Navigating the Future of 3D Laparoscopic Liver Surgeries: Visualization of Internal Anatomy on Laparoscopic Images With Augmented Reality.

INTRODUCTION: Liver tumor resection requires precise localization of tumors and blood vessels. Despite advancements in 3-dimensional (3D) visualization for laparoscopic surgeries, challenges persist. We developed and evaluated an augmented reality (AR) system that overlays preoperative 3D models onto laparoscopic images, offering crucial support for 3D visualization during laparoscopic liver surgeries. METHODS: Anatomic liver structures from preoperative computed tomography scans were segmented using open-source software including 3D Slicer and Maya 2022 for 3D model editing. A registration system was created with 3D visualization software utilizing a stereo registration input system to overlay the virtual liver onto laparoscopic images during surgical procedures. A controller was customized using a modified keyboard to facilitate manual alignment of the virtual liver with the laparoscopic image. The AR system was evaluated by 3 experienced surgeons who performed manual registration for a total of 27 images from 7 clinical cases. The evaluation criteria included registration time; measured in minutes, and accuracy; measured using the Dice similarity coefficient. RESULTS: The overall mean registration time was 2.4±1.7 minutes (range: 0.3 to 9.5 min), and the overall mean registration accuracy was 93.8%±4.9% (range: 80.9% to 99.7%). CONCLUSION: Our validated AR system has the potential to effectively enable the prediction of internal hepatic anatomic structures during 3D laparoscopic liver resection, and may enhance 3D visualization for select laparoscopic liver surgeries.

Long-term outcomes of liver transplantation using grafts from donors with active hepatitis B virus replication: a multicenter cohort study.

Purpose: Liver grafts from donors with HBV infection contributed to expanding the donor pool under the hepatitis B immunoglobulin and antiviral agents (nucleos(t)ide analogues) in the HBV-endemic area. We report long-term outcomes of liver transplantations (LTs) using grafts from donors with active or chronic HBV infection. Methods: Overall, 2,260 LTs performed in 3 major hospitals in Seoul from January 2000 to April 2019 were assessed for inclusion. Twenty-six grafts (1.2%) were obtained from HBsAg (+), HBeAb (+), or HBcAb (+) donors, and recipient outcomes were retrospectively reviewed. Donor and recipient demographics and transplantation outcomes were analyzed. Results: Sixteen deceased donor LTs were performed using active HBsAg (+) grafts. Ten other LTs were sourced from 10 living donors. There was no significant difference in survival in patients who received deceased donor LTs compared with that in those who underwent LT with non-hepatitis virus-infected grafts. Fourteen patients who were followed up for >5 years were stable, and no difference in hepatocellular carcinoma recurrence rate was observed 5 years after transplantation between transplants from donors with and those without HBV. Conclusion: Considering long-term outcomes, liver grafts from donors with active HBV replication can be safely used for LT.

Should we be reluctant to perform pancreatectomy in patients with chronic liver disease? A single center 10-year experience.

PURPOSE: Many studies have shown extra-hepatic surgery in patients with chronic liver disease (CLD) with or without portal hypertension can result in complications. The aim of this study was to analyze the results of major pancreatectomy in patients with CLD including cirrhosis and to evaluate their efficacy and safety. METHODS: We retrospectively reviewed 319 patients undergoing open pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in our center. Those who received PD and DP in patients without CLD were classified into groups A and D, and those with CLD into groups B and C, respectively. Group B and C were subdivided into groups 1 and 2 according to the presence of portal hypertension. RESULTS: Forty-three patients (13.5%) had CLD. Of the 221 patients who received PD, 25 had CLD. Of the 98 patients who received DP, 18 (Group C) had CLD. In the PD group, patients with portal hypertension (group B1) had longer operative time. However, the transfusion rate and complication rate were not significantly different from other groups. There was no mortality in patients with CLD without portal hypertension (group B2) and the complication and mortality rate was comparable to patients with normal liver function (group A). In the DP group, the transfusion rate, complication rate and mortality rate were significantly higher in patients with portal hypertension (group C1). CONCLUSIONS: Acceptable outcomes were obtainable following pancreatic surgery in cirrhotic, non-portal hypertensive patients with surgical outcomes equivalent to non-cirrhotic patients.AbbreviationsCLDchronic liver diseasePDpancreaticoduodenectomyDPdistal pancreatectomy.

Long-term clinical outcomes and predictive factors in patients with chronic ocular graft-versus-host disease.

We investigate long-term clinical outcomes and predictive factors associated with poor vision outcomes in patients with ocular graft-versus-host disease (oGVHD). This retrospective cohort study involved 94 patients with chronic oGVHD, classified into severe (n = 25) and non-severe (n = 69) groups. Factors associated with oGVHD severity and poor vision outcomes were examined using multivariate logistic regression. In the severe oGVHD group, the disease activity pattern tended to be persistent, whereas flare-up episodes were more frequent and occurred over shorter intervals in this group. Myelodysplastic syndrome (MDS) and lung GVHD were more common and systemic calcineurin inhibitors were used more frequently in the severe group than in the non-severe group. Finally, 5-year survival rates were poorer in the severe group. Multivariate analysis revealed that MDS, lung GVHD involvement, and no history of systemic calcineurin inhibitor use were risk factors for severe oGVHD. Risk factors for poor vision outcomes were conjunctival scarring and persistent epithelial defects. In conclusion, MDS, lung GVHD, and no history of systemic calcineurin inhibitors are associated with severe oGVHD. Conjunctival scarring and persistent epithelial defects are risk factors for poor vision outcomes.

Right posterior bile duct stricture after central bisectionectomy or anterior sectionectomy.

PURPOSE: Before performing anterior sectionectomy (AS) or central bisectionectomy (CBS), the anatomy of the right posterior bile duct (RPBD) must be cautiously assessed owing to the many variations of the RPBD and its variations could be related to bile duct injury. METHODS: Clinical data of patients who underwent AS or CBS from 2009 to 2018 were reviewed. The bile duct anatomy according to Okubo's criteria and the right bile duct (RBD) length were evaluated using MRI, and we performed a risk factor analysis of the RPBD stricture (RPBDS). RESULTS: A total of 68 patients were included. Type A bile ducts were the most common (n = 36, 52.9%). Five (7.2%) patients had RPBDS requiring intervention. RPBDS only occurred in patients with a type A bile duct and a type A portal vein undergoing surgery using the Glissonian sheath approach. Moreover, when the RBD length was > 12 mm, the sensitivity and specificity were 0.8 and 0.889, respectively. In multivariate analysis, RBD length of > 12 mm was significant. CONCLUSION: A careful review of RPBD anatomy especially in patient with long RBD and caution when using the anterior Glissonian sheath approach might be helpful to prevent RPBDS during AS or CBS.

Effects of eye drops containing a mixture of 3% diquafosol sodium and tocopherol acetate (vitamin E) on the ocular surface of murine dry eye.

PURPOSE: To investigate the efficacy of topical application of 3% diquafosol sodium (DQS) and tocopherol (TCP) acetate mixtures in a mouse model of experimental dry eye (EDE). METHODS: After exposure to desiccating stress for 5 days, eye drops consisting of 3% DQS alone, 0.01% TCP alone, or 3% DQS and 0.005% or 0.01% TCP mixture were applied for the treatment of EDE. Tear volume, tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS), and tear film lipid layer grades (TFLLG) were measured at 0, 5 and 10 days after treatment. The 2',7'-dichlorodihydrofluorescein diacetate assay (DCFDA) for reactive oxygen species (ROS) production, enzyme-linked immunosorbent assay (ELISA) for malondialdehyde (MDA), and flow cytometry for CD4 + interferon (IFN)-γ+ T cells were evaluated on the ocular surface at 10 days after treatment. In addition, levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and chemokine CC motif ligand 4 (CCL4) in the conjunctiva were measured using a multiplex immunobead assay, and conjunctival goblet cells were counted by periodic acid-Schiff staining at 10 days after treatment. RESULTS: Both the TCP mixture groups indicated a significant improvement in TBUT, ROS production, and MDA concentrations compared to those in the DQS alone group. Furthermore, the 0.01% TCP mixture group also showed higher tear film lipid layer grades and conjunctival goblet cell density and lower corneal fluorescein staining scores, number of CD4 + IFN-γ+ T cells, and levels of TNF-α, IL-1ß, and CCL4 than the DQS alone group (P < 0.05). CONCLUSIONS: Application of eye drops containing the mixture of DQS and TCP could stabilize the tear film lipid layer, improve TBUT and corneal epithelial damages, decrease ROS production, inflammatory molecules, and T cells, and increase conjunctival goblet cell density on the ocular surface. Topical DQS and TCP mixtures may have a greater therapeutic effect on clinical signs, oxidative damage, and inflammation of dry eye than DQS eye drops.

Clinical Implication of Liquid Biopsy in Colorectal Cancer Patients Treated with Metastasectomy.

BACKGROUND & AIMS: The application of circulating tumor DNA (ctDNA) has been studied for predicting recurrent disease after surgery and treatment response during systemic treatment. Metastasectomy can be curative for well-selected patients with metastatic colorectal cancer (mCRC). This prospective study investigated the ctDNA level before and after metastasectomy in patients with mCRC to explore its potential as a predictive biomarker. METHODS: We collected data on 98 metastasectomies for mCRC performed from March 2017 to February 2020. Somatic mutations in the primary and metastatic tumors were identified and tumor-informed ctDNAs were selected by ultra-deep targeted sequencing. Plasma samples were mandatorily collected before and 3-4 weeks after metastasectomy and serially, if patients agreed. RESULTS: Data on 67 of 98 metastasectomies (58 patients) meeting the criteria were collected. ctDNA was detected in 9 (29%) of 31 cases treated with upfront metastasectomy and in 7 (19.4%) of 36 cases treated with metastasectomy after upfront chemotherapy. The detection rate of ctDNA was higher in liver metastasis (p = 0.0045) and tumors measuring ≥1 cm (p = 0.0183). ctDNA was less likely to be detected if the response to chemotherapy was good. After metastasectomy, ctDNA was found in 4 (6%) cases with rapid progressive disease. CONCLUSION: The biological factors affecting the ctDNA shedding from the tumor should be considered when applying ctDNA assays in a clinical setting. After metastasectomy for oligometastatic lesions in good responders of chemotherapy, most ctDNA was cleared or existed below the detection level. To assist clinical decision making after metastasectomy for mCRC using ctDNA, further studies for improving specific outcomes are needed.

Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study.

BACKGROUND: Several studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT. METHODS: Data of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data. RESULTS: Of the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients. CONCLUSION: De novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.

Long-term Survival of 10,116 Korean Live Liver Donors.

OBJECTIVE: To evaluate the long-term mortality of Korean live liver donors using data from a national donor registry by comparing it with the mortality of the general population. SUMMARY OF BACKGROUND DATA: Although live liver donors generally have a healthy status, their long-term mortality has not been properly addressed in a large donor registry. METHODS: Data of 10,116 live liver donors were drawn from a mandated national registry of Korean live liver donors between 2000 and 2015. Matched controls were selected from the Korean National Health Insurance System-National Sample Cohort (NHIS-NSC). Median (range) follow-up of liver donors was 5.7 (0-15.9) years. Donors were 1:3 individually matched to controls by sex and 5-year age group; potential controls were from the whole NHIS-NSC (Control 1) or from NHIS-NSC after excluding people with contraindications to be organ donors (Control 2) (donor, n = 7538; Control 1, n = 28,248; Control 2, n = 28,248). RESULTS: Fifty-three deaths occurred after donation. Ten-year cumulative mortality of live liver donors was 0.9%. The most common cause of death was suicide (n = 19) followed by cancer (n = 9) and traffic accident (n = 7). In the matched control analysis, overall risk of death was significantly lower in donors than in Control 1 (P < 0.001), but higher than in Control 2 (P < 0.001). CONCLUSIONS: Liver donors have increased long-term mortality risk compared to similar healthy controls without contraindications to be organ donors. Therefore, long-term follow-up, including psychosocial support, is needed for live liver donors.

Lipidomic signatures of post-hepatectomy liver failure using porcine hepatectomy models.

BACKGROUND: Clinical diagnosis of post-hepatectomy liver failure (PHLF) can only be made on or after the 5th postoperative day. Biomarker for early diagnosis is considered as a critical unmet need. METHODS: Twenty domestic female crossbreed (Yorkshire-landrace and duroc) pigs underwent sham operation (n=6), 70% (n=7) and 90% (n=7) partial hepatectomy (PH). A comprehensive lipidomic analysis was conducted using sera collected at pre-operation (PO), 14, 30, and 48 h after PH using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Of the 184 quantified lipids, 14 lipids showed significant differences between the two resection groups starting at 30 h after surgery. Four phosphatidylcholine (PC) plasmalogen species (P-16:0/16:0, P-18:0/18:2, P-18:0/20:4, and P-18:0/22:6) and PC 32:2 significantly increased in the 90% PH group while these returned to PO level after 30 h in the 70% PH group, presumably implying the failure markers. In contrast, eight triacylglycerol (TG) species (40:0, 42:1, 42:0, 44:1, 44:2, 46:1, 46:2, and 48:3) and sphingomyelin d18:1/20:0 showed an opposite trend, wherein they significantly decreased in the 90% PH group while these in the 70% PH group were abruptly increased until 30 h but returned to near PO levels at 48 h, implying the recovery markers. Same trends could also be observed in the level of whole lipid classes of PC plasmalogens and TGs, in addition to selected individual lipid species. CONCLUSIONS: Characteristic lipidomic signatures of PHLF could be identified using large animal models. These candidates have a potential to serve as a tool for early diagnosis and may open new paths to the study to overcome PHLF.

Sirolimus and MMF are insufficient immunosuppressants for regulation of the proliferation of CD133+EpCAM+ cell populations in HCC cell lines.

Studies on effective immunosuppressive strategies for the management of patients undergoing a liver transplantation (LT) due to hepatocellular carcinoma (HCC) are limited. In the present study, immunosuppressive candidates predicted to exhibit beneficial immunosuppressive and tumor-suppressive effects in patients with HCC were assessed using Huh7 and HEP3B HCC cells, which have high proportions of CD133+EpCAM+ cancer stem cell (CSC) populations. The immunosuppressants assessed were sirolimus, tacrolimus, cyclosporine A and mycophenolate mofetil (MMF), and their activities were assessed on CSCs. Sirolimus and MMF reduced the proliferation of Huh7 and HEP3B cells; however, the proportion of CD133+EpCAM+ was notably increased in treated Huh7 cells. Sirolimus treatment alone resulted in G0-G1 cell cycle arrest at all doses in all Huh7 and CD133-EpCAM- populations; however, CD133+EpCAM+ populations showed only slight G1 arrest at higher doses only. In contrast, S-phase arrest was induced at all doses in the Huh7, CD133-EpCAM- and CD133+EpCAM+ populations by MMF. Sirolimus and MMF effectively reduced the proliferation of Huh7 and HEP3B cells, but did not exert a notable effect on the CD133+EpCAM+ cells. Therefore, therapeutic strategies utilizing Sirolimus and MMF should be further studied in vivo for regulation of CSC populations in order to reduce HCC recurrence rates.

Clinical characteristics of dry eye with ocular neuropathic pain features: comparison according to the types of sensitization based on the Ocular Pain Assessment Survey.

BACKGROUND: To compare the clinical characteristics of dry eye patients with ocular neuropathic pain features according to the types of sensitization based on the Ocular Pain Assessment Survey (OPAS). METHODS: Cross-sectional study of 33 patients with dry eye and ocular neuropathic pain features. All patients had a comprehensive ophthalmic assessment including detailed history, the intensity and duration of ocular pain, the tear film, ocular surface, and Meibomian gland examination, and OPAS. Patients with < 50% improvement in pain intensity after proparacaine challenge test were assigned to the central-dominant sensitization group (central group) and those with ≥50% improvement were assigned to the peripheral-dominant sensitization group (peripheral group). All variables were compared between the two groups. RESULTS: No significant differences were observed in age, sex, underlying diseases, history of ocular surgery, duration of ocular pain, tear film, ocular surface and Meibomian gland parameters (all p > 0.05). Ocular pain and non-ocular pain severity and the percentage of time spent thinking about non-ocular pain were significantly higher in the central group than in the peripheral group (all p < 0.05). Central group complained more commonly of a burning sensation than did the peripheral group (p = 0.01). CONCLUSIONS: Patients with central-dominant sensitization may experience more intense ocular and non-ocular pain than the others and burning sensation may be a key symptom in those patients.

A survey investigating the current situation of the international visiting scholar program at the department of surgery in Korea.

PURPOSE: The number of international visiting scholars has been on the increase in Korea and we aim to investigate the program's current situation. METHODS: This cross-sectional study is based on an online survey questionnaire responded by international visiting scholars in surgical departments of 8 Korean hospitals between 2014 and 2018 about their experiences and satisfaction with the visiting scholar program. RESULTS: A total of 1,496 international scholars from 80 countries visited various surgical departments in 8 Korean hospitals between 2014 and 2018. The numbers have been on the increase over the years. Out of 355 visiting scholars in 2018, 71 replied to the online survey, of whom 52 were male and 19 female, and mostly in their 30s and 40s. Information about the program was accessed mostly through friends or colleagues (42.3%) and international conferences (36.6%). The commonest funding source was private (35.2%) and more than half stayed for less than 3 months. The visiting scholar's main roles were mostly observation or participation in surgery and clinical research. All but 1 were satisfied with the program (98.6%) and would recommend it to friends and colleagues, although the language barrier was identified as an inconvenience. Those aged 20-39 years with governmental or institutional funding were associated with stays of more than 1 year. CONCLUSION: The number of international visiting scholars at surgical departments in Korean hospitals has been on the increase with high satisfaction levels. Improvements need to be made on funding sources and lengthening visiting period to maximize the benefits of the program.

Sirolimus Prolongs Survival after Living Donor Liver Transplantation for Hepatocellular Carcinoma Beyond Milan Criteria: A Prospective, Randomised, Open-Label, Multicentre Phase 2 Trial.

Sirolimus (SRL) has been reported to benefit patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). This study aimed to compare SRL with tacrolimus (TAC) in living-donor LT (LDLT) recipients beyond the Milan criteria. This study was initially designed to enrol 45 recipients who underwent LDLT for HCC beyond the Milan criteria. At 1 month after LT, the patients were randomly assigned to either SRL or TAC-based treatment, with both groups receiving mycophenolate mofetil. The primary outcome was three-year recurrence-free survival (RFS) and the secondary outcome was overall survival (OS). A total of 42 patients completed the study. HCC recurrence occurred in 8 of 22 (36.4%) patients in the SRL group and in 5 of 22 (25%) patients in the TAC group. No differences in RFS and OS were found between the two groups in simple comparison. The type of immunosuppressant remained a nonsignificant factor for recurrence in multivariate analysis; however, SRL significantly prolonged OS (TAC hazard ratio: 15 [1.3-172.85], p = 0.03) after adjusting for alpha-fetoprotein and positron emission tomography standardised uptake value ratio (tumour/background liver). In conclusion, SRL does not decrease HCC recurrence but prolongs OS after LDLT for HCC beyond the Milan criteria.

Effects of Eurya japonica extracts on human corneal epithelial cells and experimental dry eye.

Eurya japonica (EJ) leaves have been indicated to exert anti-oxidative and anti-inflammatory effects. Dry eye disease (DED) is a chronic inflammatory disease and oxidative stress is closely associated with DED. The aim of the present study was to analyze the therapeutic efficacy of EJ in DED using human corneal epithelial (HCE) cells and a mouse model of experimental dry eye (EDE). EJ extracts (0.001, 0.01 and 0.1%) were used to treat HCE cells. Cell viability and mitochondrial function were detected using a EZ-Cytox cell viability assay kit and mitochondrial membrane potential assays. Dichlorofluorescein diacetate (DCF-DA) assay was used to measure cellular reactive oxygen species (ROS) levels. Subsequently, eye drops consisting of BSS or 0.001%, 0.01 and 0.1% EJ extracts were applied for treatment of EDE. At 7 days, conjunctival ROS production was measured using a DCF-DA assay. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, 10 kDa interferon gamma-induced protein 10 (IP-10) and monokine induced by interferon-γ (MIG) levels in the conjunctiva were analyzed using a multiplex immunobead assay. Tear film and ocular surface parameters were measured. Treatment with EJ extracts in HCE cells effectively improved cell viability, ROS levels and mitochondrial function. Mice treated with 0.01 and 0.1% EJ extracts indicated a significant decrease in ROS, TNF-α, IL-1ß, IP-10 and MIG levels compared with the EDE or BSS groups. Furthermore, a significant improvement in all clinical parameters was observed in the 0.01 and 0.1% EJ extract groups. EJ extracts could decrease cytotoxicity and ROS production in HCE cells. Additionally, topical EJ extracts reduced oxidative damage and inflammation and improved clinical signs of EDE, suggesting that EJ extracts may be used as an adjunctive therapy for DED.

Feasibility and safety of bisegmentectomy 7-8 while preserving hepatic venous outflow of the right liver - A retrospective cohort study.

BACKGROUND: When a hepatic tumor is deeply located in segments 7 and 8 around the right hepatic vein (RHV), right hemihepatectomy (RH) could be excessive owing to the resection of large tumor-free segments. This study aimed to evaluate the feasibility and safety of bisegmentectomy 7-8 (S7-8) and to compare its surgical outcomes with those of RH. MATERIALS AND METHODS: Consecutive patients who underwent S7-8 and RH were enrolled in this study. In the S7-8 group, 14 patients with an obvious inferior right hepatic vein (IRHV) (median: 6 mm; range: 3.6-8.8 mm) underwent S7-8 without hepatic vein reconstruction. RHV reconstruction was performed in six patients without an IRHV, involving direct anastomosis of the RHV in five patients and reconstruction using a cryo-preserved iliac vein in one patient. RESULTS: A total of 61 patients were included (20 in S7-8 group; 41 in RH group). No significant differences were observed other than higher a model of end-stage liver disease score in the RH group than in the S7-8 group (7 [6-20] vs. 6 [6-9], P = 0.003). Post-hepatectomy liver failure including severe grades was more frequent in the RH group (43.9% vs. 10%, P = 0.008). In the S7-8 group, two patients with direct RHV reconstruction had RHV anastomosis obstruction, and eventually required insertion of a metallic stent. However, computed tomography performed 4 weeks after the operation showed intact venous outflow of the right liver in the S7-8 group. CONCLUSION: S7-8 can be performed safely in selected patients with a thick IRHV. For patients with no obvious IRHV, RHV reconstruction could be a good surgical strategy to retain venous outflow of the right liver with feasible outcomes.

Explorative study of serum biomarkers of liver failure after liver resection.

Conventional biochemical markers have limited usefulness in the prediction of early liver dysfunction. We, therefore, tried to find more useful liver failure biomarkers after liver resection that are highly sensitive to internal and external challenges in the biological system with a focus on liver metabolites. Twenty pigs were divided into the following 3 groups: sham operation group (n = 6), 70% hepatectomy group (n = 7) as a safety margin of resection model, and 90% hepatectomy group (n = 7) as a liver failure model. Blood sampling was performed preoperatively and at 1, 6, 14, 30, 38, and 48 hours after surgery, and 129 primary metabolites were profiled. Orthogonal projection to latent structures-discriminant analysis revealed that, unlike in the 70% hepatectomy and sham operation groups, central carbon metabolism was the most significant factor in the 90% hepatectomy group. Binary logistic regression analysis was used to develop a predictive model for mortality risk following hepatectomy. The recommended variables were malic acid, methionine, tryptophan, glucose, and γ-aminobutyric acid. Area under the curve of the linear combination of five metabolites was 0.993 (95% confidence interval: 0.927-1.000, sensitivity: 100.0, specificity: 94.87). We proposed robust biomarker panels that can accurately predict mortality risk associated with hepatectomy.

Anti-inflammatory effects of glycine thymosin ß4 eye drops in experimental dry eye.

The aim of the present study was to investigate the anti-inflammatory effects of glycine thymosin ß4 (Gly-Tß4) eye drops, and to compare the efficacy of topical Gly-Tß4 with Cyclosporine A (CsA) in a mouse model of experimental dry eye (EDE). Eye drops consisting of balanced salt solution (BSS), 0.1% Gly-Tß4 or 0.05% CsA were used for treatment of EDE. Tear volume, tear film break-up time and corneal staining scores were measured after 7 and 14 days. Periodic acid-Schiff staining for conjunctival gobleT cells, TUNEL assay for corneal apoptotic positive cells, multiplex immunobead assay for interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and interferon-γ levels, and flow cytometry for CD4+/CCR5+ T cells were performed after 14 days. All clinical parameters showed improvement in the Gly-Tß4 and CsA groups (all P<0.05). Significantly increased conjunctival gobleT cells and decreased corneal TUNEL positive cells were observed in the Gly-Tß4 and CsA groups. The Gly-Tß4 and CsA treated groups showed significantly reduced inflammatory cytokine levels and T cells in the conjunctiva compared with the EDE and BSS groups (all P<0.05). However, there were no significant differences observed in the inflammatory and clinical parameters between the Gly-Tß4 and CsA treatment groups. Topical application of 0.1% Gly-Tß4 significantly reduced inflammation on the ocular surface, as well as clinical parameters of EDE, with a similar efficacy to that of 0.05% CsA emulsions, suggesting that Gly-Tß4 eye drops may be used as a therapeutic agent for treatment of dry eye disease.

Effect of epidermal growth factor ointment on persistent epithelial defects of the cornea.

BACKGROUND: Healthy corneal epithelium acts as a barrier against damage to the deeper structures in the eye. Failure in the mechanisms of corneal epithelization can lead to persistent epithelial defects of the cornea (PEDs) and can compromise its function. Epidermal growth factor (EGF) promotes the proliferation, migration, and differentiation of epithelial cells, endothelial cells, and fibroblasts during wound healing and may be beneficial in treating patients with PEDs. We, therefore, investigated the effect of EGF ointment on patients with PEDs. METHODS: Fifteen patients with PEDs refractory to conventional treatment were treated twice a day with EGF ointment. Patient demographics and comorbidities were noted. The epithelial healing time was determined along with the primary outcome measures in the areas of the epithelial defects, visual acuity, visual analog scale (VAS) scores, and esthesiometer scores 1 month and 2 months after treatment. RESULTS: Five eyes of herpetic keratitis (33.3%), 3 eyes of dry eye disease (20.0%), 3 eyes of bacterial keratitis (20.0%), 2 eyes of limbal stem cell deficiency (13.3%), 1 eye of diabetic neurotrophic keratitis (6.7%), and 1 eye of filamentary keratitis (6.7%) were associated with PEDs, respectively. Two months following treatment with EGF ointment, there was a reduction in the area of the epithelial defects (5.7 ± 3.9 to 0.1 ± 0.3 mm2) as well as a significant improvement in best-corrected visual acuity (0.9 ± 0.8 to 0.6 ± 0.5 LogMAR) and VAS scores (4.5 ± 1.2 to 2.5 ± 0.7) in 12 eyes (80%). Among these cases, the mean epithelial healing time was 5.5 ± 1.8 weeks. Amniotic membrane transplantation was performed on the remaining 3 (20.0%) patients that did not respond to EGF treatment. CONCLUSIONS: EGF ointment could reduce symptoms and promotes corneal epithelialization of refractory PEDs. It may, therefore, be well-tolerated and a potentially beneficial addition in the management of refractory PEDs.

Risk Factors of Tumor Recurrence After Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is commonly diagnosed as hepatocellular carcinoma (HCC) preoperatively. Therefore, unexpected recurrence occurs in some patients after liver transplantation (LT). The aim of this study was to identify the risk factors of recurrence. METHODS: We retrospectively reviewed the data of 20 patients who underwent LT for cHCC-CC from January 2005 to December 2015. RESULTS: Of the 20 patients, 11 (55%) had concurrent HCC and 10 (50%) had multiple cHCC-CCs. Before LT, 13 patients had undergone transarterial chemoembolization (TACE, n = 9), radiofrequency ablation, and TACE (n = 3) or surgical resection (n = 1). Four of the patients (20%) had the classical type, whereas 16 (80%) had subtypes with stem cell features. Six of the 16 patients (37.5%) with subtypes with stem cell features and 3 of the 4 patients (75%) with the classical type showed recurrence after LT. In multivariate analysis, the classical type was significantly associated with poorer recurrence-free survival (RFS) (hazard ratio [HR]: 8.65, confidence interval [CI]: 1.25-60.05, P = .03) and poorer overall survival (HR: 8.89, CI: 1.37-57.84, P = .02). Spontaneous tumor necrosis also showed significance on RFS (P = .03) among 11 patients with nontreated lesions. CONCLUSION: In cHCC-CC, the classical type and spontaneous tumor necrosis were associated with recurrence. If these risk factors are found after LT, short-interval follow-up and strategies such as chemotherapy and/or use of mammalian target of rapamycin inhibitors to prevent recurrence are needed.