Value of prognostic scoring systems in the era of multimodal therapy for recurrent colorectal liver metastases.

BACKGROUND: Various predictive scoring systems have been developed to estimate outcomes of patients undergoing surgery for colorectal liver metastases (CRLM). However, data regarding their effectiveness in recurrent CRLM (recCRLM) are very limited. METHODS: Patients who underwent repeat hepatectomy for recCRLM at the University Hospital RWTH Aachen, Germany from 2010 to 2021 were included. Nine predictive scoring systems (Fong's, Nordlinger, Nagashima, RAS mutation, Tumor Burden, GAME, CERR, and Glasgow Prognostic score, Basingstoke Index) were evaluated by likelihood ratio (LR) χ2, linear trend (LT) χ2 and Akaike Information Criterion (AIC) for their predictive value regarding overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 150 patients, median RFS was 9 (2-124) months with a 5-year RFS rate of 10%. Median OS was 39 (4-131) months with a 5-year OS rate of 32%. For RFS and OS, the Nagashima score showed the best prognostic ability (LT χ2 3.00, LR χ2 9.39, AIC 266.66 and LT χ2 2.91, LR χ2 20.91, 290.36). DISCUSSION: The Nagashima score showed the best prognostic stratification to predict recurrence as well as survival, and therefore might be considered when evaluating patients with recCRLM for repeat hepatectomy.

Ogilvie's syndrome-is there a cutoff diameter to proceed with upfront surgery?

PURPOSE: Although Ogilvie's syndrome was first described about 70 years ago, its etiology and pathogenesis are still not fully understood. But more importantly, it is also not clear when to approach which therapeutic strategy. METHODS: Patients who were diagnosed with Ogilvie's syndrome at our institution in a 17-year time period (2002-2019) were included and retrospectively evaluated regarding different therapeutical strategies: conservative, endoscopic, or surgical. RESULTS: The study included 71 patients with 21 patients undergoing conservative therapy, 25 patients undergoing endoscopic therapy, and 25 patients undergoing surgery. However, 38% of patients (n = 8) who were primarily addressed for conservative management failed and had to undergo endoscopy or even surgery. Similarly, 8 patients (32%) with primarily endoscopic treatment had to proceed for surgery. In logistic regression analysis, only a colon diameter ≥ 11 cm (p = 0.01) could predict a lack of therapeutic success by endoscopic treatment. Ninety-day mortality and overall survival were comparable between the groups. CONCLUSION: As conservative and endoscopic management fail in about one-third of patients, a cutoff diameter ≥ 11 cm may be an adequate parameter to evaluate surgical therapy.

Prognostic evaluation of HCC patients undergoing surgical resection: an analysis of 8 different staging systems.

PURPOSE: No consensus exists regarding the most appropriate staging system to predict overall survival (OS) for hepatocellular carcinoma (HCC) in surgical candidates. Thus, we aimed to determine the prognostic ability of eight different staging systems in a European cohort of patients undergoing liver resection for HCC. METHODS: Patients resected for HCC between 2010 and 2019 at our institution were analyzed with Kaplan-Meier and Cox regression analyses. Likelihood ratio (LR) χ2 (homogeneity), linear trend (LT) χ2 (discriminatory ability), and Akaike Information Criterion (AIC, explanatory ability) were used to determine the staging system with the best overall prognostic performance. RESULTS: Liver resection for HCC was performed in 160 patients. Median OS was 39 months (95% confidence interval (CI): 32-46 months) and median RFS was 26 months (95% CI: 16-34 months). All staging systems (BCLC, HKLC, Okuda, CLIP, ITA.LI.CA staging and score, MESH, and GRETCH) showed significant discriminatory ability regarding OS, with ITA.LI.CA score (LR χ2 30.08, LT χ2 13.90, AIC 455.27) and CLIP (LR χ2 28.65, LT χ2 18.95, AIC 460.07) being the best performing staging systems. CONCLUSIONS: ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery.

Pharmacological Inhibition of mTORC2 Reduces Migration and Metastasis in Melanoma.

Despite recent advances in therapy, liver metastasis from melanoma is still associated with poor prognosis. Although targeting the mTOR signaling pathway exerts potent anti-tumor activity, little is known about specific mTORC2 inhibition regarding liver metastasis. Using the novel mTORC2 specific inhibitor JR-AB2-011, we show significantly reduced migration and invasion capacity by impaired activation of MMP2 in melanoma cells. In addition, blockade of mTORC2 induces cell death by non-apoptotic pathways and reduces tumor cell proliferation rate dose-dependently. Furthermore, a significant reduction of liver metastasis was detected in a syngeneic murine metastasis model upon therapy with JR-AB2-011 as determined by in vivo imaging and necropsy. Hence, our study for the first time highlights the impact of the pharmacological blockade of mTORC2 as a potent novel anti-cancer approach for liver metastasis from melanoma.

Characteristics of atypical large well-differentiated hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma?

BACKGROUND: Hepatocellular carcinoma (HCC) de-differentiation is thought to correlate with size, therefore well-differentiated HCC ≥3 cm are considered rare and not fully understood. METHODS: Patients who underwent hepatectomy for HCC between 1998-2016 were retrospectively analyzed. Patient's characteristics and recurrence-free (RFS) and overall (OS) survival were compared between those with atypical- (well-differentiated-HCC ≥3 cm) and typical-HCC (moderate-to-poorly-differentiated HCC ≥3 cm). RESULTS: Of 176 patients included in this study, 37 (21%) had atypical-HCC. Patients with atypical-HCC were less likely to be Asian ethnicity (3% vs. 17%, p = 0.062), have lower rate of viral infection (14% vs. 43%, p = 0.003), cirrhosis (8% vs. 27%, p = 0.015). The tumors were less likely to demonstrate vascular invasion (30% vs. 59%, p = 0.002), and were associated with a lower alpha-fetoprotein level (3.5 ng/ml vs. 33.2 ng/ml, p < 0.001). Patients with atypical-HCC had a longer RFS (5-y RFS: 58.3% vs. 35.7%, p = 0.016) and OS (5-y OS: 79.1% vs 53.3%, p = 0.029) as compared to those with typical-HCC following univariate analysis, however this did not appear following multivariate analysis. CONCLUSION: Patients with atypical-HCC have different characteristic in terms of epidemiology, etiology, cirrhosis and vascular invasion as compared to typical-HCC. The etiology of atypical-HCC may be non-alcoholic fatty liver disease-related and/or malignant transformation of hepatocellular adenoma.

Middle Hepatic Vein Roadmap for a Safe Laparoscopic Right Hepatectomy.

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.

Long-term survival after post-hepatectomy liver failure for colorectal liver metastases.

BACKGROUND: While post-hepatectomy liver failure (PHLF) accurately predicts short-term mortality, its role in prognosticating long-term overall survival (OS) remains unclear. METHODS: Patients who underwent hepatectomy for colorectal liver metastases (CRLM) after portal vein embolization during 1999-2015 were evaluated retrospectively. PHLF was defined per International Study Group of Liver Surgery (ISGLS) criteria and as PeakBil >7 mg/dl. Survival was analyzed using log-rank statistic and Cox regression; patient mortality within 90 days was excluded. RESULTS: Of 175 patients, 68 (39%) had PHLF according to ISGLS criteria, including 40 (23%) with ISGLS grade B/C, and 14 (8%) had PeakBil >7 mg/dl. Patients with PeakBil >7 mg/dl had significantly worse OS than patients without PHLF (median OS, 16 vs 58 months, p = 0.001). Patients with ISGLS defined PHLF (p = 0.251) and patients with ISGLS grade B/C PHLF (p = 0.220) did not have worse OS than patients without PHLF. CONCLUSION: Peak bilirubin >7 mg/dl impacts on long-term survival after hepatectomy for CRLM and is a better predictor of long-term survival than ISGLS-defined PHLF.

Incidental versus non-incidental gallbladder cancer: index cholecystectomy before oncologic re-resection negatively impacts survival in T2b tumors.

BACKGROUND: Conflicting data exists whether non-oncologic index cholecystectomy (IC) leading to discovery of incidental gallbladder cancer (IGBC) negatively impacts survival. This study aimed to determine whether a subgroup of patients derives a disadvantage from IC. METHODS: Patients with IGBC and non-IGBC treated at an academic USA and Chilean center during 1999-2016 were compared. Patients with T1, T4 tumor or preoperative jaundice were excluded. T2 disease was classified into T2a (peritoneal-side tumor) and T2b (hepatic-side tumor). Disease-specific survival (DSS) and its predictors were analyzed. RESULTS: Of the 196 patients included, 151 (77%) had IGBC. One hundred thirty-six (90%) patients of whom 118 (87%) had IGBC had T2 disease. Three-year DSS rates were similar between IGBC and non-IGBC for all patients. However, for T2b patients, 3-year survival rate was worse for IGBC (31% vs 85%; p = 0.019). In multivariate analysis of T2 patients, predictors of poor DSS were hepatic-side tumor hazard ratio [HR], 2.9; 95% CI, 1.6-5.4; p = 0.001) and N1 status (HR, 2.4; 95% CI, 1.6-3.6; p < 0.001). CONCLUSIONS: Patients with T2b gallbladder cancer specifically benefit from a single operation. These patients should be identified preoperatively and referred to hepatobiliary center.

RAS Mutation is Associated with Unsalvageable Recurrence Following Hepatectomy for Colorectal Cancer Liver Metastases.

BACKGROUND: RAS mutation status predicts survival after hepatectomy for colorectal liver metastases (CRLM) and survival after repeat hepatectomy for intrahepatic recurrence. This study was aimed at determining the impact of RAS mutation on amenability of recurrence to local therapy and on post-recurrence survival following hepatectomy. METHODS: CRLM patients with recurrence at any location after curative intent hepatectomy during the period 2006-2015 were retrospectively analyzed. Factors associated with recurrence not amenable to local therapy and with post-recurrence survival were evaluated. RESULTS: Of 566 patients with recurrence, 309 (54.6%) underwent chemotherapy only, 189 (33.4%) underwent surgical resection, 47 (8.3%) underwent ablation, and 21 (3.7%) underwent radiation therapy. Median post-recurrence survival was significantly longer in patients with local therapy than in those with chemotherapy only (65.1 vs. 26.5 months, p < 0.0001). RAS mutation (p = 0.01), presence of extrahepatic metastases (p = 0.0006), and positive surgical margin at prior hepatectomy (p = 0.01) were associated with recurrence not amenable to local therapy. RAS mutation [hazard ratio (HR) 1.49, p = 0.0012], disease-free interval < 12 months (HR 1.76, p < 0.0001), recurrence at multiple organs (HR 1.71, p < 0.0001), and recurrence not amenable to local therapy (HR 4.11, p < 0.0001) were independent risk factors for shorter post-recurrence survival. RAS mutation was associated with poor post-recurrence survival in both patients who received local therapy and those who received chemotherapy only. CONCLUSIONS: RAS mutation predicts recurrence not amenable to any local therapy and shorter post-recurrence survival after hepatectomy for CRLM.

ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases.

BACKGROUND: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a novel two-stage strategy to induce rapid hypertrophy of the future liver remnant (FLR) when patients are in danger of postoperative liver failure due to insufficient FLR. However, the effects of ALPPS on colorectal liver metastases (CRLM) are not clear so far. The aim of our study was to determine whether ALPPS induces proliferation, apoptosis, or vascularization compared to standard (one-stage) liver resection. METHODS: Six patients who underwent ALPPS were matched with 12 patients undergoing standard liver resection regarding characteristics of the metastases (size, number), time of appearance (syn-/metachronous), preoperative chemotherapy, primary tumor (localization, TNM stage, grading), and patient variables (gender, age). The largest resected metastasis was used for the analyses. Tissue was stained for tumor cell proliferation (Ki67), apoptosis (TUNEL, caspase-3), vascularization (CD31), and pericytes (αSMA). RESULTS: Vascularization (CD31; p = 0.149), proliferation (Mib-1; p = 0.244), and αSMA expression (p = 0.205) did not significantly differ between the two groups, although a trend towards less proliferation and αSMA expression was observed in patients undergoing ALPPS. Concerning apoptosis, caspase-3 staining showed significantly fewer apoptotic cells upon ALPPS (p < 0.0001), but this was not confirmed by TUNEL staining (p = 0.7344). CONCLUSIONS: ALPPS does not induce proliferation, apoptosis, or vascularization of CRLM when compared to standard liver resection.

Calcification of the visceral aorta and celiac trunk is associated with renal and allograft outcomes after deceased donor liver transplantation.

PURPOSE: Atherosclerosis affects clinical outcomes in the setting of major surgery. Here we aimed to investigate the prognostic role of visceral aortic (VAC), extended visceral aortic (VAC+), and celiac artery calcification (CAC) in the assessment of short- and long-term outcomes following deceased donor orthotopic liver transplantation (OLT) in a western European cohort. METHODS: We retrospectively analyzed the data of 281 consecutive recipients who underwent OLT at a German university medical center (05/2010-03/2020). The parameters VAC, VAC+, or CAC were evaluated by preoperative computed tomography-based calcium quantification according to the Agatston score. RESULTS: Significant VAC or CAC were associated with impaired postoperative renal function (p = 0.0016; p = 0.0211). Patients with VAC suffered more frequently from early allograft dysfunction (EAD) (38 vs 26%, p = 0.031), while CAC was associated with higher estimated procedural costs (p = 0.049). In the multivariate logistic regression analysis, VAC was identified as an independent predictor of EAD (2.387 OR, 1.290-4.418 CI, p = 0.006). Concerning long-term graft and patient survival, no significant difference was found, even though patients with calcification showed a tendency towards lower 5-year survival compared to those without (VAC: 65 vs 73%, p = 0.217; CAC: 52 vs 72%, p = 0.105). VAC+ failed to provide an additional prognostic value compared to VAC. CONCLUSION: This is the first clinical report to show the prognostic role of VAC/CAC in the setting of deceased donor OLT with a particular value in the perioperative phase. Further studies are warranted to validate these findings. CT computed tomography, OLT orthotopic liver transplantation.

Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer.

The mammalian target of rapamycin (mTOR) acts in two structurally and functionally distinct protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Upon deregulation, activated mTOR signaling is associated with multiple processes involved in tumor growth and metastasis. Compared with mTORC1, much less is known about mTORC2 in cancer, mainly because of the unavailability of a selective inhibitor. However, existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so far. It is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth, cell survival, metabolism, and cytoskeletal organization. It is not only implicated in tumor progression, metastasis, and the tumor microenvironment but also in resistance to therapy. Rictor, the central subunit of mTORC2, was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad prognosis. Moreover, AKT, the main downstream regulator of mTORC2/Rictor, is one of the most highly activated proteins in cancer. Primary and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment, emphasizing the need for further therapeutic options. This review, therefore, summarizes the role of mTORC2/Rictor in cancer, with special focus on primary liver cancer but also on liver metastases.

Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases.

Cholangiocarcinoma (CCA) is a rare but highly aggressive tumor entity for which systemic therapies only showed limited efficacy so far. As OSI-027-a dual kinase inhibitor targeting both mTOR complexes, mTORC1 and mTORC2 - showed improved anti-cancer effects, we sought to evaluate its impact on the migratory and metastatic capacity of CCA cells in vitro. We found that treatment with OSI-027 leads to reduced cell mobility and migration as well as a reduced surviving fraction in colony-forming ability. While neither cell viability nor proliferation rate was affected, OSI-027 decreased the expression of MMP2 and MMP9. Moreover, survival as well as anti-apoptotic signaling was impaired upon the use of OSI-027 as determined by AKT and MAPK blotting. Dual targeting of mTORC1/2 might therefore be a viable option for anti-neoplastic therapy in CCA.

Prognostic biomarkers for cholangiocarcinoma (CCA): state of the art.

Introduction:Although advances in understanding the molecular basis of cholangiocarcinoma (CCA) have been made, surgery is the only curative therapy option and the overall prognosis of patients suffering from the disease remains poor. Therefore, estimation of prognosis based on known and novel biomarkers is essential for therapy guidance of CCA in both, curative and palliative settings.Areas covered:An extensive literature search on biomarkers for CCA with special emphasis on prognosis was performed. Based on this, prognostic biomarkers from serum, tumor tissue and other compartments that are currently in use or under evaluation for CCA were summarized in this review. Furthermore, an overview of new biomarkers was provided including those determined from extracellular vesicles (EVs), metabolites and nucleic acids. Finally, prognostic markers associated with potential new therapy options for the treatment of CCA were summed up.Expert opinion:So far, an optimal prognostic biomarker for CCA has not been described. However, based on the increasing knowledge about the molecular basis of CCA but also due to novel, innovative technologies, a plethora of novel prognostic biomarkers is currently under evaluation and will be available for CCA in future.

Liver transplantation in malignant disease.

Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.

[Intraoperative radiotherapy-Indications and options in visceral surgery]. / Intraoperative Strahlentherapie ­ Indikationen und Optionen in der Viszeralchirurgie.

BACKGROUND: Intraoperative radiotherapy (IORT) enables a high precision through surgical exposure of the tumor and the tumor bed, which leads to a maximum radiation dose to the tumor while simultaneously protecting normal tissue from radiation as the dose-limiting factor. Therefore, IORT can be particularly advantageous if local tumor control decisively impacts on long-term survival and enables functional preservation. OBJECTIVE: This review summarizes the knowledge gained from a literature search to enable an evidence-based approach with respect to indications and treatment options of IORT for intra-abdominal tumors. RESULTS AND CONCLUSION: Although the effectiveness of IORT cannot be finally assessed due to limited evidence, IORT is established in the clinical practice as a supplement to the multimodal treatment of (recurrent) rectal cancer and sarcomas. Gastric and pancreatic carcinomas are further indications but additional studies are necessary to clearly define the role of IORT in these tumor entities. An important factor to achieve a benefit with IORT seems to be patient selection in order to obtain good local control of local recurrences as well as overall survival rates for patients with primary or recurrent cancer.

[Intraoperative radiotherapy in abdominal surgery-Own experiences]. / Intraoperative Strahlentherapie in der Abdominalchirurgie ­ eigene Erfahrungen.

BACKGROUND: Intraoperative radiotherapy (IORT) can be applied for locally advanced tumors and expected or unavoidable R1 situations combined with surgical resection. The aim is to improve local tumor control and long-term survival. The indications are primary and recurrent intra-abdominal and retroperitoneal tumors. This study aimed to evaluate own data and experiences with IORT combined with surgical visceral resection. METHODS: Patients who underwent IORT combined with abdominal tumor resection in the Department of General and Visceral Surgery at the University Medical Center Freiburg between January 2008 and December 2018 were included in this study. The results were retrospectively evaluated regarding short-term and long-term outcomes. RESULTS: The most frequent indications for IORT were sarcoma followed by rectal and anal cancers. The median IORT dose used was 15 Gy (range 8-19 Gy). With a median comprehensive complication index (CCI) of 11.9, complications occurred in 24% of patients (Dindo-Clavien ≥ °III). The 90-day mortality was 0%. Especially in recurrent anal cancer the local control after 1 year was insufficient despite R0 resection. CONCLUSION: In this cohort of patients IORT could be applied with acceptable morbidity. Nevertheless, the indications and patient selection are critical factors for carrying out the treatment. The effect of IORT to improve local tumor control and long-term survival should be evaluated in further studies.

Anatomic Resection Is Not Required for Colorectal Liver Metastases with RAS Mutation.

BACKGROUND: Non-anatomic resection (NAR) has emerged as a safe and effective technique for resection of colorectal liver metastases (CRLM). More recently, RAS mutation has been identified as an important indicator of aggressive disease, which may require anatomic resection (AR). In this retrospective study, we compared the long-term outcomes of AR versus NAR in CRLM patients with and without RAS mutations. METHODS: Patients with known RAS mutation status who underwent AR or NAR for CRLM between 2006 and 2016 were included. Differences in baseline characteristics were adjusted using 1:1 propensity score matching, including the most important factors that contributed to the decision to use the resection technique. Overall survival (OS), recurrence-free survival (RFS), and liver-specific recurrence-free survival (L-RFS) were compared between cohorts. RESULTS: Among 622 total patients, 338 (54%) underwent AR and 284 (46%) NAR. There was no difference in OS or L-RFS between the AR and NAR groups, regardless of mutation status. There was increased RFS in the RAS WT patients with NAR (P = 0.034), but no difference in RFS in the whole cohort or RAS mutant group. After propensity score matching, 360 patients were analyzed, and no differences in OS, RFS, or L-RFS rates were seen between any groups. There was also no difference in margin recurrence. CONCLUSIONS: Similar outcomes can be achieved with both AR and NAR, regardless of RAS mutation status. These data do not support a universal requirement for AR in RAS mutant CRLM when not necessary to achieve an R0 resection.

Preoperative Prognosticators of Safe Laparoscopic Hepatocellular Carcinoma Resection in Advanced Cirrhosis: a Propensity Score Matching Population-Based Analysis of 1799 Western Patients.

BACKGROUND: The safety and oncologic outcomes of patients with advanced cirrhosis undergoing laparoscopic liver resection (LLR) compared to open resection (OLR) for hepatocellular carcinoma (HCC) remain unclear. METHODS: Patients with HCC resection during 2010-2014 were identified from the National Cancer Database. Patients with severe fibrosis; single lesions; M0; and known grade, margin status, tumor size, length of hospital stay, 30- and 90-day mortality, 30-day readmission, surgical approach, and complete follow-up were included. A 1:1 propensity score matching analysis of LLR:OLR was performed. Prognostic effect of LLR was assessed by multivariable Cox proportional hazards model. RESULTS: A total of 1799 hepatectomy patients (minor (n = 491, 27.3%); major (n = 1308, 72.7%)) were included. Of 193 (10.7%) LLR patients, 190 were eligible for matching. The LLR vs OLR did not differ for patient characteristics, resection margin status, and 30-day (p = 0.141), 90-day mortality (p = 0.121), or 30-day readmission (p = 0.784). Median hospital stay was shorter for LLR (6 vs 8 days, p = 0.001). Median overall survival (OS) was similar for LLR vs OLR (44.2 and 39.5 months, respectively, p = 0.064). Predictors of worse OS were older age (hazard ratio (HR) 1.04, p = 0.034), > 2 comorbidities (HR 1.29, p = 0.012), grade 3-4 disease (HR 1.81, p = 0.025), N1 disease (HR 1.04, p = 0.048), and R1 margins (HR 1.34, p = 0.002). After adjustment for confounders, LLR vs OLR was not a significant risk factor for OS (HR 1.14, 95% CI 0.76-1.71, p = 0.522). CONCLUSION: While LLR in advanced cirrhosis for patients with HCC proved safe, optimal patient selection based on the preoperatively available factors comorbidities, age, degree of underlying liver disease, and high-quality oncologic surgery will determine long-term survival.

Loss of muscle mass during preoperative chemotherapy as a prognosticator for poor survival in patients with colorectal liver metastases.

BACKGROUND: The survival impact of specific body composition changes during preoperative chemotherapy in patients with colorectal liver metastases undergoing curative-intent surgery remains unclear. This study aimed to determine the impact of changes in body weight and muscle mass during preoperative chemotherapy on survival after hepatectomy in patients with colorectal liver metastases. METHODS: Consecutive patients with colorectal liver metastases undergoing preoperative chemotherapy and curative hepatectomy during 2009-2013 were retrospectively analyzed. Recurrence-free and overall survival were examined according to body compositions, including muscle mass, as measured by skeletal muscle index (area of muscle [cm2]/square of height [m2]), and body weight before and after preoperative chemotherapy. RESULTS: The median follow-up duration in overall 169 patients was 47 months. Skeletal muscle index and body weight changed significantly during chemotherapy (skeletal muscle index: -0.52 cm2/m2, P = .03; body weight: +1.1 kg, P = .002). Patients with major muscle mass loss (≥7%) had significantly shorter median RFS than patients with no or minor muscle mass loss (<7%) (9.6 months vs 15.9 months; P = .02). Although major muscle mass loss was associated with poor outcome, skeletal muscle index before or after preoperative chemotherapy was not associated with recurrence-free or overall survival. On multivariate analysis, major muscle mass loss was independently associated with poorer recurrence-free survival (hazard ratio, 1.76; P = .045). CONCLUSION: Major loss of muscle mass but not body weight loss during preoperative chemotherapy is significantly associated with poor recurrence-free survival after hepatectomy in patients with colorectal liver metastases. The mechanisms mediating this association may inform future trials on maintaining muscle mass with dedicated nutrition and exercise programs to improve outcomes.