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Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor. As a result of advanced disease being often present at diagnosis, only a small percentage of patients are amenable to curative-intent treatment options such as surgical resection and liver transplantation. Systemic therapy consisting of tyrosine kinase inhibitors such as sorafenib had been used for over a decade with limited efficacy. More recently, treatment with immune checkpoint inhibitors has revolutionized the treatment landscape of various malignant tumors. With this shifting paradigm, recent data have demonstrated encouraging outcomes among patients with HCC. In particular, several trials have investigated the safety and efficacy of various immune checkpoint inhibitors (ICI) either as monotherapy or in the form of combined treatments. We sought to provide an overview of recent clinical trials among patients with advanced HCC as well as to highlight predictors of response and immune-related adverse events and to review the evidence on perioperative administration of ICI in patients with resectable HCC. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Background: The objective of the current study was to summarize and evaluate all published evidence regarding viscoelastic testing in the field of liver surgery. Methods: A systematic search of the literature was performed using Medline/PubMed, Scopus, Cochrane Library Central, Google Scholar, and clinicaltrials.gov databases. The following keywords were used:“Thromboelastography”, “Thromboelastometry”, “Viscoelastic tests OR testing”, “Sonoclot Devices”, “Point-of-care tests OR testing”, “Coagulation OR Haemostasis OR Hemostasis”, “Liver OR Hepatic Surgery”, “Cirrhosis.” Results: A total of 12 studies analyzing 348 patients who underwent viscoelastic testing of coagulation during liver surgery for benign or malignant diseases were included; 7 (58.3%) studies reported on the use of thromboelastography (TEG), and 5 (41.7%) reported on rotational thromboelastometry (ROTEM). Viscoelastic testing (TEG and ROTEM) identified normo-, hyper- and hypo-coagulable status in 77% (n = 268/348), 18.4% (n = 64/348), and 4.6% (n = 16/348) of patients, respectively. In contrast, conventional coagulation tests indicated normo-coagulability in 111 patients (34.2% out of 325) and hypo-coagulability in 214 (65.8% out of 325) patients following liver resection. No patient (0% out of 291) experienced postoperative hemorrhage, whereas 5.8% (n = 17/291) experienced postoperative thromboembolic events. Conclusions: Global viscoelastic testing may be a reasonable adjunct to conventional coagulation testing to provide a more robust assessment of the coagulation status of patients undergoing liver surgery. © 2020 International Hepato-Pancreato-Biliary Association Inc.

Introduction: Cholangiocarcinoma is a malignant disease of the biliary tract and accounts for 3% of all gastrointestinal tumors. Surgical intervention is currently the only potentially curative strategy for cholangiocarcinoma. For patients with unresectable, advanced or metastatic disease, the combination of gemcitabine with cisplatin is considered the standard treatment. However, currently available therapeutic options have only a marginal benefit, especially among patients with relapsed/refractory tumors. Areas covered: We reviewed targeted agents under clinical evaluation for patients with cholangiocarcinoma. FGFR and IDH inhibitors are at the most advanced stage of clinical investigation. EGFR inhibitors have demonstrated contradictory results, whereas inhibition of other molecular pathways, including the RAS/RAF/MEK/ERK, the MET, the PI3K/AKT/mTOR and angiogenetic pathways, has shown minimal or null benefit. Expert opinion: Several targeted approaches are being investigated for advanced cholangiocarcinoma. However, randomized clinical trials are needed to define the optimal treatment regimen and address issues including the option of monotherapy or combination regimens, the optimal sequence of different treatments, ways to overcome resistance to targeted treatments, as well as determining the right time and tissue for assessing molecular signatures. Targeted therapies and immunotherapy hold promise for improving patient outcomes in the future. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) represents a novel surgical technique which provides rapid and effective liver regeneration allowing for the resection of lesions initially deemed unresectable. The objective of this systematic review is to summarize all technical modifications of the original ALPPS approach (mALPPS) for primary liver malignancies and evaluate short- and long-term outcomes. A systematic search of the literature was conducted using PubMed, Scopus, Cochrane Library Central, Google Scholar, and clinicaltrials.gov databases until July, 31 2019. The following keywords were utilized: “Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy”, “ALPPS”, “Portal Vein Embolization (PVE) And In Situ Split”, “Portal Vein Ligation (PVL) And In Situ Split”. A total of 24 studies were identified incorporating data on 83 patients who underwent a mALPPS for a primary liver malignancy. Median FLR hypertrophy after ALPPS-1 was 54% (range, 6.7–133%) and median EBL during the ALPPS 1 and ALPPS 2 stages was 200 mL (range 0–1000) and 700 ml (range 100–4000), respectively. R0 resections were achieved in all patients (100%). Most complications occurred post ALPPS- 2 (n = 33/72, 45.8%), while overall 30-day mortality was 13.3%. After a median follow up of 7 months (range 3–60), recurrence rate was 18.9%. Disease-free survival ranged from 3 to 60 months with a median of 10 months and overall survival ranged from 3 to 60 months with a median of 11 months. ALPPS with the various technical modifications offers a reasonable chance of complete tumor resection among patients with initially unresectable primary liver tumors. Further advances in patient selection, surgical techniques and perioperative management are required to minimize complications rates. Large scale prospective trials are needed to validate the role of the technical modifications of ALPPS in the treatment of patients with primary liver malignancies in an individualized setting. © 2020 Elsevier Ltd

The following reference in this paper refers to a paper that has been since retracted. 70. Zhao C, Pei SL, Cucchetti A, Tong TJ, Ma YL, Zhong JH, et al. Systematic review: benefits and harms of transarterial embolisation for treating hepatocellular adenoma. Aliment Pharmacol Ther. 2017. © 2019, The Society for Surgery of the Alimentary Tract.

Background: There has been a dramatic increase in worldwide health care spending over the last several decades. Operative procedures and perioperative care in the USA represent some of the most expensive episodes per patient. In view of both the rising cost of health care in general and the rising cost of surgical care specifically, policymakers and stakeholders have sought to identify ways to increase the value—improving quality of care while controlling (or diminishing) costs. In this context, we reviewed data relative to achieving the “value proposition” in the delivery of gastrointestinal surgical care. Methods: The National Library of Medicine online repository (PubMed) was text searched for human studies including “cost,” “quality,” “outcomes,” “health care,” “surgery,” and “value.” Results from this literature framed by the Donabedian conceptual model (identifying structures, processes, and outcomes), and the resulting impact of efforts to improve quality on costs. Results: The relationship between quality and costs was nuanced. Better quality care, though associated with better outcomes, was not always reported as concomitant with low costs. Moreover, some centers reported higher costs of surgical care commensurate with higher quality. Conversely, higher costs in health care delivery were not always linked to improved outcomes. While higher quality surgical care can lead to lower costs, higher costs of care were not necessarily associated with better outcomes. Strategies to improve quality, reduce cost, or achieve both simultaneously included regionalization of complex operations to high-volume centers of excellence, overall reduction in complications, introducing evidence-based improvements in perioperative care pathways including as enhanced recovery after surgery (ERAS), and elimination of inefficient or low-value care. Conclusions: The relationship between quality and cost following gastrointestinal surgical procedure is complex. Data from the current study should serve to highlight the various means available to improve the value proposition related to surgery, as well as encourage surgeons to become more engaged in the national conversation around the Triple Aim of better health care quality, lower costs, and improved health care outcomes. © 2020, The Society for Surgery of the Alimentary Tract.

While colorectal and hepatic resections are commonly performed through a laparoscopic approach, the safety and feasibility of total laparoscopic synchronous resections (LSR) of colorectal liver metastasis (CRLM) have not been established. In this systematic review, short- and long-term outcomes were comparable for patients undergoing LSR and open synchronous resection. LSR was safe and feasible for patients with synchronous CRLM and should be considered in well-selected patients. © 2018 Wiley Periodicals, Inc.

Advances in systemic chemotherapy have resulted in a significant increase in the reported response rates of colorectal liver metastases (CRLM) over time. Although radiologic response is usually prognostic of favorable outcomes, complete shrinkage of CRLM after chemotherapy, namely “disappearing liver metastases” (DLMs) poses significant therapeutic dilemmas. A systematic review of the literature was conducted to evaluate the existing evidence on the imaging and management of patients with DLMs using the PubMed (Medline), Embase and Cochrane library through December 21st, 2018. The following algorithm was used: “(disappearing OR vanishing OR missing OR (residual tiny)) AND ((liver OR hepatic) AND (metastasis OR metastases OR metastatic OR secondary)).” From the 225 records retrieved, 15 studies were finally deemed eligible. A total of 479 patients with DLMs with a median age of 59.5 years (range, 30–83) were identified. Median number of DLM per patient ranged from 1 to 8.8. Median size of LMs prior to chemotherapy was 1.07 cm (range 0.3–3.5). The systemic treatment used to achieve DLMs included systemic chemotherapy alone (only 2 studies) or in combination with targeted agents (11 studies). The median number of chemotherapy cycles in the included studies was 7.8 (range 6–12). Identified factors predisposing to the development of DLM were small size (

Introduction: Patients with midgut neuroendocrine tumors (MNETs) frequently present with metastatic disease at the time of diagnosis. Although combined resection of the primary MNET and liver metastases (NELM) is usually recommended for appropriate surgical candidates, primary tumor resection (PTR) in the setting of extensive, inoperable metastatic disease remains controversial. Methods: A systematic review was performed according to PRISMA guidelines utilizing Medline (PubMed), Embase, and Cochrane library—Cochrane Central Register of Controlled Trials (CENTRAL) databases until September 30, 2018. Results: Among patients with MNET and NELM, 1226 (68.4%; range, 35.5–85.1% per study) underwent PTR, whereas 567 (31.6%; range, 14.9–64.5%) patients did not. Median follow-up ranged from 55 to 90 months. Cytoreductive liver surgery was performed in approximately 15.7% (range, 0–34.8%) of patients. Pooled 5-year overall survival (OS) among the resected group was approximately 73.1% (range, 57–81%) versus 36.6% (range, 21–46%) for the non-resection group. For patients without liver debulking surgery, PTR remained associated with a decreased risk of death at 5 years compared with patients who did not have the primary tumor resected (HR 0.36, 95% CI 0.16 to 0.79, p = 0.01; I 2 58%, p = 0.12). For patients undergoing PTR, 30-day postoperative mortality ranged from 1.43 to 2%. Conclusion: PTR was safe with a low peri-operative risk of mortality and was associated with an improved OS for patients with MNET and unresectable NELM. Given the poor quality of evidence, however, strong evidenced-based recommendations cannot be made based on these retrospective single center–derived data. Future well-design randomized controlled trials will be critical in elucidating the optimal treatment strategies for patients with MNET and advanced metastatic disease. © 2019, The Society for Surgery of the Alimentary Tract.

Background: While reduction of portal venous (PV) blood flow has been described in animal models of intra-abdominal hypertension, reports on compensatory changes in hepatic arterial (HA) flow, known as the hepatic arterial buffer response are controversial. Materials and Methods: Pneumoperitoneum with helium was induced in 13 piglets. Hemodynamic measurements and pathological assessment were conducted at baseline and during the three subsequent phases: Phase A: 45 minutes with a stable intraabdominal pressure of 25 mmHg; phase B: 45 minutes with a stable intra-abdominal pressure of 40 mmHg; and phase C during which the abdomen was re-explored and reperfusion of the liver was allowed to take place. Results: Phase B pressure was significantly greater than phase A pressure in both the PV and the inferior vena cava, demonstrating a positive association between escalating intra-abdominal hypertension and the pressure in these two vessels (all p

Background: Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0–1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. Methods: Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. Results: Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04–2.67; P = 0.04, and HR 2.14, 1.46–3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41–2.65; P < 0.001). Conclusions: Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies. © 2018, The Society for Surgery of the Alimentary Tract.