Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

Surgical outcomes of hepatocellular carcinoma with extrahepatic bile duct tumor thrombus: a multicenter study.

Background: The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT. Methods: A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS. Conclusion: Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.

Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.

Should associating liver partition and portal vein ligation for staged hepatectomy be applied to hepatitis B virus-related hepatocellular carcinoma patients with cirrhosis? A multi-center study.

BACKGROUND: It is unclear whether associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can be performed in hepatitis B virus-related hepatocellular carcinoma (HCC) patients with cirrhosis. We explored the efficacy of ALPPS in HCC patients. METHODS: Data of 54 patients who underwent ALPPS between August 2014 and July 2020 at three centers were collected. Adverse factors affecting their prognosis were analyzed and subsequently compared with 184 patients who underwent transcatheter arterial chemoembolization (TACE). RESULTS: Overall survival rates of the ALPPS group at 1, 3, and 5 years were 70.6%, 38.4%, and 31.7%, respectively; corresponding disease-free survival rates were 50.5%, 22.4%, and 19.2%, respectively. The ALPPS group had a significantly greater long-term survival rate than the TACE group (before propensity score matching, P < 0.001; after propensity score matching, P = 0.002). Multivariate analysis demonstrated that multifocal lesions (P = 0.018) and macroscopic vascular invasion (P = 0.001) were prognostic factors for HCC patients who underwent ALPPS. After the propensity score matching, the multifocal lesions (P = 0.031), macroscopic vascular invasion (P = 0.003), and treatment type (ALPPS/TACE) (P = 0.026) were the factors adversely affecting the prognosis of HCC patients. CONCLUSION: ALPPS was feasible in hepatitis B virus-related HCC patients with cirrhosis and resulted in better survival than TACE.

Outcomes of laparoscopic bile duct exploration for choledocholithiasis with small common bile duct.

BACKGROUND: Laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct (CBD) exploration (LCBDE) is one of the main treatments for choledocholithiasis with CBD diameter of larger than 10 mm. However, for patients with small CBD (CBD diameter ≤ 8 mm), endoscopic sphincterotomy remains the preferred treatment at present, but it also has some drawbacks associated with a series of complications, such as pancreatitis, hemorrhage, cholangitis, and duodenal perforation. To date, few studies have been reported that support the feasibility and safety of LCBDE for choledocholithiasis with small CBD. AIM: To investigate the feasibility and safety of LCBDE for choledocholithiasis with small CBD. METHODS: A total of 257 patients without acute cholangitis who underwent LC + LCBDE for cholecystolithiasis from January 2013 to December 2018 in one institution were reviewed. The clinical data were retrospectively collected and analyzed. According to whether the diameter of CBD was larger than 8 mm, 257 patients were divided into large CBD group (n = 146) and small CBD group (n = 111). Propensity score matching (1:1) was performed to adjust for clinical differences. The demographics, intraoperative data, short-term outcomes, and long-term follow-up outcomes for the patients were recorded and compared. RESULTS: In total, 257 patients who underwent successful LC + LCBDE were enrolled in the study, 146 had large CBD and 111 had small CBD. The median follow-up period was 39 (14-86) mo. For small CBD patients, the median CBD diameter was 0.6 cm (0.2-2.0 cm), the mean operating time was 107.2 ± 28.3 min, and the postoperative bile leak rate, rate of residual CBD stones (CBDS), CBDS recurrence rate, and CBD stenosis rate were 5.41% (6/111), 3.60% (4/111), 1.80% (2/111), and 0% (0/111), respectively; the mean postoperative hospital stay was 7.4 ± 3.6 d. For large CBD patients, the median common bile duct diameter was 1.0 cm (0.3-3.0 cm), the mean operating time was 115.7 ± 32.0 min, and the postoperative bile leak rate, rate of residual CBDS, CBDS recurrence rate, and CBD stenosis rate were 5.41% (9/146), 1.37% (2/146), 6.85% (10/146), and 0% (0/146), respectively; the mean postoperative hospital stay was 7.7 ± 2.7 d. After propensity score matching, 184 patients remained, and all preoperative covariates except diameter of CBD stones were balanced. Postoperative bile leak occurred in 11 patients overall (5.98%), and no difference was found between the small CBD group (4.35%, 4/92) and the large CBD group (7.61%, 7/92). The incidence of CBDS recurrence did not differ significantly between the small CBD group (2.17%, 2/92) and the large CBD group (6.52%, 6/92). CONCLUSION: LC + LCBDE is safe and feasible for choledocholithiasis patients with small CBD and did not increase the postoperative bile leak rate compared with chole-docholithiasis patients with large CBD.

Effective approach to greatly enhancing selective secretion and expression of three cytoplasmic enzymes in Escherichia coli through synergistic effect of EDTA and lysozyme.

An effective approach to greatly enhancing the selective secretion and expression of recombinant cytoplasmic enzymes in Escherichia coli was successfully developed through the synergistic effect of ethylenediaminetetraacetate (EDTA) and lysozyme. The method was applied to two endoglucanases (EGs) and an amylase. The optimal culture conditions of temperature and concentration of isopropyl-ß-D: -1-thiogalactopyranoside (IPTG) were 23-30 °C and 0.2 mM, respectively, under which the three enzymes could be expressed in active form. Among all the chemicals tested, EDTA was found to be most suitable for enhancing the secretion of EG-I-1A into the medium. Addition of lysozyme alone had little influence on the secretion and expression. In contrast, on the basis of the addition of 5 g EDTA/L at the induction time of 12 h, the simultaneous addition of 0.15 g lysozyme/L further significantly increased the secretion and expression of the three enzymes, demonstrating the synergistic effect of EDTA and lysozyme. The production of EG-I-1A in the culture medium by adding 5 g EDTA/L and 0.15 g lysozyme/L under the optimal culture conditions of 23 °C and 0.2 mM IPTG was over 260-fold higher than that without EDTA and lysozyme under the standard conditions of 37 °C and 1 mM IPTG. In summary, the advantage of this novel cultivation approach for secretion was that not only did it selectively enhance the secretion of the proteins of interest, but also greatly increased the expression of the three enzymes by over 80 %.

Enhanced secreting expression and improved properties of a recombinant alkaline endoglucanase cloned in Escherichia coli.

An alkaline endoglucanase from Bacillus akibai III-3A was successfully expressed in Escherichia coli in active form, and secretion was greatly enhanced by addition of 5 g/l ethylenediamine tetraacetic acid (EDTA) to the culture medium at the induction time of 12 h. Under the optimal culture conditions, extracellular and total endoglucanase activities were 18.5 and 31.2 U/ml, respectively. Both the recombinant and native enzymes exhibited similar properties with respect to broad pH stability, good thermostability, and resistibility to various metal ions and reagents examined. However, unlike the native endoglucanase that was partly inhibited by sodium dodecyl sulfate (SDS), the recombinant enzyme had good resistibility to SDS, being very stable in the commercial detergents, and no decrease in residual activity was observed in 0.2% (w/v) laundry detergent, indicating that it was suitable for application in detergents industry.