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The prognosis impact of positive margins after resection of colorectal liver metastases (CLM) in patients treated with modern effective chemotherapy has not been elucidated. The objective was to compare oncologic outcomes after R0 and R1 resections in the era of modern effective chemotherapy. Between 1999 and 2010, all consecutive patients undergoing liver resection for CLM were analyzed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumor, treated with combined radiofrequency, or not treated with chemotherapy were excluded. Survival and recurrence after R0 (tumor-free margin >0 mm) and R1 resections were analyzed. Among 466 patients undergoing hepatectomy for CLM, 191 were eligible. Of them, 164 (86 %) received preoperative chemotherapy and 105 (55 %) received postoperative chemotherapy. R1 resection (10 %) was comparable in patients treated or not by preoperative chemotherapy. R1 status was associated with more intrahepatic recurrences. Overall survival (OS) (44 vs. 61 %; p = 0.047) and disease-free survival (DFS) (8 vs. 26 %; p = 0.082) were lower in patients after R1 compared to R0 resection (32 months of median follow-up). Preoperative chemotherapy and major hepatectomy were prognostic factors of survival, whereas postoperative chemotherapy was a protective factor from recurrences. In patients treated with preoperative chemotherapy, OS and DFS were similar between R1 and R0 resections (40 vs. 55 %, p = 0.104 and 9 vs. 22 %, p = 0.174, respectively). In the era of modern effective chemotherapy, R1 resection leads to more intrahepatic recurrences but did not affect OS in selected patient responders to neoadjuvant chemotherapy. Postoperative chemotherapy protects from recurrences whatever the margin resection status.

Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is a challenge to determine a patient's prognosis. We aimed to identify new prognostic markers of patients with HCC treated by liver resection.We collected 314 HCC samples from patients at Bordeaux (1998-2007) and Créteil (2003-2007) hospitals in France. We analyzed the gene expression patterns of the tumors and compared expression patterns with patient survival times. Using the coefficient and regression formula of the multivariate Cox model, we identified a "5-gene score" associated with survival times. This molecular score was then validated in 2 groups of patients from Europe and the United States (n = 213) and China (n = 221).The 5-gene score, based on combined expression level of HN1, RAN, RAMP3, KRT19, and TAF9, was associated with disease-specific survival times of 189 patients with resected HCC in Bordeaux (hazard ratio = 3.5; 95% confidence interval: 1.9-6.6; P.0001). The association between the 5-gene score and disease-specific survival was validated in an independent cohort of 125 patients in Créteil (hazard ratio = 2.3; 95% confidence interval: 1.1-4.9; P.0001). The 5-gene score more accurately predicted patient outcomes than gene expression signatures reported previously. In multivariate analyses, the 5-gene score was associated with disease-specific survival, independent of other clinical and pathology feature of HCC. Disease-specific survival was also predicted by combining data on microvascular invasion, the Barcelona Clinic Liver Cancer classification system, and the 5-gene score in a nomogram. The prognostic accuracy of the 5-gene score was further validated in European and US patients with hepatitis C, cirrhosis, and HCC (overall survival P = .002) and in Asian patients with HCC with hepatitis B (overall survival, P = .02). Combining the 5-gene score with the expression pattern of 186 genes in corresponding cirrhotic tissues increased its prognostic accuracy.The molecular 5-gene score is associated with outcomes of patients with HCC treated by resection in different clinical settings worldwide. This new biomarker should be tested in clinical trials to stratify patients in therapeutic decisions.

International audience; BACKGROUND & AIMS: Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.METHODS: We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation.RESULTS: Symptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with β-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively.CONCLUSIONS: Using sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients' risk factors for HCA, disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients with HCA.

Hepatocellular carcinomas (HCCs) are a heterogeneous group of tumors that differ in risk factors and genetic alterations. We further investigated transcriptome-genotype-phenotype correlations in HCC. Global transcriptome analyses were performed on 57 HCCs and 3 hepatocellular adenomas and validated by quantitative RT-PCR using 63 additional HCCs. We determined loss of heterozygosity, gene mutations, promoter methylation of CDH1 and CDKN2A, and HBV DNA copy number for each tumor. Unsupervised transcriptome analysis identified 6 robust subgroups of HCC (G1-G6) associated with clinical and genetic characteristics. G1 tumors were associated with low copy number of HBV and overexpression of genes expressed in fetal liver and controlled by parental imprinting. G2 included HCCs infected with a high copy number of HBV and mutations in PIK3CA and TP53. In these first groups, we detected specific activation of the AKT pathway. G3 tumors were typified by mutation of TP53 and overexpression of genes controlling the cell cycle. G4 was a heterogeneous subgroup of tumors including TCF1-mutated hepatocellular adenomas and carcinomas. G5 and G6 were strongly related to beta-catenin mutations that lead to Wnt pathway activation; in particular, G6 tumors were characterized by satellite nodules, higher activation of the Wnt pathway, and E-cadherin underexpression. CONCLUSION: These results have furthered our understanding of the genetic diversity of human HCC and have provided specific identifiers for classifying tumors. In addition, our classification has potential therapeutic implications because 50% of the tumors were related to WNT or AKT pathway activation, which potentially could be targeted by specific inhibiting therapies.

The aim of this study was to compare survival between radiofrequency ablation (RFA) and surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within Milan criteria.From January 2004 to December 2013 we consecutively and retrospectively included all patients with first occurrence of HCC within Milan criteria receiving SR or RFA as first-line treatment. The cumulative overall survival (OS) and disease-free survival (DFS) were compared after inverse probability weighting (including confounding factor).A total of 281 patients (RFA 178, SR 103) were enrolled. In multivariate Cox regression RFA and SR were not independent predictors of survival or recurrence. The respective weighted 5 years OS and DFS for patients with propensity scores between 0.1-0.9 in the SR and RFA groups were 54-33% and 60-16.9%, P = 0.695 and P = 0.426, respectively. Local tumour progression rate did not differ according to treatment (P = 0.523). Major complication rate was higher in the SR group, P = 0.001. Hospitalisation duration was lower in the RFA group (mean 2.19 days, range 2-7) than in the SR group (mean 10.2 days, range 3-30), P0.001.This large Western study has shown that OS and DFS did not differ after RFA (using mainly multipolar devices) and SR, for HCC within the Milan criteria in a European population, with a shorter hospitalisation time and a lower complication rate for RFA.

Background The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The impact of postoperative morbidity of TME on longterm survival has never been described. We retrospectively analyzed factors that might influence survival after TME for rectal cancer, including postoperative morbidity. Study design From 1994 to 2001, 300 patients (192 men and 108 women; mean age, 64 years) had TME for rectal cancer. Preoperative radiotherapy was given in 202 patients. Age, gender, tumor height, size and circular invasion of the tumor, pathologic tumor and nodal status, distal and circumferential margins, number of lymph nodes analyzed, type of surgery, postoperative pelvic sepsis, preoperative radiotherapy, and adjuvant chemotherapy were examined; their association with overall and disease-free survival was evaluated by the log-rank test in univariate analysis and by multivariable Cox proportional hazards analysis. Results Postoperative morbidity was 38% (113 of 300 patients) and included 18% (54 of 300 patients) pelvic sepsis. The local recurrence rate was 6% (18 of 300 patients), and the distant metastasis rate was 24% (73 of 300 patients). Recurrence was three times more frequent distally than locally, including patients with pelvic sepsis The 5-year overall and disease-free survival rates were 72% and 60%, respectively. Independent predictors of overall survival were age older than 64 years (odds ration [OR]=2.19, 95% CI 1.32 to 4.17), pelvic sepsis (OR=2.06, 95% CI 1.10 to 3.87), circumferential surgical margin (OR=3.19, 95% CI 1.67 to 6.09), pathologic tumor (OR=2.69, 95% CI1.23 to 5.88), and nodal status (OR=3.18, 95% CI 1.79 to 5.64). Independent predictors of disease-free survival were pelvic sepsis (OR=2.17, 95% CI 1.31 to 3.58), circumferential surgical margin (OR=2.61, 95 CI 1.52 to 4.49), pathologic tumor (OR=1.82, 95% CI 1.04 to 3.20), and nodal status (OR=2.67, 95% CI 1.68 to 4.23). Patients with pelvic sepsis had a 5-year disease-free survival of 39% compared with 65% without pelvic sepsis (p Conclusions After TME for rectal cancer, pelvic sepsis is a common complication that is associated with increased risk of distant recurrence and decreased longterm survival. Efforts are necessary to decrease postoperative morbidity in surgical treatment of rectal cancer.

Background The incidence of hepatocellular carcinoma (HCC) in cirrhotic and noncirrhotic liver is increasing in the world, probably because of the high prevalence of infections by hepatitis B and C viruses. Despite numerous publications on hepatic resection, prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. Study design One hundred eight consecutive patients with HCC in noncirrhotic liver have been treated by hepatic resection in the past 18 years in our center. Clinical, biologic, and histopathologic parameters of these patients were collected. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. Results Postoperative morbidity and mortality rates were 23% and 6.5%, respectively. The 3- and 5-year disease-free and overall survival rates were 55% and 43%, and 43% and 29%, respectively. Blood transfusion, absence of tumor capsule, and daughter nodules were independently associated with overall survival. But the only risk factors for recurrence were blood transfusion, absence of tumor capsule, daughter nodules, and margin resection Conclusions In the treatment of HCC without cirrhosis, hepatectomy remains a safe and legitimate treatment, but longterm results are impaired by a high rate of early recurrence likely related to metastatic dissemination. Only histopathologic factors related to the tumor are predictive of recurrence and overall survival.

Telangiectatic focal nodular hyperplasia (TFNH) of the liver is generally believed to belong to the focal nodular hyperplasia (FNH) family. The aim of this study was to use molecular markers, in addition to morphologic features, to better characterize TFNH.Thirteen patients with TFNH were compared with 28 patients with FNH and 17 patients with hepatocellular adenoma. Full clinical and morphologic data were analyzed. Molecular markers included determination of clonality by examining the active X chromosome, genome-wide allelotyping, a search for hepatocyte nuclear factor 1alpha (HNF1alpha) mutations, and determination of ANGPT1/ANGPT2 transcript levels.No clinical differences were evident between patients with TFNH and adenoma; in particular, bleeding was observed in 77% and 53% of the cases, respectively. Patients with TFNH were more likely to experience nodule recurrence and the presence of multiple nodules than those with either FNH or adenoma. All TFNH and adenoma samples that were available for analysis were monoclonal, in contrast to 40% of the FNH samples. Chromosome losses confirmed monoclonality and were significantly less frequent in TFNH and FNH (22% and 26%) than in adenoma (53%). HNF1alpha mutations were found exclusively in half of the adenomas. ANGPT2 was overexpressed in TFNH and down-regulated in adenoma (P.01) and FNH (P.0005).TFNHs are monoclonal lesions frequently subject to bleeding that are similar to adenomas not carrying HNF1alpha mutations and require a similar type of treatment. However, morphologic and molecular data support the hypothesis that TFNH is a separate entity.

To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE).Institutional review board did not require its approval or patient informed consent for this study. The adverse events that occurred during PPVE or until planned hepatic surgery was performed or cancelled were retrospectively obtained from clinical, imaging, and laboratory data files in 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16-78 years). Liver resection was planned for metastases (n = 137), hepatocarcinoma (n = 31), cholangiocarcinoma (n = 15), fibrolamellar hepatoma (n = 1), and benign disease (n = 4). PPVE was performed with a single-lumen 5-F catheter and a contralateral approach with n-butyl cyanoacrylate mixed with iodized oil as the main embolic agent. The rate of complications in patients with cirrhosis was compared with that in patients without cirrhosis by using the chi(2) test.Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P.001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1).PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.

Vitamin D controls calcium homeostasis and the development and maintenance of bones through vitamin D receptor activation. Prolonged therapy with rifampicin or phenobarbital has been shown to cause vitamin D deficiency or osteomalacia, particularly in patients with marginal vitamin D stores. However, the molecular mechanism of this process is unknown. Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16alpha-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists. Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16alpha-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D(3). Transfection of PXR in human embryonic kidney cells resulted in rifampicin-mediated induction of CYP24 mRNA. Analysis of the human CYP24 promoter showed that PXR transactivates the sequence between -326 and -142. We demonstrated that PXR binds to and transactivates the 2 proximal vitamin D-responsive elements of the human CYP24 promoter. These data suggest that xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D(3) hormonal activity and calcium homeostasis through the activation of PXR.

BACKGROUND: Macroscopic hepatic lymph node involvement is usually a contraindication to hepatic resection. Only a few studies have investigated the impact of hepatic lymph node involvement on survival. The aim of this retrospective study was to assess microscopic hepatic lymph node involvement in resectable colorectal liver metastasis and outcomes in patients with such involvement. STUDY DESIGN: From January 1985 to December 2000, 156 patients underwent curative liver resection in association with systematic hepatic lymph node dissection for colorectal liver metastasis. A first analysis was performed to assess the association between hepatic lymph node metastasis and patients' characteristics. A second analysis assessed survival after resection of liver colorectal metastasis by using the Kaplan-Meier method. RESULTS: Twenty-three of the 156 patients (15%) had microscopically involved hepatic lymph nodes. No predictive factor of lymph node metastasis was identified. Multivariate analysis showed that lymph node metastasis, preoperative carcinoembryonic antigen level, number of metastases, and morbidity were factors influencing survival. The 3- and 5-year survival rates of patients with lymph node metastasis were 27% and 5%, respectively, compared with 56% and 43% without lymph node metastasis (p = 0.0001). CONCLUSIONS: During resection of liver colorectal metastasis, microscopic lymph node involvement occurred in 15% of the patients and was associated with a poor 5-year survival. Hepatic lymph node dissection should be performed systematically to select high-risk patients.

This study was designed to investigate the ability of long-term primary cultures of adult human hepatocytes to secrete the main haemostasis proteins. Factors II, V, VII, VIII, PIVKA-II (protein induced by vitamin K 1 absence or antagonist II), fibrinogen and antithrombin were quantified in culture medium by immunological methods and by measuring the coagulant activity of factors II, V and VII. All the haemostasis protein antigens except the factor VIII antigen (FVIII:Ag) were found in the culture medium throughout the culture period. The clotting activity of each factor correlated well with antigen level. In addition, fibrinogen and fibrin were detected in the fibrillar material following incubation of the culture medium with thromboplastin. Moreover, adding vitamin K 1 to the culture medium resulted in a significant increase of factors II and VII and a reciprocal decrease of the PIVKA-II, and adding von Willebrand factor resulted in a drastic increase of the level of FVIII:Ag. We conclude that, in our culture system, normal adult human hepatocytes retain their capacity to secrete haemostasis proteins for at least 30 days.

During the inflammatory response, intrahepatic cholestasis and decreased drug metabolism are frequently observed. At the hepatic level, the orphan nuclear constitutive androstane receptor (CAR) (NR1I3) controls phase I (cytochrome P450 [CYP] 2B and CYP3A), phase II (UGT1A1), and transporter (SLC21A6, MRP2) genes involved in drug metabolism and bilirubin clearance in response to xenobiotics such as phenobarbital or endobiotics such as phenobarbital or endobiotics such as bilirubin. We investigated the negative regulation of CAR, a glucocorticoid-responsive gene, via proinflammatory cytokine interleukin 1β (IL-1β) and lipopolysaccharides (LPSs) in human hepatocytes. We show that IL-1β decreases CAR expression and decreases phenobarbital- or bilirubin-mediated induction of CYP2B6, CYP2C9, CYP3A4, UGT1A1, GSTA1, GSTA2, and SLC21A6 messenger RNA. This occurs via nuclear factor kB (NF-kB) p65 activation, which interferes with the enhancer function of the distal glucocorticoid response element that we have identified recently in the CAR promoter. We demostrate that: (1) LPSs, IL-1β, or overexpression of p65Re1A inhibit glucocorticoid receptor (GR)-mediated CAR transactivation; (2) these suppressive effects can be blocked both by pyrrolidine dithiocarbamate, an inhibitor of NF-kB activation, or by overexpression of SRIkBα, a NF-kB repressor; and (3)the GR agonist dexamethasone induces histone H4 acetylation at the proximal CAR promoter region, whereas LPSs and IL-1β inhibit this acetylation as assessed via chromatin immunoprecipitation assay. In conclusion, GR/NF-kB interaction affects CAR gene transcription through chromatin remodeling and provide a mechanistic explanation for the long-standing observation that inflammation and sepsis inhibit drug metabolism while inducing intrahepatic cholestasis or hyperbilirubinemia. Supplementary material for this article can be found on the Hepatology website (http:/interscience.wiley.com/jpages/0270–9139/suppmat/index.html). (Hepatology 2004;40:951-960).

Background The feasibility of laparoscopic rectal resection in patients with mid or low rectal cancer was studied prospectively with regard to quality of mesorectal excision, autonomic pelvic nerve preservation and anal sphincter preservation. Methods Laparoscopic rectal excision was performed in 32 patients (21 men) with rectal carcinoma located 5 cm from the anal verge. Most patients had T3 disease and received preoperative radiotherapy. The surgical procedure was performed 6 weeks after radiotherapy and included total mesorectal excision, intersphincteric resection, transanal coloanal anastomosis with coloplasty and loop ileostomy. Results Three patients needed conversion to a laparotomy. Postoperative morbidity occurred in ten patients, related mainly to coloplasty. Macroscopic evaluation showed an intact mesorectal excision in 29 of 32 excised specimens; microscopically, 30 of the 32 resections were R0. Sphincter preservation was achieved in 31 patients. The hypogastric nerves and pelvic plexuses were identified and preserved in 24 of the 32 patients. Sexual function was preserved in ten of 18 evaluable men. Conclusion A laparoscopic approach can be considered in most patients with mid or low rectal cancer.

International audience; In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non–paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance ≥ 60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level \textless 200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level \textgreater 20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level \textless 200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non–paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance. Liver Transpl 21:512-523, 2015. © 2015 AASLD.

Chronic nephrotoxicity is one of the most serious side-effects of calcineurin inhibitor treatment and a factor in mortality and morbidity after liver transplantation. In our transplant centre, among patients who underwent a liver transplantation between January 1989 and December 2000, 14 liver graft recipients (6.86%) developed de novo severe renal dysfunction as defined by a serum creatinine concentration above 200 micromol/L. Renal biopsy was performed in nine cases and evidenced histological lesions compatible with chronic nephrotoxicity related to calcineurin inhibitor treatment. For nine patients, we report the results of a prospective non-randomized study consisting of cyclosporine or tacrolimus withdrawal associated with administration of mycophenolate mofetil or azathioprine. Despite this therapeutic modification, we did not observe a significant renal function improvement but on the other hand, there was no graft rejection.

Resume Les complications apres DPC, frequentes et graves, sont pour la plupart attribuees a l’activite exocrine du moignon pancreatique qui reste mal connue. Le but de ce travail est d’evaluer l’evolution de la secretion exocrine du pancreas restant dans la periode post operatoire precoce. Patients et methodes : Soixante-quinze patients traites par DPC pour tumeur ont ete inclus dans une etude prospective multicentrique. Lors de la confection de l’anastomose pancreatico-digestive, un catheter etait laisse en place dans le canal pancreatique afin de deriver le suc pancreatique vers l’exterieur. Le volume recueilli ainsi que l’activite amylasique et lipasique etaient mesures quotidiennement. Les meme mesures etaient effectuees au niveau des produits du drainage peripancreatique qui etait systematique. Tous les patients recevaient pendant les 7 premiers jours post operatoires une nutrition parenterale totale et apres randomisation soit un placebo, soit une perfusion continue de Somatostatine-14 (6 mg/24 h de j1 a j6, 3 mg/24 h a j7). La fistule pancreatique a ete definie comme le drainage de plus de 100 cc par jour d’un liquide riche en amylase (plus de 5 fois la limite superieure de la normale pour le plasma) apres le 3e jour post operatoire, persistant apres le 12e jour ou associe a des symptomes ou necessitant un traitement specifique. Resultats : Le debit de suc pancreatique etait quantitativement faible le premier jour suivant l’intervention puis augmentait progressivement pour se stabiliser vers le 5e jour post operatoire. La concentration en amylase dans le suc pancreatique etait tres elevee le premier jour suivant l’intervention. Les concentrations en amylase et lipase dans les produits de drainage etaient elevees pendant les 3 premiers jours ; comme le taux de fistule pancreatique, elles etaient reduites significativement par l’administration de Somatostatine. Conclusions : Dans les premiers jours post operatoires, les secretions du moignon pancreatique sont quantitativement peu abondantes mais tres riches en enzymes avec des fuites enzymatiques vers le peritoine. L’administration de Somatostatine reduit les fuites enzymatiques peripancreatiques.

To evaluate the complications and oncologic and functional results of preoperative radiochemotherapy and sphincter-saving resection for T3 cancers of the lower third of the rectum.Carcinomas of the lower third of the rectum (i.e., located at or below 6 cm from the anal verge) are usually treated by abdominoperineal resection, especially for T3 lesions. Few data are available evaluating concomitant chemotherapy with preoperative radiotherapy for increasing sphincter-saving resection in low rectal cancer.Between 1995 and 1999, 43 patients underwent preoperative radiochemotherapy with conservative surgery for a low rectal tumor located a mean of 4.5 cm from the anal verge (range 2-6); 70% of the lesions were less than 2 cm from the anal sphincter. There were 40 T3 and 3 T4 tumors. Patients received preoperative radiotherapy with a mean dose of 50 Gy (range 40-54) and concomitant chemotherapy with 5-FU in continuous infusion (n = 36) or bolus (n = 7). Sphincter- saving resection was performed 6 weeks after treatment, in 25 patients by using intersphincteric resection. Coloanal anastomoses were associated with a colonic pouch in 86% of the patients, and all patients had a protecting stoma.There were no deaths related to preoperative radiochemotherapy and surgery. Acute toxicity was mainly due to diarrhea, with 54% of grade 1 to 2. Four anastomotic fistulas and two pelvic hematomas occurred; all patients but one had closure of the stoma. Distal and radial surgical margins were respectively 23 +/- 8 mm (range 10-40) and 8 +/- 4 mm (range 1-20) and were negative in 98% of the patients. Downstaging (pT0-2N0) was observed in 42% of the patients (18/43) and was associated with a greater radial margin (10 vs. 6 mm; P =.02). After a median follow-up of 30 months, the rate of local recurrence was 2% (1/43), and four patients had distal metastases. Overall and disease-free survival rates were both 85% at 3 years. Functional results were good (Kirwan continence I, II) in 79% of the available patients (n = 37). They were slightly altered by intersphincteric resection (57 vs. 75% of perfect continence; NS) but were significantly improved by a colonic pouch (74 vs. 16%; P =.01).These results suggest that preoperative radiochemotherapy allowed sphincter-saving resection to be performed with good local control and good functional results in patients with T3 low rectal cancers that would have required abdominoperineal resection in most instances.

Background It remains debatable whether somatostatin can prevent pancreatic fistula and other pancreatic stump-related complications following pancreaticoduodenectomy. This study assessed the effects of somatostatin-14 (S-14) on pancreatic remnant exocrine secretion. Methods This was a double-blind, randomized, placebo-controlled trial in patients undergoing pancreaticoduodenectomy for malignancy. Patients received a continuous infusion of S-14 (n = 38) or placebo (n = 37) for 7 days. Pancreatic juice and peripancreatic drainage fluid was collected and measured, and pancreatic enzymes were monitored daily. Postoperative complications were recorded. Results S-14 infusion was associated with a decrease in median daily pancreatic juice and pancreatic amylase output. Amylase concentration and output in the peripancreatic drain fluid were significantly lower after S-14 infusion than in the control group (both P < 0·05). The incidence of clinical pancreatic fistula (two of 38 versus eight of 37; P < 0·05) and total pancreatic stump-related complications (five of 38 versus 12 of 37; P < 0·05) was lower in patients treated with S-14. Duration of hospital stay was shorter after S-14 (18 versus 26 days; P = 0·01). Conclusion Although the effect of S-14 on exocrine secretion remains difficult to demonstrate, it did reduce pancreatic juice leakage from the pancreatic remnant.

Background After abdominoperineal resection (APR), anorectal reconstruction with dynamic graciloplasty has been proposed to avoid abdominal colostomy and improve quality of life. Graciloplasties involving one or two gracilis muscles with various configurations have been described. The aim of this study was to evaluate morbidity and functional results in a homogeneous series of patients undergoing double dynamic graciloplasty following APR for rectal cancer. Patients and methods From May 1995 to May 1998, 15 patients (ten men and five women; mean age 54 (range 39–77) years) underwent anorectal reconstruction with double dynamic graciloplasty after APR for low rectal carcinoma. All patients had preoperative radiotherapy (45 Gy), 11 with concomitant chemotherapy, eight had intraoperative radiotherapy (15 Gy) and ten received adjuvant chemotherapy for 6 months. The surgical procedure was performed in three stages: APR with coloperineal anastomosis and double graciloplasty (double muscle wrap); implantation of the stimulator 2 months later; and ileostomy closure after a training period. Results There was no operative death. At a mean of 28 (range 3–48) months of follow-up, there was no local recurrence; two patients had lung metastases. Early and late morbidity occurred in 11 patients, mainly related to the neosphincter (12 of 16 complications). The main complication was stenosis of the neosphincter (n = 6), which developed with electrical stimulation. Of 12 patients available for functional outcome, seven were continent, two were incontinent and three had an abdominal colostomy (two for incontinence, one for sepsis). Compared with patients without stenosis, patients with neosphincter stenosis required major reoperations (four versus zero) and had a poor outcome (two of six versus five of six with a good result). Conclusion The double dynamic graciloplasty is associated with a high risk of neosphincter stenosis, which may entail morbidity, reintervention and poor functional results. The stenosis is a heterogeneous feature of the neosphincter induced by asymmetrical traction of both gracilis muscles. It is suggested that single dynamic graciloplasty should be used for anorectal reconstruction after APR.

Background/Aims: Histological and biochemical iron overload has been reported in non-tumoral liver of most patients presenting an hepatocellular carcinoma (HCC) developed in non-cirrhotic liver (NCL). The aim of our study was to investigate HFE mutations in patients with HCC in NCL. Methods: Thirty-five patients with HCC in NCL were included either retrospectively or prospectively. Clinical data, iron and viral status, and HFE gene mutations were compared between groups with (I+, n =19) or without histological iron overload (I−, n =16). Results: Twenty per cent of patients were HBV or HCV positive. Fifty-four per cent had hepatocytic iron overload at histology. Mean hepatic iron concentration was 100.2±14.6 μmol/g in I+ versus 23.2±2.1 μmol/g in I− ( p Conclusions: In patients with HCC in NCL, HBV and HCV markers are rare (20%), and mild iron overload is frequent (54%). In patients with HCC in NCL and iron overload, C282Y mutations are frequent (36.8% of cases) and significantly increased ( p

PURPOSE: Quality of life is altered after abdominoperineal resection, because of permanent iliac colostomy. Psychological rehabilitation is even more difficult after extended abdominoperineal resection to the vagina, because of the loss of both continence and sexual functions. We report the first case of total anorectal and vaginal reconstruction using dynamic graciloplasty and colonic vaginoplasty after extended abdominoperineal resection. METHODS: A 46-year-old female underwent extended abdominoperineal resection with posterior colpectomy for a low rectal adenocarcinoma infiltrating the anal sphincter and vagina. Anorectal reconstruction was performed with coloperineal anastomosis and double dynamic graciloplasty. Vaginal reconstruction was performed using a 10-cm, isolated, rotated sigmoid loop. The procedure was performed in three stages, including abdominoperineal resection with reconstruction, implantation of the stimulator, and closure of the temporary ileostomy. RESULTS: Resting and electrostimulated pressures of the neosphincter were 40 and 110 cm H2O respectively. Continence was achieved for formed stools two months after closure of the stoma, with spontaneous defecations (30–90 minutes). The patient experienced regular sexual activity six months after closure of the stoma. CONCLUSION: This new original technique can be proposed in selected young females after extended abdominoperineal resection, to preserve continence, sexual activity, and body image.

A 30-year-old man with presinusoidal portal hypertension was transplanted for cryptogenic cirrhosis. On the explanted liver, few intrahepatic stones, biliary cirrhosis, chronic cholangitis of the large bile ducts and a peculiar proliferation of small dilated bile ducts at the periphery of the portal tracts led to the diagnosis of secondary biliary cirrhosis and cholangitis, possibly linked to ductal plate malformation, including congenital hepatic fibrosis associated with a minor form of Caroli's disease. Ex vivo portogram and histology showed the paucity of portal vein branches and the hypertrophy of the peribiliary vascular plexus. This hypertrophy, which has been reported in livers with presinusoidal hypertension, is another indirect argument to suggest the diagnosis of congenital hepatic fibrosis.

Background The most important surgical complication following rectal resection with anastomosis is symptomatic anastomotic leakage, which is associated with a 6–22 per cent mortality rate. The aim of this retrospective study was to evaluate the risk factors for clinical anastomotic leakage after anterior resection for cancer of the rectum. Methods From 1980 to 1995, 272 consecutive anterior resections for rectal cancer were performed by the same surgical team; 131 anastomoses were situated 5 cm or less from the anal verge. The associations between clinical anastomotic leakage and 19 patient-, tumour-, surgical- and treatment-related variables were studied by univariate and multivariate analysis. Results The rate of clinical anastomotic leakage was 12 per cent (32 of 272). Multivariate analysis of the overall population showed that only male sex and level of anastomosis were independent factors for development of anastomotic leakage. The risk of leakage was 6·5 times higher for anastomoses situated less than 5 cm from the anal verge than for those situated above 5 cm; it was 2·7 times higher for men than for women. In a second analysis of low anastomoses (5 cm or less from the anal verge; n = 131), obesity was statistically associated with leakage. Conclusion A protective stoma is suitable after sphincter-saving resection for rectal cancer for anastomoses situated at or less than 5 cm from the anal verge, particularly for men and obese patients.

Hepatocellular carcinoma treated by sorafenib with complete radiological response according to mRECIST criteria: Could we stop the treatment? About four cases

Background/Aims: Currently, surgical treatment of hepatocellular carcinoma in patients with cirrhosis is not clearly defined. The objective of this study was, in patients with cirrhosis with hepatocellular carcinoma, to compare liver resection to transplantation assessed by patient survival and to determine whether the tumor recurrence might be influenced by prognostic factors. Methods: We have gathered all the available data from six French Medical Universities, for 215 patients with cirrhosis with hepatocellular carcinoma surgically treated either by liver resection (102) or by transplantation (113). Results: The overall 5-year survival rate was similar in the transplantation group and in the resection group (32% vs. 31%, p 0.7). However, the 5-year survival rate without recurrence was higher in the transplantation group than in the resection group (60% vs. 14%, p p p p Conclusions: These results and this prognostic index are encouraging for liver transplantation as treatment of hepatocellular carcinoma in selected patients with cirrhosis.

Background The aim of this retrospective study was to compare the risk of local recurrence between two groups of patients with low rectal cancer treated by either abdominoperineal resection (APR) or anterior resection. Methods From 1982 to 1992, 106 low rectal cancers (tumour situated 3–8 cm from the anal verge), of Dukes stage B and C were treated by curative surgery, 52 by APR and 54 by anterior resection. Mean follow-up was 60 months after APR and 50 months after anterior resection. Results The local recurrence rate of low rectal cancer was 16 of 52 (31 per cent) after APR and 15 of 54 (28 per cent) after anterior resection. The risk of local recurrence in univariate and multivariate analysis was not associated with clinical and histological variables, nor with the type of intervention. Conclusion Sphincter-saving resection can be performed for low rectal cancer without an increased risk of local recurrence.

In Europe and North America, hepatocellular adenomas (HCA) occur, classically, in middle-aged woman taking oral contraceptives. Twenty percent of women, however, are not exposed to oral contraceptives; HCA can more rarely occur in men, children, and women over 65 years. HCA have been observed in many pathological conditions such as glycogenosis, familial adenomatous polyposis, MODY3, after male hormone administration, and in vascular diseases. Obesity is frequent particularly in inflammatory HCA. The background liver is often normal, but steatosis is a frequent finding particularly in inflammatory HCA. The diagnosis of HCA is more difficult when the background liver is fibrotic, notably in vascular diseases. HCA can be solitary, or multiple or in great number (adenomatosis). When nodules are multiple, they are usually of the same subtype. HNF1α-inactivated HCA occur almost exclusively in woman. The most important point of the classification is the identification ofβ-catenin mutated HCA, a strong argument to identify patients at risk of malignant transformation. Some HCA already present criteria indicating malignant transformation. When the whole nodule is a hepatocellular carcinoma, it is extremely difficult to prove that it is the consequence of a former HCA. It is occasionally difficult to identify HCA remodeled by necrosis or hemorrhage.

We examined 41 consecutive cirrhotic liver explants from French patients for the presence of nodules of adenomatous hyperplasia (AH) and then analyzed these lesions, together with underlying cirrhosis (C) and associated hepatocellular carcinoma (HCC), for various histological parameters, cellular density, and proliferative activity. Thirty-five AHs were identified in 10 livers (prevalence, 24%); seven of 10 were HCV positive. Hepatocellular carcinoma was more frequent in patients with AH than in patients without. The AHs consisted of 17 ordinary (OAH) and 18 atypical (AAH) adenomatous hyperplasia lesions. There was a malignant focus in five of the 18 AAHs. Wide areas of large liver cell dysplasia were frequent in OAH but never found in AAH. Obvious steatosis was frequent in HCC but exceptional in AAH and absent in OAH. There was a significant increase in cellular density in AAH and HCC as compared with C and OAH. Proliferative cell nuclear antigen immunostaining similarly showed an increase in proliferation from OAH or C to AAH and HCC. These data suggest that, in Europe as in Japan, one pathway of hepatocarcinogenesis is a multistep process in which AAH should be considered as a premalignant lesion very close to grade I HCC, while OAH seems to correspond to a regenerative nodule with limited proliferative ability.

Patient: A patient, born in 1955, presented with episodes of documented variceal bleeding in 1978 due to portal hypertension. Liver function tests were normal. An end-to-side portacaval shunt was performed in 1980. The liver was reported to be macroscopically subnormal. A liver biopsy was interpreted as'incomplete cirrhosis'without inflammation. Results: Six years later, the patient developed a voluminous tumour (9.5 cm in diameter) occupying the entire right liver lobe. Surgical removal of the tumour was necessary since it was a large hepatocellular adenoma with a possibility of fatal uncontrollable haemorrhage and eventual malignant transformation. In the non-tumoral liver, the parenchyma showed varying abnormalities with the characteristic features of idiopathic portal hypertension

We took advantage of the reported genotype/phenotype classification to analyze our surgical series of hepatocellular adenoma (HCA). The series without specific known etiologies included 128 cases (116 women). The number of nodules varies from single,5, andor=5 in 78, 38, and 12 cases, respectively. The resection was complete in 95 cases. We identified 46 HNF1alpha-inactivated HCAs (44 women), 63 inflammatory HCAs (IHCA, 53 women) of which nine were also beta-catenin-activated, and seven beta-catenin-activated HCAs (all women); six additional cases had no known phenotypic marker and six others could not be phenotypically analyzed. Twenty-three of 128 HCAs showed bleeding. No differences were observed in solitary or multiple tumors in terms of hemorrhagic manifestations between groups. In contrast, differences were observed between the two main groups. Steatosis (tumor), microadenomas (resected specimen), and additional benign nodules were more frequently observed in HNF1alpha-inactivated HCAs (P0.01) than in IHCAs. Body mass index25, peliosis (tumor), and steatosis in background liver were more frequent in IHCA (P0.01). After complete resection, new HCAs in the centimetric range were more frequently found during follow-up (1 year) in HNF1alpha-inactivated HCA. After incomplete resection (HCA left in nonresected liver), the majority of HCA remained stable in the two main groups and even sometimes regressed. Six patients of 128 developed hepatocellular carcinoma (HCC) (all were beta-catenin-activated, whether inflammatory or not).There were noticeable clinical differences between HNF1alpha-inactivated HCA and IHCA; there was no increased risk of bleeding or HCC related to the number of HCAs; beta-catenin-activated HCAs are at higher risk of HCC. As a consequence, we believe that management of HCA needs to be adapted to the phenotype of these tumors.

We present 2 cases of hepatocyte nuclear factor 1alpha (HNF1alpha)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities.

Liver sinusoids are special capillaries that are limited by fenestrated endothelial cells, without a genuine basement membrane, surrounded by perisinusoidal cells storing vitamin A, and harbouring Kupffer cells and pit cells, resident macrophages, and large granular lymphocytes, respectively. Each nonparenchymal cell and parenchymal cell of the liver interacts with all others and with the extracellular matrix. Therefore, the functional ability of each cell is constantly being modified by the metabolic activity of the others. Human liver biopsies (132), needle or surgical, perfusion-fixed with glutaraldehyde and processed for transmission electron microscopy (TEM), and occasionally for scanning electron microscopy (SEM), were examined. The study included liver diseases (such as alcoholic liver diseases, benign and malignant liver tumors, cholestasis of various origins, fulminant hepatitis, acute rejection after orthotopic liver transplantation, Budd-Chiari syndrome), as well as general or extrahepatic diseases (such as diabetes, hemochromatosis, hypervitaminosis A, various hematological disorders), and normal controls. Ultrastructural abnormalities are described and illustrated under two different headings: 1) elementary lesions of sinusoidal cells (endothelial, Kupffer, perisinusoidal and pit cells), nonsinusoidal cells (in the space of Disse and/or in the lumen), the extracellular matrix; and 2) the major pathological entities including perisinusoidal fibrosis, capillarization of sinusoids, sinusoidal dilatation, and peliosis. In the discussion, an overview of the major abnormalities reported in the literature is presented, and some specific questions regarding 1) perisinusoidal fibrosis in liver with normal histology, 2) the overload of perisinusoidal cells with lipids in non-hypervitaminosis A intoxication and 3) the etiological relationship of sinusoidal dilatation, peliosis, perisinusoidal fibrosis, or sinusoidal tumors with drugs and toxic compounds are discussed. In the event that lesions are not specific to any diagnosis, the knowledge of the ultrastructure of sinusoids is extremely useful from the perspective of the liver as an ecosystem.

Unmyelinated nerve fibres are visible in the human hepatic lobule. They extend through the Disse space, surrounded by Schwann cell processes, often close to perisinusoidal cell processes. A few bare nerve endings or varicosities are found contiguous to either hepatocytes or perisinusoidal cells. These nerve endings or varicosities contain large and small granular vesicles and small clear vesicles. This heterogeneity probably corresponds to the presence of various neurotransmitters (noradrenaline, acetylcholine, various neuropeptides...). The effect of nerves on perisinusoidal cells has not yet been elucidated. However, the location, shape, morphology and origin of perisinusoidal cells would suggest that they play a role in the hemodynamic regulation of sinusoidal blood flow. It has recently been shown how important non-parenchymal-parenchymal communication is in the action of nerves on glucose release by hepatocytes; the cell to cell communications may also apply to nerves and sinusoidal cells for the hemodynamic regulation of sinusoidal blood flow.

Background High rates of conversion to open operation and morbidity have been reported after laparoscopic total mesorectal excision (TME) with sphincter preservation for rectal cancer. This study examined risk factors for conversion and morbidity to determine which patients with rectal cancer could benefit from a laparoscopic resection. Methods Two hundred patients (117 men) with mid and low rectal cancer treated by laparoscopic TME were studied. The impact of clinical and pathological characteristics on conversion and complications was assessed by multivariable analysis. Results Reconstruction after TME included 79 low colorectal and 121 coloanal anastomoses. Conversion was necessary in 31 patients (15·5 per cent), and was independently associated with sex, type of anastomosis and intraoperative rectal fixity. Postoperative morbidity in 50 patients (25·0 per cent) was independently associated with sex and type of anastomosis. Men with a stapled anastomosis had a threefold higher rate of conversion (13 (34 per cent) of 38 versus 18 (11·1 per cent) of 162; P < 0·001) and morbidity (22 (58 per cent) versus 28 (17·3 per cent); P < 0·001) than other patients. Conclusion Laparoscopic TME is a good option for women and for men treated by coloanal anastomosis. Technical improvement of laparoscopic stapling is needed before the laparoscopic approach can be offered to all patients.

Hepatocellular adenomas (HCA) with activated -catenin present a high risk of malignant transformation. To permit robust routine diagnosis to allow for HCA subtype classification, we searched new useful markers. We analyzed the expression of candidate genes by quantitative reverse transcription polymerase chain reaction QRT-PCR followed by immunohistochemistry to validate their specificity and sensitivity according to hepatocyte nuclear factor 1 alpha (HNF1) and -catenin mutations as well as inflammatory phenotype. Quantitative RT-PCR showed that FABP1 (liver fatty acid binding protein) and UGT2B7 were downregulated in HNF1-inactivated HCA (P < 0.0002); GLUL (glutamine synthetase) and GPR49 overexpression were associated with -catenin–activating mutations (P < 0.0005), and SAA2 (serum amyloid A2) and CRP (C-reactive protein) were upregulated in inflammatory HCA (P 0.0001). Immunohistochemistry validation confirmed that the absence of liver-fatty acid binding protein (L-FABP) expression rightly indicated HNF1 mutation (100% sensitivity and specificity), the combination of glutamine synthetase overexpression and nuclear -catenin staining were excellent predictors of-catenin–activating mutation (85% sensitivity, 100% specificity), and SAA hepatocytic staining was ideal to classify inflammatory HCA (91% sensitivity and specificity). Finally, a series of 93 HCA was unambiguously classified using our 4 validated immunohistochemical markers. Importantly, new associations were revealed for inflammatory HCA defined by SAA staining with frequent hemorrhages (P 0.003), telangiectatic phenotype (P < 0.001), high body mass index, and alcohol intake (P < 0.04). Previously described associations were confirmed and in particular the significant association between -catenin–activated HCA and hepatocellular carcinomas (HCC) at diagnosis or during follow-up (P < 10 -5 ). Conclusion: We refined HCA classification and its phenotypic correlations, providing a routine test to classify hepatocellular adenomas using simple and robust immunohistochemistry. (HEPATOLOGY 2007;46:740-748.)

We report the imaging of a localized fibrous tumor of the liver, focusing on color Doppler US, CT, MR imaging, and angiographic findings. We discuss the differential diagnosis of such a rare, benign lesion of the liver. Detailed imaging of this tumor has not been reported in the literature previously.

Although the liver is a frequent site for tumor metastases, the mechanisms for the development of liver metastases differ based on the location of the primary tumor site. In patients with primary tumors of the gastrointestinal tract (colorectal adenocarcinoma and gut-associated endocrine tumors), the most likely mode of spread to the liver is through portal venous drainage or via direct intraabdominal lymphatic channels. The rationale for liver resection in these cases is that the majority of the patient's tumor burden may be confined to the abdomen. Therefore, adequate treatment of the primary tumor combined with liver resection may provide a chance for cure. This rationale has proven to be correct for colorectal liver metastases, where 5-year survivals are routinely reported to be 40% and 10-year survivals as high as 25% have been documented.1–5 In contrast, most other liver metastases originate from tumors outside of the intraabdominal cavity. Most commonly, metastases from these tumors reach the liver via the systemic circulation, implying that extrahepatic sites may have an equal probability of being involved. Based on this rationale, hepatic resection of noncolorectal liver metastases has been approached with caution. Many of the first reports to examine outcomes for patients with noncolorectal liver metastases treated with hepatic resection included patients with both endocrine and nonendocrine metastases6–15 (Table 1). These analyses demonstrated that patients with endocrine metastases were a unique group with a better prognosis than patients with noncolorectal nonendocrine metastases. Several subsequent studies on this topic have accounted for these survival differences and have excluded patients with endocrine metastases.16–23 TABLE 1. Review of Reports Describing Patients With Noncolorectal Liver Metastases Treated With Hepatic Resection These studies have suggested that hepatic resection is safe and approximately as effective as hepatic resection for colorectal liver metastases, with reported 5-year survivals between 30% and 40% (Table 1). Although these data have contributed to our understanding of the natural history of these diseases and their responses to surgical therapy, the efficacy of liver surgery for patients with noncolorectal nonendocrine metastases has remained unclear because of the heterogeneity of primary tumor types, the frequent inclusion of patients with endocrine tumor metastases, and the limited numbers of patients reported. To minimize the limitations of previous studies, our study was designed to analyze the outcomes for a large number of patients with noncolorectal nonendocrine metastases treated with hepatic resection at multiple centers. Overall survivals in this cohort were determined and analysis of prognostic factors was robust enough to create a risk-model for prognosis that may be helpful in selecting patients for resection.

Background/Aims Hepatic undifferentiated (embryonal) sarcoma (HUS) is an exceptional hepatic malignant tumor in adults. Genetic studies were never reported in adult cases. Methods In this study concerning three cases of HUS occurring in adult, we studied the three classical ways of carcinogenesis i.e. the TP53 (p53), Wnt (CTNNB1/β-catenin and AXIN1) and telomerase (hTERT) pathways. We studied the expression of p53, β-catenin and telomerase catalytic subunit hTERT by immunohistochemistry in the three cases; we determined TP53 gene mutation in two cases and the genome-wide allelotype, AXIN1, and CTNNB1/β-catenin gene mutation in one case. Results Immunohistochemistry showed an overexpression of p53 in more than 80% of tumoral cells; furthermore, mutations of TP53 were observed in two cases, involving the sequence-specific DNA binding domain. In contrast, no mutation was found in CTNNB1/β-catenin and AXIN1 genes. Tumoral cells did not show hTERT staining nor nuclear expression of β-catenin. In addition, allelotype analysis in one case showed loss of heterozygosity of chromosome 7p, 11p, 17p, 22q, and allelic imbalance of 1p, 8p, 20q. Conclusions In this report of HUS in three adult patients, we emphasize the role of TP53 pathway in carcinogenesis of this rare tumor. This point could be of interest for therapeutic strategies.