Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Optimizing the Safe Washout Period for Liver Transplantation Following Immune Checkpoint Inhibitors with Atezolizumab, Nivolumab, or Pembrolizumab.

BACKGROUND: Using immune checkpoint inhibitors (ICIs) as a downstaging therapy for liver transplantation (LT) has improved outcomes for patients with advanced hepatocellular carcinoma (HCC). However, this therapy carries a risk of post-transplant graft rejection. The washout (WO) period between the last ICI dose and LT seems critical in preventing postoperative rejection. This study aimed to optimize the WO period by balancing tumor burden suppression and rejection prevention using ICIs before LT. METHODS: We reviewed published case reports or series from March 2020 to December 2022 regarding LT for HCC after downstaging or bridge therapy with ICIs and included 4 of our cases. Most patients received atezolizumab, nivolumab, or pembrolizumab; these ICIs shared a half-life of around 28 days. Therefore, we excluded cases without definite WO period data and those using non-atezolizumab/nivolumab/pembrolizumab ICIs and ultimately enrolled 22 patients for analysis. We compared their clinical outcomes and estimated the rejection-free survival for every 0.5 half-life interval. RESULTS: Most study subjects received nivolumab (n = 25). Six patients had severe rejections (nivolumab group, n = 5) and needed rescue management. Of the 6 cases, 1 patient died after rejection, and 2 underwent re-transplantation. The median WO period in these 6 patients was 22 days (IQR: 9-35 days). In addition, we found that a 1.5 half-life (42 days) was the shortest safe WO period associated with significant rejection-free survival (P = .005). CONCLUSIONS: Our results showed that 42 days was the safest WO period before LT for HCC after ICI with atezolizumab, nivolumab, or pembrolizumab.

Long-term outcomes of liver transplantation for alcohol-related liver disease.

BACKGROUND: Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes. METHODS: A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups. RESULTS: The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients. CONCLUSION: LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

BACKGROUND: Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. METHODS: Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. RESULTS: A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). CONCLUSION: Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus.

BACKGROUND: Pancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged. METHODS: In total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups. RESULTS: Majority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups. CONCLUSIONS: T2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.

First-Pass Arrival Interval of Ultrasound Contrast Medium in the Hepatic Artery and Portal Vein as a Marker for Assessment of Liver Transplant Recipients.

BACKGROUND: This study measures the first-pass arrival times in the hepatic artery and portal vein of the transplanted liver using contrast-enhanced ultrasound (CEUS) and assess its correlation with graft performance in the early posttransplant period. METHODS: This study evaluated 35 liver transplant recipients who underwent CEUS examination within 1 month of transplant surgery. CEUS under contrast-specific harmonic imaging mode were recorded for 60 seconds immediately after intravenous administration of microbubble ultrasound contrast medium (Sonazoid, GE Healthcare, Oslo, Norway). The recorded video clips were reviewed by 2 readers to determine the first-pass arrival times in the hepatic artery and portal vein, and the difference between the 2 was defined as the arterial-portal arrival interval (APAI). Laboratory data on the same date of CEUS examination were collected as indicators to correlate with APAI. RESULTS: The intra- and inter-rater reliability for APAI measurement were excellent, with intraclass correlation coefficients > .95. The mean APAI was 4.5 ± 1.8 seconds (range, 2.0-10.5 seconds). The APAI was positively correlated with the serum total bilirubin level (r = 0.357, P = .035) and negatively correlated with the platelet count (r = -0.354, P = .037). At the 5 second cutoff point, a total serum bilirubin of >8 mg/dL was reported in 5 of 11 patients (45.4%) with APAI of >5 seconds and in only 3 of 24 patients (12.5%) with APAI of <5 seconds (P < .05). CONCLUSIONS: The APAI is a quantitative marker that links the hemodynamics and the clinical status of the liver graft.

Living donor liver transplantation for small infants aged less than 6 months: The experience of a single institute.

PURPOSE: Liver transplantation (LT) for small infants < 6 months old is rare but becoming common as perioperative care improves. In Taiwan, living donor LT (LDLT) has expanded indications but is rarely performed for this age group because of unfavorable outcomes in the literature. We evaluated LDLT outcomes of patients <6 months old. METHODS: We identified infants < 6 months old undergoing LDLT between 2004 and 2019 at our hospital. Variables related to recipients, donors, surgeries, and outcomes were analyzed. RESULTS: Nine patients were identified. Indications for LT were biliary atresia (n = 2), Alagille syndrome (n = 1), protein C deficiency (n = 1), and acute liver failure (n = 5), including two patients with neonatal hemochromatosis, one with herpes simplex hepatitis, one with giant cell hepatitis with autoimmune hemolytic anemia, and one with hemophagocytic lymphohistiocytosis. Median age and weight at LT were 129 days and 4.8 kg, respectively. Graft types included left lateral segment (LLS, n = 4), hyper-reduced LLS (n = 4), and monosegment (n = 1). The median graft-to-recipient weight ratio was 4%. The median follow-up period was 14 months (range, 8 days to 127 months) with two mortalities, and two patients were totally weaned off immunosuppressants. Adjuvant therapies were required for patients with giant cell hepatitis and hemophagocytosis. Preoperative reconstructive imaging for estimating graft thickness facilitated surgical planning. CONCLUSION: Although LDLT is difficult to perform for small infants, outcomes are favorable and mainly dependent on underlying causes in addition to technical innovations.

Safe Strategy to Initiate Total Laparoscopic Donor Right Hepatectomy: A Stepwise Approach From a Laparoscopy-Assisted Method.

BACKGROUND: Total laparoscopic donor right hepatectomy (TLDRH) for adult living liver donors has been reported by a few experienced centers, but with limited cases, its safety and feasibility remain controversial. We report our experience initiating TLDRH using a stepwise approach to gradually convert laparoscopy-assisted donor right hepatectomy (LADRH) to TLDRH. METHODS: We retrospectively analyzed the data of 61 LADRHs, 56 conventional open donor right hepatectomies (CODRHs), and 3 TLDRHs performed between March 2014 and June 2018. RESULTS: There were no significant differences in perioperative outcomes between donors undergoing LADRH and CODRH, except for a slight elevations in the operative time (436.5 vs 392.9 min, p < 0.001) and the graft warm ischemic time (5.4 vs 4.0 min, p < 0.001) in the LADRH group. The recipients' posttransplant one-year survival rates in the LADRH and CODRH groups were also similar (93.2% and 94.6%, p = 0.384). For three donors in whom TLDRH was converted from LADRH in a stepwise manner, the average operative time and blood loss were 570 min and 316.7 ml, respectively. Donors were discharged on postoperative day 10 without any surgical complications. CONCLUSIONS: LADRH can be performed routinely on liver living donors. A stepwise approach could be adopted to "covert" suitable donors from LADRH to a total laparoscopic procedure to maximize donor safety. This strategy is reliable and could be reproduced in most LDLT centers.

Minimization or withdrawal of immunosuppressants in pediatric liver transplant recipients.

BACKGROUND: We aimed to minimize the dose of tacrolimus in pediatric patients undergoing liver transplantation prospectively. METHODS: Pediatric liver transplant recipients with stable graft function >1year (transplant at <1year of age), or 2years (transplant at >1year of age) post transplant were screened. After baseline graft biopsy, patients were enrolled into our protocol for elective tacrolimus dose reduction. Patients were assessed by liver function test and protocol biopsy during and after tacrolimus dose reduction. RESULTS: From January 2011 to December 2012, 16 patients were recruited, of whom 15 completed follow-up at a mean 40.75±5.98months. Six patients were preliminarily weaned off tacrolimus, and five remained tacrolimus-free for more than 2years. Of the 10 patients who were not weaned off tacrolimus, six experienced seven episodes of clinical rejection. Five patients had a reduction in tacrolimus dosage to an undetectable trough level, another five to a trough level <4ng/ml, including one patient who was off the study. At the last patient visit, all of the patients had normal liver function test results with no graft loss. Three patients had low-grade graft fibrosis. The patients with metabolic liver disease (p=0.039) and who were recruited earlier after transplantation (p=0.028) were more likely to be weaned off tacrolimus. CONCLUSION: Tacrolimus withdrawal is feasible in select pediatric liver transplant recipients, and long-term follow-up for these patients is suggested.

Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

BACKGROUND: To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. METHODS: Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. RESULTS: The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. CONCLUSIONS: Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

Correlation of histopathologic and dynamic tissue perfusion measurement findings in transplanted kidneys.

BACKGROUND: Cortical perfusion of the renal transplant can be non-invasively assessed by color Doppler ultrasonography. We performed the Dynamic Tissue Perfusion Measurement (DTPM) of the transplant's renal cortex using color Doppler ultrasonography (PixelFlux technique), and compared the results with the histopathological findings of transplant biopsies. METHODS: Ninety-six DTPM studies of the renal transplant's cortex followed by transplant biopsies were performed in 78 patients. The cortical perfusion data were compared with the parameter of peritubular inflammatory cell accumulation (PTC 0 to 3) based on Banff-classification system. RESULTS: A significant decrease of cortical perfusion could be demonstrated as the inflammatory cells accumulation in peritubular capillaries increased. Increasing peritubulitis caused a perfusion loss from central to distal layers of 79% in PTC 0, of 85% in PTC 1, of 94% in PTC 2, and of 94% in PTC 3. Furthermore, the perfusion loss due to peritubular inflammation was more prominent in the distal cortical layer. The extent of perfusion decline with increasing peritubulitis (from PTC 0 to PTC 3) was 64% in proximal 20% cortical layer (p20), 63% in proximal 50% cortical layer (p50), increased to 76% in distal 50% cortical layer (d50), and peaked at 90% in the distal 20% cortical layer (d20). For those without peritubulitis (PTC 0), the increase in the the Interstitial Fibrosis/Tubular Atrophy (IF/TA) score was accompanied by a significantly increased cortical perfusion. A Polyomavirus infection was associated with an increased cortical perfusion. CONCLUSIONS: Our study demonstrated that the perfusion of the renal transplant is associated with certain pathological changes within the graft. DTPM showed a significant reduction of cortical perfusion in the transplant renal cortex related to peritubular capillary inflammation.

A bidirectional approach for portal vein stent placement in a child with complete portal vein occlusion after living donor liver transplantation.

Delayed PV complications are not rare in pediatric liver transplantation. Although PTPV offers a treatment and minimizes surgical revision, in case of complete PV thrombosis (PVT), the failure rate of PTPV is high. Herein, we report a successful technique of PTPV in a case of complete PVT with a stent placement using a bidirectional approach in a child with living donor liver transplantation.

Liver transplantation for a renal transplantation recipient with secondary sclerosing cholangitis by choledochoduodenal fistula.

Choledochoduodenal fistula (CDF) complicated by peptic diseases or following surgical or endoscopic approaches of the common bile duct is not uncommon. However, it usually occurs without significant symptoms and can be well controlled with conservative treatment in normal immunized patients. Here we report a case involving a 58-year-old male patient with diabetic nephropathy, who received a choledocholithotomy for choledocholithiasis in November 2007 and renal transplantation in March 2008. The patient had recurring cholangitis during the 5 months following his renal transplantation. Cholangiography and liver biopsy revealed sclerosing cholangitis. The patient underwent liver transplantation (LT) in May 2009 because radiological and endoscopic procedures failed to control his jaundice. A proximal CDF was found during the LT procedures. We considered that the patient's advanced secondary sclerosing cholangitis was induced by this fistula. At the 16 months' follow-up, the patient was surviving well and the graft remained intact. To our knowledge, this is the first report of a renal transplantation recipient receiving LT because of uncontrolled cholangitis caused by a CDF.

Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery.

Plasma-containing products are given during the pre-anhepatic stage of liver transplant surgery to correct abnormal thromboelastogram (TEG) values and prevent blood loss due to coagulation defects. However, evidence suggests that abnormal TEG results do not always predict bleeding. We questioned what effect using higher TEG values to initiate treatment would have on blood loss. A single transfusion protocol was used for all patients who underwent liver transplantation between 2007 and 2010. Thirty-eight patients received coagulation products when standard TEG cutoff values were exceeded, whereas another 39 patients received coagulation products when the TEG values were 35% greater than normal. The results of postoperative coagulation tests for total blood loss and the use of blood products were compared for the 2 groups. When the critical TEG values for transfusion were higher, significantly fewer units of fresh frozen plasma (5.58 ± 6.49 versus 11.53 ± 6.66 U) and pheresis platelets (1.84 ± 1.33 versus 3.55 ± 1.43 U) were used. There were no differences in blood loss or postoperative blood product use. In conclusion, the use of higher critical TEG values to initiate the transfusion of plasma-containing products is not associated with increased blood loss. Further testing is necessary to identify what TEG value predicts bleeding due to a deficit in coagulation factors.

Defining the severity of liver dysfunction in patients with hepatocellular carcinoma by the model for end-stage liver disease-derived systems.

BACKGROUND: The model for end-stage liver disease (MELD) and serum sodium (Na) are important markers for liver functional reserve in patients with hepatocellular carcinoma. We aimed to determine the best model to define the severity of liver dysfunction in terms of outcome prediction among the 4 currently used systems (MELD, MELDNa, MELD-Na and ReFit MELDNa). METHODS: A total of 2308 prospectively enrolled patients with hepatocellular carcinoma were analysed. The prognostic ability was compared by the Akaike information criterion. RESULTS: MELDNa had the best prognostic accuracy overall, and for patients receiving curative and non-curative treatments, followed by MELD-Na, MELD and ReFit MELDNa. When patients were categorized into <8, 8-12, 12-16, 16-20 and >20, the adjusted risk ratios for MELDNa were 1.065 (p=0.46), 0.996 (p=0.973), 1.38 (p=0.048) and 1.563 (p=0.003) for the scores of 8-12, 12-16, 16-20 and >20, respectively, compared to the group with scores <8. The adjusted risk ratio for MELDNa was 1.014 (95% confidence interval, 1.001-1.027; p=0.034) per unit score increment in the Cox model. CONCLUSIONS: The MELDNa is the best marker to define the severity of liver dysfunction in hepatocellular carcinoma patients independent of treatment strategy. The ReFit MELDNa does not enhance the predictive accuracy of the MELD.

Liver transplantation for a patient with homocystinuria.

A 24-yr-old man was diagnosed with HCU during neonatal screening and remained on a pyridoxine, vitamin B12, folic acid, and betaine regimen with dietary methionine restriction for more than 10 yr. He had normal mental development, marfanoid appearance, myopia because of lens dislocation, and recurrent ankle subluxation during adolescence. Thereafter, he was a poor adherent to the conventional diet-restrictive therapy, and LT was considered when he developed hypertension and multiple infarctions over the right cerebellum early in the second decade of his life despite taking aspirin as a prophylaxis from 17 yr of age. In November 2009, he received a deceased whole LT from a blood group compatible donor. Along with the success of the transplantation, he was completely disease free without dietary or nutritional control. To the best of our knowledge, this is the first case of LT intended to cure HCU, and with promising results. This case provides an insight into the role of LT for this congenital metabolic disease, for which the decision should be made by judging between the severity of the disease and the risk of the operation, as well as the life quality of the patient.

Living donor liver transplantation using a graft from a donor with Dubin-Johnson syndrome.

DJS is an autosomal recessive disorder that causes an increase in conjugated bilirubin without elevation of liver enzymes. Most patients are asymptomatic and have normal life spans, but to the best of our knowledge, their livers have never been reported to be grafts in liver transplantation. Herein, we report an infant patient with MMA that received a partial liver graft from his mother, who had DJS. A biliary anastomosis stricture was noted five months after transplantation and was successfully treated with radiological interventions. Otherwise, the patient's liver functions were normal, and a liver biopsy showed a pathognomonic picture of DJS nine months after the transplantation. The patient was followed for one yr, and the results were satisfactory for an increase in oral intake and protein uptake, no recurrence of metabolic stroke and there was a gradual catch-up with regard to physical development despite having a persistently abnormal profile of amino acid analysis. From the experience of our case, we suggest that a liver from a donor with DJS can be used as a graft for liver transplantation, although long-term follow-up is mandatory to examine the grafted liver under the use of immunosuppressive medications.

Comparison of surgical resection and transarterial chemoembolization for hepatocellular carcinoma beyond the Milan criteria: a propensity score analysis.

BACKGROUND: Treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) is controversial. This study compared the long-term survival of patients beyond the Milan criteria who received surgical resection (SR) or transarterial chemoembolization (TACE). METHODS: A total of 268 and 455 HCC patients beyond the Milan criteria undergoing SR and TACE, respectively, were retrospectively evaluated. After propensity score analysis to adjust for baseline differences, 146 pairs of matched patients were selected from each treatment arm. Long-term survival was compared by the Kaplan-Meier method. Independent prognostic predictors were determined by the Cox proportional hazards model. RESULTS: Long-term survival was significantly better for the SR group by univariate survival analysis (P < .001). In the Cox model, SR was identified as an independent predictor of better prognosis (hazard ratio = 0.3, 95% confidence interval [95% CI]: 0.23-0.4; P < .001). Despite similar baseline characteristics in the propensity score model, patients who underwent SR had significantly better survival than patients who underwent TACE (P < .001). Patients receiving TACE had 2.56-fold increased risk of long-term mortality in the propensity model (95% CI: 1.73-3.78). The SR and TACE groups had comparable 30- and 90-day posttreatment mortality. The Cox model consistently disclosed the significant superiority of SR in terms of long-term survival in the propensity score model (P < .001). CONCLUSIONS: For HCC patients beyond the Milan criteria, SR is considered equally safe as TACE and provides better long-term survival. SR may be regarded as the priority treatment for these patients.

High-surgical-volume hospitals associated with better quality and lower cost of kidney transplantation in Taiwan.

BACKGROUND: Only a small proportion of patients with end-stage renal disease can receive kidney transplants because of insufficiency of kidney donors in Taiwan. Hospitals compete with each other for kidney transplant surgeries. This study examined the association between hospital surgical volume of kidney transplants and patients' outcomes and utilizations. METHODS: Claims data of all kidney transplants between 1996 and 2003 were retrieved from the National Health Insurance Research Database for analysis. Every kidney recipient was followed up for 3 years until the end of 2006. Hospitals were classified as high-surgical-volume hospitals (HSVHs) if their total number of kidney transplants was 72 or more between 1996 and 2003; otherwise, they were grouped into the low-surgical-volume hospitals (LSVHs). The differences in quality (infection rate, graft rejection rate, readmission rate, mortality, and survival rates of patients and transplanted grafts at 1, 2, and 3 years after surgery) and cost (length of stay, total transplant cost, and annual medical cost for 3 years) of kidney transplants were examined between the two groups. RESULTS: Totally, 1,060 kidney transplants were analyzed, 77% of which were conducted at 6 of 29 qualified hospitals. Compared with those performed at LSVHs, transplant surgeries at HSVHs were associated with lower bacteria (35.1% vs. 48.8%, p<0.001), fungus (0.2% vs. 1.3%, p=0.008), and cytomegalovirus (1.2% vs. 4.6%, p=0.003) infection; lower mortality (1.1% vs. 5.0%, p<0.001); and higher 1-, 2-, and 3-year survival rates for patients (96.3%, 94.1%, 93.5% vs. 91.2%, 87.1%, 85.4%, respectively, p<0.01) and for transplanted grafts (89.5%, 81.0%, 80.5% vs. 85.8%, 74.6%, 73.3%, respectively, p<0.015). The transplant cost was lower for HSVHs than for LSVHs (New Taiwan $221,977 vs. New Taiwan $257,992, p=0.018). CONCLUSION: Seventy-seven percent of kidney transplant surgeries were concentrated at six hospitals in Taiwan. There were significant differences in quality and cost between HSVHs and LSVHs. We suggest adopting volume-based strategies for nonurgent kidney transplants.

Autophagy inhibition enhances apoptosis triggered by BO-1051, an N-mustard derivative, and involves the ATM signaling pathway.

In a previous study, BO-1051, an N-mustard linked with a DNA-affinic molecule, was shown to target various types of cancer cell lines. In the present study, we aimed to investigate the cytotoxicity, as well as the underlying mechanism, of BO-1051. We found that BO-1051 simultaneously induced apoptosis and autophagy in hepatocellular carcinoma cell lines. DNA double strand breaks induced by BO-1051 activated the ATM signaling pathway and subsequently resulted in caspase-dependent apoptosis. When autophagy was inhibited in its early or late stages, apoptosis was significantly enhanced. This result indicated autophagy as a cytoprotective effect against BO-1051-induced cell death. We further inhibited ATM activation using an ATM kinase inhibitor or ATM-specific siRNA and found that while apoptosis was blocked, autophagy also diminished in response to BO-1051. We not only determined a signaling pathway induced by BO-1051 but also clarified the linkage between DNA damage-induced apoptosis and autophagy. We also showed that BO-1051-induced autophagy acts as a cytoprotective reaction and downstream target of the ATM-signaling pathway. This research revealed autophagy as a universal cytoprotective response against DNA damage-inducing chemotherapeutic agents, including BO-1051, cisplatin, and doxorubicin, in hepatocellular carcinoma cell lines. Autophagy contributes to the remarkable drug resistance ability of liver cancer.