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In colorectal cancer liver metastases (CRLM), the density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy have been associated with oncological outcomes after complete resection. However, the prognostic significance of the heterogeneity of these features in patients with multiple CRLMs remains under investigation. We used a tissue microarray of 220 mismatch repair-gene proficient CRLMs resected in 97 patients followed prospectively to quantify CD3 + T cells and MHC-I by immunohistochemistry. Histopathological response to preoperative chemotherapy was assessed using standard scoring systems. We tested associations between clinical, immunological, and pathological features with oncologic outcomes. Overall, 29 patients (30.2%) had CRLMs homogeneous for CD3+ T cell infiltration and MHC-I. Patients with immune homogeneous compared to heterogeneous CRLMs had longer median time to recurrence (TTR) (30 vs. 12 months, p  = .0018) and disease-specific survival (DSS) (not reached vs. 48 months, p  = .0009). At 6 years, 80% of the patients with immune homogeneous CRLMs were still alive. Homogeneity of response to preoperative chemotherapy was seen in 60 (61.9%) and 69 (80.2%) patients according to different grading systems and was not associated with TTR or DSS. CD3 and MHC-I heterogeneity was independent of response to pre-operative chemotherapy and of other clinicopathological variables for their association with oncological outcomes. In patients with multiple CRLMs resected with curative intent, similar adaptive immune features seen across metastases could be more informative than pathological response to pre-operative chemotherapy in predicting oncological outcomes., Competing Interests: Outside the submitted work, S.T. has received consultant fees from Bristol Myers Squibb and Turnstone Biologics, speaking fees from Celgene and Astra Zeneca, and has research funding from Iovance Biotherapeutics and Turnstone Biologics., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: After resection, colorectal cancer liver metastases (CRLM) surrounded by a desmoplastic rim carry a better prognosis than the metastases replacing the adjacent liver. However, these histopathological growth patterns (HGPs) are insufficient to guide clinical decision-making. We explored whether the adaptive immune features of HGPs could refine prognostication., Methods: From 276 metastases resected in 176 patients classified by HGPs, tissue microarrays were used to assess intratumoral T cells (CD3), antigen presentation capacity (MHC class I) and CD73 expression producing immunosuppressive adenosine. We tested correlations between these variables and patient outcomes., Results: The 101 (57.4%) patients with dominant desmoplastic HGP had a median recurrence-free survival (RFS) of 17.1 months compared to 13.3 months in the 75 patients (42.6%) with dominant replacement HGP (p = 0.037). In desmoplastic CRLM, high vs. low CD73 was the only prognostically informative immune parameter and was associated with a median RFS of 12.3 months compared to 26.3, respectively (p = 0.010). Only in dominant replacement CRLM, we found a subgroup (n = 23) with high intratumoral MHC-I expression but poor CD3 + T cell infiltration, a phenotype associated with a short median RFS of 7.9 months., Conclusions: Combining the assessments of HGP and adaptive immune features in resected CRLM could help identify patients at risk of early recurrence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

In multifocal intrahepatic cholangiocarcinoma (IHC), intrahepatic metastases (IM) represent a contraindication to surgical resection, whereas satellite nodules (SN) do not. However, no consensus criteria exist to distinguish IM from SN. The purpose of this study was to determine genetic alterations and clonal relationships in surgically resected multifocal IHC. Next-generation sequencing of 34 spatially separated IHC tumors was performed using a targeted panel of 201 cancer-associated genes. Proposed definitions in the literature were applied of SN located in the same liver segment and ≤2 cm from the primary tumor; and IM located in a different liver segment and/or >2 cm from the primary tumor. Somatic point mutations concordant across tumors from individual patients included BAP1, SMARCA4 and IDH1. Small insertions and deletions (indels) present at the same genome positions among all tumors from individuals included indels in DNA repair genes, CHEK1, ERCC5, ATR and MSH6. Copy number alterations were also similar between all tumors in each patient. In this cohort of multifocal IHC, genomic profiles were concordant across all tumors in each patient, suggesting a common progenitor cell origin, regardless of the location of tumors in the liver. The decision to perform surgery should not be based upon a perceived distinction between IM and SN., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Neoadjuvant therapy (NT) remains controversial in early-stage pancreatic ductal adenocarcinoma (PDAC), defined as clinical (c)Stage I-II. Our aim was to analyze rates of pathologic upstaging/downstaging for resectable PDAC treated with surgery-first (SF) vs. NT., Methods: Utilizing the National Cancer Data Base (NCDB), patients with cStage I-II PDAC who underwent pancreatoduodenectomy in 2006-2013 were pathologically staged using the AJCC 8th edition and compared by treatment sequencing., Results: Among 13,871 patients, 15.3% received NT. Despite higher pre-treatment T-stage (cT2: 71.9% vs. 56.3%, p < 0.001), NT patients had lower rates of pathologic nodal metastases (46.2% vs. 69.2% in SF, p < 0.001), suggesting higher rates of pathologic downstaging. In cStage II, 33.0% were upstaged to stage III after SF, vs. only 14.0% after NT. In cStage I, 65.5% were upstaged following SF, vs. 46.7% after NT (all p < 0.001). Patients with NT (HR-0.77, p < 0.001) or downstaging (HR-0.80, p < 0.001) had improved overall survival (OS)., Conclusion: NT is associated with reduction in unexpected upstaging, reduction in nodal positivity, and improved OS, compared to SF approach in putatively early-stage PDAC. Because clinical staging underestimates the underlying disease burden in resectable PDAC, patients with cStage I-II should be considered for NT., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The intraoperative air cholangiogram, or "air leak test" (ALT), at the time of hepatectomy can significantly reduce the rates of bile leak and symptomatic fluid collection after high-risk procedures.1 , 2 Because a bile leak in the setting of an en bloc diaphragm resection and mesh reconstruction would be a particularly dreaded complication, this video shows the technique for resection, reconstruction, and ALT., Presentation: The video presents the case of a 29-year-old woman who had metastatic teratoma with an 8 × 7-cm liver metastasis in segment 7 and diaphragm invasion to the level of the right hepatic vein., Operation: The authors performed a formal right posterior sectionectomy with en bloc diaphragm resection. The 12 × 8-cm diaphragmatic defect was reconstructed using biologic mesh (Surgimend, Integra LifeSciences, Plainsboro, NJ). An intraoperative ALT (air injection into the cystic duct with finger compression of the distal bile duct) identified several areas of bubbles from biliary radicles on the cut surface of the liver, which were ligated with 4-0 polypropylene. The ALT was repeated until no bubbles remained. Because no evidence of bubbles was observed, no surgical drain was needed. The patient did well postoperatively with no complications., Conclusion: In cases of combined liver and diaphragmatic resection, prevention of bile leak, with subsequent contamination of the diaphragm repair and even the thoracic cavity, is particularly vital. An easily replicated intraoperative air leak test can mitigate the risk of bile leak and organ-space infection, as well as associated sequelae on quality of life, return to intended oncologic therapy, and oncologic outcomes.

Purpose of Review: The aim of this review is to discuss existing data on liver transplantation for colorectal liver metastasis, emerging controversies, and future directions., Recent Findings: Contemporary experience with transplanting patients with liver metastasis from colon cancer is mainly derived from European centers, with a large proportion being from a single institution (SECA study), made possible in part by a relatively high donor pool. The initial results prove to be encouraging by demonstrating an overall survival advantage over unresectable patients with liver-limited disease managed with chemotherapy only. Recurrence patterns, however, suggest a need for better patient selection and treatment sequencing optimization. In North America, the main barriers in establishing similar protocols result from national liver graft shortage, which represents an issue of competing resources when indications have yet to be well defined. Evolving strategies in transplantation, such as the utilization of marginal liver grafts and living donor liver transplantation might constitute potential solutions., Summary: Evidence suggests a potential survival benefit of liver transplantation for a subset of patients with unresectable liver-limited CRLM. Further prospective trials are needed to clarify the role and feasibility of this treatment strategy in oncotransplantation.

Introduction: Patients with locally advanced pancreatic cancer (LAPC) represent a challenging group to treat, given the involvement of major vascular structures. In selected patients with favorable biology, temporary mesocaval shunt can facilitate the resection and allow for a safer procedure with enhanced exposure to the superior mesenteric vessels., Methods: We present a video of a pancreaticoduodenectomy (PD) with temporary mesocaval shunt with left internal jugular (LIJ) vein conduit., Results: A 65-year-old woman presented with LAPC in the uncinate, causing total occlusion of the superior mesenteric vein (SMV) and encasement of the first jejunal artery. After neoadjuvant therapy and evidence of disease stability, a decision was made to perform a PD with a temporary mesocaval shunt to divert mesenteric flow to reduce blood loss and prevent bowel ischemia. During the procedure, the main mesenteric collateral (ileocolic vein) was divided to create the shunt to the inferior vena cava (IVC) with LIJ interposition. The remaining mesenteric tributaries involved by the tumor were divided. The uncinate dissection was performed using a superior mesenteric artery-first approach. Once the resection was completed, the shunt was stapled from the IVC and the graft transposed to the upper SMV. Standard reconstruction was performed. Total operative time was 536 min, and estimated blood loss was 250 cc without transfusions. No perioperative complications occurred., Conclusion: In selected patients with LAPC, PD with temporary mesocaval shunt can facilitate resection and venous reconstruction in patients with complete portal vein/SMV occlusion.

Background: Recurrence rates are high for patients who have undergone two-stage hepatectomy (TSH) for bilateral colorectal liver metastases, and there is no established treatment approach for recurrent disease. This study aimed to determine the feasibility, safety, and prognostic impact of surgical resection for recurrence after TSH and the prognostic role of RAS mutation in this cohort., Methods: The study included 137 patients intended to undergo TSH for bilateral colorectal metastases during 2003-2016. Clinicopathologic factors were compared using univariate and multivariate analyses., Results: One hundred eleven patients (81%) completed TSH. The median recurrence-free survival in these patients was 12 months. Of the 83 patients with subsequent recurrence, 31 (37%) underwent resection for recurrence, and 11 underwent multiple resections for recurrence. Forty-eight operations were performed for recurrence: 23 repeat hepatectomies, 14 pulmonary resections, 5 locoregional resections, and 6 concurrent resections in multiple organ sites. The median overall survival (OS) among patients with recurrence was 143 months for patients who underwent resection and 49 months for those who did not (P < 0.001). On multivariate analysis, resection for recurrence (hazard ratio [HR] 0.25; 95% CI 0.10-0.54, P < 0.001) was associated with better OS, whereas RAS mutation (HR 2.25; 95% CI 1.16-4.50, P = 0.016) and first recurrence in multiple sites (HR 2.28; 95% CI 1.17-4.37, P = 0.016) were independent predictors of worse overall survival., Conclusions: In patients who have undergone TSH for bilateral colorectal liver metastases, recurrence is frequent and should be treated with resection whenever possible. Patients with wild-type RAS fare particularly well with resection for recurrence.

Background: When performing a right hepatectomy, the middle hepatic vein (MHV) should guide the parenchymal transection. MHV hotspots for bleeding can be anticipated when applying the previously developed MHV Roadmap to a minimally invasive approach.1 This video demonstrates application of the MHV Roadmap to perform a safe laparoscopic right hepatectomy., Patient: A 44-year-old woman with a solitary and large breast cancer liver metastasis in the right liver was considered for a laparoscopic right hepatectomy following an excellent response to neoadjuvant chemotherapy. The MHV anatomy was reconstructed using automated vascular reconstruction software (Synapse, Fuji) ahead of surgery., Technique: With the patient in the French position, the hilar vessels are exposed and the inflow is controlled. Parenchymal transection begins along the demarcation line.2 , 3 The constant relationship between the portal bifurcation and the V5 ventral and dorsal allows for easy intraparenchymal identification of the MHV. The parenchymal transection is performed in a convex fashion to optimize exposure of the MHV. Using MHV guidance, the parenchymal transection is continued and V8 is safely identified. The operation is completed with division of the anterior fissure and right hepatic vein., Conclusion: Outlining the MHV anatomy according to the MHV Roadmap preoperatively helps to anticipate hotspots of bleeding. Guidance along the MHV through the parenchymal transection allows for early identification of tributaries, thereby preventing injury and remnant liver ischemia.

Background: In patients with stage IV colorectal cancer (CRC), minimally invasive surgery (MIS) may offer optimal oncologic outcome with low morbidity. However, the relative benefit of MIS compared to open surgery in patients requiring multistage resections has not been evaluated., Methods: Patients who underwent totally minimally invasive (TMI) or totally open (TO) resections of CRC primary and liver metastases (CLM) in 2009-2016 were analyzed. Inverse probability of weighted adjustment by propensity score was performed before analyzing risk factors for complications and survival., Results: The study included 43 TMI and 121 TO patients. Before and after adjustment, TMI patients had significantly less cumulated postoperative complications (41% vs. 59%, p = 0.001), blood loss (median 100 vs. 200 ml, p = 0.001) and shorter length of hospital stay (median 4.5 vs. 6.0 days, p < 0.001). Multivariate analysis identified TO approach vs. MIS (OR = 2.4, p < 0.001), major liver resection (OR = 4.4, p < 0.001), and multiple CLM (OR = 2.3, p = 0.001) as independent risk factors for complications. 5-year overall survival was comparable (81% vs 68%, p = 0.59)., Conclusion: In patients with CRC undergoing multistage surgical treatment, MIS resection contributes to optimal perioperative outcomes without compromise in oncologic outcomes., (Published by Elsevier Ltd.)

Background: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs., Methods: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined., Results: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006)., Conclusions: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.

Purpose: To assess frequency of adverse events, efficacy, and clinical outcomes of percutaneous portal vein embolization (PVE) in patients with bilobar colorectal liver metastases undergoing staged hepatectomy with preservation of segment IV ± I only., Materials and Methods: Retrospective analysis was performed of 40 consecutive patients who underwent right PVE after successful left lobectomy between 2005 and 2013. Rates of adverse events, future liver remnant (FLR) > 30% compared with baseline liver volume, clinical success (completion of staged hepatectomy with clearance of liver metastases), and overall survival were analyzed., Results: PVE was performed using polyvinyl alcohol particles (n = 7; 17.5%), particles plus coils (n = 23; 57.5%), and N-butyl cyanoacrylate glue plus ethiodized oil (n = 10; 25%). Technical success was 100%. After PVE, 20% (n = 8) of patients exhibited portal venous thrombosis, ranging from isolated intrahepatic portal branch thrombosis to massive thrombosis of the main portal vein (n = 3) and responsible for periportal cavernoma and portal hypertension in 5 patients. Of patients, 23 (57.5%) had FLR ≥ 30%, and 21 (52.5%) had clinical success. Six patients had significant stenosis or occlusion of the left portal vein or biliary system after original left lobectomy, which was independently associated with FLR < 30% (R 2 = 0.24). Clinical success was the only independent variable associated with survival (R 2 = 0.25)., Conclusions: PVE for staged hepatectomy with preservation of segment IV ± I only is technically feasible, leading to adequate hypertrophy and clinical success rates in these patients with poor oncologic prognosis. Portal venous thrombosis is greater after the procedure than in the setting of standard PVE., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Portal vein embolization (PVE) can be required to stimulate liver regeneration before hepatectomy for colorectal liver metastasis (CRCLM), however PVE may also trigger CRCLM progression in patients initially exhibiting chemotherapy response. Using RNA-seq, we aimed to determine the molecular networks involved in metastatic progression in this context. A prospective study including all CRCLM patients undergoing PVE prior to hepatectomy was conducted. Paired biopsies of metastatic lesions were obtained prior to and after PVE and total RNA was isolated and used to prepare Illumina rRNA-depleted TruSeq stranded cDNA libraries for HiSeq 100 bp paired-end sequencing. Patients were classified with progression of disease (PD PVE ) or stable disease (SD PVE ) post-PVE using 3D-CT tumor volumetric analysis., Results: Twenty patients were included, 13 (65.0%) in the PD PVE group (median 58.0% (18.6-234.3) increase in tumor volume) and 7 (35.0%) in the SD PVE group exhibiting continuous chemotherapy response (median -14.3% (-40.8 to -2.8) decrease in tumor volume) (p < 0.0001). Our results showed that progressive CRCLM after PVE undergo gene expression changes that indicate activation of core cancer pathways (IL-17 (p = 5.94 × 10 -03 ), PI3K (p = 8.71 × 10 -03 ), IL6 and IGF-1 signaling pathways), consistent with changes driven by cytokines and growth factors. Differential expression analysis in a paired model of progression (EdgeR, DeSeq) identified significantly dysregulated genes in the PD PVE group (FOS, FOSB, RAB20, IRS2)., Conclusion: Differentially expressed genes and pathways with known links to cancer and metastasis were identified post-PVE in patients with disease progression. Highlighting these molecular changes is a crucial first step towards development of targeted therapeutic strategies that may mitigate the effects of PVE on tumor growth.

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy., Competing Interests: Competing finanical interests None of the authors declared any competing financial interests.

Background/aim: To elucidate colorectal cancer (CRC) disease patterns, demographics, characteristics, stage at presentation, metastases, and survival rates of patients, particularly those with liver metastases, at our center as the first report from the Kingdom of Saudi Arabia., Patients and Methods: We performed a retrospective, single-center database study based on the histological diagnosis of CRC in patients seen at the King Khalid University Hospital between 2007 and 2011., Results: 427 cases of CRC with a mean age at diagnosis of 55.47 ΁ 12.85 years, out of which 96% were resected. Stage II was predominant at presentation, followed by both stage III and IV, with the remainder being stage I. One hundred patients had distant metastases, of which the liver was the only location in 54 patients. Mean survival was 3.0 years. Overall survival rates for CRC patients with liver metastases who underwent resection were 30% at 2 years and 17% at 5 years, and the mean survival rate was 1.4 years., Conclusions: Both the mean survival rate of our CRC patients with resectable liver metastases and the 5-year survival rate of these patients are lower than global averages. This discrepancy is likely due to late diagnoses rather than more aggressive disease.

Background: Driven by disease trends, such as obesity and metabolic syndrome, that are increasingly prevalent in the general population, we aimed to evaluate the comorbidities and attributes of the brain-dead organ donor population over time in a longitudinal study., Methods: We compared overall health and baseline attributes of organ donors between 2000-2005 and 2006-2012 using our prospective transplant database. Descriptive and comparative analyses of the 2 historical cohorts were performed., Results: A total of 1040 brain-dead organ donors were included in our analysis: 496 from the 2000-2005 period and 544 from the 2006-2012 period. Our analysis revealed that donors from the recent (2006-2012) period were more likely to have increased body mass index (26.4 ± 6.0 v. 25.0 ± 4.8, p = 0.003), smoking history (57.0% v. 27.2%, p < 0.001), coronary artery disease (14.3% v. 3.2%, p = 0.015) and dyslipidemia (19.1% v. 4.2%, p < 0.001), but less likely to have concurrent infection (1.1% v. 7.9%, p < 0.001) than those from the earlier period., Conclusion: Our data suggest that the characteristics and comorbidities of brain-dead organ donors have somewhat deteriorated over the last decade. Further studies are needed to evaluate the impact of these health attributes on donated organ utilization and outcomes.

Background and Objectives: Treatment strategies for colorectal cancer liver metastasis (CRCLM) such as major hepatectomy and portal vein embolization (PVE) rely on liver regeneration. We aim to investigate the effect of neoadjuvant chemotherapy on liver regeneration occurring after PVE and after major hepatectomy., Methods: CRCLM patients undergoing PVE or major resection were identified retrospectively from our database. Liver regeneration data (expressed as future liver remnant [FLR] and percentage of liver regeneration [%LR]), total liver volume (TLV) and clinical characteristics were collected., Results: Between 2003 and 2013, 226 patients were included (85 major resection, 141 PVE). The median chemotherapy cycles was six in both groups. The median time interval between the last chemotherapy and the intervention was 51 days in the PVE group and 79 days in the hepatectomy group. In the PVE group, chemotherapy was not associated with altered liver regeneration (number of cycles [P = 0.435], timing [P = 0.563], or chemotherapy agent [P = 0.116]). Similarly in the major hepatectomy group, preoperative chemotherapy (number of cycles [P = 0.114]; agent [P = 0.061], timing [P = 0.126]) were not significantly associated with differences in liver regeneration (P = 0.592). In both groups, the predicted FLR% was inversely correlated with the %LR (P < 0.001)., Conclusion: Chemotherapy does not affect liver regeneration following PVE or major resection. J. Surg. Oncol. 2016;113:449-455. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Surgical resection of colorectal liver metastases (CRLM) has a well-documented improvement in survival. To benefit from this intervention, proper selection of patients who would be adequate surgical candidates becomes vital. A combination of imaging techniques may be utilized in the detection of the lesions. The criteria for resection are continuously evolving; currently, the requirements that need be met to undergo resection of CRLM are: the anticipation of attaining a negative margin (R0 resection), whilst maintaining an adequate functioning future liver remnant. The timing of hepatectomy in regards to resection of the primary remains controversial; before, after, or simultaneously. This depends mainly on the tumor burden and symptoms from the primary tumor. The role of chemotherapy differs according to the resectability of the liver lesion(s); no evidence of improved survival was shown in patients with resectable disease who received preoperative chemotherapy. Presence of extrahepatic disease in itself is no longer considered a reason to preclude patients from resection of their CRLM, providing limited extra-hepatic disease, although this currently is an area of active investigations. In conclusion, we review the indications, the adequate selection of patients and perioperative factors to be considered for resection of colorectal liver metastasis.

Colorectal liver metastasis (CRLM) is the major cause of death in patients diagnosed with colorectal cancer. The gold standard treatment of CRLM is surgical resection. Yet, in the past, more than half of these patients were deemed unresectable due to the inadequate future liver remnant (FLR). The introduction of efficient portal vein embolization (PVE) preoperatively allowed more resections of metastasis in CRLM patients by stimulating adequate liver hypertrophy. However, several experimental and clinical studies reported tumor progression after PVE which critically influences the subsequent management of these patients. The underlying pathophysiological mechanism of tumor progression post-PVE is still not fully understood. In spite of the adverse effects of PVE, it remains a potentially curative procedure in patients who would remain otherwise unresectable because of the insufficient FLR. Currently, the challenge is to halt tumor proliferation following PVE in patients who require this technique. This could potentially be achieved by either attempting to suppress the underlying oncologic stimulus or by inhibiting tumor growth once observed after PVE, without jeopardizing liver regeneration. More research is still required to better identify patients at risk of experiencing tumor growth post-PVE.

Background: Currently, there is no universally accepted method to evaluate liver function post-orthotopic liver transplant (OLTx) and there are no early surrogate function markers to assess the impact of perioperative interventions in trial settings., Material and Methods: In total, 495 patients were included in the study. On multivariate analysis, PTLF score, defined as normal (score <4) or dysfunctional (score ≥ 4), was the only significant variable for determining significant complications (P=0.014) and graft survival (P=002) during the perioperative period., Results: In total, 495 patients were included in the study. On multivariate analysis, PTLF score, defined as normal (score <4) or dysfunctional (score ≥ 4), was the only significant variable for determining significant complications (P=0.014) and graft survival (P=002) during the perioperative period., Conclusions: PTLF score shows promise as an early surrogate marker of post-orthotopic liver transplantation mortality and morbidity by providing results within the first 7 days post-transplantation. PTLF score can potentially be used as a tool to assess the impact of perioperative interventions by predicting long-term outcomes early in the clinical course of transplant patients.

Severe acute necrotising pancreatitis is associated with numerous local and systemic complications. Abdominal compartment syndrome requiring urgent decompressive laparotomy is a potential complication of this disease process and is associated with increased morbidity and mortality. We describe the case of a pancreaticoatmospheric fistula following decompressive laparotomy in a patient with severe acute necrotising pancreatitis. While this fistula was managed successfully using the current standard of care for pancreatic fistulas, the wound care for in this patient with drainage of the fistula through an open abdomen, is a significant challenge., (2014 BMJ Publishing Group Ltd.)

Aim: To evaluate the ability of the McGill Brisbane Symptom Score (MBSS) to predict survival in resectable pancreatic head adenocarcinoma (PHA) patients., Methods: All PHA patients (n = 83) undergoing pancreaticoduodenectomy at the McGill University Health Center, Quebec between 1/2001-1/2010 were evaluated. Data related to patient and cancer characteristics, MBSS variables, and treatment were collected; univariable and multivariable survival analyses were performed. We obtained complete follow-up until February 2011 in all patients through the database of the provincial health insurance plan of Quebec. The unique health insurance numbers of these patients were used to retrieve information from this database which captures all billable clinical encounters, and ensures 100% actual survival data., Results: Median survival was 23 mo overall: 45 mo for patients with low MBSS, 17 mo for high MBSS (P = 0.005). At twelve months survival was 83.3% (95%CI: 66.6-92.1) vs 58.1% (95%CI: 42.1-71.2) in those with low vs high MBSS, and 24 mo survival was 63.8% (95%CI: 45.9-77.1) and 34.0% (95%CI: 20.2-48.2) respectively. In the multivariate Cox model (stratified by chemotherapy), after addition of clinically meaningful covariates, MBSS was the variable with the strongest association with survival (HR = 2.63; P = 0.001). Adjuvant chemotherapy interacted with MBSS category such that only high MBSS patients accrued a benefit. In univariate analysis we found a lower mortality in high MBSS but not low MBSS patients receiving adjuvant chemotherapy. This interaction variable, on Cox model, resulted in an adjusted mortality HR for the high MBSS (compared to low MBSS) of 4.14 (95%CI: 1.48-11.64) without chemotherapy and 2.11 (95%CI: 1.06-4.17) with chemotherapy., Conclusion: The MBSS is a simple prognostic tool for resectable PHA. Preoperative categorization of patients according to the MBSS allows effective stratification of patients to guide therapy.

Objectives: This study describes the management of patients with bilobar colorectal liver metastases (CRLM)., Methods: A retrospective collection of data on all patients with CRLM who were considered for staged resection (n= 85) from January 2003 to January 2011 was performed. Patients who underwent one hepatic resection were considered to have had a failed staged resection (FSR), whereas those who underwent a second or third hepatic resection to produce a cure were considered to have had a successful staged resection (SSR). Survival was calculated from the date of diagnosis of liver metastases. Complete follow-up and dates of death were obtained from the Government of Quebec population database., Results: Median survival was 46 months (range: 30-62 months) in the SSR group and 22 months (range: 19-29 months) in the FSR group. Rates of 5-year survival were 42% and 4% in the SSR and FSR groups, respectively. Fifteen of the 19 patients who remained alive at the last follow-up date belonged to the SSR group., Conclusions: In patients in whom staged resection for bilobar CRLM is feasible, surgery would appear to offer benefit., (© 2012 International Hepato-Pancreato-Biliary Association.)

Objectives: Portal vein embolization (PVE) can facilitate the resection of previously unresectable colorectal cancer (CRC) liver metastases. Bevacizumab is being used increasingly in the treatment of metastatic CRC, although data regarding its effect on post-embolization liver regeneration and tumour growth are conflicting. The objective of this observational study was to assess the impact of pre-embolization bevacizumab on liver hypertrophy and tumour growth., Methods: Computed tomography scans before and 4 weeks after PVE were evaluated in patients who received perioperative chemotherapy with or without bevacizumab. Scans were compared with scans obtained in a control group in which no PVE was administered. Future liver remnant (FLR), total liver volume (TLV) and total tumour volume (TTV) were measured. Bevacizumab was discontinued ≥ 4 weeks before PVE., Results: A total of 109 patients and 11 control patients were included. Portal vein embolization induced a significant increase in TTV: the right lobe increased by 33.4% in PVE subjects but decreased by 34.8% in control subjects (P < 0.001), and the left lobe increased by 49.9% in PVE subjects and decreased by 33.2% in controls (P= 0.022). A total of 52.8% of the study group received bevacizumab and 47.2% did not. There was no statistical difference between the two chemotherapy groups in terms of tumour growth. Median FLR after PVE was similar in both groups (28.8% vs. 28.7%; P= 0.825)., Conclusions: Adequate liver regeneration was achieved in patients who underwent PVE. However, significant tumour progression was also observed post-embolization., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: Neuroendocrine tumours (NET) frequently metastasize to the liver. NET liver metastasis has been shown to respond to Yttrium-90 microspheres therapy. The aims of the present study were to define factors that predict the response to radio-embolization in patients with NET liver metastases., Methods: From January 2006 until March 2009, all patients with NET liver metastasis that received radio-embolization using TheraSphere® (glass microspheres) were reviewed. The response was determined by a change in the percentage of necrosis (ΔN%) after the first radio-embolization based on the modified RECIST criteria (mRECIST) criteria. The following confounding variables were measured: age, gender, size of the lesions, liver involvement, World Health Organization (WHO) classification, the presence of extra-hepatic metastasis, octereotide treatment and previous operative [surgery and (RFA)] and non-operative treatments (chemo-embolization and bland-embolization)., Results: In all, 25 patients were identified, with a median follow-up of 21.7 months. The median age was 64.6 years, 28% had extra-hepatic metastasis and 56% were WHO stage 2. Post-treatment, the mean ΔN% was 48.4%. Previous surgical therapy was a significant predictor of the response with a response rate of 66.7 ΔN% vs. 31.5 ΔN% (P= 0.02). Bilateral liver disease, a high percentage of liver involvement and large metastatic lesions were inversely related to the degree of tumour response although did not reach statistical significance., Conclusion: Radio-embolization increased the necrosis of NET liver metastasis mainly in patients with less bulky disease. This may imply that surgical therapy before radio-embolization would increase the response rates., (© 2011 International Hepato-Pancreato-Biliary Association.)

Background: This study attempts to define clinical predictors of survival in patients with unresectable pancreatic adenocarcinoma (UPA)., Methods: A retrospective study of 94 consecutive patients diagnosed with UPA from 2001 to 2006 was performed. Using data for these patients, a symptom score was devised through a forward stepwise Cox proportional hazards model based on four weighted criteria: weight loss of >10% of body weight; pain; jaundice, and smoking. The symptom score was subsequently validated in a distinct cohort of 32 patients diagnosed with UPA in 2007., Results: In the original cohort, the overall median survival was 9.0 months (95% confidence interval [CI] 7.6-10.4). This altered to 10.3 months (95% CI 6.1-14.5) in patients with locally advanced disease, and 6.6 months (95% CI 4.2-9.0) in patients with distant metastasis. Median survival was 14.6 months (95% CI 13.1-16.1) in patients with a low symptom (LS) score and 6.3 months (95% CI 4.1-8.5) in patients with a high symptom (HS) score. A total of 73% of LS score patients survived beyond 9 months, compared with only 38% of HS score patients (P<0.001). The discrimination of the LS score was greater than that of any conventional method, including imaging. The validation cohort confirmed the discriminative ability of the symptom score for survival., Conclusions: A simple and clinically meaningful point-based symptom score can successfully predict survival in patients with UPA., (© 2010 International Hepato-Pancreato-Biliary Association.)