Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome.

BACKGROUND: Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM: To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS: A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS: Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION: In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.

Effect of Ursodeoxycholic Acid on Preventing SARS-CoV-2 Infection in Patients With Liver Transplantation: a multicenter retrospective cohort study.

BACKGROUND: Immunosuppressed recipients of liver transplantation (LT) are more likely to develop coronavirus disease 2019 (COVID-19) and may have an increased risk of developing worse outcomes. AIM: To assess the effect of ursodeoxycholic acid (UDCA) on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. DESIGN: Adult patients (aged ≥ 18 years) who underwent LT between January 1st, 2015, and December 31st, 2022, were included and categorized into two groups according to their use of UDCA. METHODS: The prevalence and severity of COVID-19 among transplantation patients between the UDCA and non-UDCA groups were estimated and compared. RESULTS: Among the 897 LT patients who met the inclusion criteria, infection rate of SARS-CoV-2 was 78.4%, and the rate of severe illness was 5.1% from January 2022 to January 2023 in China. In the multivariate analysis, only UDCA treatment (P = 0.006) was found to be a protective factor against SARS-CoV-2 infection. After propensity score matching, the SARS-CoV-2 infection rate in the UDCA group was lower than that in the non-UDCA group (74.1% vs. 84.6%, P = 0.002). This rate was further reduced to 62.1% (P = 0.002) when the oral administration dose was greater than 15 mg/kg/d. There was no difference in the rates of severe COVID-19 illness, ICU admission, or ventilation rate or length of hospital stay with or without UDCA treatment (all P > 0.05). CONCLUSIONS: The use of UDCA in LT patients significantly reduced the SARS-CoV-2 infection rate and showed a dose-dependent protective effect.

Overexpression of HSF2 binding protein suppresses endoplasmic reticulum stress via regulating subcellular localization of CDC73 in hepatocytes.

BACKGROUND: Endoplasmic reticulum (ER) stress plays an important role in the occurrence and development of various liver diseases. However, there are no effective prevention and treatment strategies. We aimed to determine the role of heat shock factor 2 binding protein (HSF2BP) in ER stress. METHODS: HSF2BP expression in mice and cultured hepatocytes was measured during ER stress induced by tunicamycin, and its importance in ER stress was evaluated in hepatocyte-specific HSF2BP transgenic (TG) and knockout (KO) mice. The effects and mechanisms of HSF2BP on ER stress were further probed in hepatic ischemia-reperfusion (I/R) injury. RESULTS: HSF2BP expression was significantly upregulated during tunicamycin-induced ER stress in mice and cultured hepatocytes. Liver injury and ER stress were reduced in HSF2BP overexpressing mice after treating with tunicamycin, but were aggravated in HSF2BP knockout mice compared to the controls. In hepatic I/R injury, HSF2BP expression was significantly upregulated, and HSF2BP overexpressing mice had reduced liver injury and inflammation. These improvements were associated with ER stress inhibition. However, these results were reversed in hepatocyte-specific HSF2BP knockout mice. HSF2BP overexpression increased cytoplasmic CDC73 levels and inhibited the JNK signaling pathway. CDC73 knockdown using siRNA eliminated the protection exerted by HSF2BP overexpression in hypoxia/reoxygenation (H/R)-induced ER stress in hepatocytes. CONCLUSION: HSF2BP is a previously uncharacterized regulatory factor in ER stress-likely acts by regulating CDC73 subcellular localization. The feasibility of HSF2BP-targeted treatment in ER stress-related liver disease deserves future research.

The application of magnetic anchoring traction device in assisting donor liver bench surgery in classic orthotopic liver transplantation.

OBJECTIVE: To explore the clinical application of a newly developed magnetic anchoring traction (MAT) system in the liver bench trimming and transplantation surgery. BACKGROUND: The conventionally limited space, vision, and exposure have always been a challenge for the quality of surgery in the liver bench trimming due to the fact that the exposure depends largely on the experience of surgeon. To deal with this problem, a MAT system is developed as an alternative support to enhance exposure. The preliminarily experiments on animals verified its feasibility and reliability in the practical use, and its clinical application and effects were examined in the present research. METHODS: A total of 20 DCD (donation of cardiac death) donor livers were collected and divided evenly between the magnetic anchor traction (MAT) assisted group (n = 10) and the manual assisted group (n = 10). The results and quality assessment from experts about the liver bench surgery performed by two groups were examined and compared. RESULTS: The MAT system can be employed effectively to compete and replace the manual assistance to achieve a better exposure in the liver bench trimming. No statistical difference was found regarding the baseline data between the MAT and the manual groups. In the inferior vena cava and hepatic artery trimming, the MAT group outperformed the manual group remarkably in many aspects. The surgery time for liver bench shortened considerably after a quick grasp of MAT skills by surgeons. CONCLUSION: The MAT system provides a more stable, reliable and qualified local exposure in the liver bench surgery, and can preferably be employed to replace the manual assistance in the procedures of liver transplantation.

Glycoproteomic analysis reveals the effects of bisecting GlcNAc in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second major subtype of primary liver cancer and has caused more and more attention with increasing incidence and mortality worldwide. Our previous study found that bisecting N-glycans are commonly increased in ICC, while the effects and potential functions of bisecting GlcNAc in ICC are still largely unclear. In this study, we further confirmed that the structures of bisecting GlcNAc were significantly up-regulated in ICC compared with paracancer tissues by glycoproteomic data and lectin histochemistry. The expression of its glycosyltransferase MGAT3 was also up-regulated in ICC tissues at both mRNA and protein levels, and expression of MGAT3 is negatively correlated with overall survival explored by bioinformatic analyses and published datasets from 255 patients. Next, the silencing of MGAT3 could inhibit the growth and invasion of ICC cells, and overexpressing of MGAT3 only promoted ICC cell invasion. Further glycoproteomic analysis showed that the commonly glycoproteins modified by bisecting GlcNAc after MGAT3-overexpression in two ICC cell lines were mainly involved in cell movement-related biological processes, such as cell adhesion, integrin-related and ECM-receptor interaction. This study sheds light on the potential effects of bisecting GlcNAc in ICC cells and suggests that MGAT3 might be used as a potential target in the therapy of ICC.

The Management of Portal Vein Thrombosis after Adult Liver Transplantation: A Case Series and Review of the Literature.

BACKGROUND: Portal vein thrombosis (PVT) after adult liver transplantation (LT) is a rare but serious complication with no consensus on the ideal treatment. We report a case series and a comprehensive review of the literature on PVT after LT to discuss the therapeutic options. METHODS: The clinical data of 360 adult patients (≥18 years of age) who underwent LT from January 2017 to January 2020 were reviewed, and a comprehensive search of PubMed and Web of Science was conducted. Patients diagnosed with PVT after LT were identified, and relevant risk factors and therapies were analyzed. RESULTS: Among the 360 patients, 7 (1.94%) developed PVT after LT. Onset of PVT within one week after LT was found in six patients (85.71%). Four of the seven patients with PVT received systemic anticoagulation (low molecular weight heparin and warfarin) therapy. Minimally invasive interventional therapies combined with systemic anticoagulation (heparin and warfarin) were applied for three patients, two of whom died because of severe abdominal hemorrhage and liver failure. Of the 33 cases reported in the literature, minimally invasive interventional therapy combined with systematic anticoagulation or sclerotherapy were the most-used methods (20/33). Systemic anticoagulation was administered to four patients, and surgical operation (thrombectomy; portosystemic shunt and retransplantation) was performed for nine patients. Among these 33 patients, 4 eventually died. CONCLUSIONS: Interventional therapy combined with systemic anticoagulation is a good choice for the management of PVT after LT, and in our experience, systemic anticoagulation alone can also have a positive effect for early PVT patients.

Utilization of elderly donors in liver transplantation for patients with hepatocellular carcinoma: A national retrospective cohort study of China.

BACKGROUND: Profound organ shortages worldwide have led to the increased utilization of marginal organs from older individuals. However, the effectiveness of liver transplantation (LT) with organs from elderly donors for patients with hepatocellular carcinoma (HCC) remains controversial. The objective of the current study was to assess the overall survival (OS) and disease-free survival (DFS) of patients with HCC following LT using grafts from deceased donors over 60 years old. MATERIAL AND METHODS: Patients with HCC who underwent LT between 2015 and 2018 were identified in the China Liver Transplant Registry database. The overall survival and disease-free survival of older liver donors (OLDs) were compared with those of younger liver donors (YLDs) after propensity score matching. RESULTS: From January 2015 to December 2018, a total of 4971 HCC patients were enrolled in the study according to the screening criteria. The absolute and relative utilization of liver grafts from elderly patients over 60 years for HCC patients increased every year, from 65 (9.3%) in 2015 to 268 (14.5%) in 2018. Disease-free survival (DFS) was significantly lower in HCC patients with elderly donors (both P < 0.05) after propensity score matching. The OLD group had worse DFS than YLD group if patients had tumors beyond the Milan criteria (P < 0.05). CONCLUSIONS: The use of older donors for LT has been growing quickly in the last few years in China. Grafts from older donors can be safely used in HCC recipients with similar OS and comparable perioperative complications. However, further investigation into whether older donor has an impact on recurrence is warranted, especially among those with tumors beyond the Milan criteria.

Numerical analysis and animal study of noninvasive handheld electroporation delivery device for skin superficial lesion treatment.

INTRODUCTION: This study aims to investigate the feasibility of a noninvasive handheld electroporation pulses delivery device (EPDD) for electroporation-based treatment (EBT) of skin superficial lesions through numerical analysis and animal study. METHODS: Finite element analysis was performed to investigate the performance of the EPDD. The electric field, temperature, EI and TI were calculated under pulse voltages of 600, 800, and 1000 V. A mouse subcutaneous tumor model was established to evaluate the performance of the EPDD through histopathology and survival analyses. RESULTS: The electrical field strength increased from 151 (600 V) to 252 V/cm (1000 V) in the skin and from 1302 (600 V) to 2171 V/cm (1000 V) in the tumor. The volume of EI grew and reached a plateau at the 165th pulse, whereas the maximum volume of EI increased with higher voltage. The growth tendency of TI differed between groups, and it was higher in the high-voltage group (HVG) than in the low-voltage group. Histopathological analysis showed that the depth and range of the ablation area could be controlled by adjusting pulse voltage. Survival analysis showed that the survival of the HVG was better than that of the low-voltage and the control group (p < 0.01). CONCLUSIONS: The results demonstrate that the EPDD is feasible, safe, and effective for skin EBT. The volume of EP tissue injury can be controlled by adjusting the pulse voltage, pulse number, and other parameters. The proposed noninvasive handheld EPDD can be a potential therapeutic tool for EBT of superficial skin lesions in the future.

Education curriculum for surgical interns that improves stress management and grit levels.

INTRODUCTION: Overwhelming stress or burnout has been observed in medical students, including 69% of surgical interns. This study aimed to assess the stress levels of fifth-year medical students during surgical training. An education curriculum with both clinical and research sessions was evaluated for its effect on the interns' stress and grit levels. METHOD: A blinded, prospective study was conducted to evaluate the efficacy of an educational program on the recognition and management of stress. The State-Trait Anxiety Inventory (STAI) was used to assess anxiety. The Grit Scale was used to quantify the interns' grit, conscientiousness, and self-control. RESULTS: The STAI survey results showed that the STAI state scores but not the trait scores were significantly lower in the intervention group than in the control group (p < 0.05). Additionally, the postintervention STAI score and the change in the STAI score were both lower in the intervention group (p < 0.05). There was a significant increase in grit among the medical students in the intervention group from baseline to post-intervention (p < 0.001). The scores of the consistency and perseverance subscales of the Grit Scale also increased significantly from baseline to post-intervention (both p < 0.001). CONCLUSION: The education curriculum can improve interns' stress management and grit levels. We believe this curriculum needs to be implemented in medical education, and we plan to continue the program.

Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.

Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem. Although ICC is clinically different from HCC, their molecular differences are still largely unclear. In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation. By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors. Notably, glycans with uncommon LacdiNAc (GalNAcß1-4GlcNAc) structures were distinguished from their isomeric glycans. In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC. More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of ß1-4 GalNAc transferases in ICC at both mRNA and protein expression levels. The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.

Diagnosis and treatment of acute graft-versus-host disease after liver transplantation: Report of six cases.

BACKGROUND: Graft-versus-host disease (GVHD) following liver transplantation (LT) is an unpredictable complication with poor outcome. However, consensus regarding the diagnosis and therapeutic regimen for the disease is yet lacking. The present study summarized the clinical experience on the diagnosis and treatment of acute GVHD (aGVHD) following LT and reviewed the pertinent literature. CASE SUMMARY: Between January 1st, 2000 and December 31st, 2020, a total of 1053 LT were performed in the First Affiliated Hospital of Xi'an Jiaotong University. Six recipients developed aGVHD with clinical symptoms of fever, rash, diarrhea, and pancytopenia. The incidence of aGVHD was 0.57%. The median time from LT to the clinical presentation of aGVHD was 22.17 d. The median time from the beginning of the clinical symptom to histopathological diagnosis was 7.5 d. All six cases underwent treatment of immunosuppressant adjustment, corticosteroids, human normal immunoglobulin, and antithymocyte globulin/IL-2 antagonists. Despite intensive treatment strategies, 4 patients were deceased due to sepsis, multiple organ failure, and cerebral hemorrhage. The remaining two cases were discharged as treatment successfully. However, one died because of tuberculosis infection on the 6th month of follow-up, the other one was alive healthy during 30 mo of follow-up. CONCLUSION: The rapid diagnosis of aGVHD is mainly based on the time from the first symptom, histopathological features, and the donor T-lymphocyte chimerism. Our cases report highlights massive corticosteroid therapy and age difference between donors and recipients could accelerate to aGVHD. Moreover, gut microbial interventions and donor-targeted serotherapy may provide novel therapeutics.

A modified animal model of hepatic regeneration induced by hilar bile duct ligation.

Mechanisms of the proliferation of liver are mainly studied in animal model of liver regeneration after partial hepatectomy (PH). However, the PH model involves complex regeneration mechanisms, including hemodynamic factors, cytokines, growth factors, and metabolites. Among liver metabolites, bile acid (BA) is a key signaling molecule that regulates liver regeneration. This study aimed to establish a new type of rapid liver hyperplasia model induced mainly by bile acid pathway through hepatoenteral circulation with hilar bile duct ligation (HBDL). We first established the HBDL model by ligating the bile duct of all hepatic lobes but the right lateral lobe in rabbits and compared with the PVL model and sham operation group. Changes in the liver lobe and hemodynamics were observed. Liver function and the bile acid level were also analyzed. Then we verified the HBDL model in mice. Liver function and the levels of bile acids and cytokines were tested. The protein and mRNA levels of FXR, FGF15, CYP7A1 and FoxM1b in liver tissue were also analyzed. After hilar ligation of the biliary tract, the unligated liver lobes proliferated significantly. Compared with those in the sham group, the volume and weight of the unligated right lateral lobe of the liver in the HBDL group and the PVL group increased significantly (P < 0.05). Transient liver function impairment occurred both in the HBDL group and PVL group in the rabbit model as well as the mouse models. The bile acid levels in the HBDL groups of the rabbit model and mouse model increased significantly within first week after surgery (P < 0.05). The immunohistochemistry results confirmed the proliferation of hepatocytes in the unligated liver lobe. Compared with those in the sham group, the levels of FXR, FGF15 and FoxM1b in the HBDL group were significantly increased (P < 0.05), while the expression of CYP7A1 was inhibited. Compared with those in the HBDL group, the postoperative hemodynamic changes in the PVL group were significant (P < 0.05). The levels of IL-6 and TNF-α in the HBDL group were higher than those in the sham group. The HBDL model is simple to establish and exhibits good surgical tolerance. The model has definite proliferative effect and strong specificity of bile acid pathway. This is an ideal animal model to study the mechanism of liver regeneration through bile acid pathway.

The effect of aging on VEGF/VEGFR2 signal pathway genes expression in rat liver sinusoidal endothelial cell.

Liver sinusoidal endothelial cells (LSECs) play a key role in the initiation and neoangiogenesis of liver regeneration. We presume that the abnormity of the VEGF/VEGFR2 and its pathway gene Id1, Wnt2 and HGF expression in aged LSECs may be an important mechanism to affect liver regeneration of the elderly. LSECs from two different groups (adult and old) were isolated in a rodent model, and observed by SEM and TEM. The adult and old rats were underwent 70% partial hepatectomy. The proliferation of hepatocytes and LSECs were analyzed by Immunofluorescence staining. The expression of VEGF/VEGFR2 and its pathway gene in isolated LSECs and liver tissue after hepatectomy were detected by qRT-PCR and Western blot. There is a decreased number of endothelial fenestrae in the LSECs of the old group, compared to the adult group. The old group had a lower expression of VEGF/VEGFR2 and its pathway gene than the adult groups (p < 0.01). The results of western blot were consistent with those of qRT-PCR. The hepatocytes had a high proliferation rate at first 4 days after hepatectomy, and a significantly higher proliferation rate in the adult group. The LSECs began to proliferate after 4 days of hepatectomy, and showed a quantity advantage in the adult group. The adult group had a significantly higher expression of VEGF/VEGFR2 and its pathway gene after hepatectomy than the old group (p < 0.01). LSCEs turn to be defenestration in structure and have a low expression of VEGF/VEGFR2 and its pathway gene with aging.

Acute and subacute effects of irreversible electroporation on normal common bile ducts in a rabbit model.

BACKGROUND/PURPOSE: This study aimed to evaluate the acute and subacute effects of irreversible electroporation (IRE) on normal common bile ducts (CBDs). METHODS: Cell susceptibility to IRE was assessed in vitro with cholangiocarcinoma and normal cell lines. The electric field and temperature distributions were evaluated with a two-dimensional simulation model of bile duct. In vivo bile duct IRE was performed in 28 adult rabbits. RESULTS: Different cells showed different susceptibility to the effect of IRE, cancer cell line HUCC-T1 was the least sensitive to IRE. Simulations predicted the distributions of electric field and temperature during the IRE process, and the maximum temperature of tissue was below 43℃. Complications were observed in 8/28 animals (biliary dilatation, n = 4; biliary stricture, n = 4) by postoperative days 7, 14, and 28. Histopathological analyses revealed complete cell death with bile duct wall integrity. Bile duct epithelial recovery was completed between post-IRE days 14-28. CONCLUSIONS: The normal CBD retains the lumen wall integrity following IRE with immediate periductal placement of the electrode. However, the risk of biliary dilatation and stricture is a reminder that the parameters of IRE need to be determined more precisely to ensure the treatment efficacy and reduce the risk of collateral damage.

Heterogeneities of Site-Specific N-Glycosylation in HCC Tumors With Low and High AFP Concentrations.

Hepatocellular carcinoma (HCC) is still one of the malignant tumors with high morbidity and mortality in China and worldwide. Although alpha-fetoprotein (AFP) as well as core fucosylated AFP-L3 have been widely used as important biomarkers for HCC diagnosis and evaluation, the AFP level shows a huge variation among HCC patient populations. In addition, the AFP level has also been proved to be associated with pathological grade, progression, and survival of HCC patients. Understanding the intrinsic heterogeneities of HCC associated with AFP levels is essential for the molecular mechanism studies of HCC with different AFP levels as well as for the potential early diagnosis and personalized treatment of HCC with AFP negative. In this study, an integrated N-glycoproteomic and proteomic analysis of low and high AFP levels of HCC tumors was performed to investigate the intrinsic heterogeneities of site-specific glycosylation associated with different AFP levels of HCC. By large-scale profiling and quantifying more than 4,700 intact N-glycopeptides from 20 HCC and 20 paired paracancer samples, we identified many commonly altered site-specific N-glycans from HCC tumors regardless of AFP levels, including decreased modifications by oligo-mannose and sialylated bi-antennary glycans, and increased modifications by bisecting glycans. By relative quantifying the intact N-glycopeptides between low and high AFP tumor groups, the great heterogeneities of site-specific N-glycans between two groups of HCC tumors were also uncovered. We found that several sialylated but not core fucosylated tri-antennary glycans were uniquely increased in low AFP level of HCC tumors, while many core fucosylated bi-antennary or hybrid glycans as well as bisecting glycans were uniquely increased in high AFP tumors. The data provide a valuable resource for future HCC studies regarding the mechanism, heterogeneities and new biomarker discovery.

Safety and efficacy of magnetic anchoring electrode-assisted irreversible electroporation for gastric tissue ablation.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.

Redefining Conditional Overall and Disease-Free Survival After Curative Resection for Intrahepatic Cholangiocarcinoma: a Multi-institutional, International Study of 1221 patients.

OBJECTIVES: To assess conditional survival (CS) according to recurrence status, as well as conditional disease-free survival (cDFS) among patients with intrahepatic cholangiocarcinoma (ICC). METHODS: CS and cDFS were evaluated among ICC patients who underwent curative-intent resection for ICC by using a multi-institutional database. Five-year CS (CS5) at "x" years was calculated separately for patients who did and did not experience recurrence. The cDFS3 at "x" years was defined as the chance to be disease-free for an additional 3 years after not having experienced a recurrence for "x" years postoperatively. RESULTS: Among 1221 patients, median OS was 36.8 months. While estimated actuarial OS decreased over time, CS5 increased as patients survived over longer periods of time and reached 93.9% at 4 years among 139 patients who did not experience a recurrence. Among the 725 (59.4%) patients who did experience a tumor recurrence, CS5 decreased to 17.7% the first postoperative year; however, CS5 subsequently increased to 79.7% for 81 patients who had survived 4 years after surgery. While actuarial DFS decreased from 54.6% at 1 year to 28.2% at 5 years, estimated cDFS3 following liver resection increased over time. Of note, patients with known risk factors for recurrence had even more marked improvements in cDFS3 over subsequent years versus patients without risk factors for recurrence. CONCLUSION: CS and cDFS changed over time according to the presence of disease-specific risk factors, as well as the presence of recurrence.

Tube feeding associated postoperative intussusceptions: A single center case series study.

RATIONALE: Postoperative intussusception in adults is a rare but serious complication after gastrointestinal anastomosis surgery. Postoperative intussusception in adults caused by tube feeding was rarely been reported before. The aim of the current study was to summarize the clinical data on a group of patients with tube feeding associated postoperative intussusceptions. The possible etiology and preventive measures will also be discussed. PATIENT CONCERNS: During the period from May 2013 to January 2018, patients who received gastrointestinal anastomosis in our center were retrospectively reviewed. Preoperative variables including standard demographic and pathological characteristics as well as the treatment and prognosis were also analyzed. DIAGNOSES: Tube feeding associated postoperative intussusceptions. INTERVENTIONS: 7 patients were identified with tube feeding associated postoperative intussusceptions with a prevalence of 0.38%. Intussusceptions occurred from 10 to 69 days (median 25.7 days) postoperatively in an acute form. OUTCOMES: None of the patients had spontaneous reduction and all patients underwent surgery. Antegrade efferent limb intussusceptions were found in all the cases. Intussusception occurred at efferent loop at 23.6 cm (range 15-60) from the gastrointestinal or Braun anastomosis. None of the patients was found recurrence throughout the follow-up period. LESSONS: In contrast with other postoperative intussusceptions, the tube feeding associated postoperative intussusceptions have special clinical manifestations. It is more likely to occur in early period of time after the surgery and in an acute form. Surgical correction is recommended for most of patients. Several measures have been proposed to prevent such complications after gastrointestinal surgery, however more research and information are still needed.

Electrical and thermal analyses of catheter-based irreversible electroporation of digestive tract.

Introduction: Irreversible electroporation (IRE) combined with a catheter-based electrode during endoscopy is a potential alternative treatment method for digestive tract tumors. The aim of this study was to investigate the electrical injury (EI) and thermal injury (TI) to the digestive tract via numerical analyses and to evaluate the role and impact of electrode configurations and pulse settings on the efficacy and outcomes of IRE. Materials and methods: A finite element method was used to solve the numerical model. A digestive tract model having 4-mm-thick walls and two catheter-based electrode configuration models were constructed. The distributions of electric fields, temperature, electrical conductivity, tissue injury and limitation on the pulse number required for IRE were calculated and compared. Results: Electrode length is an important geometric parameter for electrodes in the monopolar model (MPM), while electrode spacing affects the outcomes in the bipolar model (BPM). Increasing the pulse voltage reduces the pulse number required for tissue ablation, while increasing the risk of TI. In total, there were 6 NT-IRE protocols, 12 thermal-IRE protocols and 30 TI protocols. All of the NT-IRE protocols were set in BPMs with a voltage of 0.50 kV. With increasing electrode spacing, the minimum pulse number decreased. However, thermal effects were inevitable in the MPM. Conclusions: The electrode configuration and pulse settings are adjusted to achieve NT-IRE synergistically. The BPM is more reliable for achieving NT-IRE in 4-mm-thick digestive wall. Future in vitro and in vivo studies are needed to support and validate this conclusion.

Pathophysiologic Characterization of a Novel Rabbit Model of Biliary Tract Infection-Derived Sepsis.

Biliary tract infection (BTI)-derived sepsis remains a serious problem with significant morbidity and mortality in the modern era of critical care management. Current animal models of BTI have relied mostly on injecting purified bacteria or their toxins into the biliary tract. These models do not fully reflect pathophysiology or disease processes of clinical cholangitis or cholecystitis. In the current study, we developed a novel model of BTI by performing cholecystocolonic anastomosis (CCA) in rabbits and characterized pathophysiologic changes in this model. This model is intended to mimic the clinical process of cholecystocolonic fistula with reflux cholangitis, a severe form of BTI. Adult male rabbits were subjected to BTI-derived sepsis through an anastomosis of the gall bladder to the colon (i.e., CCA). The animals were monitored for 7 days to record survival. In additional groups of animals, various bacterial, hemodynamic, histological and biochemical parameters were measured at 12, 24, 48 and 72 h after CCA. The anastomosis between the gallbladder and the colon required about 5-8 min to finish. The median survival time for rabbits after CCA was 96 h. The positive rates of bacterial culture at 72 h after CCA were 83.3% and 100% in the blood and liver, respectively. The most common microorganism was Escherichia coli followed by Enterococcus. Plasma Tumor Necrosis Factor-α (TNF-α), Lnterleukin-10 (IL-10), Lnterleukin-6 (IL-6), and High-mobility group box 1 protein (HMGB-1) levels were greatly elevated after CCA. The cardiac index and heart rate increased slightly at 12 h after CCA and then continued to decrease. Systemic hypotension developed 48 h after CCA. Histological studies showed reflux cholangitis with acute lung and kidney injury. Cholecystocolonic anastomosis produces polymicrobial sepsis in rabbits, which mimics many aspects of human BTI-derived sepsis. It is reproducible and easy to perform and may serve as an excellent model for future sepsis research.