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Supplementary Tables 1-7 from Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Background Liver resection is a well-established treatment for colorectal, neuroendocrine and sarcomatous metastases but remains ill-defined for metastases from other primary sites. This study aimed to analyze the outcomes of hepatic resection for metastases not of colorectal, neuroendocrine, sarcomatous, or ovarian (NCNSO) origin and to identify predictors of outcome. Methods Retrospective analysis of patients undergoing resection for NCNSO metastases in three western centers. Patients were analyzed according to the primary cancer. Outcomes were recurrence and survival. Results We analyzed 188 patients, divided in: gastrointestinal (59), breast (59) and “others” (70). Median time to recurrence was 15.3 months, while median survival was 52 months. Survival at 1, 3, and 5 years was 78%, 60.4% and 47.8%, respectively. In term of prognostic factors, metastases >35 mm from gastrointestinal tumors were associated with lower survival (p = 0.029) and age>60 years was associated with better survival in breast metastases (p = 0.018). Conclusions Liver resection for NCNSO metastases is feasible and results in long-term survival are similar to colorectal metastases. In gastrointestinal metastases, size (

Background. We report the histopathological results of a novel ‘‘inversed’’ strategy designed to manage patients with colorectal cancer (CRC) who have synchronous liver metastases by using chemotherapy first, liver surgery second, and resection of the primary tumor as a final step. This study was designed to compare the response to chemotherapy in liver metastases, primary tumors, and locoregional lymph nodes. Methods. Twenty-nine patients with stage IV CRC received a combination of oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin (OCFL) for 3–4 months. Histological response to chemotherapy was assessed by using a tumor regression grading (TRG) score based on presence of residual tumor cells and extent of fibrosis. Results. Median age of patients was 56 (range, 37–69) years. Primary tumor location was right colon ( n= 5), left colon ( n= 7), and rectum ( n= 17 patients). TRG scores correlated across disease sites (Spearman correlation coefficients for TRG in the primary tumor and lymph nodes was 0.59 [ P= 0.005]; for the primary tumor and metastases 0.44 [ P= 0.021]; and for lymph nodes and metastases 0.58 [ P= 0.006]). Complete absence or poor tumor response (TRG4/5) was significantly more frequent in primary tumors (35.7%) and locoregional lymph nodes (38%) than in liver metastases (6.9%; McNemar test, P= 0.02). Two patients had a complete pathologic response (pT0N0M0). Conclusions. In patients with stage IV colorectal cancer, liver metastases exhibit a better histological response than primary tumors to OCFL neoadjuvant chemotherapy.

Summary: Since PEI is a treatment based on imaging techniques, the radiologist should be familiar with the various findings that may be observed after PEI on US, CT, and MR images immediately after treatment and during later follow-up. Although US is well suited for performing PEI, contrast-enhanced CT currently is the most commonly used imaging method to evaluate the effect of PEI. Residual, nodular areas of contrast enhancement correlate well with residual tumor and warrant additional treatment. Although the findings on MR images obtained after PEI are more complex, MR imaging may be used as an alternative to CT

Objective: The purpose of the study was to analyze clinical presentation, surgical management, and long-term outcome of patients suffering from biliary diverticulum, namely Todani type II congenital bile duct cyst (BDC). Background: The disease incidence ranges between 0.8% and 5% of all reported BDC cases with a lack of information about clinical presentation, management, and outcome. Methods: A multicenter European retrospective study was conducted by the French Surgical Association. The patients' medical records were included in a Web site database. Diagnostic imaging studies, operative and pathology reports underwent central revision. Results: Among 350 patients with congenital BDC, 19 type II were identified (5.4%), 17 in adults (89.5%) and 2 in children. The biliary diverticulum was located at the upper, middle, and lower part of the extrahepatic biliary tree in 11, 4, and 4 patients (58%, 21%, and 21%, respectively). Complicated presentation occurred in 6 patients (31.6%), including one case of synchronous carcinoma. Surgical techniques included diverticulum excision in all patients. Associated resection of the extrahepatic biliary tree was required in 11 cases (58%) and could be predicted by the presence of complicated clinical presentation. There was no mortality. Long-term outcome was excellent in 89.5% of patients (median follow-uptime: 52 months). Conclusions: According to the present largest Western series of Todani type II BDC, the type of clinical presentation rather than BDC location, was able to guide the extent of biliary resection. Excellent long-term outcome can be achieved in expert centers.

Background: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. Patients and methods: A large series of surgically resected liver metastases (n = 153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (α-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. Results: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. Conclusions: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990-12/2011, medium follow-up 7.9 yr). One-, five-, and 10-yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26-fold) and early HAT (48 yr (increase 1.09-fold) and MELD score >30 (increase 1.2-fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary-enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.

Liver resection is generally restricted to patients without clinically significant portal hypertension (Hepatic Venous Pressure Gradient - HVPG - ⩽10mmHg) and several teams perform transjugular HVPG measurements as part of the pre-operative work-up. The present study investigates whether a non-invasive Computed Tomography (CT)-based assessment could be as accurate as the invasive transjugular measurement.A cohort of patients with hepatocellular carcinoma (HCC) treated by resection (n=36) or transplantation (n=39) was selected (mean age: 61±9.2years, male/female ratio: 4/1). Pre-operative CTs were read by two independent investigators, and potential CT-based HVPG predictors were compared to the transjugular HVPG measurements. A validation was conducted on another cohort of 70 non-surgical patients.The invasive HVPG values were significantly correlated to liver/spleen volume ratio, spleen volume, platelet count, and peri-hepatic ascites (p0.001), which all showed high inter-observer agreements (intra-class correlation coefficients ⩾0.927, Kappa ⩾0.945). The presence of a HVPG10mmHg was best predicted by the liver/spleen volume ratio (AUC: 0.883 [0.805-0.960]) and the peri-hepatic ascites (p0.001). These two variables were combined into an accurate model for predicting HVPG10mmHg (AUC: 0.911 [0.847-0.975]), with sensitivity, specificity, and positive and negative predictive values of 92%, 79%, 91%, and 81%. The model was also accurate in the validation cohort with an AUC of 0.820 [0.719-0.921]. The computed formula was:The proposed CT-based model showed a high accuracy in the prediction of HVPG and, if further confirmed by prospective validation, could replace the invasive transjugular assessment in patients not requiring a biopsy of the non-tumoral liver.

SummaryThe vascular anatomy of the liver can be described at three different levels of complexity according to the use that the description has to serve. The first – conventional – level corresponds to the traditional 8-segments scheme of Couinaud and serves as a common language between clinicians from different specialties to describe the location of focal hepatic lesions. The second – surgical – level, to be applied to anatomical liver resections and transplantations, takes into account the real branching of the major portal pedicles and of the hepatic veins. Radiological and surgical techniques exist nowadays to make full use of this anatomy, but this requires accepting that the Couinaud scheme is a simplification, and looking at the vascular architecture with an unprejudiced eye. The third – academic – level of complexity concerns the anatomist, and the need to offer a systematization that resolves the apparent contradictions between anatomical literature, radiological imaging, and surgical practice. Based on the real number of second-order portal branches that, although variable averages 20, we submit a system called the “1-2-20 concept”, and suggest that it fits best the number of actual – as opposed to idealized – anatomical liver segments.

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/m2 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.

Robotic surgery is an emerging technique for the management of patients with liver disease, and only a limited number of reports are available. A systematic search of electronic databases (PubMed, Embase and Cochrane), including only case series with more than five patients, identified nine series (with one from our institution), which totaled to 232 patients. Overall, the peri-operative outcomes of the reported patients are similar to those utilizing the laparoscopic and open approaches. Robotic surgery appears to be a valid option for selected hepatic resections in experienced hands. It could represent a bridge toward minimally invasive approaches for confirmed liver surgeons. By contrast, the long-term oncological outcomes remain uncertain and need further studies.

Hepatic ischemia/reperfusion (I/R) injury is a common clinical challenge. Despite accumulating evidence regarding its mechanisms and potential therapeutic approaches, hepatic I/R is still a leading cause of organ dysfunction, morbidity, and resource utilization, especially in those patients with underlying parenchymal abnormalities. In the oncological setting, there are growing concerns regarding the deleterious impact of I/R injury on the risk of post-surgical tumor recurrence. This review aims at giving the last updates regarding the role of hepatic I/R and liver parenchymal quality injury in the setting of oncological liver surgery, using a "bench-to-bedside” approach. Relevant medical literature was identified by searching PubMed and hand scanning of the reference lists of articles considered for inclusion. Numerous preclinical models have depicted the impact of I/R injury and hepatic parenchymal quality (steatosis, age) on increased cancer growth in the injured liver. Putative pathophysiological mechanisms linking I/R injury and liver cancer recurrence include an increased implantation of circulating cancer cells in the ischemic liver and the upregulation of proliferation and angiogenic factors following the ischemic insult. Although limited, there is growing clinical evidence that I/R injury and liver quality are associated with the risk of post-surgical cancer recurrence. In conclusion, on top of its harmful early impact on organ function, I/R injury is linked to increased tumor growth. Therapeutic strategies tackling I/R injury could not only improve post-surgical organ function, but also allow a reduction in the risk of cancer recurrence.

Background: Central pontine and extrapontine myelinolysis (CPEPM) is a rare but potentially fatal complication after orthotopic liver transplantation (OLT). The aim of this study was to identify risk factors for development of CPEPM after OLT and to assess patient outcome. Methods: We reviewed the clinical data of 1,378 patients who underwent OLT between 1987 and 2009 in Geneva, Switzerland and Edmonton, Canada. Nineteen patients (1.4%) developed CPEPM. We compared their characteristics with control patients, matched by age, gender, date of OLT, and MELD score. Results: The 19 patients with CPEPM (7F, mean age 52.1±2years) had a mean MELD score of 26±2.2. Before OLT, patients who develop CPEPM presented more frequently low (2 of these conditions were strongly associated with CPEPM (p=0.00015). Mortality at 1 year of patients developing CPEPM was higher (63 vs. 13%, p

We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy.CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear.Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases.A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively).TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment.

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.

Obesity is associated with poor health outcomes in the general population, but the evidence surrounding the effect of body mass index (BMI) on postliver transplantation survival is contradictory. The aim of this study was to assess the impact of wait list BMI and BMI changes on the outcomes after liver transplantation. Using the Scientific Registry of Transplant Recipients, we compared survival among different BMI categories and examined the impact of wait list BMI changes on post-transplantation mortality for patients undergoing liver transplantation. Cox proportional hazards multivariate regression was carried out to adjust for confounding factors. Among 38 194 recipients, underweight patients had a poorer survival compared with normal weight (HR = 1.3, 95% CI: 1.13-1.49). Conversely, overweight and mildly obese men experienced better survival rates compared with their lean counterparts (HR = 0.9, 95% CI: 0.84-0.96, and HR = 0.86, 95% CI: 0.79-0.93 respectively). Female patients gaining weight over 18.5 kg/m(2) while on the wait list showed improving outcomes (HR = 0.46, (95% CI: 0.28-0.76)) compared with those remaining underweight. This study supports the harmful impact of underweight on postliver transplant survival, and highlights the need for a specific monitoring and management of candidates with BMIs close to 18.5 kg/m(2) . Obesity does not constitute an absolute contraindication to liver transplantation.

International audience; BACKGROUND:Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation.METHODS:A retrospective cross-sectional study, from 27 European high-volume HPB units.RESULTS:573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients.DISCUSSION:Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered.

Contains fulltext : 171468pub.pdf (Publisher’s version ) (Open Access) Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care.

Low-molecular-weight heparin (LMWH) has been suggested to reduce the risk of cancer progression in both preclinical and clinical studies but the underlying mechanisms remain poorly explored. The aim of the study was to investigate the anti-metastatic role of enoxaparin, a clinically-used LMWH, in a murine model of colon cancer and to explore its underlying mechanisms.Using a reproducible mouse model of colon carcinomas, we assessed the capacity of enoxaparin, a LMWH, to affect tumor metastasis of colon carcinoma cell lines in mice.The hepatic growth of colon carcinoma metastases was strongly inhibited by enoxaparin compared to (Ctrl) group (p=0.001). This effect was associated to an inhibition of heparanase mRNA expression and protein production both in vivo and in vitro. In addition, enoxaparin inhibited the liver and serum production of interferon gamma (Ifnγ)-inducible chemokine receptor ligands. Overexpression of heparanase prompted proliferation, migration and growth of colon carcinoma in vitro and in vivo to a point that was not affected by enoxaparin in vivo anymore.Enoxaparin decreased liver metastases in a mouse model of colon carcinoma. These results suggest that enoxaparin may benefit patients with cancer and deserves further laboratory and clinical investigations.

The aim of the present study was to assess the efficiency of cell-based immune assays in the detection of alloreactivity after islet transplantation and to correlate these results with clinical outcome. Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients ( n = 14), donors, or third party. The immune reactivity was assessed by the release of IFN-γ (ELISpot), cell proliferation (FACS analysis for Ki67), and cytokine quantification (Bioplex). Islet function correlated with the number of IFN-γ-secreting cells following incubation with donor cells ( p = 0.007, r = –0.50), but not with third party cells ( p = 0.61). Similarly, a high number of donor-specific proliferating cells was associated with a low islet function ( p = 0.006, r = −0.51). Proliferating cells were mainly CD3+CD4+ lymphocytes and CD3-CD56+ natural killer cells (with low levels of CD3+CD8+ lymphocytes). Patients with low islet function had increased levels of CD4+Ki67+cells ( p ≤ 0.0001), while no difference was observed in CD8+Ki67+ and CD56+Ki67+ cells. IFN-γ, IL-5, and IL-17 levels were increased in patients with low islet function, but IL-10 levels tended to be lower. IFN-γ-ELISpot, proliferation, and cytokines were similarly accurate in predicting clinical outcome (AUC = 0.77 ± 0.088, 0.85 ± 0.084, and 0.88 ± 0.074, respectively). Cellular immune reactivity against donor cells correlates with posttransplant islet function. The tested assays have the potential to be of substantial help in the management of islet graft recipients and deserve prospective validation.

BACKGROUND. Surgical strategy for hilar cholangiocarcinoma often includes hepatectomy, but the role of portal vein resection (PVR) remains controversial. In this study, the authors sought to identify factors associated with outcome after surgical management of hilar cholangiocarcinoma and examined the impact of PVR on survival.Three hundred five patients who underwent curative-intent surgery for hilar cholangiocarcinoma between 1984 and 2010 were identified from an international, multi-institutional database. Clinicopathologic data were evaluated using univariate and multivariate analyses.Most patients had hilar cholangiocarcinoma with tumors classified as T3/T4 (51.1%) and Bismuth-Corlette type II/III (60.9%). Resection involved extrahepatic bile duct resection (EHBR) alone (26.6%); or hepatectomy and EHBR without PVR (56.7%); or combined hepatectomy, EHBR, and PVR (16.7%). Negative resection (R0) margin status was higher among the patients who underwent hepatectomy plus EHBR (without PVR, 64.2%; with PVR, 66.7%) versus EHBR alone (54.3%; P.001). The median number of lymph nodes assessed was higher among the patients who underwent hepatectomy plus EHBR (without PVR, 6 lymph nodes; with PVR, 4 lymph nodes) versus EHBR alone (2 lymph nodes; P.001). The 90-day mortality rate was lower for patients who underwent EHBR alone (1.2%) compared with the rate for patients who underwent hepatectomy plus EHBR (without PVR, 10.6%, with PVR, 17.6%; P.001). The overall 5-year survival rate was 20.2%. Factors that were associated with an adverse prognosis included lymph node metastasis (hazard ratio [HR], 1.79; P = .002) and R1 margin status (HR, 1.81; P.001). Microscopic vascular invasion did not influence survival (HR, 1.23; P = .19). Among the patients who underwent hepatectomy plus EHBR, PVR was not associated with a worse long-term outcome (P = .76).EHBR alone was associated with a greater risk of positive surgical margins and worse lymph node clearance. The current results indicated that hepatectomy should be considered the standard treatment for hilar cholangiocarcinoma, and PVR should be undertaken when necessary to extirpate all disease. Combined hepatectomy, EHBR, and PVR can offer long-term survival in some patients with advanced hilar cholangiocarcinoma.

Background. Kaposi’s sarcoma (KS) in transplant recipients is about 400 to 500 times rate in the general population. It is strongly associated to Human herpesvirus-8 (HHV-8) infection which has been found in 95% of KS lesions. The optimal approach to managing posttransplantation KS is to reduce or discontinue immunosuppressive therapy but this strategy carries a risk of the acute rejection of the graft. Recently, the use of an mTOR inhibitor has added new opportunities for KS treatment and prevention.Case Report. We report a case of 24 years-old Turkish woman with visceral HHV-8-associated Kaposi's sarcoma after orthotopic liver transplantation.Conclusion. Posttransplantation KS is considered an experimental model of virus induced tumor suggesting the usefulness of HHV-8 screening in transplant recipient and donor. Therapeutic approaches are complex and require a multidisciplinary team.

IntroductionHydatid liver cysts can rupture into neighboring structures in 15–60% of patients, and most often involves the bile duct, the bronchi, and the peritoneal/pleural cavities. Rarely, chest or abdominal wall involvement occurs that are challenging to manage. This case report and literature review describes the management of patients with chest wall and rib invasion.Presentation of caseA 74-year-old woman, of Spanish origin, presented with right upper quadrant abdominal pain and tender localized swelling. On computer tomography (CT) assessment, the rupture of a hydatid cyst into the right anterior chest wall was identified. Partial involvement of the 10th and 11th rib were noted. The diagnosis was confirmed by a serological test. Surgical treatment involved a radical en bloc right hepatic resection together with resection of the involved ribs, diaphragm and subcutaneous tissue. Primary diaphragm and wall closures were performed. The postoperative course was uneventful with three weeks of albendazole treatment. CT follow-up at six months demonstrated the absence of recurrence.DiscussionComplete resection is the gold standard treatment of patients with hydatid cysts with the aim to remove all parasitic and pericystic tissues.ConclusionThe present report illustrates that an aggressive surgical en bloc resection is feasible and should be preferred for the treatment of hydatid cysts with rupture into the chest wall, even when the ribs are involved.

BACKGROUND: Resection of hepatic metastases is indicated in selected stage IV colorectal cancer (CRC) patients. A minority will eventually develop pulmonary metastases and may undergo lung surgery with curative intent. The aims of the present study were to assess clinical outcome and identify parameters predicting survival after pulmonary metastasectomy in patients who underwent prior resection of hepatic CRC metastases.¦METHODS: We performed a retrospective analysis of 27 consecutive patients (median age 62 years; range: 33-75 years) who underwent resection of pulmonary metastases after previous hepatic metastasectomy from CRC in two institutions from 1996 to 2009. All patients underwent complete resection (R0) for both colorectal and hepatic metastases.¦RESULTS: Median follow-up was 32 months (range: 3-69 months) after resection of lung metastases and 65 months (range: 19-146 months) after resection of primary CRC. Three- and 5-year overall survival rates after lung surgery were 56 and 39%, respectively, and median survival was 46 months (95% CI 35-57). Median disease-free survival after pulmonary metastasectomy was 13 months (95% CI 5-21). At the time of last follow-up, seven patients (26%) had no evidence of recurrent disease and 6 of these 7 patients presented initially with a single lung metastasis.¦CONCLUSIONS: Resection of lung metastases from CRC patients may result in prolonged survival, even after previous hepatic metastasectomy. Yet, prolonged disease-free survival remains the exception, and seems to occur only in patients with a single lung lesion.

Background & Aims Herpes simplex virus hepatitis is a rare, but severe disease, thus far only documented by case reports and short series. The present study was based on the SRTR registry, and included all listed patients for liver transplantation from 1985 to 2009 with a diagnosis of HSV hepatitis. Methods We assessed demographics and outcome of all listed patients, and further conducted a case–control study, matching each transplanted patient with 10 controls. Matching criteria included: transplant status, MELD score ±5, transplant date ±6months, and age at transplant ±5years. During the study period, 30 patients were listed for HSV hepatitis. Of the 30 listed patients, seven recovered spontaneously and five died, prior to transplantation. The remaining 10 children and eight adults were transplanted. Results The chance of recovery was significantly higher in children than in adults (7/19 vs. 0/11, p =0.02). In children, survival was similar between HSV patients and the matched controls (5-year survival: 69% vs. 64%, p =0.89). Conversely, survival was poor in adult HSV (5-year survival: 38% vs. 65%, p =0.006), with 62% of them dying within the first 12months. All three reported post-transplant deaths in children were independent from HSV. Among the seven adult post-transplant deaths, four were related to infection (bacterial, fungal, or viral). Conclusions Children listed for HSV hepatitis have a significantly better survival than adults both prior and after liver transplantation. While HSV fulminant hepatitis is an appropriate indication for liver transplantation in children, it should only be performed in selected adult patients in otherwise good condition.

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.

We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. Conclusion: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.

Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS. Mol Cancer Ther; 10(4); 687–96. ©2011 AACR.

Herpes simplex virus (HSV) hepatitis is an uncommon cause of acute liver failure (ALF), primarily affecting immunocompromised patients. So far, 148 cases have been published, of which 9 underwent liver transplantation (LT). The reported post-transplant survival is poor, with over 60% dying in the first year. Dosing and duration of antiviral therapy after LT are not established. Concerns include both the risk of hepatic recurrence after LT and emergence of viral resistance during prolonged therapy. HSV DNA plasma levels might be helpful to monitor therapeutic response and guide duration of therapy. We present a case of ALF complicating a primary HSV-1 infection in an immunocompetent host, who required emergency LT. We further discuss the value of measuring serial HSV DNA plasma loads to monitor antiviral therapy.

The aim of this study was to evaluate the tolerability of the conversion from calcineurin inhibitor (CNI) to everolimus (ERL) in maintenance liver transplant (LT) recipients.

BACKGROUND AND AIMS: Injecting drug use (IDU) before and after liver transplantation (LT) is poorly described. The aim of this study was to quantify relapse and survival in this population and to describe the causes of mortality after LT. METHODS: Past injection drug users were identified from the LT listing protocols from four centers in Switzerland and France. Data on survival and relapse were collected and used for uni- and multivariate analysis. RESULTS: Between 1988 and 2006, we identified 59 patients with a past history of IDU. The mean age at transplantation was 42.4 yr and the majority of patients were men (84.7%). The indication for LT was for the vast majority viral cirrhosis accounting for 91.5% of cases, while alcoholic cirrhosis was 5.1%. There were 16.9% of patients who had a substitution therapy before and 6.8% who continued after LT. Two patients (3.4%) relapsed into IDU after LT and died at 18 and 41 months. The mean follow-up was 51 months. Overall survival was 84%, 66%, and 61% at 1, 5, and 10 yr after transplantation. CONCLUSIONS: Documented IDU was rare in liver transplanted patients. Past IDU was not associated with poorer survival after LT, and relapse after LT occurred in 3.4%.

In the treatment of hepatocellular carcinomas, therapies such as trans-arterial chemo-embolisation, trans-arterial radioembolisation, percutaneous ethanol injection and radio-frequency ablation can decrease the size (and overall viability) of the tumours, thus potentially increasing the proportion of patients qualifying for resection and transplantation. While the use of such downstaging therapies is straightforward when resection is the aim, in a similar way to other neo-adjuvant treatments in the surgery of tumours that are too large or awkwardly placed to be primarily resected the issues related to transplantation are more complex. In the context of transplantation the word "downstaging" designates not only a neo-adjuvant treatment, but also a selection strategy to allow patients who are initially outside accepted listing criteria to benefit from transplantation should the neo-adjuvant therapy be successful in reducing tumour burden. The effectiveness of downstaging as a selection strategy, at first questioned because of methodological bias in the studies that described it, has been recently demonstrated by more solid prospective investigations. Several issues however remain open, such as inclusion criteria before the strategy is implemented (size/number, surrogate markers of differentiation/vascular invasion such as alpha-fetoprotein), the choice of which downstaging therapy, the end-points of treatment, and the need and duration of a period of observation proving disease response or stabilisation before the patient can be listed. The present review discusses which treatments and strategies are available for downstaging HCC on the basis of the published literature.

BACKGROUND: Traditionally, survival estimates have been reported solely as survival from the time of surgery, but future survival probability likely changes based on the survival time already accumulated after therapy-otherwise known as conditional survival (CS). We sought to assess the comparative performance of various colorectal liver metastasis prognostic scoring systems, as well as to investigate the CS of patients who underwent resection of colorectal liver metastasis. STUDY DESIGN: Between 1982 and 2008, 949 patients who underwent colorectal liver metastasis resection were identified from an international multi-institutional database. Various prognostic scoring systems were evaluated using Cox proportional hazards models and calculated concordance index (c). CS estimates were calculated as CS = S(x+5)/S-(x). RESULTS: Overall survival after liver resection was 65% at 3 years and 45% at 5 years, with a median survival of 52 months. All of the prognostic scoring systems had poor-to-moderate prognostic discriminatory ability (Fong c = 0.57, Nordlinger c = 0.56, Memorial Sloan-Kettering Cancer Center nomogram c = 0.58). Using CS, the probability of surviving an additional 5 years, given that the patient had already survived 1, 3, or 5 years, was 41%, 40%, or 50%, respectively. The inadequate performance of the prognostic scoring systems was explained by the fact that as survival from liver resection increased from 0 to 5 years, the 5-year observed CS improved substantially for patients who were initially predicted to have poor survival at the time of surgery. CONCLUSIONS: Colorectal liver metastasis prognostic scoring systems have fair-to-moderate performance. CS can provide more accurate prognostic information for patients and physicians after colorectal liver metastasis resection and should be incorporated into the quantification of survival. (I Am Coll Surg 2010;210:755-766. (C) 2010 by the American College of Surgeons)

AIMS: Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxaliplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist's perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage. METHODS AND RESULTS: The spectrum of oxaliplatin-associated liver lesions was investigated in a multi-institutional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moderate/severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal/venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX/bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an incidence of moderate/severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular/venular fibrosis (31.4% versus 52%, respectively) (P < 0.001). CONCLUSIONS: Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.

The expression of interleukin 7 receptor alpha(high) (IL-7Ralpha(high)) discriminates between activated CD25(+)CD45RO(+)CD4(+) T cells [IL-7Ralpha(high) and forkhead box P3-negative (FoxP3(-))] and regulatory T cells (IL-7Ralpha(low) and FoxP3(+)). The IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population has been shown to be expanded in the blood and tissues of patients after kidney transplantation and to contain alloreactive T cells (activated T cells). In the present study, we analyzed the distribution of IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cells in the blood of 53 patients after liver transplantation. The IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population was significantly expanded (P < 0.0001) in stable transplant recipients versus healthy donors. However, the magnitude of the expansion was significantly higher (P < 0.0001) in liver transplant recipients with no hepatitis C virus (HCV) infection in comparison with those with a preexisting HCV infection. Interestingly, effective suppression of HCV viremia after antiviral therapy was associated with an increase in the IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population to levels comparable to those of liver transplant recipients not infected with HCV. The present results indicate that (1) the IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population is expanded after liver transplantation, (2) it is a valuable immunological marker for monitoring activated and potential alloreactive CD4 T cells in liver transplantation, and (3) a preexisting HCV infection negatively influences the expansion of this population in liver transplant recipients.

Objective(s): To investigate rates and patterns of recurrence in patients following curative intent surgery for colorectal liver metastasis. Background: Outcomes following surgical management of colorectal liver metastasis have largely focused on overall survival. Contemporary data on rates and patterns of recurrence following surgery for colorectal liver metastasis are limited. Methods: One thousand six hundred sixty-nine patients treated with surgery (resection +/- radiofirequency ablation [RFA]) for colorectal liver metastasis between 1982 and 2008 were identified from an international multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. Results: At the time of the initial liver-directed surgery, surgical treatment was resection only (90.2%), resection plus RFA (8.0%), or RFA alone (1.8%). While 5-year overall survival was 47.3%, 947 (56.7%) patients recurred with a median RFS time of 16.3 months. First recurrence site was intrahepatic only (43.2%), extrahepatic only (35.8%), intra- and extrahepatic (21.0%). There was no difference in RFS based on site of recurrence (intrahepatic: 16.9 months; extrahepatic: 16.6 months; intra- and extrahepatic: 16.2 month; P > 0.05). Receipt of adjuvant chemotherapy was associated with overall recurrence risk (hazard ratio [HR] = 0.56), while history of RFA (HR = 2.39, P = 0.001) and RI margin status (HR = 1.36) were predictive of intrahepatic recurrence. Pattern of recurrence and RYS remained similar following repeat surgery for recurrent disease. Conclusions: While 5-year survival following surgery for colorectal liver metastasis approaches 50%, over one-half of patients develop recurrence within 2 years. The pattern of failure is distributed relatively equally among intrahepatic, extrahepatic, and intra-plus extrahepatic sites. Patients undergoing repeat surgery for recurrent metastasis have similar patterns of recurrence and RFS time.

BACKGROUND AND OBJECTIVES: Oxaliplatin is a chemotherapeutic drug for colorectal adenocarcinoma able to extend the indications for resection of colorectal liver metastases. However, the drug may severely injure hepatic sinusoids, inducing a sinusoidal obstruction syndrome in non-tumoral parenchyma with a risk of decreased regeneration in the remnant liver following partial hepatectomy. METHODS: We then investigated the evolution of hepatic functions and liver regeneration following partial hepatectomy in rats with sinusoidal obstruction syndrome. The sinusoidal obstruction syndrome was induced with a single intragastric administration of monocrotaline (MCT). RESULTS: MCT administration induced obstruction of the hepatic microcirculation and increased portal pressure, hepatic VEGF expression, and Ki67 positive hepatocytes. A mild cholestasis was present without modification of hepatic tests. Following a 70% hepatectomy, liver regeneration was significantly impaired by MCT administration and this impaired regeneration was associated with hepatocellular injury evidenced 1 week after hepatectomy. CONCLUSIONS: The presence of sinusoidal obstruction syndrome impairs hepatic regeneration in this rat model of sinusoidal obstruction syndrome.

Fulminant hepatic failure is characterized by the presence of hepatic encephalopathy in the setting of acute liver injury that occurs in a noncirrhotic organ. Brain edema is the ultimate complication of advanced hepatic encephalopathy as it often leads to cerebral herniation and death. Thus, the presence of fulminant hepatic failure indicates the need for urgent liver transplantation to prevent death or irreversible brain damage. We report a very unusual evolution of fulminant hepatic failure complicated by brain edema and hepatic coma in a 45-year-old woman admitted with acute viral hepatitis E infection.

After adult liver transplantation (LT), post-transplant lymphoproliferative disorder (PTLD) is an uncommon but serious complication of immunosuppression (IMS) in presence of an acute or latent EBV infection. The clinical pres- entation of this disease is aspecific, and, after LT, it may mimic anastomotic bile duct stricture. We report the cases of 2 adult patients who developed, 3 months and 8 years after OLT, an EBV-associated PTLD with diffuse intrinsic infiltration of bile duct mimicking anastomotic biliary stricture. In the absence of liver or hilar nodes in- volvement, percutaneous biopsies were non contributive and the diagnosis were made by surgical biopsy. After reduction of IMS and Rituximab treatment, both patients are alive without recurrence 5 and 6 years after diagnosis. In conclusion, PTLD is one of the differential diagnosis of biliary tree obstruction after OLT. Diagnosis requires surgical biopsies and treatment consists in IMS reduction and Rituximab.

Combined liver-kidney transplantation is considered a low risk for immunologic complication. We report an unusual case of identical ABO liver-kidney recipient without preformed anti-human leukocyte antigen (HLA) antibodies, transplanted across a T- and B-cell-negative cross-match and complicated by early acute humoral and cellular rejection, first in the liver then in the kidney. While analyzing the immunologic complications in our cohort of 12 low-risk combined liver-kidney recipients, only one recipient experienced a rejection episode without detection of anti-HLA antibody over time. Although humoral or cellular rejection is rare after combined kidney-liver transplantation, our data suggest that even in low-risk recipients, the liver does not always systematically protect the kidney from acute rejection. Indeed, the detection of C4d in the liver should be carefully followed after combined liver-kidney transplantation.

BACKGROUND: The surgical management of hepatocellular carcinoma in patients with well-compensated cirrhosis is controversial. The purpose of the current study was to compare the outcome of patients with well-compensated cirrhosis and early stage hepatocellular carcinoma treated with initial hepatic resection versus transplantation. METHODS: Between 1985 and 2008, 245 patients underwent hepatic resection, and 134 patients underwent liver transplantation for early stage hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic factors were evaluated using univariate and multivariate analyses; survival was calculated using the Kaplan-Meier method. RESULTS: Compared with transplantation, patients undergoing resection had larger tumors and a higher incidence of microscopic vascular invasion. Transplantation was associated with better 5-year disease-free and overall survival compared with resection. Hepatitis status, presence of microscopic vascular invasion, and tumor size were predictors for recurrence, while the presence of microscopic vascular invasion and tumor size conferred an increased risk of death. The disease-free survival advantage with transplantation was more pronounced in hepatitis C patients compared with non-hepatitis and hepatitis B patients. The overall survival advantage with transplantation persisted in cases of solitary lesions < or = 3 cm, but was attenuated in patients with a MELD score < or = 8. CONCLUSION: In well-compensated cirrhotic patients with early stage hepatocellular carcinoma, transplantation was associated with longer disease-free and overall survival. Patients undergoing resection did, however, have tumors with more advanced pathologic features. Patients best suited for initial resection as the treatment of hepatocellular carcinoma were those with a MELD score

BACKGROUND: The outcome of liver resection for colorectal liver metastases (CRLM) appears to be improving despite the fact that surgery is offered to patients with more-severe disease. To quantify this assumption and to understand its causes we analyzed a series of patients on the basis of a standardized severity score and changes in management occurring over the years. METHODS: Patients' characteristics, operative data, chemotherapies and follow-up were recorded. CRLM severity was quantified according to Fong's clinical risk score (CRS), modified to take into account the presence of bilateral liver metastases. Three periods were analyzed, in which different indications, surgical strategies and uses of chemotherapy were applied: 1984-1992, 1993-1998, and 1999-2005. RESULTS: Between January 1984 and December 2005, 210 liver resections were performed in 180 patients (1984-1992, 43 patients; 1993-1998, 42 patients; 1999-2005, 95 patients). CRLM severity increased throughout the time periods, as did the use of neoadjuvant chemotherapies, repeat resections, and multistep procedures. While the disease-free survival did not improve over time, the 1-, 3- and 5-year overall survival rate increased from 85%, 30%, and 23% in the first period, to 88%, 60%, and 34% in the second period, and to 94%, 69%, and 46% in the third period. CONCLUSIONS: Analysis according to the CRS showed that despite the fact that patients had more severe disease, the overall survival improved over the years, mainly thanks to more aggressive treatment of recurrent disease. Management of advanced CRLM should, from the start, take into account the likelihood of secondary procedures.

To examine clinical features and outcome of patients who underwent hepatic resection for colorectal liver metastases (LM) involving the caudate lobe.Consecutive patients who underwent hepatic resection for LM from May 1990 to September 2004 were analyzed from a multicenter database. Demographics, operative data, pathologic margin status, recurrence, and survival were analyzed.Of 580 patients, 40 (7%) had LM involving the caudate. Six had isolated caudate LM and 34 had LM involving the caudate plus one or more other hepatic segments. Patients with caudate LM were more likely to have synchronous primary colorectal cancer (63% vs. 36%; P = 0.01), multiple LM (70% vs. 51%; P = 0.02) and required extended hepatic resection more often than patients with non-caudate LM (60% vs. 18%; P0.001). Only four patients with caudate LM underwent a vascular resection; three at first operation, one after recurrence of a resected caudate tumor. All had primary repair (vena cava, n = 3; portal vein, n = 1). Perioperative complications (43% vs. 28%) and 60-day operative mortality (0% vs. 1%) were similar (caudate vs. non-caudate LM, both P0.05). Pathological margins were positive in 15 (38%) patients with caudate LM and in 43 (8%) with non-caudate LM (P0.001). At a median follow-up of 40 months, 25 (64%) patients with caudate LM recurred compared with 219 (40%) patients with non-caudate LM (P = 0.01). Patients with caudate LM were more likely to have intrahepatic disease as a component of recurrence (caudate: 51% vs. non-caudate: 25%; P = 0.001). No patient recurred on the vena cava or portal vein. Patients with caudate LM had shorter 5-year disease-free and overall survival than patients with non-caudate LM (disease-free: 24% vs. 44%; P = 0.02; overall: 41% vs. 58%; P = 0.02).Patients who undergo hepatic resection for caudate LM often present with multiple hepatic tumors and tumors in proximity to the major hepatic veins. Extended hepatectomy is required in the majority, although vascular resection is not frequently necessary; when performed, primary repair is usually possible. Despite resection in this population of patients with multiple and bilateral tumors, and despite close-margin and positive-margin resection in a significant proportion, recurrence on the portal vein or vena cava was not observed, and long-term survival is accomplished (41% 5-year overall survival).