Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy.

Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.

HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG-I.

RIG-I is a key cytosolic sensor that detects RNA viruses through its C-terminal region and activates the production of antiviral interferons (IFNs) and proinflammatory cytokines. While posttranslational modification has been demonstrated to regulate RIG-I signaling activity, its significance for the sensing of viral RNAs remains unclear. Here, we first show that the RIG-I C-terminal region undergoes deacetylation to regulate its viral RNA-sensing activity and that the HDAC6-mediated deacetylation of RIG-I is critical for viral RNA detection. HDAC6 transiently bound to RIG-I and removed the lysine 909 acetylation in the presence of viral RNAs, promoting RIG-I sensing of viral RNAs. Depletion of HDAC6 expression led to impaired antiviral responses against RNA viruses, but not against DNA viruses. Consequently, HDAC6 knockout mice were highly susceptible to RNA virus infections compared to wild-type mice. These findings underscore the critical role of HDAC6 in the modulation of the RIG-I-mediated antiviral sensing pathway.

Validation of the prognostic performance in various nodal staging systems for gallbladder cancer: results of a multicenter study.

BACKGROUND: Although the current nodal staging system for gallbladder cancer (GBC) was changed based on the number of positive lymph nodes (PLN), it needs to be evaluated in various situations. METHODS: We reviewed the clinical data for 398 patients with resected GBC and compared nodal staging systems based on the number of PLNs, the positive/retrieved LN ratio (LNR), and the log odds of positive LN (LODDS). Prognostic performance was evaluated using the C-index. RESULTS: Subgroups were formed on the basis of an restricted cubic spline plot as follows: PLN 3 (PLN = 0, 1-2, ≥ 3); PLN 4 (PLN = 0, 1-3, ≥ 4); LNR (LNR = 0, 0-0.269, ≥ 0.27); and LODDS (LODDS < - 0.8, - 0.8-0, ≥ 0). The oncological outcome differed significantly between subgroups in each system. In all patients with GBC, PLN 4 (C-index 0.730) and PLN 3 (C-index 0.734) were the best prognostic discriminators of survival and recurrence, respectively. However, for retrieved LN (RLN) ≥ 6, LODDS was the best discriminator for survival (C-index 0.852). CONCLUSION: The nodal staging system based on PLN was the optimal prognostic discriminator in patients with RLN < 6, whereas the LODDS system is adequate for RLN ≥ 6. The following nodal staging system considers applying different systems according to the RLN.

Predicting Safe Liver Resection Volume for Major Hepatectomy Using Artificial Intelligence.

(1) Background: Advancements in the field of liver surgery have led to a critical need for precise estimations of preoperative liver function to prevent post-hepatectomy liver failure (PHLF), a significant cause of morbidity and mortality. This study introduces a novel application of artificial intelligence (AI) in determining safe resection volumes according to a patient's liver function in major hepatectomies. (2) Methods: We incorporated a deep learning approach, incorporating a unique liver-specific loss function, to analyze patient characteristics, laboratory data, and liver volumetry from computed tomography scans of 52 patients. Our approach was evaluated against existing machine and deep learning techniques. (3) Results: Our approach achieved 68.8% accuracy in predicting safe resection volumes, demonstrating superior performance over traditional models. Furthermore, it significantly reduced the mean absolute error in under-predicted volumes to 23.72, indicating a more precise estimation of safe resection limits. These findings highlight the potential of integrating AI into surgical planning for liver resections. (4) Conclusion: By providing more accurate predictions of safe resection volumes, our method aims to minimize the risk of PHLF, thereby improving clinical outcomes for patients undergoing hepatectomy.

Inflachromene ameliorates Parkinson's disease by targeting Nrf2-binding Keap1.

Parkinson's disease (PD) is the most common neurodegenerative disease characterized by movement disorder. Despite current therapeutic efforts, PD progression and the loss of dopaminergic neurons in the substantia nigra remain challenging to prevent due to the complex and unclear molecular mechanism involved. We adopted a phenotype-based drug screening approach with neuronal cells to overcome these limitations. In this study, we successfully identified a small molecule with a promising therapeutic effect for PD treatment, called inflachromene (ICM), through our phenotypic screening strategy. Subsequent target identification using fluorescence difference in two-dimensional gel electrophoresis (FITGE) revealed that ICM ameliorates PD by targeting a specific form of Keap1. This interaction led to upregulating various antioxidants, including HO-1, NQO1, and glutathione, ultimately alleviating PD symptoms. Furthermore, ICM exhibited remarkable efficacy in inhibiting the loss of dopaminergic neurons and the activation of astrocytes and microglia, which are critical factors in PD pathology. Our findings suggest that the phenotypic approach employed in this study identified that ICM has potential for PD treatment, offering new hope for more effective therapeutic interventions in the future.

Cytomegalovirus infection-associated fulminant hepatitis in an immunocompetent adult requiring emergency living-donor liver transplantation: report of a case.

Human cytomegalovirus (CMV) infection is usually self-limiting in healthy adults, but it can lead to significant complications. This report presents the case of an immunocompetent adult with fulminant hepatitis caused by a CMV infection requiring emergency living-donor liver transplantation. A 39-year-old female with persistent fever for 6 weeks was referred for fulminant hepatitis, but the underlying etiology was not identified. Rapid deterioration of consciousness led to an emergency living-donor liver transplant using a modified right lobe graft. She showed increasing CMV antigenemia after surgery and the explant liver pathology showed massive hepatic necrosis with positive staining for CMV protein. Treatment with ganciclovir improved the graft liver function and her general condition recovered. This report presents a rare case of CMV-associated fulminant hepatitis which led to emergency liver transplantation. Although CMV is rare, it should be included in the differential diagnosis of patients with severe hepatitis, even immunocompetent patients, after other more common etiologies have been excluded.

Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data.

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

Hepatic parenchymal atrophy induction for intractable segmental bile duct injury after liver resection.

Liver resection can result in various types of bile duct injuries but their treatment is usually difficult and often leads to intractable clinical course. We present an unusual case of hepatic segment III duct (B3) injury, which occurred after left medial sectionectomy for large hepatocellular carcinoma and was incidentally detected 1 week later due to bile leak. Since the pattern of this B3 injury was not adequate for operative biliary reconstruction, atrophy induction of the involved hepatic parenchyma was attempted. This treatment consisted of embolization of the segment III portal branch to inhibit bile production, induction of heavy adhesion at the bile leak site and clamping of the percutaneous transhepatic biliary drainage (PTBD) tube to accelerate segment III atrophy. This entire procedure, from liver resection to PTBD tube removal took 4 months. This patient has shown no other complication or tumor recurrence for 4 years to date. These findings suggest that percutaneous segmental portal vein embolization, followed by intentional clamping of external biliary drainage, can effectively control intractable bile leak from segmental bile duct injury.

Intensive pulmonary support using extracorporeal membrane oxygenation in adult patients undergoing liver transplantation.

BACKGROUND/AIMS: Adult liver transplantation (LT) recipients occasionally show serious acute cardiopulmonary dysfunction, requiring intensive care. We have assessed the feasibility of extracorporeal membrane oxygenation (ECMO) support in adult LT recipients facing acute pulmonary failure and refractory to conventional mechanical ventilation and concurrent nitric oxide gas inhalation. METHODOLOGY: From January 2008 to June 2009, 9 adult LT recipients required ECMO support due to pneumonia (n=5) and adult respiratory distress syndrome (n=4). Mean age was 52.6 ± 5.9 years and mean model for end-stage liver disease score was 29.0 ± 7.5. Five patients underwent living-donor LT and four underwent deceased-donor LT. RESULTS: Veno-venous access mode was used and continuous veno-venous hemodiafiltration was performed concurrently in all 9 patients. No procedure related complications occurred. Successful ECMO weaning was achieved in 4 patients (44.4%) at the first attempt, after mean ECMO support of 12.0 ± 6.8 days but the other five died due to overwhelming infection prior to ECMO weaning. Univariate analysis revealed no significant risk factors for failing ECMO support before ECMO start. CONCLUSIONS: ECMO as rescue therapy seems beneficial to be considered as a final therapeutic option for LT recipients with refractory pulmonary dysfunction who would otherwise die due to hypoxemia.

De Novo Intrahepatic Cholangiocarcinoma After Deceased Donor Liver Transplant in an Adult Patient.

Survival after liver transplant has progressively improved over recent decades. Recurrent or de novo malignancy, however, remains a major cause of patient death after transplant. Here, we have described a patient who developed de novo intrahepatic cholangiocarcinoma in the graft liver after orthotopic liver transplant. The 48-year-old male patient had end-stage liver disease from hepatitis B-related liver cirrhosis and a Model for End-Stage Liver Disease score of 26 and was listed for liver transplant. Recurrent esophageal variceal hemorrhage, severe ascites, and splenomegaly had complicated the liver disease. He underwent emergent whole organ, deceased donor liver transplant for liver cirrhosis. The donor liver was procured through the standard donation after brain death process from a 72-year-old man who died of intracranial hemorrhage. The graft weighted 1500 g and had normal color, and cold ischemia time was 5 hours upon arrival at our hospital. The patient's early postoperative course was uneventful. Two months posttransplant, the patient presented to the emergency department with fever, abdominal pain, and skin rash. Computed tomography revealed a focal biliary stricture in the right hepatic duct. Magnetic resonance cholangiopancreatography identified intrahepatic duct dilatations. Subsequent endoscopic retrograde cholangiography demonstrated marked intra- and extrahepatic biliary dilatation. We considered it to be a benign stricture and inserted plastic stents. He recovered from biliary stricture-related cholangitis. Approximately 10 months posttransplant, the patient was admitted with fever and skin rash. Marked dilatation of the intrahepatic bile duct was shown with a poorly enhancing tumor in the right lobe of the graft. Percutaneous transhepatic biliary drainage and tumor biopsy confirmed intrahepatic cholangiocarcinoma. We believe this to be the first case of de novo intrahepatic cholangiocarcinoma in a patient with hepatitis B-related end-stage liver disease after liver transplant without primary sclerosing cholangitis.

Outcomes of Pure Laparoscopic Living Donor Right Hepatectomy at a Small-Volume Center.

OBJECTIVES: Laparoscopic liver donor surgery is a technically difficult and demanding procedure. Our aim was toevaluate its feasibility at an established transplant center. Although our hospital is a small-volume center with <20 liver transplants per year, laparoscopic donor surgery has been performed regularly. In this study, we have reported our experiences with laparoscopic donor right hepa-tectomy and its outcomes. MATERIALS AND METHODS: Between May 2014 and March 2021, 26 deceased donor liver transplants and 37 living donor liver transplants, approved by the Korean Network for Organ Sharing, were performed at out center. From these, we reviewed the medical records, including clinical and demographic characteristics and operative outcomes, of 3 living donors who under-went pure laparoscopic donor right hepatectomy and their recipients. RESULTS: Each of the 3 laparoscopic donor right hepatectomies took over 10 hours with the prolonged Pringle maneuver time and warm ischemic time. However, there were no significant events during surgery or critical postoperative complications. In the recipients, posttransplant complications included middle hepatic vein obstruction, postoperative bleeding, bile leak, septic shock, and primary nonfunction of the graft. We managed and resolved these complications using various approaches, including retransplant, and all 3 recipients recovered and survived. CONCLUSIONS: Laparoscopic donor right hepatectomy had a relatively long operative time at our small-volume center. We believe that successful laparoscopic donor hepatectomy is possible if the donor is selected appropriately according to the center's experiences and there are constant efforts to overcome the learning curve.

Usefulness of External Biliary Stent Buried Suture for Reducing Stent-Related Complications In Liver Transplantation.

BACKGROUND: External bile stents may be used to prevent biliary complications. However, the external biliary stent itself has a risk of complications. This study evaluated the frequency and treatment of complications associated with external bile stent. METHODS: From May 2015 to September 2019, 18 deceased donor liver transplantations (DDLTs) and 25 living donor liver transplantations (LDLTs) were performed. We retrospectively reviewed these patients' demographic profiles, type of transplantation and presence of biliary complications, external bile stent-related complications, and treatment results. RESULTS: Overall biliary complications occurred in 12 patients (27.9%): 3 strictures (6.9%), 2 leakages (4.6%), and 7 external bile stent-related complications (16.2%). Among the 7, 4 were self-removal or stent fractures at home, and 2 occurred after removal by a physician. One patient had ileus with peritonitis. Local peritonitis was controlled by antibiotics and fluid therapy, but 1 patient needed an operation because of intestinal obstruction with recurrent local peritonitis. All biliary complications occurred in LDLT, and external biliary stent-related complications also occurred only in LDLT, not in DDLT (P = .014). Interestingly, only 1 of 7 external bile stent-related complications occurred after we adopted the stent buried suture technique on the duodenum (P = .062). CONCLUSIONS: External bile stent-related complications were higher in LDLT than in DDLT. When performing external bile stent implantation, the stent buried suture technique will help reduce stent-related complications, especially in LDLT.

The importance of muscle mass in predicting intradialytic hypotension in patients undergoing maintenance hemodialysis.

BACKGROUND: Patients undergoing hemodialysis are susceptible to sarcopenia. As intracellular reservoirs of water, skeletal muscles are important contributors to intradialytic hypotension. This study was designed to determine the role of skeletal muscle mass in intradialytic hypotension. METHODS: In a cross-sectional study, the body composition of 177 patients was measured immediately after hemodialysis using bioelectrical impedance analysis. The parameters measured were skeletal muscle mass, intracellular and extracellular water contents, total body water, and cell-membrane functionality (in phase angle at 50 kHz). Data from laboratory tests, chest radiography, measurements of handgrip strength and mid-arm circumference, and questionnaires were collected. The main outcome was intradialytic hypotension, defined as more than two episodes of hypotension (systolic blood pressure of <90 mmHg) with intervention over the 3 months following enrollment. Logistic regression models including each parameter related to sarcopenia were compared with a clinical model. RESULTS: Patients with a low ratio of skeletal muscle mass to dry body weight (SMM/WT) had a higher rate of intradialytic hypotension (40.7%). Most low-SMM/WT patients were female, obese, diabetic, and had a lower handgrip strength compared with the other patients. In the high-SMM/WT group, the risk of intradialytic hypotension was lower, with an odds ratio of 0.08 (95% confidence interval [CI], 0.02-0.28) and adjusted odds ratio of 0.06 (95% CI, 0.01-0.29). CONCLUSION: Measurement and maintenance of skeletal muscle can help prevent intradialytic hypotension in frail patients undergoing hemodialysis.

Inhibition of histone deacetylase 6 suppresses inflammatory responses and invasiveness of fibroblast-like-synoviocytes in inflammatory arthritis.

BACKGROUND: To investigate the effects of inhibiting histone deacetylase (HDAC) 6 on inflammatory responses and tissue-destructive functions of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). METHODS: FLS from RA patients were activated with interleukin (IL)-1ß in the presence of increasing concentrations of M808, a novel specific HDAC6 inhibitor. Production of ILs, chemokines, and metalloproteinases (MMPs) was measured in ELISAs. Acetylation of tubulin and expression of ICAM-1 and VCAM-1 were assessed by Western blotting. Wound healing and adhesion assays were performed. Cytoskeletal organization was visualized by immunofluorescence. Finally, the impact of HDAC6 inhibition on the severity of arthritis and joint histology was examined in a murine model of adjuvant-induced arthritis (AIA). RESULTS: HDAC6 was selectively inhibited by M808. The HDAC6 inhibitor suppressed the production of MMP-1, MMP-3, IL-6, CCL2, CXCL8, and CXCL10 by RA-FLS in response to IL-1ß. Increased acetylation of tubulin was associated with decreased migration of RA-FLS. Inhibiting HDAC6 induced cytoskeletal reorganization in RA-FLS by suppressing the formation of invadopodia following activation with IL-1ß. In addition, M808 tended to decrease the expression of ICAM-1 and VCAM-1. In the AIA arthritis model, M808 improved the clinical arthritis score in a dose-dependent manner. Also, HDAC6 inhibition was associated with less severe synovial inflammation and joint destruction. CONCLUSION: Inhibiting HDAC6 dampens the inflammatory and destructive activity of RA-FLS and reduces the severity of arthritis. Thus, targeting HDAC6 has therapeutic potential.

Effectiveness of Albumin-bilirubin Score as a Predictor of Post-hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

Backgrounds/Aims: Post-hepatectomy liver failure (PHLF) is a major concern for patients with hepatocellular carcinoma (HCC) who have undergone liver resection. The albumin-bilirubin (ALBI) score is a novel model for assessing liver function. We aimed to investigate the effectiveness of the ALBI score as a predictor of PHLF in HCC patients who have undergone hepatectomy in South Korea. Methods: Between January 2014 and November 2018, HCC patients who underwent hepatectomy and indocyanine retention rate at 15 min (ICG-R15) test were enrolled in this study. Results: A total of 101 patients diagnosed with HCC underwent hepatectomy. Thirty-two patients (31.7%) experienced PHLF. The ALBI score (OR 2.83; 95% CI 1.22-6.55; p=0.015), ICG-R15 (OR 1.07; 95% CI 1.02-1.12; p=0.007) and ALBI grade (OR 2,86; 95% CI 1.08-7.58; p=0.035) were identified as independent predictors of PHLF by multivariable analysis. The area under the receiver operating characteristic curve of the ALBI score and ICG-R15 were 0.676 (95% CI 0.566-0.785) and 0.632 (95% CI 0.513-0.752), respectively. The optimal cutoff value of the ALBI score in predicting PHLF was -2.62, with a sensitivity of 75.0% and a specificity of 56.5%. Conclusions: The ALBI score is an effective predictor of PHLF in patients with HCC, and its predictive ability is comparable to that of ICG-R15.

Exchange living donor liver transplantation to overcome ABO incompatibility in adult patients.

ABO incompatibility is the most common cause of donor rejection during the initial screening of adult patients with end-stage liver disease for living donor liver transplantation (LDLT). A paired donor exchange program was initiated to cope with this problem without ABO-incompatible LDLT. We present our results from the first 6 years of this exchange adult LDLT program. Between July 2003 and June 2009, 1351 adult LDLT procedures, including 16 donor exchanges and 7 ABO-incompatible LDLT procedures, were performed at our institution. Initial donor-recipient ABO incompatibilities included 6 A to B incompatibilities, 6 B to A incompatibilities, 1 A to O incompatibility, 1 A+O (dual graft) to B incompatibility, 1 O to AB incompatibility, and 1 O to A incompatibility. Fourteen matches (87.5%) were ABO-incompatible, but 2 (12.5%) were initially ABO-compatible. All ABO-incompatible donors were directly related to their recipients, but 2 compatible donors were each undirected and unrelated directed. After donor reassignment through paired exchange (n = 7) or domino pairing (n = 1), the donor-recipient ABO status changed to A to A in 6, B to B in 6, O to O in 1, A to AB in 1, A+O to A in 1, and O to B in 1, and this made all matches ABO-identical (n = 13) or ABO-compatible (n = 3). Two pairs of LDLT operations were performed simultaneously on an elective basis in 12 and on an emergency basis in 4. All donors recovered uneventfully. Fifteen of the 16 recipients survived, but 1 died after 54 days. In conclusion, an exchange donor program for adult LDLT appears to be a feasible modality for overcoming donor-recipient ABO incompatibility.

A clinical assessment of mycophenolate drug monitoring after liver transplantation.

BACKGROUND: Recent findings have suggested the clinical utility of therapeutic drug monitoring (TDM) in patients treated with mycophenolate mofetil (MMF). AIM: To assess whether routine mycophenolic acid (MPA) TDM is beneficial and how to utilize it. METHODS: A series of short-term prospective studies on TDM for MPA and/or tacrolimus was performed at a large-volume center. RESULTS: The 673 adult liver transplants were divided into four groups based on immunosuppressive regimens as tacrolimus monotherapy (n = 369), tacrolimus-MMF therapy (n = 270), MMF-minimal tacrolimus therapy (n = 17), and MMF monotherapy (n = 17). There was a significant difference of tacrolimus concentration between the groups receiving tacrolimus monotherapy and tacrolimus-MMF therapy during the first two yr (at two yr: 8.4 +/- 2.7 vs. 6.3 +/- 2.6 ng/mL; p < or = 0.002). MMF-minimal tacrolimus therapy and MMF monotherapy were applied after first three months and MPA levels ranged from 1.8 to 5.3 microg/mL. Correlation between MMF dosage and MPA concentration showed wide interindividual variations (n = 304, r(2) = 0.271, p < 0.001), in which r(2) was fluctuating from 0.056 to 0.213 according to the post-transplant period over five yr; wide intraindividual variation was also observed during the first two months (n = 12, r(2) < 0.2, p > 0.195). About 10% of patients were classified as poor MMF absorber and excluded from MMF usage. Mean MPA level leading to successful MMF monotherapy or MMF-minimal tacrolimus therapy was > or =1.0 microg/mL in 87% and >2.0 microg/mL in 56.5%. CONCLUSION: MPA TDM-based MMF dosage adjustment enabled us to administer MMF more confidently than categorical dosing. MPA TDM appears to be a useful tool to cope with the wide pharmacokinetic variability of MMF after liver transplantation.

Pancreatoduodenectomy for local intrapancreatic recurrence after bile duct resection of mid bile duct carcinoma.

Cancers originating from the proximal and mid portions of the common bile duct exhibit a variable degree of longitudinal tumor spread, thus curative resection with attainment of sufficient resection margins is often difficult to achieve. Not surprisingly, local tumor recurrence after noncurative resection occurs frequently, but most recurrences are not considered viable indications for a second operative intervention. We describe our experience of attempting to achieve curative repeat resection after local recurrence of bile duct carcinoma. Two male patients, aged 49 and 58 years, had localized tumor recurrence in the intrapancreatic bile duct 25 and 43 months after segmental bile duct resection for proximal-to-mid duct carcinoma. Following close observation for 3-4 months to determine operability, these 2 patients underwent pylorus-preserving pancreatoduodenectomy, in which both pre-existing hepaticojejunostomy and Roux jejunal limb were effectively used. There was no further recurrence for 65 and 37 months after repeat resection, respectively. Repeat resection with pancreatoduodenectomy may be a feasible treatment modality for selected patients showing late intrapancreatic recurrence after prior segmental bile duct resection.

The usefulness of the totally intra-corporeal pringle maneuver with Penrose drain tube during laparoscopic left side liver resection.

BACKGROUNDS/AIMS: The Pringle maneuver is generally performed to reduce the amount of blood loss during hepatic resection. During laparoscopic liver resection, the Pringle maneuver can be used in several ways. We have developed a new Pringle maneuver (PM) with Penrose drain tube to sufficiently control blood loss during laparoscopic liver resection. This study was performed to determine the safety and outcome during laparoscopic left-sided hepatectomy performed using this new method. METHODS: We describe the technique and results of the left-sided liver resection with totally intracorporeal PM with Penrose drain tube. We performed 37 laparoscopic left-sided hepatic resections with (PM group) or without the Penrose PM (No PM group). We retrospectively compared the short-term operative outcome between the No PM group (n=12) and the PM group (n=25) during laparoscopic left-sided liver resection. RESULTS: Median PM duration was 34.3 min. The median duration of the surgery using the totally intracorporeal PM with Penrose drain tube was 174 min, while the surgical duration required for resection without the PM was 156 min. The median volume of operative blood loss was lower in the PM group than in the No PM group (No PM group (341 ml) vs. PM group (165 ml)). There was no postoperative mortality and no open conversion. CONCLUSIONS: The totally intracorporeal PM with Penrose drain tube for laparoscopic hepatectomy is safe, reproducible, and can facilitate liver dissection during left-sided liver resection.

Liver transplantation for azithromycin-induced severe liver injury.

Drug-induced liver injury is the most common cause of acute liver failure in Western countries by prescription drugs and herbal medications. Liver injury due to azithromycin has rarely been reported. This is a brief report of a patient administered azithromycin and who developed acute liver failure leading to liver transplantation. We report the case of a 68-year-old woman who developed jaundice 1 week after she started taking a azithromycin. On the 3rd day of hospitalization, her hepatic function rapidly deteriorated and level of consciousness decreased to drowsiness. The model for end-stage liver disease score was confirmed to be 33, and liver transplantation was considered. On the 8th day of hospitalization, she underwent emergency living donor liver transplantation, receiving a right lobe liver graft from a 35-year-old male donor, the patient's son. Currently, she is alive with good liver function after 25 months of transplant. This case suggests that azithromycin may cause rare hepatitis with liver failure. Therefore, at the beginning of the azithromycin treatment, patients should visit the hospital immediately if symptoms such as jaundice and abdominal pain are experienced.