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Background: Intraoperative indocyanine green (ICG) fluorescence imaging has been shown to be a new and innovative way to illustrate the optimal resection margin in hepatectomy for hepatocellular carcinoma. This study investigated its accuracy in resection margin determination by looking into the correlation of ICG intensity gradients with pathological examination results of resected specimens. Methods: This was a prospective, single-center, non-randomized controlled study. Patients who had liver tumors indicating liver resection were recruited. The hypothesis was that the use of intraoperative near-infrared/ICG fluorescence imaging would be a promising guiding tool for removing hepatocellular carcinoma with a better resection margin. Patients were given ICG (0.25 mg/kg) 1 day before operation. Resected specimens were inspected under a fluorescent imaging system. Biopsies were taken from tumors and normal tissue. Color signals obtained from ICG fluorescence imaging were compared with biopsies for analysis. Results: Twenty-two patients were recruited for study. The median size of their tumors was 2.25 cm. One patient had resection margin involvement. Under ICG fluorescence, the tumors typically lighted up as yellow color, wrapped by a zone of green color. Tumors of 17 patients (77.3%) displayed yellow color and were confirmed malignancy, while tumors of 12 patients (54.5%) displayed green color and were confirmed malignancy. Receiver operating characteristic curve was used to measure the sensitivity and specificity of the green color to look for a clear resection margin. The area under the curve was 85.3% (p = 0.019, 95% confidence interval 0.696–1.000), with a sensitivity of 0.706 and specificity of 1.000. Conclusion: The use of ICG fluorescence can be helpful in determining resection margins. Resection of tumor should include complete resection of the green zone shown in the fluorescence image. [ABSTRACT FROM AUTHOR]

Objective: This study is to examine the impact of perioperative (intraoperative/postoperative) blood transfusion on the outcomes of curative hepatectomy for hepatocellular carcinoma. Summary background data: Hepatectomy is a well-established curative treatment for hepatocellular carcinoma, and blood transfusion cannot always be avoided in treating the disease. Methods: A retrospective study of patients having curative hepatectomy for hepatocellular carcinoma from January 2010 to December 2019 at a single center was conducted. The patients were stratified by their disease stage. Patients with and without perioperative blood transfusion were matched by propensity-score matching and compared for each disease stage. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival for each stage. Results: A total of 846 patients were studied. Among them, 125 received perioperative blood transfusion and 720 did not. Patients with blood transfusion had worse disease-free and overall survival. After stratification and matching, the ratios of transfusion to non-transfusion were 33:165 (stage 1), 28:140 (stage 2), and 45:90 (stage 3). Perioperative blood transfusion was associated with a higher incidence of postoperative complications in all three disease stages (p = 0.004/0.006/0.017), and hence longer hospitalization (p < 0.001 in all stages), but had no significant impact on hospital mortality (p = 0.119/0.118/0.723), 90-day mortality (p = 0.259/0.118/0.723), disease-free survival (p = 0.128/0.826/0.511), or overall survival (p = 0.869/0.122/0.122) in any disease stage. Prognostic factors for overall survival included tumor size, tumor number, alpha-fetoprotein level, and postoperative complication of grade ≥ 3A. Conclusion: Perioperative blood transfusion was associated with a higher incidence of complications but had no significant impact on survival after curative hepatectomy for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Cytokines are key regulators of post-transplant inflammation responses which reconstitute post-transplant hepatic and systemic environments to influence the likelihood of tumor relapse. This study investigated the prognostic value of post-transplant cytokines on tumor recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods: A retrospective analysis was conducted in prospectively collected 150 adult HCC patients who received liver transplantation from 1997 to 2015. The post-transplant 41 inflammatory cytokines were quantified by multiplexing analysis and determined their prognostic value for predicting post-LT tumor recurrence by receiver operative characteristic analysis. A prediction model for post-LT tumor recurrence was generated by the logistic regression and internally validated Bootstrapping and compared with external prediction models. Results: Post-transplant circulating CCL11, IFNα2, and IL17A cytokines were identified to be significant predictors of post-LT tumor recurrence and survival. A prediction score composed of the post-transplant 3-cytokine (P3C) signature, UCSF criteria, and pre-LT AFP was established. The P3C-UCSF-AFP score significantly predicted post-LT tumor recurrence and poor survival both in deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). The P3C-UCSF-AFP score was validated to significantly predict post-LT 2-year and 5-year tumor recurrence, outperforming the RETREAT score, French AFP model, up-to-seven, UCSF criteria, and Milan criteria. Importantly, the P3C-UCSF-AFP score could cost-effectively stratify high-risk recipients subjected to a refinement of post-recurrence survival. Conclusion: The integrated P3C-UCSF-AFP score not only compensated for the pre-LT unpredictability and predicted post-LT tumor recurrence accurately, but also guided the clinical refinements of post-LT surveillance and therapeutic strategies in transplant oncology. [ABSTRACT FROM AUTHOR]

The application of steatotic liver graft has been increased significantly due to the severe donor shortage and prevalence of non-alcoholic fatty liver disease. However, steatotic donor livers are vulnerable to acute phase inflammatory injury, which may result in cancer recurrence. Alternative splicing events (ASEs) are critical for diverse transcriptional variants in hepatocellular carcinoma (HCC). Here, we aimed to depict the landscape of ASEs, as well as to identify the differential ASEs in steatotic liver graft and their association with tumor recurrence after transplantation. The overall portrait of intragraft transcripts and ASEs were elucidated through RNA sequencing with the liver graft biopsies from patients and rat transplant models. Various differential ASEs were identified in steatotic liver grafts. CYP2E1, ADH1A, CYP2C8, ADH1C, and HGD, as corresponding genes to the common pathways involved differential ASEs in human and rats, were significantly associated with HCC patients' survival. The differential ASEs related RNA-binding proteins (RBPs) were enriched in metabolic pathways. The altered immune cell distribution, particularly macrophages and neutrophils, were perturbated by differential ASEs. The cancer hallmarks were enriched in steatotic liver grafts and closely associated with differential ASEs. Our work identified the differential ASE network with metabolic RBPs, immune cell distribution, and cancer hallmarks in steatotic liver grafts. We verified the link between steatotic liver graft injury and tumor recurrence at post-transcriptional level, offered new evidence to explore metabolism and immune responses, and provided the potential prognostic and therapeutic markers for tumor recurrence. [ABSTRACT FROM AUTHOR]

Background: Surgical resection is indicated for resectable colorectal liver metastases (CLM), but it is controversial for non-colorectal liver metastases (NCLM). This study aimed to compare survival outcomes of patients with resection of NCLM versus CLM and to identify prognostic factors for resection of NCLM. Methods: Consecutive patients who underwent surgical resection of liver metastases at Queen Mary Hospital, Hong Kong from January 1989 to December 2019 were retrospectively reviewed. Patients with resected NCLM were compared to those with CLM. Overall and recurrence-free survival were determined. Subgroup analyses with patients grouped according to the year of liver resection, from 1989 to 2004 and from 2005 to 2019, were conducted. Univariate and multivariate analyses were performed to identify prognostic factors. Results: Among 674 patients included, 151 (22.4%) had NCLM while 523 (77.6%) had CLM. There were no statistically significant differences in median overall survival (65.2 vs 43.6 months, p = 0.555) and recurrence-free survival (12.5 vs 11.7 months, p = 0.425). The 1-year, 3-year, 5-year and 10-year overall survival rates were 89.8% vs 91.5%, 59.4% vs 58.8%, 50.6% vs 38.7% and 34.1% vs 26.3% in NCLM and CLM groups, respectively. Subgroup analyses demonstrated no statistically significant difference in overall survival between resection of NCLM versus CLM in both time intervals. In the NCLM group, better overall survival was found in liver metastasis of gastrointestinal stromal tumour (GIST) origin (hazard ratio (HR) 0.138, p = 0.003) and with a longer time interval from resection of primary tumour to resection of NCLM (HR 0.982, p = 0.042). Poor prognostic factors were presence of blood transfusion (HR 5.588, p = 0.013) and post-operative complications of Clavien-Dindo Grade IIIa or above (HR 74.853, p = 0.003). Conclusions: Surgical resection of NCLM had comparable survival outcomes with CLM. With appropriate patient selection, the indication of liver resection could be expanded to NCLM. [ABSTRACT FROM AUTHOR]

Introduction: Liver resection is the best treatment option for patients with resectable colorectal liver metastasis (CRLM). A 10-year follow-up can reflect the true curative potential of resection. This retrospective study investigated factors for long-term survival of CRLM patients. Method: Data of patients who underwent liver resection for CRLM without extrahepatic disease from 1990 to 2012 at our hospital were reviewed. Patients who survived for > 10 years were compared with those who survived for < 10 years. Results: Totally, 315 patients were included in the study. They were divided into 2 groups: < 10-year group and > 10-year group. Patients in the < 10-year group had more tumor nodules (P = 0.016), more bilobar involvement (P = 0.004), narrower resection margin (P < 0.001), and worse disease-free and overall survival (P < 0.001). On multivariate analysis, low preoperative hemoglobin level, large number of tumor nodules, and bilobar involvement were poor prognostic factors for overall survival, while adjuvant chemotherapy was a favorable factor. Further analysis of patients with bilobar disease showed that perioperative blood transfusion was a poor prognostic factor for overall survival while adjuvant chemotherapy was a favorable one. In patients with multiple bilobar tumor nodules, adjuvant chemotherapy had a positive impact on disease-free survival and overall survival. Conclusions: Patients who survived for > 10 years after liver resection for CRLM tended to have normal preoperative hemoglobin level, unilobar disease, fewer tumor nodules, and have received adjuvant chemotherapy. Adjuvant chemotherapy favorably affected long-term survival of CRLM patients. [ABSTRACT FROM AUTHOR]

It is uncertain whether tumour biology affects radical treatment for post-transplant hepatocellular carcinoma (HCC) oligo-recurrence, i.e. recurrence limited in numbers and locations amendable to radical therapy. We conducted a retrospective study on 144 patients with post-transplant HCC recurrence. Early recurrence within one year after transplant (HR 2.53, 95% CI 1.65–3.88, p < 0.001), liver recurrence (HR 1.74, 95% CI 1.12–2.68, p = 0.01) and AFP > 200 ng/mL upon recurrence (HR 1.62, 95% CI 1.04–2.52, p = 0.03) predicted mortality following recurrence. In patients with early recurrence and liver recurrence, radical treatment was associated with improved post-recurrence survival (early recurrence: median 18.2 ± 1.5 vs. 9.2 ± 1.5 months, p < 0.001; liver recurrence: median 28.0 ± 4.5 vs. 11.6 ± 2.0, p < 0.001). In patients with AFP > 200 ng/mL, improvement in survival did not reach statistical significance (median 18.2 ± 6.5 vs. 8.8 ± 2.2 months, p = 0.13). Survival benefits associated with radical therapy were reduced in early recurrence (13.6 vs. 9.0 months) and recurrence with high AFP (15.4 vs. 9.3 months) but were similar among patients with and without liver recurrence (16.9 vs. 16.4 months). They were also diminished in patients with multiple biological risk factors (0 risk factor: 29.0 months; 1 risk factor: 19.7 months; 2–3 risk factors: 3.4 months): The survival benefit following radical therapy was superior in patients with favourable biological recurrence but was also observed in patients with poor tumour biology. Treatment decisions should be individualised considering the oncological benefits, quality of life gain and procedural morbidity. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that ICG fluorescence cholangiography (ICG-FC) helps to identify critical structures during laparoscopic cholecystectomy (LC) and hence reduce biliary injuries and conversions. In LC, biliary injury and conversion often happen if the biliary anatomy is misidentified.Methods: This was a single-center randomized controlled trial from 2017 to 2019. Patients with acute cholecystitis requiring LC were assessed for eligibility for the trial. Patients in the trial were randomized to undergo either conventional LC (conventional arm) or LC with ICG-FC (ICG arm). Conversion rate and biliary injury incidence were outcome measures.Results: Totally 92 patients participated (46 patients in each arm). The median age was 61 years in both arms (p = 0.472). The conventional arm had 22 men and 24 women; the ICG arm had 24 men and 22 women (p = 0.677). The two arms were comparable in all perioperative parameters. The time from ICG injection to surgery was 67 (16-1150) min. Both arms had an 8.7% conversion rate (p = 1.000). The median operative time was 140.5 min in the conventional arm and 149.5 min in the ICG arm (p = 0.086). The complication rate was 15.2% in the former and 10.9% in the latter (p = 0.536), and both had a 2.2% bile leakage rate. The median hospital stay was 3.5d in the former and 4.0d in the latter (p = 0.380).Conclusion: ICG-FC did not make any difference in conversion or complication rate. Its routine use in LC is questionable. However, it may be helpful in difficult cholecystectomies and may be used as an adjunct.Trial Registration: The trial was registered with the Institutional Review Board of University of Hong Kong/Hospital Authority Hong Kong West Cluster ( http://www.med.hku.hk/en/research/ethics-and-integrity/human-ethics ).Registration Number: UW17-492. [ABSTRACT FROM AUTHOR]

Simple Summary: For 657 cases of segment or less repeat liver resection with results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery, the indicators were compared before and after surgery. There were 268 open repeat after open and 224 cases laparoscopic repeat after laparoscopic liver resection. The background factors and liver functional indicators before and after surgery, and the changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Though laparoscopic group had poorer performance status and liver function, changes of the values and overall survivals were similar between both groups. Plasma levels of albumin and bilirubin and ALBI score could be the liver functional indicators for liver functional deterioration after liver resection. The laparoscopic group with poorer conditions showed a similar deterioration of liver function and overall survival to the open group. Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group. [ABSTRACT FROM AUTHOR]

Background/Aim: Alpha-fetoprotein (AFP) had been used as a prognostic factor in hepatocellular carcinoma but it was unknown what level of AFP could predict the survival of patients with ruptured hepatocellular carcinoma (rHCC) after resection. This retrospective study was to identify the best cutoff value of AFP for this prediction. Methods: Data of patients having hepatectomy for rHCC from 1989 to 2015 were reviewed. The receiver operating characteristic curve and Youden's index were used to identify the cutoff value of AFP affecting survival. The patients were then divided into two groups by the cutoff for comparison. Results: Totally 114 patients were included. An AFP level of 256 ng/ml was found to affect survival (area under curve 63.1%, 95% confidence interval 0.514–0.748, p = 0.027; sensitivity 0.6, specificity 0.706). The 114 patients were divided into Group A (AFP < 256 ng/ml, n = 56) and Group B (AFP ≥ 256 ng/ml, n = 58). The median AFP level was 13.0 ng/ml (range, 2–253 ng/ml) in Group A and 11206.5 ng/ml (range, 259–481,000 ng/ml) in Group B (p < 0.001). Group A had a larger proportion of patients receiving transarterial embolization at the time of rupture, and the time to hepatectomy was longer in this group. Patients in Group B had more blood loss, more complications, larger tumors, and more cases of macrovascular/microvascular invasion. Overall survival (p = 0.013) and disease-free survival (p = 0.024) were significantly better in Group A. On multivariate analysis, AFP ≥ 256 ng/ml was an independent risk factor for overall survival. Conclusion: AFP ≥ 256 ng/ml had an adverse impact on the survival of patients with rHCC after resection. [ABSTRACT FROM AUTHOR]

Background: Salvage liver transplantation (SLT) is the ideal treatment for patients with recurrent hepatocellular carcinoma (HCC) and liver cirrhosis. The optimal timing for offering SLT was controversial. This study aimed at investigating the impact of time to recurrence and other prognostic factors on survival outcome after SLT.Methods: Between May 2000 and April 2019, patients who had undergone hepatectomy or ablation for HCC and later received SLT in Queen Mary Hospital were included. Clinico-pathological data during primary treatment and SLT were retrospectively reviewed. Kaplan-Meier analysis and log-rank test were used to determine overall and disease-free survival after SLT. Prognostic factors affecting overall and disease-free survival were determined by multivariate analysis using Cox regression analysis. P-value of less than 0.05 was considered statistically significant.Results: Fifty-three patients were identified within the specified period including 22 patients in early recurrence group (ER group, time to recurrence within 1 year) and 31 patients in late recurrence group (LR group, time to recurrence more than 1 year). The 1-, 5-, and 10-year overall survival after primary treatment was 100%, 76.6%, and 61.1% in the ER group and 100%, 90%, and 76.4% in the LR group (p = 0.59). There were no statistical differences in overall survival (p = 0.84) and disease-free survival (p = 0.85) after SLT between ER and LR group. Pre-transplant alpha-fetoprotein >  = 400 ng/mL (p = 0.007) and macrovascular invasion in explant (p = 0.002) were independent risk factors for shorter overall survival after primary treatment.Conclusion: Time to recurrence after primary treatment of HCC did not affect survival outcome after SLT. With careful patient selection, SLT could be offered to patient with early or late tumor recurrence. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatectomy is a well-established curative treatment for hepatocellular carcinoma. However, the role of adjuvant therapy is controversial. This study examines the efficacy of adjuvant transarterial chemotherapy for hepatocellular carcinoma. Methods: The data of hepatocellular carcinoma patients undergoing curative hepatectomy was reviewed. Those with adjuvant transarterial chemotherapy were matched with those without using propensity score analysis, by tumour size and number, indocyanine green retention rate, disease staging and Child–Pugh grading. The groups were compared. Results: Eighty-seven patients with hepatocellular carcinoma who underwent hepatectomy received adjuvant transarterial chemotherapy (TAC group), and were matched with 870 patients who did not (no-TAC group). The groups were largely comparable in patient and disease characteristics, but the TAC group experienced more blood loss, higher transfusion rates, narrower margins and more positive margins. The two groups were found to be comparable in disease-free and overall survival rates. In margin-positive patients, those given TAC survived longer than those without, and margin-positive patients in the TAC group had overall survival rates similar to margin-negative patients in the no-TAC group. Conclusions: Margin involvement is an adverse factor for survival in HCC. Adjuvant transarterial chemotherapy may offer survival benefits to hepatocellular carcinoma patients with positive surgical margins. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective, single-center study aimed to investigate the importance of chemotherapy and to come up with the optimal liver resection margin length for patients with resectable colorectal liver metastasis (CRLM). Methods: Patients who had undergone any form of liver resection for CRLM were reviewed and analyzed. The analyses were broken down into three parts: (1) overall effect of chemotherapy, (2) effect of chemotherapy with positive/negative resection margin, and (3) result of discriminative analysis with optimal margin length analysis. Results: In total, 381 patients were studied. Among them, 279 received chemotherapy whereas 102 did not. Survival was significantly better in patients with chemotherapy (5-year, 43.6% vs. 25.8%) (p < 0.001). Patients who received chemotherapy (n = 93) with negative margins had better survival than patients (n = 8) with positive margins (5-year, 28.1% vs. 0%) (p = 0.019). On multivariate analysis, margin involvement was the poor prognostic factor for survival. Patients who had chemotherapy (n = 238) with negative margin showed a trend of better survival than patients (n = 41) with positive margins (5-year, 45.7% vs. 29.3%) (p = 0.085). Patients (n = 93) with negative margin and no chemotherapy and patients (n = 41) with positive margin and chemotherapy had comparable survival at 5 years (p = 0.422). On multivariate analysis, tumor number was the prognostic factor for survival. By the discriminant method, 1.09 cm (sensitivity 0.242, specificity 0.718) was determined as the cut-off for optimal margin length. Patients who had margin ≥ 1.09 cm (n = 81) enjoyed significantly better survival (5-year, 54.3% vs. 33.5%) (p = 0.041). On multivariate analysis, margin length ≥ 1.09 cm was the prognostic factor for favorable survival. Conclusion: The results demonstrated the important effect of perioperative chemotherapy and negative margin liver resection in management of patients suffered from CRLM. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) has been shown to be a valuable tool in the management of small liver tumors such as hepatocellular carcinoma (HCC). It has been shown to be a safe and effective means to ablate small HCC even in the presence of advanced cirrhosis. This review examines the challenges faced during HIFU ablation when the target tumors are located in difficult locations such as the liver dome, close to the rib cage, near large blood vessels or the heart, or adjacent to hollow viscera; and the special maneuvers employed to tackle such lesions. [ABSTRACT FROM AUTHOR]

Background: Treatment of hepatocellular carcinoma (HCC) recurrences following liver transplant (LT) is challenging. Most clinical trials of systemic therapies for advanced HCC excluded patients with any history of organ transplant. We aimed to assess the outcomes in using various systemic therapies in patients with post-LT recurrence. Methods: Consecutive patients with HCC and recurrences following LT at a large tertiary centre from 2005 to 2018 were reviewed. Overall survival (OS), response rates and adverse events (AEs) were analysed. Results: Forty-three consecutive patients with a recurrence of HCC following LT were identified from 2005 to 2018. Median OS from diagnosis of recurrence was 17 months (CI 11.3, 22.7). Early recurrence within 12 months of transplant was associated with a significantly worse median survival of 10 months (CI 8.5, 11.4) compared to 26 months (CI 18.8, 33.2) when recurrences occurred after 12 months from transplant (p < 0.001) with a hazard ratio of 0.104 (log-rank test, p < 0.001). A total of 41 patients had received systemic therapies and 79.1% of them were on sorafenib as the first-line treatment. Among these patients treated with sorafenib, median OS from recurrence was 14 months (CI 7.3, 20.7). Hand-foot syndrome (34.7%) was most common among AEs followed by diarrhoea (26.7%). Overall, AEs led to dose interruptions in 8.8% of patients. Notably, 47.1% of patients received subsequent lines of systemic therapies after sorafenib. Conclusions: Early recurrence within 1 year from transplant was the most significant risk factor. Treatment efficacy and adverse events and tolerability of sorafenib were comparable with those in the setting of advanced HCC without transplant. [ABSTRACT FROM AUTHOR]

The physical microenvironment is a critical mediator of tumor behavior. However, detailed biological and mechanistic insight is lacking. The present study reveals the role of chemotherapy‐enriched CD133+ liver cancer stem cells (CSCs) with THBS2 deficiency. This subpopulation of cells contributes to a more aggressive cancer and functional stemness phenotype in hepatocellular carcinoma (HCC) by remodeling the extracellular matrix (ECM) through the regulation of matrix metalloproteinase (MMP) activity, collagen degradation, and matrix stiffness. The local soft spots created by these liver CSCs can enhance stemness and drug resistance and provide a route of escape to facilitate HCC metastasis. Interestingly, a positive feed‐forward loop is identified where a local soft spot microenvironment in the HCC tumor is enriched with CD133 expressing cells that secrete markedly less ECM‐modifying THBS2 upon histone H3 modification at its promoter region, allowing the maintenance of a localized soft spot matrix. Clinically, THBS2 deficiency is also correlated with low HCC survival, where high levels of CSCs with low THBS2 expression in HCC are associated with decreased collagen fiber deposits and an invasive tumor front. The findings have implications for the treatment of cancer stemness and for the prevention of tumor outgrowth through disseminated tumor cells. [ABSTRACT FROM AUTHOR]

Hepatic ischemia–reperfusion (IR) injury is a critical issue during liver transplantation (LT). Recent studies have demonstrated that IL‐17a contributes to IR injury and steatohepatitis. However, the underlying mechanism is not understood. This study aimed to examine the role of IL‐17a on hepatic IR injury in fatty liver and to investigate the underlying mechanisms. The correlation between serum IL‐17a levels and liver function was analyzed in LT patients receiving fatty (n = 42) and normal grafts (n = 44). Rat LT model was applied to validate the clinical findings. IL‐17a knockout (KO) and wild‐type mice were fed with high‐fat diets to induce fatty liver and subjected to hepatic IR injury with major hepatectomy. Frequency of circulating neutrophils and IL‐17a expression on PBMCs were analyzed by flow cytometry. Mitochondrial outer membrane permeabilization (MOMP) was examined by a living intravital image system. Serum IL‐17a was elevated after human LT, especially with fatty grafts. The aspartate aminotransferase and alanine transaminase levels were increased in recipients with fatty grafts compared with normal grafts. In rat LT model, the intragraft IL‐17a expression was significantly higher in fatty grafts than normal ones post‐LT. KO of IL‐17a in mice notably attenuated liver damage after IR injury in fatty liver, characterized by better‐preserved liver architecture, improved liver function, and reduced neutrophil infiltration. MOMP triggered cell death after hepatic IR injury in a caspase‐independent way via IL‐17a/NF‐κB signaling pathway. KO of IL‐17a protected the fatty liver against IR injury through the suppression of neutrophil infiltration and mitochondria‐driven apoptosis. [ABSTRACT FROM AUTHOR]

Background. Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are commonly used for assessing pancreatic lesions. This study aimed to evaluate the diagnostic yield and accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a single tertiary institution. Methods. Consecutive patients who underwent EUS-FNA of the pancreas at Queen Mary Hospital, Hong Kong, from January 2015 to March 2016 were retrospectively reviewed. Endoscopic findings and FNA results were analysed. For patients who subsequently underwent surgical resection of pancreatic lesion, EUS-FNA diagnoses were compared to histopathological findings of surgical specimens to determine its diagnostic accuracy. Results. One hundred twelve EUS-FNA were performed in 99 patients within the study time period and were included for analysis. Sixty-six (66.7%) pancreatic lesions were solid in nature and 33 (33.3%) were cystic. The overall diagnostic yield of EUS-FNA was 70.5% (n = 79). On multivariate analysis, more passes of needle were associated with a higher diagnostic yield (odds ratio = 2.000, P =.049). 57.1% (n = 64) of EUS-FNA results had an impact on management. Sixteen patients with diagnostic EUS-FNA subsequently underwent surgery for resection of the pancreatic lesion. Upon correlation to the histopathological findings of surgical specimens, there were 12 true-positive, 2 true-negative, 0 false-positive, and 2 false-negative cases. Sensitivity was 85.7%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 50%. The diagnostic accuracy of EUS-FNA was 87.5%. Conclusion. EUS-FNA is accurate and reliable for diagnosing pancreatic lesions. [ABSTRACT FROM AUTHOR]

Background: The aggressive approach of vascular resection plus reconstruction in curative resection of hilar cholangiocarcinoma (HC) remains controversial. This retrospective study investigated its short‐ and long‐term outcomes. Methods: Data of HC patients from 1989 to 2016 were reviewed. Operated patients were divided into two groups (with and without vascular resection) and compared in terms of perioperative results. Patients who had unresectable HC were also compared with patients who had been operated. Results: Ninety patients underwent curative HC resection. They were divided into group A (without aggressive approach, n = 68) and group B (with aggressive approach, n = 22). The groups were comparable in all parameters including rates of overall and major complication and in‐hospital, 30‐day and 90‐day mortality except that group B had more patients with more advanced disease (P = 0.008), more patients with tumour invasion of the vasculature (40.9% versus 7.4%, P = 0.001), and fewer patients with blood transfusion (27.3% versus 52.9%, P = 0.036). The groups had similar disease‐free survival (group A: median, 17.9 months, 5 years, 27.4%; group B: median, 11.7 months, 5 years, 14.3%; P = 0.427) and overall survival (group A: median, 22.0 months, 5 years, 26.5%; group B: median, 26.5 months, 5 years, 14.7%; P = 0.90). Two hundred patients with unresectable HC were compared with patients who had received operation and found to have worse survival outcomes (P < 0.001). Conclusions: Vascular resection plus reconstruction in HC resection was feasible and safe and might improve the long‐term survival of patients with advanced HC. This aggressive approach should be adopted if the expertise is available and the patient's condition allows. [ABSTRACT FROM AUTHOR]

Background: Anatomical resection (AR) for colorectal liver metastasis (CLM) is disputable. We investigated the impact of AR on short-term outcomes and survival in CLM patients. Methods: Patients having hepatectomy with AR or nonanatomical resection (NAR) for CLM were reviewed. Comparison was made between AR and NAR groups. Group comparison was performed again after propensity score matching with ratio 1:1. Results: AR group (n = 234 vs n = 89 in NAR group) had higher carcinoembryonic antigen level (20 vs 7.8 ng/mL, p ≤ 0.001), more blood loss (0.65 vs 0.2 L, p < 0.001), more transfusions (19.2% vs 3.4%, p = 0.001), longer operation (339.5 vs 180 min, p < 0.001), longer hospital stay (9 vs 6 days, p < 0.001), more tumors (p < 0.001), larger tumors (4 vs 2 cm, p < 0.001), more bilobar involvement (20.9% vs 7.9%, p = 0.006), and comparable survival (overall, p = 0.721; disease-free, p = 0.695). After propensity score matching, each group had 70 patients, with matched tumor number, tumor size, liver function, and tumor marker. AR group had more open resections (85.7% vs 68.6%, p = 0.016), more blood loss (0.556 vs 0.3 L, p = 0.001), more transfusions (17.1% vs 4.3%, p = 0.015), longer operation (310 vs 180 min, p < 0.001), longer hospital stay (8.5 vs 6 days, p = 0.002), comparable overall survival (p = 0.819), and comparable disease-free survival (p = 0.855). Conclusion: Similar disease-free survival and overall survival of CLM patients were seen with the use of AR and NAR. However, AR may entail a more eventful postoperative course. NAR with margin should be considered whenever feasible. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to study the effect of FTY720 treatment in reducing circulating Tregs level and then suppressing liver tumor metastasis after hepatectomy and I/R injury in animal models. Furthermore, we also investigated the synergistic anti-tumor effect of FTY720 combined with rapamycin on hepatocellular carcinoma. Methods: The effect of FTY720 on suppressing Tregs mobilization and tumor metastasis after hepatectomy was investigated in an orthotopic liver tumor rat model with hepatectomy and hepatic ischemia/reperfusion (I/R) injury. The synergistic anti-tumor effect of FTY720 combined with rapamycin was further explored both in in vitro functional study and in orthotopic liver tumor mouse model. Results: In rat model, hepatic I/R promoted tumor metastasis and increased circulating Tregs after hepatectomy. The treatment of FTY720 reduced liver tumor metastasis and the number of circulating Tregs. Furthermore, FTY720 enhanced the anti-tumor capacity of rapamycin by inhibiting tumor cell proliferation and migration in vitro and reducing tumor growth in vivo through suppressing hepatic stellate cell activation and tumor angiogenesis. Conclusion: FTY720 suppressed liver tumor growth and metastasis by reducing the population of circulating Tregs and enhancing the anti-tumor effect of rapamycin. It was suggested that FTY720 single or combined with rapamycin might provide novel insight for suppressing tumor growth and metastasis for HCC patients. [ABSTRACT FROM AUTHOR]

Objective: We sought to develop a nomogram for the prediction of tumor recurrence after resection of hepatocellular carcinoma (HCC) within the Milan criteria. Method: Consecutive HCC patients admitted for hepatectomy between 1994 and 2014 were enrolled in this study. Patients were excluded if they had recurrent HCC or tumors beyond the Milan criteria. Patients were randomized and assigned to the derivation and validation sets in a 1:1 ratio. Independent factors for disease-free survival were identified using the Cox regression model. A nomogram was derived and validated with the receiver-operating characteristic (ROC) and calibration curves. Results: There were 617 eligible patients included in the analysis. The median age was 59 years, 481 were male, and 87.8% of the patients were hepatitis B virus carriers. The median follow-up was 68.7 months. The 5-year overall survival rate was 73.3% and HCC recurrence was detected in 55% of the patients. In the derivation set, a nomogram was constructed based on the seven independent factors for disease-free survival: age, alpha-fetoprotein, preoperative prothrombin time, magnitude of hepatectomy, postoperative complication, number of tumor nodules, and presence of microvascular invasion. A satisfactory discrimination ability was observed in both the derivation and validation sets (c-stat 0.672 and 0.665, respectively). The calibration plot yielded agreement between the predicted and observed outcomes, using the derived nomogram. Conclusion: A validated nomogram quantifies the risk of recurrence after hepatectomy for HCC within the Milan criteria, and assists with the planning of individual postoperative surveillance protocols. [ABSTRACT FROM AUTHOR]

Background: Previous studies comparing outcomes of hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) showed conflicting results, and most studies measured survival outcomes from the time of liver transplantation (LT). Method: This retrospective study was aimed to evaluate the long-term outcomes of HCC patients listed for LT using intention-to-treat (ITT) and propensity score matching (PSM) analyses. Clinicopathological data were retrieved from a prospectively collected database. Results: From 1995 to 2014, 375 HCC patients were listed for LT. ITT-LDLT group had 188 patients, whereas ITT-DDLT group had 187 patients. Twenty-seven patients (14.4%) and 122 patients (65.2%) were delisted from LDLT and DDLT waitlist, respectively. The 1-, 3- and 5-year overall survival rates were significantly better in ITT-LDLT group than ITT-DDLT group (94.1 vs. 77.5%, 81.4 vs. 48.7% and 75.9 vs. 40.8%). High alphafetoprotein (AFP) and ITT-DDLT treatment arm were independent poor prognostic factors affecting overall survival. LDLT group (n = 161) had more young patients, poorer liver function, higher AFP, more tumors outside Milan/UCSF criteria, when compared with DDLT group (n = 85). After PSM, the 1-, 3- and 5-year overall (95.4 vs. 98.5%, 80.0 vs. 92.3% and 73.4 vs. 84.4%) and recurrence-free (87.7% vs. 90.8%, 76.9% vs. 83.1% and 72.2% vs. 81.5%) survival rates were comparable between the matched LDLT and the matched DDLT group, respectively. Conclusion: Survival benefit of LDLT was observed for HCC patients with ITT analysis. Despite a more advanced tumor stage, overall and recurrence-free survival rates were comparable between LDLT and DDLT using PSM analysis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the merits of the anterior approach, if any, in colorectal liver metastasis (CRLM) resection.Methods: Data of patients who underwent partial hepatectomy for CRLM were reviewed. Patients treated by the anterior approach were compared with patients treated by the conventional approach.Results: Ninety-eight patients had right hepatectomy, extended right hepatectomy, or right trisectionectomy. Among them, 71 patients underwent the conventional approach (CA group) and 27 underwent the anterior approach (AA group). The two groups were comparable in demographic, pathological, and perioperative characteristics except that the AA group had higher levels of aspartate transaminase (median, 41 vs. 31 U/L; p = 0.006) and alanine transaminase (median, 27 vs. 22 U/L; p = 0.009), larger tumors (median, 7 vs. 4 cm; p = 0.000), and more extensive resections (p < 0.001). The median overall survival was 40 months (range, 0.69-168.6 months) in the CA group and 33.7 months (range, 0.95-99.8 months) in the AA group (p = 0.22), and the median disease-free survival was 9.7 months (range, 0.62-168.6 months) in the CA group and 6.2 months (range, 0.72-99.8 months) in the AA group (p = 0.464). Univariate and multivariate analyses identified 4 independent prognostic factors for overall survival: lymph node status of primary tumor (HR 1.352, 95% CI 0.639-2.862, p = 0.034), intraoperative blood loss (HR 1.253, 95% CI 1.039-1.510, p = 0.018), multiple liver tumor nodules (HR 1.775, 95% CI 1.029-3.061, p = 0.039), and microvascular invasion (HR 2.058, 95% CI 1.053-4.024, p = 0.035).Conclusions: The two approaches resulted in comparable survival outcomes even though the AA group had larger tumors and more extensive resections. The anterior approach allows better mobilization and easier removal of large tumors once the liver is opened up. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B virus (HBV) infection is associated with a lower incidence of colorectal liver metastases. We explored the impact of HBV carrier status on outcomes of surgical treatment of colorectal liver metastases.Methods: A retrospective analysis was conducted for consecutive patients undergoing liver resection for colorectal liver metastases from 2000 to 2016. HBV carriers were matched with controls by propensity scoring.Results: 304 patients with known HBV carrier status who underwent resection of colorectal liver metastases were studied. From the 21 (6.9%) hepatitis B carriers, a more prolonged prothrombin time (12.1 vs. 11.3 s, OR 1.42, p = 0.027) was observed, and fewer major resections were performed (19.0 vs. 47.3%, OR 0.262, p = 0.018). After 1:5 propensity score matching, they were compared with 105 controls with similar liver function, tumour status and receiving similar treatments. Patients with chronic hepatitis B enjoyed better median disease-free survival (15.8 vs. 9.20 month, p = 0.032). Overall survivals (50.0 vs. 43.6 month, p = 0.15) were similar. Operating time (227 vs. 240 min, OR 1.00, p = 0.33), blood loss (0.50 vs. 0.37 L, OR 1.15, p = 0.62), hospital stay (6 vs. 6 day, OR 1.02, p = 0.48), operative morbidity (9.5 vs. 16.2%, OR 0.545, p = 0.44) and mortality (0 vs. 1.0%, OR 1.62, p = 0.77) were comparable. The use of antiviral agents did not affect survival of HBV carriers.Conclusions: Chronic HBV infection confers oncological benefit to surgical treatment of colorectal liver metastases. Given satisfactory liver reserve, HBV carrier status did not affect operative morbidity or mortality. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of intraoperative blood transfusion on the long‐term outcomes of liver transplantation for hepatocellular carcinoma. Method: Adult patients who had non‐salvage liver transplantation at our centre between January 2005 and December 2012 for hepatocellular carcinomas that were within the University of California, San Francisco criteria and could not be resected or ablated were divided into groups with and without intraoperative blood transfusion. Comparisons were made between groups. Results: Ninety‐nine patients were included in the study. Sixty‐two (62.6%) patients received intraoperative blood transfusion. Patients without transfusion were younger (54 versus 56 years; P = 0.04) and had a lower Model for End‐stage Liver Disease score (11 versus 14; P < 0.001). Most of them had stage‐I tumours (64.9 versus 37.1%; P = 0.007) and fewer of them had postoperative complications of grade IIIA or above in the Clavien‐Dindo classification (21.6 versus 48.4%; P = 0.008). The groups were comparable in hospital mortality (3.2 versus 2.7%; P = 1.00), 5‐year overall survival (90.8 versus 89.2%; P = 0.611) and 5‐year disease‐free survival (90.5 versus 89.2%; P = 0.835). On multivariate analysis, postoperative complications of grade IIIA or above were associated with worse survival (hazard ratio, 7.108; 95% confidence interval, 1.455–34.712; P = 0.015). Conclusion: Intraoperative blood transfusion was shown to have no significant impact on the long‐term outcomes of liver transplantation for hepatocellular carcinoma, whereas postoperative complications of grade IIIA or above were associated with worse recipient survival. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Laparoscopic hepatectomy is considered an acceptable treatment of choice in selected patients with primary hepatocellular carcinoma (HCC). Whether indocyanine green (ICG) immunofluorescence, a new technology, may improve surgery outcomes has yet to be tested. The aim of the present study was to investigate and compare the effect of ICG fluorescence imaging on the outcomes of pure laparoscopic hepatectomy and open hepatectomy for primary HCC with background cirrhosis. Methods: From January 2015 to June 2016, 20 patients with HCC and liver cirrhosis underwent laparoscopic hepatectomy with ICG immunofluorescence. The outcomes of pure laparoscopic hepatectomy with ICG immunofluorescence were compared with those of open hepatectomy. To avoid selection bias, patients were propensity score matched in a ratio of 1 : 6, with 20 patients in the laparoscopic group and 120 in the open group. Results: The laparoscopic group had 20 patients, and the open group had 120 patients. The laparoscopic group had less blood loss (125 vs 450 mL, P < 0.001), a shorter operation time (200 vs 250 min, P = 0.003), and a shorter hospital stay (5 vs 6 days, P < 0.001). The complication rate was 0% in the laparoscopic group compared to 15.0% in the open group (P = 0.135). All patients in the laparoscopic group had negative margin involvement. Four patients (3.3%) in the open resection group had positive margin involvement. Two patients in the ICG immunofluorescence group had additional lesions identified and resected during operation. Conclusion: Pure laparoscopic hepatectomy with ICG immunofluorescence for primary HCC can be carried out safely with favorable short‐term outcomes even in cirrhotic patients. Better identification of the bile duct structure and better assessment of the tumor resection margin and perfusion are advantages of this new technique. [ABSTRACT FROM AUTHOR]

A case study is presented of 62-year-old man presented with advanced rectal carcinoma. Radiological and endoscopic assessments showed tumor; further laparoscopic lower anterior resection was performed of the residual lesion over the mucosal side. He was treated with ultra-low rectal carcinoma using transanal endoscopic operation device in laparoscopic assisted transanal total mesorectal excision.

Background: Uncommon primary hepatic malignancies such as intrahepatic cholangiocarcinoma (ICC) and hepatocholangiocarcinoma (HCC-CC) were generally considered contraindications for liver transplantation(LT), and studies comparing the efficacy of LT and resection (LR) for ICC/HCC-CC were scarce.Objective: To compare the survival outcomes of ICC/HCC-CC patients treated by LT and LR in a propensity score-matched population.Method: This is a retrospective study from 1995 to 2015. Consecutive patients with the pathological diagnosis of ICC or HCC-CC in the surgical specimens were included. All patients had either hepatectomy or LT with curative intent. Factors associated with survival were identified with multivariate analysis using cox-regression model. Propensity score-matched analysis was performed.Result: There were 181 patients diagnosed to have ICC/HCC_CC. Nine patients received LT (all with incidental ICC/HCC-CC) and 172 received hepatectomy. The median follow-up period was 27.5 months. The median age was 60 years (range 3-86); Hepatitis B and C carrier status was found in 48.1 and 2.3% of the patients, respectively. The median tumor size was 6 cm and 71.3% of them had solitary tumor. Microvascular invasion was present in 47% of the patients. After propensity score matching, there were 54 (9 in LT and 45 in LR group) patients for analysis. Cox-regression analysis showed that early AJCC (7th) staging and LT were the independent factors associated with overall survival. Patients in the LT group had significantly better overall survival (5-year OS 77.8 vs 36.6%, log-rank p = 0.013).Conclusion: ICC/HCC-CC are uncommon tumors with poor long-term oncological outcomes despite curative hepatectomy. Liver transplantation might be a better treatment option for patients with early ICC/HCC-CC. [ABSTRACT FROM AUTHOR]

Objectives: Role of 18-FDG PET/CT had been well established in other more prevalent malignancies such as colorectal and lung cancer; however, this is not as well defined in cholangiocarcinoma. Literature focusing on the prognostic values of preoperative PET/CT for resectable cholangiocarcinoma is scarce.Method: This is a retrospective cohort of 66 consecutive patients who had received curative resection for cholangiocarcinoma from 2010 to 2015. All patients had preoperative 18-FDG PET/CT performed. Accuracy of metastatic lymph node detection of PET/CT and the prognostic value of maximum standard uptake value (SUV-max) was explored.Results: There were 38 male and 28 female recruited, and the median age was 66. Intrahepatic cholangiocarcinoma (ICC) constituted the majority (59.1%) of the cases, followed by hilar cholangiocarcinoma (22.8%), gallbladder cancer (13.6%) and common bile duct cancer (4.5%). The 3-year disease-free survival (DFS) and overall survival (OS) of the whole population were 27.1 and 39.2%, respectively. The median follow-up duration was 27 months. The accuracy of PET/CT in metastatic lymph node detection was 72.7% (P = 0.005, 95% CI 0.583–0.871) and 81.8% (P = 0.011, 95% CI 0.635–0.990) in whole population and ICC subgroup analysis, respectively. SUV-max was shown by multivariate analysis to be an independent factor for DFS (P = 0.007 OR 1.16, 95% CI 1.04–1.29) and OS (P = 0.012 OR 1.145, 95% CI 1.030–1.273) after resection. SUV-max of 8 was shown to be a discriminant cut-off for poor oncological outcomes in patients with early cholangiocarcinoma (TNM stage I or II) after curative resection (3-year DFS: 21.2 vs. 63.2%, P = 0.004, and 3-year OS: 29 vs. 74% P = 0.048, respectively).Conclusion: PET/CT is a reliable imaging modality for metastatic lymph node detection in cholangiocarcinoma. Tumour SUV-max is an independent factor for oncological outcomes in patients with resectable disease. For patients who have TNM stage I or II cholangiocarcinoma, tumour SUV-max over 8 is associated with significantly inferior disease-free and overall survival even after curative resection. [ABSTRACT FROM AUTHOR]

Background and Aims: We explored the difference in treatment efficacy of endoscopic self-expendable metal stent (SEMS) and surgical bypass (SB) in the management of malignant biliary obstruction (MBO) secondary to pancreatic cancer.Method: A retrospective analysis was conducted using consecutive patients who were admitted from 2008 to 2016 receiving either endoscopic SEMS or SB. Diagnosis other than pancreatic cancer and SEMS placement as a pre-operative drainage before Whipple's operation was excluded. Propensity score (PS) matching was performed to eliminate the confounding effect of heterogeneity between patients from two treatment groups. The rate of early, late treatment-related events, readmission and re-intervention, the duration of hospitalization, and the cost of treatment were compared.Results: There were 98 patients undergoing endoscopic SEMS or SB in the study period. The median age was 68.5 years and 52% of the patients had metastatic disease with median survival of 6 months. After 1:1 PS matching, 30 patients from each group were analyzed. The hospital stay was significantly longer in the SB group (13 vs. 5 days, P < 0.001) with a trend of higher rate of early treatment-related events (24.1 vs. 6.7%, P = 0.113). None of the patients in SB group developed recurrent biliary obstruction. Higher readmission rate (36.7 vs. 3.3%, P = 0.004) and re-intervention rate (36.7 vs. 10%, P = 0.033) were found in the SEMS group. The 3-, 6-, and 9-month re-intervention rates for endoscopic SEMS and SB group were 24.9, 29.4, 45.7, and 11.2, 11.2, and 11.2%, respectively (P = 0.03). When all subsequent readmissions were taken into account, there was no significant difference in hospital stay in both groups (7.5 vs. 14 days, P = 0.359); however, the total cost of treatment in SB group was significantly higher than that in the SEMS group (13,307 vs. 7113 USD, P = 0.035).Conclusion: Despite being more invasive and expensive, surgical bypass provides durable relief of biliary obstruction. Endoscopic SEMS is associated with minimal procedural risks and low re-intervention rate, which are important considerations for frail patients with limited life expectancy. [ABSTRACT FROM AUTHOR]