying studies comparing perioperative administration of intravenous steroids with standard care or placebo, in the setting of liver surgery. Randomized Controlled trials (RCTs) and non-RCTs were included. Critical appraisal and meta-analysis were carried out according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement. RESULTS: Six articles were included; five were RCTs. Pooling the results revealed that patients receiving intravenous glucocorticoids were 24 per cent less likely to suffer postoperative morbidity compared with controls (risk ratio 0.76, 95 per cent confidence interval 0.57 to 0.99; P = 0.047). The treated group experienced a significantly greater rise in early postoperative interleukin (IL) 10 levels compared with controls. In addition, steroids significantly reduced postoperative blood levels of bilirubin, and of inflammatory markers such as IL-6 and C-reactive protein. There was no evidence supporting a risk difference in infectious complications and wound healing between study groups. CONCLUSION: Perioperative steroids have a favourable impact on postoperative outcomes after liver resection.

Liver transplantation for hepatocellular carcinoma: five steps to prevent recurrence.

Liver transplantation is the best treatment of patients with unresectable early hepatocellular carcinoma, allowing disease-free survival rates of 60-80% at 5 years. Despite these good results, some 10% of recipients experience a posttransplant HCC recurrence, which leads to death in almost all patients. Recurrence is either due to the growth of occult metastases or to the engraftment of circulating tumor cells. It can be hypothesized that strategies to decrease the engraftment of circulating tumor cells could decrease the risk of recurrence and, in addition, extend access to transplantation to patients with more advanced HCC. These potential strategies can be schematized into five steps, including (1) selecting recipients with low baseline levels of circulating HCC cells, by adding biological markers (such as alpha fetoprotein or molecular signatures) to the accepted combination of morphological criteria; (2) decreasing the perioperative release of HCC cells, with careful perioperative handling of the tumors; (3) preventing the engraftment of circulating HCC cells by decreasing liver graft ischemia-reperfusion injury, which has been shown to promote cancer cell engraftment and growth; (4) using anticancer drugs, including mammalian target of rapamycin inhibitors and (5) tuning immunity toward HCC clearance.

[Management of hepatocellular carcinoma]. / Prise en charge du carcinome hépatocettulaire en 2010.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.

False serologic evidence for acute primary toxoplasmosis during liver transplantation for fulminant hepatitis B: a case report.

Acute primary Toxoplasma gondii infection is usually considered to be a contraindication for solid organ transplantation. Recent reports of acute T. gondii infection have highlighted the need to include T. gondii serology in the pretransplant screening of solid-organ transplant recipients. However such serology might be misleading. We describe the case of a 25-year-old woman who received a liver transplantation for life-threatening liver failure due to hepatitis B virus infection. The presence of high IgM titers against T. gondii, as detected by membrane immunoassay, immunofluorescence, and mu-capture ELISA tests, together with the absence of IgG antibodies in the immediate pretransplant serology screening suggested acute primary T. gondii infection at the time of transplantation. We initiated a preemptive therapy with intravenous clindamycin and cotrimoxazole. However, negative PCR and IgA capture assays, together with the absence of a sustained IgG response finally excluded the initial diagnosis of primary toxoplasmosis, leading to discontinuation of antitoxoplasmosis therapy. This case illustrates the problem that, in the context of fulminant hepatitis B, serologic markers for acute primary toxoplasmosis can be falsely positive. Confirmation by PCR and IgA antibody determinations is required to confirm this diagnosis.

Dangerous halo after neoadjuvant chemotherapy and two-step hepatectomy for colorectal liver metastases.

BACKGROUND: Bilobar colorectal metastases are a therapeutic challenge and require a multidisciplinary approach. The aim of this study was to describe the clinical and histological outcomes of patients having neoadjuvant chemotherapy and two-step hepatectomy with right portal vein occlusion for advanced bilateral colorectal metastases. METHODS: A series of 23 consecutive patients treated with curative intent according to a standardized multidisciplinary management protocol was reviewed. RESULTS: Of 23 patients, 22 completed the programme. There was no mortality and no Clavien grade III morbidity. Median survival from the start of treatment was 45 months, and 1-, 3- and 5-year Kaplan-Meier estimates were 95, 73 and 27 per cent respectively. On histology at the first operation, ten patients had a dangerous halo of proliferating tumour cells infiltrating the surrounding liver parenchyma, of variable importance (six focal and four diffuse), regardless of the response to chemotherapy of the metastases. The dangerous halo increased in prevalence and importance (six focal and seven diffuse) between the first and second operation. CONCLUSION: Neoadjuvant chemotherapy followed by two-step hepatectomy with right portal vein occlusion is feasible, safe and may be advantageous to the patient. The appearance of a dangerous halo around the liver metastases may require adaptation of the surgical technique to decrease the risk of local recurrence.

Biliary cystadenoma revealed by obstructive jaundice.

Biliary cystadenoma is a rare cystic tumour of the liver that can be difficult to differentiate from other types of benign hepatic cysts. We report the case of a 32-year-old woman who presented with obstructive jaundice due to a large cystic lesion of the left hepatic lobe. Resection of the mass revealed a mucinous cystadenoma with protrusion of a pedunculated extension into the left hepatic duct and the common bile duct. We describe the clinical features, the radiological findings, the surgical management and the pathology of this rare entity.

[Complex liver resections: where are the limits?]. / Résections hépatiques complexes: jusqu'où peut-on aller?

Due to the progress in the management of liver cancer, the resection's limits have been pushed back and the concept of complex hepatectomy has become relevant. We identify five major factors affecting the complexity of hepatectomies. 3 with a direct effect on the peri-operative complications: 1) residual liver volume and quality; 2) the need of a vascular or biliary reconstruction and 3) the presence of co-morbidities. In addition to these factors, 2 major elements affect the long-term survival: 4) the extent of the tumoral disease and 5) the anatomical proximity of tumoral lesions to vascular or biliary structures. All these factors impact the ultimate outcome, requiring careful planning, operation and follow-up. This review summarizes the state of the art approach to complex hepatectomies.

Treatment strategies for the management of advanced colorectal liver metastases detected synchronously with the primary tumour.

The review summarises the contributions of chemotherapy, interventional radiology and surgery to the improved survival observed in patients with colorectal liver metastases. The rationale in favour of modern neoadjuvant chemotherapy regimens, of pro-generative manoeuvres to increase the volume of the future remnant liver, and of resection techniques that preserve its function is discussed. For advanced synchronous colorectal metastases, the arguments in favour of a reversed approach with systemic chemotherapy, liver surgery and colon surgery in that order, as opposed to the traditional approach of colon surgery first, or to a simultaneous liver and large bowel resection, are presented.

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.

BACKGROUND: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. PATIENTS AND METHODS: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. RESULTS: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. CONCLUSION: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.

Primary invasive aspergillosis of the digestive tract: report of two cases and review of the literature.

BACKGROUND: Disseminated aspergillosis is thought to occur as a result of vascular invasion from the lungs with subsequent bloodstream dissemination, and portals of entry other than sinuses and/or the respiratory tract remain speculative. METHODS: We report two cases of primary aspergillosis in the digestive tract and present a detailed review of eight of the 23 previously-published cases for which detailed data are available. RESULTS AND CONCLUSION: These ten cases presented with symptoms suggestive of typhlitis, with further peritonitis requiring laparotomy and small bowel segmental resection. All cases were characterized by the absence of pulmonary disease at the time of histologically-confirmed gastrointestinal involvement with vascular invasion by branched Aspergillus hyphae. These cases suggest that the digestive tract may represent a portal of entry for Aspergillus species in immunocompromised patients.

[Management of patients after liver transplantation]. / Suivi pratique des patients après transplantation hépatique.

The success of liver transplantation essentially depends on the prevention and treatment of long term complications, which may be due to surgery, opportunistic infections, organ rejection and relapse of the initial liver disease. The side effects of immunosuppressive drugs--arterial hypertension, glucose intolerance and diabetes, dyslipidemia and obesity, renal failure, osteoporosis, malignancy, and anaemia--should be regularly screened and treated without delay. Surgical procedures in transplanted patients are safe and rarely followed by complications. Although pregnancy in this setting is considered at risk, because of prematurity and low birth weight, overall outcomes are favourable. The yearly influenza vaccination is strongly recommended. The survival and the quality of life of liver transplant patients also depend on a good communication between the general practitioner and the transplantation centre.

[When should cholecystectomy be practiced? Not always an easy decision]. / Quand faut-il réaliser une cholécystectomie? Une décision pas toujours simple.

Gallstone disease is a frequent medical problem. Cholelithiasis affects 10% of the population and 30% of patients with gallstones will undergo surgery. The treatment of choice for symptomatic gallstones remains cholecystectomy. A prophylactic cholecystectomy is indicated for asymptomatic patients in the presence of polyps, porcelain gallbladder or during bariatric surgery. The management of the complications of gallstone disease is discussed. At present, common bile duct stones, even if discovered preoperatively, should be managed by a multidisciplinary team including surgeons trained in laparoscopic techniques and gastroenterologists. This review is complemented by the information from a prospective database generated by a program called "DODIG" on 1099 cholecystectomies performed in our institution.

Hepatopulmonary syndrome increases the postoperative mortality rate following liver transplantation: a prospective study in 90 patients.

Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of patients with end-stage liver diseases. HPS is diagnosed by hypoxemia and pulmonary vascular dilatation and is an independent risk factor of mortality. Orthotopic liver transplantation (OLT) is the only factor that modifies the natural course of HPS. Once patients with HPS have been transplanted, their long-term survival rate is similar to transplanted patients without HPS. Consequently, HPS is an indication of OLT whatever the severity of hypoxemia. However, besides the favorable long-term survival of HPS patients with OLT, a high postoperative mortality (mostly within 6 months) has been suggested. The aim of our study was to analyze the incidence of HPS and postoperative outcome after OLT in 90 consecutive patients. All patients were prospectively included and had blood gas analysis to detect HPS. Patients with hypoxemia had contrast echocardiography to confirm HPS. Nine patients had HPS with a 50 50 mmHg in all HPS patients transplanted.