Prognostic Significance of Sarcopenia and Eicosapentaenoic Acid (EPA) Levels in Patients With Unresectable Pancreatic or Biliary Tract Cancer.

Background/Aim: This study aimed to investigate the relationship between prechemotherapy blood eicosapentaenoic acid (EPA) levels, sarcopenia, and overall survival in patients with pancreatic and biliary tract cancer undergoing chemotherapy. Patients and Methods: Forty-five patients with recurrent, non-resected pancreatic or biliary tract cancer undergoing chemotherapy were retrospectively analyzed. The skeletal muscle mass was measured at the third lumbar vertebra. Sarcopenia cut-off values were based on the Japanese Society of Hepatology sarcopenia assessment criteria. Two months after starting chemotherapy, the patients received enteral nutrition containing omega-3 fatty acids. Results: Patients with pancreatic and biliary tract cancers with low pre-treatment blood EPA levels had significantly more intense sarcopenia than those with high EPA levels (p=0.023). Patients with sarcopenia before chemotherapy had significantly lower overall survival than those without sarcopenia. Multivariate analysis revealed blood EPA concentration as an independent prognostic factor (p<0.01). Lumbar muscle volume, a marker of sarcopenia, showed a clear positive correlation with prechemotherapy EPA concentration (p=0.008). In patients administered with enteral nutrition containing omega-3 fatty acids, both EPA concentration and lumbar muscle volume were significantly higher than those prior to intervention, indicating sarcopenia improvement due to the intervention. Conclusion: In patients with recurrent non-resected pancreatic and biliary tract cancer, low blood EPA levels before chemotherapy are associated with sarcopenia and poor prognosis.

A novel combined C-reactive protein-albumin ratio and modified albumin-bilirubin score can predict long-term outcomes in patients with hepatocellular carcinoma after hepatic resection.

Background: Systemic inflammatory response represented by C-reactive protein and albumin ratio (CAR) and modified albumin-bilirubin (mALBI) grade both have been associated with long-term outcome in patients with hepatocellular carcinoma (HCC). In this study, we investigated the prognostic utility of combined score of CAR and mALBI score to predict the prognosis of HCC patients after hepatic resection. Methods: This study included 214 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. Systemic inflammatory response and mALBI were evaluated preoperatively and patients were classified into three groups based on the combination of CAR and mALBI score: low CAR and low mALBI grade (score 0), either high CAR or high mALBI grade (score 1), and both high CAR and high mALBI grade ≥2b (score 2). Multivariate Cox proportional hazard models were conducted to assess disease-free and overall survival. Results: In multivariate analysis, sex (p < 0.01), HBsAg positivity (p < 0.01), serum AFP level ≥20 ng/mL (p < 0.01), microvascular invasion (p = 0.02), multiple tumors (p < 0.01), type of resection (p < 0.01), and CAR-mALBI score ≥2 (HR 2.19, 95% CI 1.39-3.44, p < 0.01) were independent prognostic factors of disease-free survival, while sex (p = 0.01), HBsAg positivity (p < 0.01), poor tumor differentiation (p = 0.03), multiple tumors (p < 0.01), CAR-mALBI score ≥2 (HR 2.70, 95% CI 1.51-4.83, p < 0.01) were independent prognostic factors of overall survival. Conclusions: CAR-mALBI score is associated with disease-free and overall survival in patients with HCC after hepatic resection, suggesting the importance of evaluating both hepatic functional reserve and host-inflammatory state in the risk assessment of HCC patients.

Analysis of Preoperative Risk Factors for Early Recurrence in Patients After Hepatic Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis even after curative-intent hepatic resection due to a high recurrence rate. The aim of this study was to investigate preoperative risk factors for early recurrence after surgery for ICC, which may help to identify patients who need preoperative chemotherapy. METHODS: We retrospectively analyzed 51 patients who had undergone primary surgery for ICC. We investigated the association of preoperative clinical variables with recurrence within 1 year after resection for ICC. We then created a high-risk ICC score using the identified preoperative factors and investigated the association of the score with disease-free and overall survival. RESULTS: Recurrence within 1 year after surgery for ICC was significantly associated with poor overall survival (P < .01). In the multivariate analysis, preoperative tumor size > 5 cm (P = .03) and elevated C-reactive protein-to-albumin ratio (CAR) (P = .04) were significantly associated with recurrence within 1 year after surgery. A high-risk ICC score of 2 was associated with poor disease-free survival (P < .01) and overall survival (P = .02) compared with a score of 0 or 1. CONCLUSIONS: Our high-risk ICC score, combining preoperative tumor size and CAR, can be an indicator of early recurrence and poor survival in patients after hepatic resection for ICC. Our findings may provide better preoperative risk stratification of patients with ICC, and the high-risk ICC patients may benefit from preoperative therapy.

Open Thoracic Drainage Followed by Proximal Splenic Artery Embolization for Massive Hydrothorax Before Living Donor Liver Transplantation.

BACKGROUND: Hepatic hydrothorax is associated with postoperative infectious complications and mortality in patients undergoing living-donor liver transplantation (LDLT). Thus, preoperative management of massive hepatic hydrothorax is essential for improving the outcomes of LDLT. This study aimed to demonstrate our successful cases and strategy for treating massive hepatic hydrothorax. METHODS: Our strategy for hepatic hydrothorax includes (a) mini-thoracotomy under general anesthesia for the drainage of hydrothorax, (b) preoperative hepatic inflow modulation by proximal splenic arterial embolization, and (c) nutritional and physical intervention to improve the general condition. RESULTS: Two patients with massive hepatic hydrothorax were treated with our strategy. Both patients had end-stage liver disease secondary to primary biliary cholangitis. Their performance status deteriorated due to massive hydrothorax. After the intervention, their performance status significantly improved. After that, LDLTs with right lobe grafts were performed. The duration of the operation was 440 and 343 minutes, with an intraoperative blood loss of 1,700 and 1,600 g, respectively. Their postoperative courses were uneventful, and they were discharged on postoperative days 16 and 14. CONCLUSION: Our pre-LDLT multimodal management strategy for massive hepatic hydrothorax, including preoperative open thoracic drainage, pre-LDLT portal inflow modulation, and nutritional intervention, improved the preoperative condition of patients undergoing LDLT, resulting in successful outcomes.

Multimodal Management for Refractory Biliary Stricture After Living Donor Liver Transplantation.

BACKGROUND: Biliary stricture is a common complication of living donor liver transplantation (LDLT). Endoscopic retrograde biliary drainage (ERBD) is the primary treatment of biliary stricture, which is sometimes refractory. This study aimed to evaluate the risk factors for biliary stricture after LDLT and present successful management for refractory biliary stricture. METHODS: Data from 26 patients who underwent LDLT were retrospectively analyzed. The relationship between the incidence of biliary strictures and clinical variables, including pre/intra/postoperative factors, was assessed. RESULTS: Univariate analysis showed that ABO incompatibility (P = .037) was a significant risk factor for biliary strictures. Case 1 was a 57-year-old woman who underwent LDLT using a left-lobe graft for primary biliary cholangitis (PBC) and developed a biliary stricture 1 month after surgery. Percutaneous transhepatic cholangiodrainage (PTCD) and embolization of the portal vein and hepatic artery were performed. Thereafter, ethanol was injected into the biliary duct, and the intervention was successfully completed. Case 2 was a 54-year-old woman who underwent LDLT using a right-lobe graft and duct-to-duct biliary reconstruction for PBC. Internal plastic stent insertion by ERBD was unsuccessful due to the significantly bending bile duct. After PTCD, the gun-site technique for the posterior branch and dual hepatic vascular embolization of the anterior branch was performed. The patient was followed up without an external fistula tube. CONCLUSION: ABO incompatibility was a risk factor for refractory biliary stricture. Appropriate procedures should be chosen based on stricture types.

Zero Mortality in Living-Donor Liver Transplantation for Primary Biliary Cholangitis in Patients With a Meld Score of <20.

BACKGROUND: Although primary biliary cholangitis (PBC) is considered a good indication for living-donor liver transplantation (LDLT), the postoperative results are not well known. METHODS: At Jikei University Hospital, 14 patients with PBC underwent LDLT from February 2007 to June 2022. We consider PBC with a Model for End-Stage Liver Disease (MELD) score of <20 to indicate LDLT. We performed a retrospective analysis of the patients' clinical records. RESULTS: The patients' median age was 53 years, and 12 of the 14 patients were female. A right graft was used in 5 patients, and 3 ABO-incompatible transplants were performed. The living donors were children in 6 cases, partners in 4 cases, and siblings in 4 cases. The preoperative MELD scores ranged from 11 to 19 (median, 15). The graft-to-recipient weight ratio ranged from 0.8 to 1.1 (median, 1.0). The median operative time for donors and recipients was 481 and 712 minutes, respectively. The median operative blood loss of donors and recipients was 173 and 1,800 mL, respectively. The median postoperative hospital stay of donors and recipients was 10 and 28 days, respectively. All recipients recovered satisfactorily and remained well during a median follow-up of 7.3 years. Three patients underwent a liver biopsy after LDLT because of acute cellular rejection without histologic findings of PBC recurrence. CONCLUSIONS: Living-donor liver transplantation provides satisfactory long-term survival for patients with PBC with a graft-to-recipient weight ratio of >0.7 and MELD score of <20 without hepatocellular damage and only portal vein hypertension.

Liver Only Living Donor Transplantation for Polycystic Disease in a Patient on Chronic Hemodialysis: Case Report.

BACKGROUND: Polycystic liver disease (PLD) is characterized by the progressive development of polycystic lesions in the kidney and the liver, possibly resulting in dual organ failure. We indicated living donor liver transplantation (LDLT) for a patient with end-stage liver and kidney disease (ELKD) due to PLD on uncomplicated chronic hemodialysis. CASE PRESENTATION: A 63-year-old man with ELKD and uncontrolled massive ascites due to PLD and hepatitis B on uncomplicated chronic hemodialysis was referred to us with a single possible 47-year-old female living donor. Because of the necessity of right lobe liver procurement from this small middle-aged donor and uncomplicated hemodialysis on this recipient, we considered LDLT, rather than dual organ transplantation, could be the most well-balanced option to save the life of this recipient with acceptable risk limits for this donor. A right lobe graft with 0.91 for graft recipient weight ratio was implanted with an uneventful operative procedure under intra- and postoperative continuous hemodiafiltration. The recipient was rescheduled on routine hemodialysis on day 6 after transplantation and recovered with a gradual decrease in ascites output. He was discharged on day 56. He continues to have a very good liver function and quality of life without ascites and uncomplicated routine hemodialysis 1 year after transplantation. The living donor was discharged 3 weeks after surgery and is also doing well. CONCLUSION: Although combined liver-kidney transplantation from a deceased donor could be the best option for ELKD due to PLD, LDLT can also be an acceptable option for ELKD with uncomplicated hemodialysis, considering the double equipoise theory for both lifesaving of the recipient and acceptable donor risk.

Thrombectomized autologous portal Y-graft inflow construction can be an option in living-donor liver transplantation: a case report.

BACKGROUND: In living-donor liver transplantation (LDLT), portal Y-graft interposition using the recipient's portal vein (PV) bifurcation has been used for right lobe grafts with double PV orifices. We herein report the use of thrombectomized autologous portal Y-graft interposition for a recipient with preoperative portal vein thrombosis (PVT) in a right lobe LDLT with double PV orifices. CASE PRESENTATION: The recipient was a 54-year-old male with end-stage liver disease due to alcoholic liver cirrhosis. There was PV thrombus in the recipient's PV. The living liver donor was his 53-year-old spouse, and a right lobe graft was planned for the transplantation. Since the donor's liver had a type III PV anomaly, autologous portal Y-graft interposition after thrombectomy was planned for PV reconstruction in the LDLT. The portal Y-graft was resected from the recipient and a thrombus extending from the main PV to the right PV branch was removed on the back table. The portal Y-graft was anastomosed to the anterior and posterior portal branches of the right lobe graft. Followed by venous reconstruction, the Y-graft was anastomosed to the recipient's main PV. The operation time was 545 min and the intraoperative blood loss was 1355 ml. The recipient was discharged on postoperative day 13 without any complications. The recipient remains well with the patency of the portal Y-graft one year after the liver transplantation. CONCLUSION: We herein report the successful use of autologous portal Y-graft interposition after thrombectomy on the back table for a recipient with PVT in a right lobe LDLT.

Impact of C-reactive protein-albumin-lymphocyte (CALLY) index on prognosis after hepatectomy for colorectal liver metastasis.

AIM: The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index is a novel inflammation-based biomarker. We aimed to investigate whether the CALLY can predict the prognosis in patients with colorectal liver metastases (CRLM) after hepatic resection. METHODS: We included 183 patients with CRLM who underwent hepatectomy. The CALLY index was defined as (albumin × lymphocytes)/(CRP × 104). We investigated the association of the CALLY index with overall survival by univariate and multivariate analyses. RESULTS: In total, 101 (55%) patients had a low CALLY index (<4). In the univariate analysis, overall survival was significantly worse in patients with lymph node metastases (p = 0.02), extrahepatic lesions (p < 0.01), and a low CALLY index (p < 0.01). In the multivariate analysis, independent and significant predictors of overall survival were lymph node metastases (p = 0.04), extrahepatic lesions (p = 0.03), and a low CALLY index (p = 0.03). Patients with a low CALLY index had significantly more postoperative complications than those with a high CALLY index (29% vs. 11%, p < 0.01). CONCLUSION: The CALLY index may be an independent and significant indicator of outcomes in patients who underwent liver resection for CRLM.

Clinical significance of cachexia index in patients with hepatocellular carcinoma after hepatic resection.

BACKGROUND: Cancer cachexia has been associated with unfavorable outcomes in several malignancies. The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been proposed as a novel biomarker of cachexia. Therefore, we here investigated prognostic value of the CXI in patients with hepatocellular carcinoma (HCC) after hepatic resection. METHODS: The study comprised 213 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. First, the skeletal muscle index (SMI) was calculated as the area of the psoas muscle at the third lumbar vertebra/(the height)2. The CXI was then calculated by the following formula: SMI x serum albumin level/neutrophil-to-lymphocyte ratio (NLR). We retrospectively investigated the relationship between the CXI and disease-free survival as well as overall survival. RESULTS: In multivariate analyses, female (p < 0.01), hepatitis B surface antigen-positivity (p < 0.01), preoperative serum alpha-fetoprotein level ≥20 ng/mL (p = 0.01), preoperative serum protein induced by vitamin K absence or antagonist-II level ≥200 mAU/mL (p = 0.02), multiple tumors (p < 0.01), macrovascular invasion (p = 0.04), type of resection (p < 0.01), and low CXI (p = 0.03) were significant predictors of disease-free survival, while Child-Pugh grade B (p < 0.01), poor tumor differentiation (p = 0.05), multiple tumors (p = 0.01), macrovascular invasion (p = 0.04), NLR (p = 0.04), and low CXI (p < 0.01) were significant predictors of overall survival. In the subgroup analysis of advanced T stage, the CXI was associated with both disease-free (p < 0.01) and overall survival (p = 0.06). CONCLUSIONS: The CXI can be a prognostic indicator in patients with HCC after hepatic resection, suggesting the importance of comprehensive biomarker which includes skeletal muscle, inflammation, and nutritional status.

Thiamine treatment preserves cardiac function against ischemia injury via maintaining mitochondrial size and ATP levels.

Thiamine (vitamin B1) is necessary for energy production, especially in the heart. Recent studies have demonstrated that thiamine supplementation for cardiac diseases is beneficial. However, the detailed mechanisms underlying thiamine-preserved cardiac function have not been elucidated. To this end, we conducted a functional analysis, metabolome analysis, and electron microscopic analysis to unveil the mechanisms of preserved cardiac function through supplementation with thiamine for ischemic cardiac disease. Male Sprague-Dawley rats (around 10 wk old) were used. Following pretreatment with or without thiamine pyrophosphate (TPP; 300 µM), hearts were exposed to ischemia (40 min of global ischemia followed by 60 min of reperfusion). We measured the left ventricle developed pressure (LVDP) throughout the protocol. The LVDP during reperfusion in the TPP-treated heart was significantly higher than that in the untreated heart. Metabolome analysis was performed using capillary electrophoresis-time-of-flight mass spectrometry, and it revealed that the TPP-treated heart retained higher adenosine triphosphate (ATP) levels compared with the untreated heart after ischemia. The metabolic pathway showed that there was a significant increase in fumaric acid and malic acid from the tricarboxylic acid cycle following ischemia. Electron microscope analysis revealed that the mitochondria size in the TPP-treated heart was larger than that in the untreated heart. Mitochondrial fission in the TPP-treated heart was also inhibited, which was confirmed by a decrease in the phosphorylation level of DRP1 (fission related protein). TPP treatment for cardiac ischemia preserved ATP levels probably as a result of maintaining larger mitochondria by inhibiting fission, thereby allowing the TPP-treated heart to preserve contractility performance during reperfusion.NEW & NOTEWORTHY We found that treatment with thiamine can have a protective effect on myocardial ischemia. Thiamine likely mediates mitochondrial fission through the inhibition of DRP1 phosphorylation and the preservation of larger-sized mitochondria and ATP concentration, leading to higher cardiac contractility performance during the subsequent reperfusion state.