Impact of TP53-induced glycolysis and apoptosis regulator on malignant activity and resistance to ferroptosis in intrahepatic cholangiocarcinoma.

TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04-3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03-4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

Aborted living-donor liver transplantation in the real-world setting, lessons from 13 937 cases of Vanguard Multi-center Study of International Living Donor Liver Transplantation Group.

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

International Multicenter Study of Ultra-Low GRWR Grafts in Adult Living Donor Liver Transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient-weight-ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multi-center study, 92 adult LDLT with a final GRWR<=0.6 performed at 12 international liver transplant (LT) centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation (PFM), development of SFSS, morbidity and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day and one-year mortality. Pre-operative MELD and inpatient status were independent predictors for SFSS (p<0.05). Pre-LT renal dysfunction was an independent predictor of survival (Hazard ratio- 3.1;95% ci 1.1,8.9, p=0.035). PFH or PFM were not predictive of SFSS or survival. We report the largest ever multi-center study of LDLT outcomes using ultralow-GRWR grafts and for the first-time validate the ILTS-iLDLT-LTSI consensus definition and grading of SFSS. Pre-operative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

Role of protein induced by vitamin-K absence-II in transplanted patients with HCC not producing alpha-fetoprotein.

Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52-2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48-2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26-3.35; p =0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.

Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma.

BACKGROUND: Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance. RESULTS: qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS. CONCLUSIONS: GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

Comparison of limb outcomes between bypass surgery and endovascular therapy in dialysis-dependent and -independent patients with chronic limb-threatening ischemia.

OBJECTIVE: To examine limb salvage (LS) and wound healing in dialysis-dependent and -independent patients with chronic limb-threatening ischemia (CLTI) after infrainguinal bypass surgery or endovascular therapy (EVT). METHODS: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) stage 2 to 4 between 2015 and 2020. The primary endpoint was LS. The secondary endpoint included wound healing, amputation-free survival (AFS), periprocedural complications, and 2-year survival. Comparison of these outcomes were made after propensity score matching. RESULTS: We analyzed 252 dialysis-dependent (318 limbs) and 305 dialysis-independent (354 limbs) patients. Propensity score matching extracted 202 pairs with no significant differences in characteristics. The LS rate in bypass surgery was better than that in EVT in dialysis-dependent patients (P < .001). There was no significant difference in the LS rates between bypass surgery and EVT in dialysis-independent patients (P = .168). The wound healing rate of bypass surgery was better than that of EVT both dialysis-dependent and -independent patients with CLTI. The AFS rate of bypass surgery was better than that of EVT in dialysis-dependent patients (P < .001). There was no significant difference in the AFS rates between bypass surgery and EVT in dialysis-independent patients (P = .099). There was no significant difference in the occurrence of Clavien-Dindo ≥ IV and V between bypass surgery and EVT in dialysis-dependent and -independent patients. Age ≥75 years, serum albumin levels <3.5 g/dL, and non-ambulatory status were risk factors for 2-year mortality in dialysis-dependent patients. The 2-year survival rates in dialysis-dependent patients with risk factors of 0, 1, 2, and 3 were 82.5%, 67.1%, 49.5%, and 10.2%, respectively (P < .001). CONCLUSIONS: For LS and wound healing, bypass surgery was preferred for revascularization in dialysis-dependent patients with WIfI stage 2 to 4. Although dialysis dependency was one of the risk factors for 2-year mortality, dialysis-dependent patients, who have 0 to 1 risk factors, may benefit from bypass surgery, as 2-year survival of >50% is expected.

Infra-inguinal bypass surgery vs endovascular revascularization for chronic limb-threatening ischemia in average- and high-risk patients.

OBJECTIVE: This study aimed to evaluate treatment outcomes after bypass surgery or endovascular therapy (EVT) in average- and high-risk patients with chronic limb-threatening ischemia (CLTI). METHODS: We retrospectively analyzed multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. A high-risk patient was defined as one with estimated 30-day mortality rate ≥5% or 2-year survival rate ≤50%, as determined by the Surgical Reconstruction vs Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) calculator. The amputation-free survival (AFS), limb salvage (LS), wound healing, and 30-day mortality were compared separately for the average- and high-risk patients between the bypass and EVT with propensity score matching. RESULTS: We analyzed 239 and 31 propensity score-matched pairs in the average- and high-risk patients with CLTI. In the average-risk patients, the 2-year AFS and LS rates were 78.1% and 94.4% in the bypass group and 63.0% and 87.7% in the EVT group (P < .001 and P = .007), respectively. The 1-year wound healing rates were 88.6% in the bypass group and 76.8% in the EVT group, respectively (P < .001). The 30-day mortality was 0.8% in the bypass surgery and 0.8% in the EVT group (P = .996). In the high-risk patients, there was no differences in the AFS, LS, and wound healing between the groups (P = .591, P = .148, and P = .074). The 30-day mortality was 3.2% in the bypass group and 3.2% in the EVT group (P = .991). CONCLUSIONS: Bypass surgery is superior to EVT with respect to the AFS, LS, and wound healing in the average-risk patients. EVT is a feasible first-line treatment strategy for high-risk patients with CLTI undergoing revascularization, based on the lack of significant differences in the 2-year AFS rate, between the bypass surgery and EVT cohorts.

Influence of inframalleolar modifier P0/P1 on wound healing in bypass surgery vs endovascular therapy in patients with chronic limb-threatening ischemia.

OBJECTIVE: This study aimed to compare the influence of inframalleolar (IM) P0/P1 on wound healing in bypass surgery vs endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). METHODS: We retrospectively analyzed the multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. IM P represents target artery crossing into foot, with intact pedal arch (P0) and absent or severely diseased pedal arch (P1). The endpoints were wound healing, limb salvage (LS), and postoperative complications. RESULTS: We analyzed 66 and 189 propensity score-matched pairs in the IM P0 and IM P1 cohorts, respectively. In the IM P0 cohort, the 1-year wound healing rates were 94.5% and 85.7% in the bypass surgery and EVT groups, respectively (P = .092), whereas those in the IM P1 cohort were 86.2% and 66.2% in the bypass surgery and EVT groups, respectively (P < .001). In the IM P0 cohort, the 2-year LS rates were 96.7% and 94.1% in the bypass surgery and EVT groups, respectively (P = .625), and those in the IM P1 cohort were 91.8% and 81.5% in the bypass surgery and EVT groups, respectively (P = .004). No significant differences were observed between the bypass surgery and EVT in terms of postoperative complication rates in either the IM P0 or P1 cohorts. CONCLUSIONS: Bypass surgery facilitated better wound healing and LS than EVT in patients with IM P1. Conversely, no differences in wound healing or LS were observed between groups in patients with IM P0. Bypass surgery should be considered a better revascularization strategy than EVT in patients with tissue loss and IM P1 disease.

Impact of ACSL4 on the prognosis of hepatocellular carcinoma: Association with cancer-associated fibroblasts and the tumour immune microenvironment.

BACKGROUND & AIMS: Recently, the association between hepatocellular carcinoma (HCC) and ferroptosis has been the focus of much attention. The expression of long chain fatty acyl-CoA ligase 4 (ACSL4), a marker of ferroptosis, in tumour tissue is related to better prognosis in various cancers. In HCC, ACSL4 expression indicates poor prognosis and is related to high malignancy. However, the mechanism remains to be fully understood. METHODS: We retrospectively enrolled 358 patients with HCC who had undergone hepatic resection. Immunohistochemistry (IHC) for ACSL4 was performed. Factors associated with ASCL4 expression were investigated by spatial transcriptome analysis, and the relationships were investigated by IHC. The association between ACSL4 and the tumour immune microenvironment was examined in a public dataset and investigated by IHC. RESULTS: Patients were divided into ACSL4-positive (n = 72, 20.1%) and ACSL4-negative (n = 286, 79.9%) groups. ACSL4 positivity was significantly correlated with higher α-fetoprotein (p = .0180) and more histological liver fibrosis (p = .0014). In multivariate analysis, ACSL4 positivity was an independent prognostic factor (p < .0001). Spatial transcriptome analysis showed a positive correlation between ACSL4 and cancer-associated fibroblasts; this relationship was confirmed by IHC. Evaluation of a public dataset showed the correlation between ACSL4 and exhausted tumour immune microenvironment; this relationship was also confirmed by IHC. CONCLUSION: ACSL4 is a prognostic factor in HCC patients and its expression was associated with cancer-associated fibroblasts and anti-tumour immunity.

Validation of JCLIMB, SPINACH, and VQI Calculators for Prediction of Two Year Survival in Patients With Chronic Limb Threatening Ischaemia After Infra-Inguinal Surgical or Endovascular Revascularisation.

OBJECTIVE: This study aimed to evaluate three survival prediction models: the JAPAN Critical Limb Ischaemia Database (JCLIMB), Surgical Reconstruction Versus Peripheral Intervention in Patients With Critical Limb Ischaemia (SPINACH), and Vascular Quality Initiative (VQI) calculators. METHODS: Multicentre data of patients who underwent infrainguinal revascularisation for chronic limb threatening ischaemia between 2018 and 2021 were analysed retrospectively. The prediction models were validated using a calibration plot analysis with the intercept and slope. The discrimination was evaluated using area under the curve (AUC) analysis. The observed two year overall survival (OS) was evaluated by the Kaplan - Meier method. The two year OS predicted by each model at < 50%, 50 - 70%, and > 70% was defined as high, medium, and low risk, respectively. RESULTS: A total of 491 patients who underwent infra-inguinal revascularisation were analysed. The rates of surgical revascularisation, endovascular therapy, and hybrid therapy were 26.5%, 70.1%, and 5.5%, respectively. The average age was 75.6 years, and the percentages of patients with diabetes mellitus and dialysis dependent end stage renal disease were 66.6% and 44.6%, respectively. The tissue loss rate was 85.7%. The intercept and slope were -0.13 and 1.18 for the JCLIMB, 0.11 and 0.82 for the SPINACH, and -0.15 and 1.10 for the VQI. The AUC for the two year OS of JCLIMB, SPINACH, and VQI were 0.758, 0.756, and 0.740, respectively. The observed two year OS rates of low, medium, and high risk using the JCLIMB calculator were 80.1%, 61.1%, and 28.5%, respectively (p < .001), using the SPINACH calculator were 81.0%, 57.0%, and 38.1%, respectively (p < .001), and using the VQI calculator were 77.8%, 45.8%, and 49.6%, respectively (p < .001). CONCLUSION: The JCLIMB, SPINACH, and VQI survival calculation models were useful, although the OS predicted by the VQI model appeared to be lower than the observed OS.

Validation of Japanese indication criteria for deceased donor liver transplantation for hepatocellular carcinoma: Analysis of US national registry data.

AIM: The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5 cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500 ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT). METHODS: Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101-300, 301-500, and >500 ng/mL. RESULTS: The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p < 0.01). Hepatocellular carcinoma recurrence at 5 years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101-300, 301-500, and >500 categories, respectively (p < 0.01). CONCLUSION: The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500 ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.

Impact of albumin-lymphocyte-platelet-C-reactive protein index as a prognostic indicator of hepatocellular carcinoma after resection: Associated with nuclear factor erythroid 2-related factor 2.

AIM: To investigate the prognostic value of the preoperative albumin-lymphocyte-platelet-C-reactive protein (ALPC) index in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. We also evaluated the relationship between the ALPC index and the phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) levels. METHODS: Data were analyzed retrospectively from 256 patients who underwent resection for HCC. For cross-validation, patients were divided into the training and testing cohort. We assessed eight combinations of inflammatory markers for predictive value for recurrence. We examined the associations of the ALPC index with recurrence-free survival and overall survival in univariate and multivariate analyses (Cox proportional hazards model). Immunohistochemical staining of p-Nrf2 was performed on tumor samples of 317 patients who underwent hepatic resection for HCC. RESULTS: A high preoperative ALPC index correlated with a high serum albumin concentration, small tumor size, low rate of poor differentiation, solitary tumor, early Barcelona Clinic Liver Cancer stage, and low rate of microscopic intrahepatic metastasis in the training dataset. A high preoperative ALPC index correlated with a high serum albumin concentration, high serum alpha-fetoprotein concentration, small tumor size, a low rate of poor differentiation and a low rate of microscopic intrahepatic metastasis in the testing dataset. A higher preoperative ALPC index was an independent predictor of longer recurrence-free survival and overall survival in the training and testing datasets. A high ALPC index was associated with negative p-Nrf2 expression in HCC tumor cells. CONCLUSIONS: We showed that a high ALPC index was an independent prognostic factor for patients with HCC undergoing curative hepatic resection.

Impact of electrical muscle stimulation on serum myostatin level and maintenance of skeletal muscle mass in patients undergoing living-donor liver transplantation: Single-center controlled trial.

AIM: Sarcopenia is reportedly associated with a poor prognosis in patients who undergo living-donor liver transplantation (LDLT), most of whom are not able to tolerate muscle strengthening exercise training. Myostatin is one of the myokines and a negative regulator of skeletal muscle growth. The clinical feasibility of an electrical muscle stimulation (EMS) system, which exercises muscle automatically by direct electrical stimulation, has been reported. In this study, we aimed to determine the effect of perioperative application of SIXPAD, which is a type of EMS system, with reference to the serum myostatin and sarcopenia in LDLT patients. METHOD: Thirty patients scheduled for LDLT were divided into a SIXPAD group (n = 16) and a control group (n = 14). In the SIXPAD group, EMS was applied to the thighs twice daily. The serum myostatin was measured in samples obtained before use of SIXPAD and immediately before LDLT. The psoas muscle index (PMI) at the level of the third lumbar vertebra and the quadriceps muscle area were compared on computed tomography images before use of SIXPAD and 1 month after LDLT. RESULTS: The preoperative serum myostatin was found to be higher in LDLT patients than in healthy volunteers and EMS significantly reduced the serum myostatin. Electrical muscle stimulation prevented a postoperative reduction not only in the area of the quadriceps muscles but also in the PMI despite direct stimulation of the thigh muscles. CONCLUSION: Stimulation of muscles by EMS decreases the serum myostatin and helps to maintain skeletal muscle in patients who have undergone LDLT.

Pretreatment eosinophil count predicts response to atezolizumab plus bevacizumab therapy in patients with hepatocellular carcinoma.

AIM: Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). METHODS: We enrolled 114 patients with u-HCC treated with ATZ/BEV (n = 48) or lenvatinib (n = 66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). RESULTS: Twenty-three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV-eosinophil-high group, which had better responses than the ATZ/BEV-eosinophil-low group (P = 0.0090). Kaplan-Meier curves revealed a trend toward significantly better progression-free survival (PFS) in the ATZ/BEV-eosinophil-high group than the ATZ/BEV-eosinophil-low group (the median PFS: 4.7 months in the ATZ/BEV-eosinophil-low group vs 12.6 months in the ATZ/BEV-eosinophil-high group; P = 0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P = 0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02-4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV-eosinophil-high group (P = 0.0285). The outcomes did not significantly differ between the LEN-eosinophil-high group and the LEN-eosinophil-low group. CONCLUSION: A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u-HCC and was associated with the incidence of AEs (≥ grade 3).

Treatment Outcomes in Octogenarians with Chronic Limb-Threatening Ischemia after Infrainguinal Bypass Surgery or Endovascular Therapy.

BACKGROUND: This study aimed to analyze the clinical outcomes after revascularization for chronic limb-threatening ischemia (CLTI) in patients aged ≥ 80 years and < 80 years. METHODS: We retrospectively analyzed multicenter data of 789 patients who underwent infrainguinal revascularization for CLTI between 2015 and 2021. The end points were 2-year overall survival (OS), amputation-free survival (AFS), limb salvage (LS), and postoperative complications. RESULTS: A total of 90 patients aged ≥ 80 years and 200 patients aged < 80 years underwent bypass surgery (BSX), and 205 patients aged ≥ 80 years and 294 patients aged < 80 years underwent endovascular therapy (EVT). Before the propensity score matching, multivariate analyses showed that age ≥ 80 years, lower body mass index and serum albumin levels, nonambulatory status, and end-stage renal disease were independent risk factors for 2-year mortality in the BSX and EVT groups. After propensity score matching, the 2-year OS was better in the < 80 years cohort than in the ≥ 80 years cohort in both the BSX and EVT groups (P = 0.018 and P = 0.035, respectively). There was no difference in the 2-year LS rates between the < 80 years and the ≥ 80 years cohorts in both the BSX and EVT groups (P = 0.621 and P = 0.287, respectively). According to the number of risk factors, except for age ≥ 80 years, there was no difference in the 2-year AFS rates between the < 80 years and ≥ 80 years cohorts for the BSX and EVT groups with 0-1 risk factor (P = 0.957 and P = 0.655, respectively). However, the 2-year AFS rate was poor, especially in the ≥ 80 years cohort in the BSX with 2-4 risk factors (P = 0.015). The Clavien-Dindo ≥ IV complication rates tended to be higher in the ≥ 80 years cohort than in the < 80 years cohort only in the BSX with 2-4 risk factors (P = 0.056). CONCLUSIONS: Patients with CLTI aged ≥ 80 years had poorer OS than those aged < 80 years. However, there was no difference in LS between the ≥ 80 years and < 80 years cohorts in both the BSX and EVT groups. Although age ≥ 80 years was associated with poorer OS, patients with 0-1 risk factor may benefit from revascularization, including BSX, because no difference was observed in AFS or Clavien-Dindo ≥ IV complications.

Venous reconstruction using a round ligament-covered prosthetic vascular graft in right­lobe living­donor liver transplantation: a technical report.

PURPOSE: To evaluate the short term-outcomes of venous reconstruction using a round ligament-covered prosthetic vascular graft and assess its effectiveness in the prevention of prosthetic vascular graft migration in right­lobe living donor liver transplantation (LDLT). METHODS AND RESULTS: Thirty patients underwent reconstruction of the middle hepatic vein (MHV) tributaries during right lobe LDLT between January, 2021 and October, 2022. These patients were divided into the autologous vascular graft group (A group, n = 24) and the round ligament-covered prosthetic vascular graft group (RP group, n = 6). The computed tomography (CT) density ratio of the drainage area in the posterior segment of patent grafts was significantly higher in the RP group than in the A group (0.91 vs. 1.06, p = 0.0025). However, the patency rates of reconstructed MHV tributaries in the A and RP groups were 61% and 67%, respectively, with no significant difference between the groups (p = 0.72). Prosthetic vascular graft migration did not occur in the RP group. CONCLUSION: Venous reconstruction using round ligament-covered prosthetic vascular grafts is a feasible and simple method to prevent prosthetic vascular graft migration in right-lobe LDLT.

Maximum resistance pressure at the time of lung tissue rupture after porcine lung transection using automatic linear staplers with different reinforcement methods.

PURPOSES: Polyglycolic acid (PGA) sheets, fibrin glue, and staple line reinforcement are frequently used to prevent air leakage during lung resection. However, the optimal staple-line reinforcement method remains unclear. METHODS: Cranial lung lobes of pigs were used to evaluate different staple line reinforcement methods (n = 6). Ventilator-assisted manometry was used to measure the maximum resistance pressure at the time of rupture of the lung tissue after stapling. RESULTS: The mean maximum resistance pressures at the time of lung tissue rupture after using the stapler alone, stapler with PGA sheet and fibrin glue, and stapler with reinforcement were 38.0 cmH2O, 51.3 cmH2O, and 62.7 cmH2O, respectively. A significant increase in the maximum resistance pressure was observed with stapler reinforcement (P < 0.001), while the differences between the other groups were not statistically significant (P = 0.055, P = 0.111). A histological assessment revealed disruption of alveolar structures near the needle-stitching site in the stapler alone, and in the stapler with PGA sheet and fibrin glue groups. Pleural rupture near the staple line was observed in the stapler with reinforcement group. CONCLUSIONS: The maximum resistance pressure before air leakage was significantly higher when using a stapler with reinforcement than when using a stapler alone.

Impact of surgical proximal and distal margins on the recurrence of resectable colon cancer: a single-center observational cohort study.

PURPOSE: Few studies have investigated the impact of the surgical proximal and distal margins on colon cancer recurrence. We conducted this study to investigate the effect of resection margins on the prognosis of resectable colon cancer. METHODS: We analyzed data on 1458 patients who underwent colorectal resection in our institute between January, 2004 and March, 2020, including 579 patients with resectable colon cancer. The association between the resection margin and recurrence for each oncological status was assessed and the value of the resection length that influenced recurrence was analyzed. RESULTS: Patients who had pT4 colon cancer with margins of more than 7 cm had a trend of fewer recurrences and longer relapse-free survival (RFS) than those with colon cancer of other stages (P = 0.033; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.20-0.89). Multivariate analysis identified a margin of < 7 cm as an independent risk factor for RFS in patients with pT4 colon cancer (P = 0.023; HR, 2.65; 95% CI 1.013-6.17). No correlation was found between resection margins and recurrence, depending on the extent of lymph node metastasis and tumor location. CONCLUSION: A resection margin of at least 7 cm should be maintained for patients with pT4 colon cancer.

Treatment strategy for hepatocellular carcinoma recurrence in the transplant era: Focusing on the Japan criteria.

PURPOSE: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. METHODS: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. RESULTS: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. CONCLUSION: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.

Feasibility of venous cuff using an open round ligament or inferior mesenteric vein around the hepatic vein for a left lobe graft in living-donor liver transplantation.

Living-donor liver transplantation (LDLT) is an established treatment for patients with end-stage liver disease or acute liver failure, and outflow reconstruction is considered one of the most vital techniques in LDLT. To date, many strategies have been reported to prevent outflow obstruction, which can be refractory to liver dysfunction and can cause life-threatening graft loss or mortality. In addition, in this era of laparoscopic hepatectomy in donor surgery, especially LDLT using a left liver graft, it has been predicted that cutting the hepatic vein with automatic linear staplers will lead to more outflow-related problems than with conventional open hepatectomy because of the short neck of the anastomosis orifice. We herein review 10 cases of venoplasty performed with a novel venous cuff system using a donor's round ligament around the hepatic vein in LDLT with a left lobe graft, which makes anastomosis of the hepatic vein sterically easy for postoperative venous patency.