Potential of using qFibrosis analysis to predict recurrent and survival outcome of patients with hepatocellular carcinoma after hepatic resection.

BACKGROUND: There remains a lack of studies addressing the stromal background and fibrosis features and its prognostic value in liver cancer. qFibrosis can identify, quantify and visualize the fibrosis features from biopsy samples. In this study, we aim to demonstrate the prognostic value of histological features by using qFibrosis analysis in liver cancer patients. METHODS: Liver specimen from 201 patients with hepatocellular carcinoma underwent curative resection were imaged and assessed using qFibrosis system, and generated a total of 33 and 156 collagen parameters from tumor part and non-tumor liver tissue, respectively. We used these collagen parameters on patients to build two combined indexes, RFS-index and OS-index, in order to differentiate patients with early recurrence and early death, respectively. The models were validated using leave-one-out method. RESULTS: Both combined indexes had significant prediction value of patients' outcome. The RFS-index of 0.52 well differentiates patients with early recurrence (p < 0.001), and the OS-index of 0.73 well differentiates patients with early death during follow-up (p = 0.02). CONCLUSIONS: Combined index calculated with qFibrosis from digital readout of fibrotic status of peri-tumor liver specimen in patients with HCC have prediction values for their disease and survival outcomes. These results demonstrated the potentials to transform histopathological features into quantifiable data that could be used to correlate with clinical outcome.

Plasma Cell-Free Adenomatous Polyposis Coli Gene Promoter Methylation as a Prognostic Biomarker for Hepatocellular Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for follow-up after treatment is a clinical challenge. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still lacking of evidence of its clinical use. This study aims to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation level (APC-MET) as a potential biomarker in HCC treatment. METHOD: A total of 96 patients with HCC at BCLC stage B underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined from the plasma of each patient before and 1 months after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment were analyzed, and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using cox regression analysis. RESULTS: Univariate cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI 1.05－8.05, p=0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI 1.16－10.4, p=0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI 1.21－3.44, p=0.007). In multivariate models, pre-op APC-MET >0 was a significant predictor of disease progression after adjusting with other two traditional biomarkers (HR, 1.82, 95% CI 1.05－3.17, p=0.034). CONCLUSIONS: Hypermethylation of APC promoter appears to be a potential biomarker that could predict patient survival and disease progression outcome in patients with intermediate stage HCC after local ablation treatment.

Automated liver volumetry and hepatic steatosis quantification with magnetic resonance imaging proton density fat fraction.

BACKGROUND: Preoperative imaging evaluation of liver volume and hepatic steatosis for the donor affects transplantation outcomes. However, computed tomography (CT) for liver volumetry and magnetic resonance spectroscopy (MRS) for hepatic steatosis are time consuming. Therefore, we investigated the correlation of automated 3D-multi-echo-Dixon sequence magnetic resonance imaging (ME-Dixon MRI) and its derived proton density fat fraction (MRI-PDFF) with CT liver volumetry and MRS hepatic steatosis measurements in living liver donors. METHODS: This retrospective cross-sectional study was conducted from December 2017 to November 2022. We enrolled donors who received a dynamic CT scan and an MRI exam within 2 days. First, the CT volumetry was processed semiautomatically using commercial software, and ME-Dixon MRI volumetry was automatically measured using an embedded sequence. Next, the signal intensity of MRI-PDFF volumetric data was correlated with MRS as the gold standard. RESULTS: We included the 165 living donors. The total liver volume of ME-Dixon MRI was significantly correlated with CT (r = 0.913, p < 0.001). The fat percentage measured using MRI-PDFF revealed a strong correlation between automatic segmental volume and MRS (r = 0.705, p < 0.001). Furthermore, the hepatic steatosis group (MRS ≥5%) had a strong correlation than the non-hepatic steatosis group (MRS <5%) in both volumetric (r = 0.906 vs. r = 0.887) and fat fraction analysis (r = 0.779 vs. r = 0.338). CONCLUSION: Automated ME-Dixon MRI liver volumetry and MRI-PDFF were strongly correlated with CT liver volumetry and MRS hepatic steatosis measurements, especially in donors with hepatic steatosis.

Hepatitis C treatment and long-term outcome of patients with hepatocellular carcinoma after resection.

BACKGROUND AND AIM: This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals [DAAs] or interferon [IFN]) in patients with hepatitis C virus who underwent liver resection for primary hepatocellular carcinoma. METHODS: This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed. RESULTS: After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio [HR] 0.475, 95% confidence interval [CI]: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events. CONCLUSION: In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.

Surgical Outcomes and Quality of Care Among Adult Appendicitis Patients: A Comparative Study of Tertiary Care Hospitals and Regional Hospitals.

BACKGROUND: Acute appendicitis is one of the most common abdominal emergencies, with management approaches that vary depending on the available resources and setting. However, there is a lack of studies on the differences of surgical outcomes and quality of care between tertiary care hospitals and regional hospitals. METHODS: This multicenter retrospective study included 2158 consecutive adult patients between January 2014 and June 2018 at three hospitals. The patient cohort was divided into regional hospital group (N = 1223) and tertiary care hospital group (N = 935). Baseline characteristics and perioperative outcomes were compared, and factors associated with surgical delay and postoperative complication were investigated. RESULTS: Patients in tertiary care hospital group had longer surgical waiting time (17.3 vs. 12.0 h, p < 0.001), higher risks of surgical delay exceeding 24 h (OR = 2.94, 95% CI 2.17-4.01, p < 0.001), longer operation time (64 vs. 50 min, p < 0.001), more appendix perforation (22.4 vs. 13.3%, p < 0.001), and higher hospital cost compared with regional hospital group. In multivariate analysis, factors associated with surgical delay were tertiary care hospital (OR = 2.94, 95% CI 2.18-4.01, p < 0.001) and delay diagnosis (OR = 18.7, 95% CI 11.7-30.1, p < 0.001), while those associated with postoperative complications were older age (OR = 1.02, 95% CI 1.00-1.04, p = 0.013), male sex (OR = 2.38, 95% CI 1.11-5.52, p = 0.031), surgical delay (OR = 2.99, 95% CI 1.30-6.47, p = 0.007), and appendix perforation (OR = 5.61, 95% CI 2.72-11.85, p < 0.001). CONCLUSIONS: Patients at tertiary care hospitals had longer waiting time, more surgical delays, and appendix perforations, and these were risk factors of postoperative complications. Establishing an effective referral system to redirect appendicitis patients with less complex medical histories from tertiary care hospitals to regional hospitals may enhance the quality of patient care and outcomes, while also reducing medical costs.

Interval dynamics of transplantability for hepatocellular carcinoma after primary curative resection: risk factors for nontransplantable recurrence.

BACKGROUND: To investigate the changes in transplantability between primary and recurrent Hepatocellular carcinoma (HCC) after hepatic resection (HR) and the risk factors for nontransplantable recurrence (NTR). METHODS: Consecutive 3122 patients who received HR for primary HCC between 2001 and 2019 were analyzed for changes in transplantability. Predictors of survival and NTR were evaluated using a competing risk analysis. RESULTS: After a median follow-up of 78.3 months, the 5-year overall survival rate was 82.6%. Also, 58.2% of them developed recurrence after a median of 45.6 months. Recurrence occurred in 1205 and 611 patients with primary transplantable and nontransplantable HCC, respectively, of whom 26.1% and 63.2%, respectively, had NTR. Tumor diameter >3 cm [subdistribution hazard ratios (95% CI), 2.00 (1.62-2.48)], major resection [1.20 (1.00-1.43)], pathological grade >2 [1.28 (1.07-1.52)], microvascular invasion [1.74 (1.45-2.08)], and early recurrence (<1 year) [9.22 (7.83-10.87)] were associated with NTR. The overall transplantable pool increased from 72.3% to 77.5%. CONCLUSION: Microvascular invasion and early recurrence were risk factors for NTR. Nonetheless, the transplantable pool increased after HR, 41.8% of the patients had no recurrence and may not require liver transplantation. If the patient's liver function is acceptable, HR should be considered the treatment of choice for HCC.

Linear radiofrequency ablation using dual switching-control mode achieves rapid and bloodless liver resection, an experimental research.

BACKGROUND: Radiofrequency (RF)-assisted devices are widely used for hemostasis during liver resection. This study compared the use of dual switching (DS) versus single switching (SS) control modes for RF-based liver resections in a pig model. METHODS: The RF-based system comprised a 200-W generator and three electrodes with 4-cm tips arranged in a linear configuration using an adaptor. Eight Lanyu pigs were used to assess ablation outcomes with electrode spacing of 2 or 3 cm, and ablation durations of 1.5, 2 or 3 min. All combinations were tested in DS and SS modes. Procedures were performed on left lateral, caudal and right anterior liver lobes, and after which transections were performed using a scalpel. Blood loss, complete ablation rate and ablation speed were compared. RESULTS: DS mode was shown to induce significantly less blood loss than SS mode when the electrode spacing was set at 2 cm and the ablation duration was 2 min or 3 min (p=.010 and .012, respectively). Extended ablation duration and narrow electrode spacing tended to induce less blood loss, regardless of operating mode. Bloodless resection was achieved using DS mode with electrode spacing of 2 cm and ablation duration of 2-3 min. The highest rate of complete ablation (11.3 cm2/min) was achieved using DS mode with electrode spacing of 2 cm and ablation duration of 1.5 min. CONCLUSION: RF-based hepatic resection using DS mode is safe and feasible, resulting in less blood loss than SS mode with a higher rate of complete ablation (i.e., superior ablation efficiency).

Irreversible Electroporation: A Novel Ultrasound-guided Modality for Non-thermal Tumor Ablation.

Ultrasound-guided tumor ablation techniques have been proven to be highly effective and minimally invasive in the treatment of many diseases. Traditional approaches to ablation include microwave and radiofrequency techniques, cryotherapy, and high-intensity focused ultrasound. However, these methods are prone to heat-sink effects that can diminish the effectiveness of treatment and damage adjacent structures, such as bile ducts, blood vessels, the gallbladder, or bowel. Irreversible electroporation (IRE) is a non-thermal ablation modality that induces cell apoptosis through the application of high-voltage current. IRE is not limited by many of the limitation which affects conventional tumor ablation techniques, and is particularly useful in treating sensitive areas of the body. The article reviews the basics of ultrasound-guided technology, including its clinical applications and effectiveness in the treatment of tumors.

Diaphragmatic injury caused by an endo-retractor during laparoscopic cholecystectomy.

Endo-retractors are convenient devices for exposure and traction during minimally invasive surgery and are widely used in laparoscopic cholecystectomy (LC). Complications associated with the use of this device are rare. We present a patient with symptomatic gallstones who underwent LC and developed a diaphragmatic laceration as a result of the inappropriate use of an endo retractor. Although the incidence of complications with endo retractors is low, this report indicates the potential risk of diaphragmatic injury while using the retractors for exposure and traction during minimally invasive surgery.

Laparoscopic resection for large gastric gastrointestinal stromal tumor (GIST): intermediate follow-up results.

BACKGROUND: Laparoscopic wedge resection has become a widely accepted treatment for small gastrointestinal stromal tumor (GIST) of the stomach. However, its feasibility as treatment for large gastric GIST is not known. In this retrospective study, the perioperative and oncologic outcomes of laparoscopic wedge resection for gastric GIST (5-8 cm) were reviewed. METHODS: Between November 2002 and December 2012, a total of 39 patients with primary gastric GIST sized 5-8 cm underwent surgery at a tertiary care center, including 18 patients who underwent laparoscopic wedge resection of the stomach (Lap group) and 21 patients who underwent open wedge resection of the stomach (Open group). Clinicopathological parameters were reviewed and compared between the groups. RESULTS: The demographics including age, gender, and body weight were similar between groups. The operative outcomes including blood loss, hospital stay, and surgical complications were also similar, except that operative time was longer in the Lap group (146.6 ± 50.2 vs. 113.3 ± 42.9 min in the Open group, p = 0.03). There was no tumor rupture, conversion of procedures, or major surgical morbidity in either group. The overall median follow-up time was 3.6 years (1.0-11.1). Only one patient in the Lap group had liver metastasis (4 months postoperatively). This patient remains alive 5 years later under imatinib treatment. One patient in the Open group and three patients in the Lap group have died of GIST-unrelated diseases. CONCLUSIONS: Laparoscopic wedge resection of the stomach for primary gastric GIST (5-8 cm) appears to be safe and feasible, with operative and oncological outcomes comparable to those of the open method.

Obstructive jaundice as a complication of a right hepatic artery pseudoaneurysm after laparoscopic cholecystectomy.

A hepatic artery pseudoaneurysm is a rare, but a potentially life-threatening complication after laparoscopic cholecystectomy (LC). Obstructive jaundice owing to a hepatic artery pseudoaneurysm after LC has never been reported. We report a patient with a hepatic artery pseudoaneurysm after LC who presented with tarry stools, bloody drainage and obstructive jaundice.

Risk factors, patterns, and outcome predictors of late recurrence in patients with hepatocellular carcinoma after curative resection: A large cohort study with long-term follow-up results.

BACKGROUND: Late recurrence of hepatocellular carcinoma after curative resection significantly influences long-term patient survival outcomes, and yet it remains understudied. This study aims to explore the risk factors and patterns of late recurrence and predictors of subsequent outcome. METHODS: This single-center retrospective study analyzed 1,701 consecutive patients who achieved a disease-free survival period exceeding 2 years after curative resection for hepatocellular carcinoma between 2001 and 2018. Univariate and multivariate analyses of factors associated with late recurrence and death after recurrence were conducted using Cox's models. RESULTS: The mean age of patients was 60.2 years, with 76.8% being male. During a median follow-up of 8.1 years, 653 patients (38.4%) experienced late recurrence, with median time to recurrence being 4.0 years (interquartile range, 2.7-6.0). Factors such as age >60, chronic hepatitis C, cirrhosis, high albumin-bilirubin grade, absence of family history, multiple tumors, satellite nodules, alpha-fetoprotein levels <400 ng/mL, and minor hepatic resection were identified as risk factors for late recurrence. Among patients with late recurrence, 131 (20.1%) underwent surgical treatment, 272 (41.7%) received radiofrequency ablation, and 27 (4.1%) exhibited extrahepatic lesions. A higher-high albumin-bilirubin grade, recurrent tumor >3 cm, and nonsurgical treatment emerged as predictors of death after late recurrence. CONCLUSION: Over one-third of patients who remain disease-free for more than 2 years postresection will experience late recurrence during subsequent follow-up. For 2-year disease-free survivors, risk factors for late recurrence differ from early recurrence. Treating underlying hepatitis is of paramount importance, given its association with both the risk of late recurrence and survival outcomes post-recurrence.

Viral Status and Treatment Efficacy in Recurrent Hepatocellular Carcinoma After Primary Resection.

BACKGROUND: The impact of viral background on long-term effectiveness of different treatment modalities for recurrent hepatocellular carcinoma (HCC) was not fully analyzed. METHOD: Consecutive 726 patients who developed intrahepatic recurrence after primary hepatectomy for HCC between 2008 and 2015 were retrospectively studied. Post-recurrence survival (PRS) and rerecurrence-free survival (R-RFS) and risk factors were analyzed. RESULTS: After a median follow-up period of 56 months, the 5-year PRS rates of the patients who underwent rehepatectomy, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE) were 79.4%, 83.0%, and 54.6%, respectively. The treatment benefit for PRS was consistently observed in patients with hepatitis B virus (HBV) and non-B, non-C subgroups, but not hepatitis C virus (HCV). For patients with late recurrence of HCC, R-RFS was superior in HBV subgroup and HCV subgroup which received antiviral treatment (compared to naïve HCV subgroup). Survival difference triaged by viral status was lost in the counterpart with early recurrence. Overall, RFA improved PRS and R-RFS in patients receiving antiviral treatment. CONCLUSION: To achieve long-term survival after HCC recurrence, rehepatectomy and RFA were comparably effective, particularly among those with HBV. Antiviral treatment complemented survivals of patients with HCV after RFA, particularly in late first recurrence.

Longitudinal analysis of transplant candidates with primary sclerosing cholangitis in an Asian liver transplant center.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a rare disease in Asia, and few studies have investigated the disease in this ethnicity, particularly in wait-listed patients for liver transplantation (LT). We aimed to investigate the prognostic factors and outcomes of wait-listed patients with PSC in an Asian transplant center. METHODS: Survival was retrospectively analyzed. RESULTS: Eighteen (10 male and 8 female) wait-listed patients with PSC, with a median age at diagnosis of 44.5 years, were included. Compared with men, women had significantly higher aspartate aminotransferase to platelet ratio index scores (3.28 vs. 1.13; P = 0.012) and bilirubin levels (7.68 vs. 4.03 mg/dl; P = 0.043) and more often presented with decompensating events, including ascites [5 (63%) vs. 1 (10%); P = 0.043] and splenomegaly [8 (100%) vs. 4 (40%); P = 0.013]. Compared with the non-LT group, the LT group exhibited a superior survival rate for women ( P = 0.004) but not for men. In the univariable analysis, significant risk factors associated with overall survival included malignancies with a hazard ratio (95% confidence interval) of 5.53 (1.00-30.51) and esophageal varices (EV) [4.18 (1.05-16.61)], whereas female gender [25.00 (1.49-500.00)], LT [0.09 (0.01-0.80)] and EV [39.03 (2.92-521.96)] were indicated in the multivariable analysis. CONCLUSIONS: For Asian wait-listed patients with PSC, EV and female gender were the risk factors related to overall survival, and LT was the protective factor. Our experiences suggested that LT brings more benefits in female patients. Strategies are needed to provide equivalent transplant benefits.

DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: Alfa-fetoprotein (AFP), as the main serum tumor marker of hepatocellular carcinoma (HCC), is limited in terms of specificity and ability to predict outcomes. This study investigated the clinical utility of DNA methylation biomarkers to predict therapeutic responses and prognosis in intermediate-stage HCC. METHODS: This study enrolled 72 patients with intermediate-stage HCC who underwent locoregional therapy (LRT) between 2020 and 2021. The immediate therapeutic response and disease status during a two-year follow-up were recorded. Analysis was performed on 10 selected DNA methylation biomarkers via pyrosequencing analysis of plasma collected before and after LRT. RESULTS: Analysis was performed on 53 patients with complete responses and 19 patients with disease progression after LRT. The mean follow-up duration was 2.4 ± 0.6 years. A methylation prediction model for tumor response (MMTR) and a methylation prediction model for early progression (MMEP) were constructed. The area under the curve (AUC) for sensitivity and specificity of MMTR was 0.79 for complete response and 0.759 for overall survival. The corresponding AUCs for sensitivity and specificity of AFP and protein induced by vitamin K absence-II (PIVKA-II) were 0.717 and 0.708, respectively. Note that the MMTR index was the only significant predictor in multivariate analysis. The AUC for sensitivity and specificity of the MMEP in predicting early progression was 0.79. The corresponding AUCs for sensitivity and specificity of AFP and PIVKA-II were 0.758 and 0.714, respectively. Multivariate analysis revealed that platelet count, beyond up-to-7 criteria, and the MMEP index were strongly correlated with early tumor progression. Combining the indexes and serum markers further improved the predictive accuracy (AUC = 0.922). Multivariate analysis revealed the MMEP index was the only independent risk factor for overall survival. DISCUSSION/CONCLUSIONS: This study indicates that these methylation markers could potentially outperform current serum markers in terms of accuracy and reliability in assessing treatment response and predicting outcomes. Combining methylation markers and serum markers further improved predictive accuracy, indicating that a multi-marker approach may be more effective in clinical practice. These findings suggest that DNA methylation biomarkers may be a useful tool for managing intermediate-stage HCC patients and guiding personalized treatment, particularly for those who are at high risk for close surveillance or adjuvant treatment after LRT.

Improved second harmonic generation and two-photon excitation fluorescence microscopy-based quantitative assessments of liver fibrosis through auto-correction and optimal sampling.

BACKGROUND: Second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy is commonly used for the quantitative assessment of liver fibrosis; however, the accuracy is susceptible to sampling error and count error due to disturbances induced by some forms of collagen in liver specimens. In this study, we sought to improve the accuracy of quantitative assessments by removing the effects of this disturbing collagen and optimizing the sampling protocol. METHODS: Large liver resection samples from 111 patients with chronic hepatitis B were scanned using SHG/TPEF microscopy with multiple adjacent images. During the quantitative assessment, we then removed SHG signals associated with three types of extraneous physiological collagen: large patches of collagen near the boundary of the capsule, collagen around tubular structures, and collagen associated with distorted vessel walls. The optimal sampling protocol was identified by comparing scans from regions of interest of various sizes (3×3 tiles and 5×5 tiles) with full scans of the same tissue. RESULTS: The proposed auto-correction algorithm detected 88 of 97 (90.7%) disturbing collagen on the images from the validation set. Removing these signals of disturbing collagen improved the correlation between Metavir stage and quantification of all 41 proposed collagen features. Through optimal sampling, five scans of 5×5 tiles or ten scans of 3×3 tiles were sufficient to minimize the mean error rate to around 2% of collagen percentage quantification and to achieve similar correlations around 0.27 with Metavir stage as using full tissue scans. CONCLUSIONS: Our results demonstrate that the quantitative assessments of liver fibrosis can be greatly enhanced in terms of accuracy and efficiency through optimal sampling and the automated removal of disturbing collagen signals. These types of image processing could be integrated in next-generation SHG/TPEF microscopic systems.

Long-Term Tacrolimus Blood Trough Level and Patient Survival in Adult Liver Transplantation.

Tacrolimus is the most widely used immunosuppressant in liver transplant (LT) patients. However, the ideal long-term target level for these patients is unknown. This retrospective study aimed to investigate the impact of tacrolimus blood concentration five years after LT on long-term patient survival outcomes in adult LT recipients. Patients who underwent LT between January 2004 and July 2014 at a tertiary medical center were included in this study (n = 189). The mean tacrolimus blood concentrations of each patient during the fifth year after LT were recorded and the overall survival rate was determined. A multivariate analysis of factors associated with long-term survival was conducted using a Cox's model. The median follow-up period was 9.63 years, and 144 patients (76.2%) underwent live donor LT. Sixteen patients died within 5 years of LT. In the Cox's model, patients with a mean tacrolimus blood trough level of 4.6-10.2 ng/mL had significantly better long-term survival than those with a mean tacrolimus blood trough level outside this range (estimated hazard ratio = 4.76; 95% confidence interval: 1.34-16.9, p = 0.016). Therefore, a tacrolimus level no lower than 4.6 ng/mL would be recommended in adult LT patients.

Irreversible Electroporation Treatment With Intraoperative Biliary Stenting for Unresectable Perihilar Cholangiocarcinoma: A Pilot Study.

BACKGROUND: Treating perihilar cholangiocarcinoma (PHCC) is particularly difficult due to the fact that it is usually in an advanced stage at the time of diagnosis. Irreversible electroporation treatment (IRE) involves the local administration of a high-voltage electric current to target lesions without causing damage to surrounding structures. This study investigated the safety and efficacy of using IRE in conjunction with intraoperative biliary stent placement in cases of unresectable PHCC. METHODS: This study enrolled 17 patients with unresectable Bismuth type III/IV PHCC who underwent IRE in conjunction with intraoperative biliary stent placement (laparotomic) in two medical centers in Asia between June 2015 and July 2018. Analysis focused on the perioperative clinical course, the efficacy of biliary decompression, and outcomes (survival). RESULTS: Mean total serum bilirubin levels (mg/dL) on postoperative day (POD) 7, POD30, and POD90 were significantly lower than before IRE (respectively 3.46 vs 4.54, p=0.007; 1.21 vs 4.54, p<0.001; 1.99 vs 4.54, p<0.001). Mean serum carbohydrate antigen 19-9 (CA19-9, U/ml) levels were significantly higher on POD3 than before the operation (518.8 vs 372.4, p=0.001) and significantly lower on POD30 and POD90 (respectively 113.7 vs 372.4, p<0.001; 63.9 vs 372.4, p<0.001). No cases of Clavien-Dindo grade III/IV adverse events or mortality occurred within 90 days post-op. The median progression-free survival was 21.5 months, and the median overall survival was 27.9 months. All individuals who survived for at least one year did so without the need to carry percutaneous biliary drainage (PTBD) tubes. CONCLUSIONS: It appears that IRE treatment in conjunction with intraoperative biliary stent placement is a safe and effective approach to treating unresectable PHCC. The decompression of biliary obstruction without the need for PTBD tubes is also expected to improve the quality of life of patients.

Clinical impact of irreversible electroporation ablation for unresectable hilar cholangiocarcinoma.

Irreversible electroporation (IRE) is a non-thermal ablation modality that has been shown to be safe and effective in its application to tumors that are close to risky areas. This study aims to assess the safety and efficacy of IRE for unresectable hilar cholangiocarcinoma. Nine patients from two medical centers in Asia received IRE treatment between June 2015 and July 2017. Before IRE treatment, percutaneous biliary decompressions had been performed on eight patients, and internal stenting had been performed on one patient. All patients tolerated the procedure well without high-grade complications. The ablated tumors had constant size without contrast enhancement for more than three months in eight patients and the level of CA19-9 decreased significantly in all patients. The percutaneous biliary drainage tube was removed from two patients with recanalization of the bile duct. The internal stent in one patient was removed without further stenting. The median overall survival period was 26 months, and the progression-free survival was 18 months. Bile ducts remained narrow in the majority (2/3) of the treated patients. Nevertheless, IRE ablation of unresectable hilar cholangiocarcinoma involving vital structures is a safe and feasible primary treatment for local tumor control and is effective in prolonging survival.