Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Rescue strategy for advanced liver malignancy with retrohepatic inferior vena cava thrombi: experience to promote surgical oncological benefit.

BACKGROUND: The prognosis of advanced liver malignancy with inferior vena cava (IVC) thrombi is poor. Many therapeutic policies are challenging for long-term prognosis. We performed the modified effective technique of transdiaphragmatic intrapericardial IVC isolation for curative resection of IVC tumors and prolonged survival time. METHODS: Between 2003 and 2015, 10 patients, sustained liver malignancy with IVC thrombi, underwent surgical intervention. Liver resection with thrombectomy under total hepatic vascular exclusion via the transdiaphragmatic intrapericardial IVC isolation method was performed for these 10 patients. The first 4 patients underwent retrohepatic IVC resection in order to complete resection, and the other 6 patients preserved the retrohepatic IVC. The last 3 patients received preoperative locoregional therapies, and all 10 patients received postoperative adjuvant chemotherapies immediately. RESULTS: All 10 patients underwent gross en bloc tumor resections with thrombectomy with R0 resection. There was no surgical mortality. Shortening of operation time and reduction of both intraoperative blood loss and hospital stay were demonstrated in the last 6 patients with preserving the retrohepatic IVC. However, similar time to recurrence and survival time were noted in the first 7 patients. The last 3 patients, who had received preoperative locoregional therapies, have better disease-free survival time. CONCLUSION: Simplified surgical procedure combined with preoperative locoregional therapies and rapid postoperative adjuvant treatment may provide a greater advantage for these patients.

The role of liver transplantation or resection for patients with early hepatocellular carcinoma.

Liver resection (LR) and liver transplantation (LT) are curative treatments for early hepatocellular carcinoma (HCC), although their performance remains debated. We compared the survival of patients with HCC conforming to the Milan criteria (MC) after LT and LR and analyzed factors affecting clinical outcomes. Between January 2006 and January 2013, 65 and 184 patients received LT and LR for HCCs fulfilling the MC, respectively. Overall survival (OS) and disease-free survival (DFS) rates were compared between the two groups. To investigate effects of liver function and living donor liver transplantation (LDLT) on survival, two subgroup analyses were performed and associations with OS and DFS were examined. We found that OS rates were higher after LT than after LR since 3 years postoperatively. DFS rates were significantly better after LT than after LR. Performance of LR, vascular invasion, and tumor multiplicity were associated with poor DFS, and factors affecting OS included the presence of vascular invasions, liver cirrhosis, and tumor multiplicity. In conclusion, despite of the effects of tumor characteristics on clinical outcomes, LT, including LDLT, should be considered the treatment of choice for patients with HCCs who met the MC. The role of LR is to identify poor prognostic factors through pathological examination.

Risk factors for the development of pulmonary oil embolism after transcatheter arterial chemoembolization of hepatic tumors.

Pulmonary oil embolism (POE) is a rare fatal complication after transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE). As risk factors have not been clearly delineated, the aim of the present study was to identify the risk factors for development of POE after TACE. A retrospective analysis was carried out on patients with unresectable hepatocellular carcinoma who received TAE or TACE at the Tri-Service General Hospital (Taiwan) between January 2005 and December 2008. The diagnosis of TAE-induced or TACE-induced POE was based on development of respiratory signs and symptoms relatively soon after the procedure, as well as based on characteristic radiographic findings. Of the 219 enrolled patients in this study, 20 were diagnosed with POE after TAE or TACE. On univariate logistic regression analysis, patients developing POE were found to be older (67.95±15.95 vs. 61.44±12.59 years, P=0.033), with a lower serum albumin level (3.25±0.58 vs. 3.62±0.57 g/dl, P=0.009), a higher grade of liver cirrhosis as classified on the basis of Child's criteria (P<0.006), a larger tumor size (8.55±4.52 vs. 4.78±3.97 cm in diameter, P<0.001), a higher lipioidol dose (22.35±11.01 vs. 13.69±7.66 ml, P=0.003), and a higher doxorubicin dose (50.27±7.05 vs. 40.75±13.61 mg, P<0.001). Following multivariate logistic regression analysis, only lipiodol dose was found to be a significant risk factor for POE (odds ratio=1.133, 95% confidence interval: 1.004, 1.279; P=0.044). The receiver operator characteristic curve cutoff point for lipiodol dose level was 14.5 ml, with a sensitivity of 80% and a specificity of 66.3%. In conclusion, the lipiodol dose could be considered as a predictive factor for POE after TAE or TACE in hepatic malignant tumor patients. On the basis of this retrospective study, the safe lipiodol dose to minimize the risk for POE is 14.5 ml or lower; however, larger, prospective studies are needed to determine the optimally safe and yet efficacious dose.

Hepatobiliary cystadenocarcinoma without mesenchymal stroma in a female patient: a case report.

BACKGROUND: Hepatobiliary cystadenocarcinoma is a rare epithelial malignant neoplasm of the liver or extrahepatic bile ducts. Early diagnosis of hepatobiliary cystadenocarcinoma is difficult because of its asymptomatic features and rarity. Moreover, the molecular pathogenesis of hepatobiliary cystadenocarcinoma remains unclear. Herein, we described a case of hepatobiliary cystadenocarcinoma in female with chronic hepatitis B and repeated hepatolithiasis. CASE PRESENTATION: A 65-year-old woman with medical history of latent hepatitis B virus infection, repeated choledocholisthiasis, and cholecystitis was admitted due to a heterogeneous cystic mass (5.6 cm × 4 cm) shown on abdominal ultrasonography during regular physical checkup. The patient complained about irregular bowel movements with intermittent diarrhea for two months before presentation. Computed tomography (CT) disclosed a multiloculated cystic lesion in the left hepatic lobe with the presence of intraductal stones and dilatation of intrahepatic ducts. Histological results obtained from left lobectomy specimens showed hepatobiliary cystadenocarcinoma without accompanied mesenchymal stroma. CONCLUSION: Notably, hepatobiliary cystadenocarcinoma without mesenchymal stroma seldom occurs in women and is usually associated with poor prognosis. We present the rare findings in this patient and suggest that chronic inflammatory insults in the intrahepatic bile ducts might shed light on the cystadenocarcinogenesis.

Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas.

BACKGROUND: Aberrant DNA methylation is associated with the development of hepatocellular carcinoma (HCC), suggesting that gene methylation could be a potential biomarker for detection of HCC. The aim of this study is to identify potential biomarkers in HCC. METHODS: We used the Infinium methylation array and a DNA-pooling strategy to analyze the genome-wide methylation profile in HCC. Quantitative methylation-specific PCR (Q-MSP) was used to validate homeobox A9 (HOXA9) methylation in 29 normal controls, 100 HCC samples and adjacent non-tumor tissues and in 74 plasma samples, including 40 patients with HCC. RESULTS: Ten genes (HOXA9, NEUROG1, TNFRSF10C, IRAK3, GFPT2, ZNF177, DPYSL4, ELOVL4, FSD1, and CACNA1G) showed differences in methylation between controls and HCCs. Of these, HOXA9 was significantly hypermethylated in HCCs (76.7%; 23/30) compared with controls (3.4%; 1/29). In addition, combination analysis of two- and three-gene sets for HCC detection showed greater sensitivity (90%-96.7%) and comparable specificity (93.1%-96.6%) to each individual gene (33.3%-76.7% and 55.2%-100.0%). HOXA9 methylation was further validated by Q-MSP in two independent set of clinical samples including 100 HCC and paired non-tumor tissues. Further, HOXA9 methylation could be detected in plasma from HCC patients (n=40) but not in normal plasma (n=34) (p<0.0005). Combined testing (either parameter positive) for α-fetoprotein (AFP, a plasma protein biomarker) and HOXA9 methylation showed greater sensitivity (94.6%) for detection of HCC than AFP alone (75.7%). CONCLUSIONS: These data suggest that methylation of HOXA9 could be a helpful biomarker to assist in HCC detection.

Safety evaluation of combination treatment of drug-eluting bead transarterial chemoembolization and immune checkpoint inhibitors for hepatocellular carcinoma: An increased risk of liver abscess with treatment interval less than one month.

PURPOSE: To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). METHOD: In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups. RESULTS: The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922). CONCLUSIONS: Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.

Machine Learning Prediction of Prediabetes in a Young Male Chinese Cohort with 5.8-Year Follow-Up.

The identification of risk factors for future prediabetes in young men remains largely unexamined. This study enrolled 6247 young ethnic Chinese men with normal fasting plasma glucose at the baseline (FPGbase), and used machine learning (Mach-L) methods to predict prediabetes after 5.8 years. The study seeks to achieve the following: 1. Evaluate whether Mach-L outperformed traditional multiple linear regression (MLR). 2. Identify the most important risk factors. The baseline data included demographic, biochemistry, and lifestyle information. Two models were built, where Model 1 included all variables and Model 2 excluded FPGbase, since it had the most profound effect on prediction. Random forest, stochastic gradient boosting, eXtreme gradient boosting, and elastic net were used, and the model performance was compared using different error metrics. All the Mach-L errors were smaller than those for MLR, thus Mach-L provided the most accurate results. In descending order of importance, the key factors for Model 1 were FPGbase, body fat (BF), creatinine (Cr), thyroid stimulating hormone (TSH), WBC, and age, while those for Model 2 were BF, white blood cell, age, TSH, TG, and LDL-C. We concluded that FPGbase was the most important factor to predict future prediabetes. However, after removing FPGbase, WBC, TSH, BF, HDL-C, and age were the key factors after 5.8 years.

Frequent concomitant epigenetic silencing of SOX1 and secreted frizzled-related proteins (SFRPs) in human hepatocellular carcinoma.

BACKGROUND AND AIM: Except for genetic mutations, epigenetic changes are also involved in the development of human cancers. Recently, we have identified SOX1, SRY (sex determining region Y)-box 1, is hypermethylated in cervical cancer and ovarian cancer. Therefore, we investigated whether promoter hypermethylation of SOX1 is common in hepatocellular carcinoma (HCC). METHODS: We used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to analyze the methyaltion level of the SOX1 promoter in seven HCC cell lines, 54 clinical HCCs, 42 cirrhotic livers, 21 livers with chronic hepatitis, and 15 control livers. Then, we employed quantitative MS-PCR (QMSP) to validate in an independent set of samples (60 paired HCCs and 30 control livers). Finally, we used luciferase reporter and colony formation assay to check the effect of SOX1 in HCC. RESULTS: Promoter methylation of SOX1 was significantly frequent in HCC cell lines and clinical HCCs, cirrhotic livers, but not in control livers (P < 0.0001). There is a significant correlation between downregulation of SOX1 expression and promoter methylation. QMSP results confirmed that promoter hypermethylation of SOX1 is significantly more frequent in HCCs than control livers (P < 0.0001). The frequency of SOX1 methylation in patients with secreted frizzled-related proteins (SFRPs) methylation is significantly higher than in patients without SFRPs methylation (P < 0.0001). Furthermore, ectopic expression of SOX1 could suppress T-cell factor-dependent transcriptional activity and colony formation number in HCCs. CONCLUSIONS: Concomitant epigenetic silencing of SOX1 and SFRPs through promoter hypermethylation is frequent in HCCs, and this might contribute to abnormal activation of canonical Wnt signal pathway.

Distilled water peritoneal lavage in patients with rupture hepatocellular carcinoma.

BACKGROUND/AIMS: Intra-peritoneal lavage is well known and used in intra-peritoneal malignancy However, the clinical role for patients with rupture of HCC has not yet been established. The aim of this study was to evaluate the clinical value of intraoperative peritoneal lavage for patients with rupture of HCC. METHODOLOGY: A retrospective study of operative findings, other factors, and outcome was performed in 66 patients with rupture of HCC who underwent distilled water peritoneal lavage (DWPL) during hepatectomy. RESULTS: There was a trend towards a higher intra-peritoneal, extra-hepatic recurrence rate in patients without DWPL. Patients who underwent DWPL had a significantly better 5-year disease-free survival rate than control group, 11.5±4.6 months and 30.2±8.4 months (p=0.018), respectively, and better overall survival rate, 21.7±6.2 months, than control group, 57.3±11.2 months (p=0.001). CONCLUSIONS: DWPL during liver resection retards tumor recurrence and improves the intraoperative survival rate in patients with spontaneously ruptured HCC.

Opportunistic Screening for Asymptomatic Left Ventricular Dysfunction With the Use of Electrocardiographic Artificial Intelligence: A Cost-Effectiveness Approach.

BACKGROUND: The burden of asymptomatic left ventricular dysfunction (LVD) is greater than that of heart failure; however, a cost-effective tool for asymptomatic LVD screening has not been well validated. We aimed to prospectively validate an artificial intelligence (AI)-enabled electrocardiography (ECG) algorithm for asymptomatic LVD detection and evaluate its cost-effectiveness for opportunistic screening. METHODS: In this prospective observational study, patients undergoing ECG at outpatient clinics or health check-ups were enrolled in 2 hospitals in Taiwan. Patients were stratified into LVD (left ventricular ejection fraction ≤ 40%) risk groups according to a previously developed ECG algorithm. The performance of AI-ECG was used to conduct a cost-effectiveness analysis of LVD screening compared with no screening. Incremental cost-effectiveness ratio (ICER) and sensitivity analyses were used to examine the cost-effectiveness and robustness of the results. RESULTS: Among the 29,137 patients, the algorithm demonstrated areas under the receiver operating characteristic curves of 0.984 and 0.945 for detecting LVD within 28 days in the 2 hospital cohorts. For patients not initially scheduled for ECG, the algorithm predicted future echocardiograms (high-risk, 46.2%; medium-risk, 31.4%; low-risk, 14.6%) and LVD (high-risk, 26.2%; medium-risk, 3.4%; low-risk, 0.1%) at 12 months. Opportunistic screening with AI-ECG could result in a negative ICER of -$7,439 for patients aged 65 years, with consistent cost-savings across age groups and particularly in men. Approximately 91.5% of the cases were found to be cost-effective at the willingness-to-pay threshold of $30,000 in the probabilistic analysis. CONCLUSIONS: The use of AI-ECG for asymptomatic LVD risk stratification is promising, and opportunistic screening in outpatient clinics has the potential to reduce costs.

Management of spontaneously ruptured hepatocellular carcinoma and hemoperitoneum manifested as acute abdomen in the emergency room.

BACKGROUND: Spontaneously ruptured hepatocellular carcinoma (HCC) with hemoperitoneum has a poor prognosis, especially in cases of cirrhosis. Patients usually present to emergency rooms (ERs) with acute abdomen. The aim of the present study was to determine the factors affecting mortality and to compare the prognosis of conservative treatment, transcatheter arterial embolization (TAE), or hepatectomy in these situations. METHODS: Fifty-four patients with spontaneously ruptured HCC diagnosed between January 2004 and August 2010 were enrolled in this retrospective review of clinical data. Grouping by survival or mortality, univariate and multivariate analyses of factors affecting 30-day mortality, and long-term survival were conducted. The outcomes of the various treatments were analyzed. RESULTS: After primary fluid resuscitation in the ER, 6 of 54 patients underwent conservative treatment. Emergency hepatectomy was performed on 19 patients; TAE was used for 29 patients, 18 of whom received staged hepatectomy thereafter. Poor liver function, prolonged international normalized ratio (INR), and conservative treatment were associated with increased 30-day mortality. Logistic regression analysis of cumulative survival revealed that INR ≥ 1.4, multiple intrahepatic HCC, and conservative treatment were related to poorer long-term survival. The patients who received hepatectomy, either immediate or staged after TAE, had higher survival rates of 85.2 % at 30 days and 62.2 % at 1 year. CONCLUSIONS: The treatment of ruptured HCC should be tailored to the individual case. Prolonged survival is possible in patients with preserved liver function through curative liver resection. Emergency physicians, radiologists, and surgeons play essential roles in managing these patients.

Malignant perivascular epithelioid cell tumor of the mesentery: a case report and literature review.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are very rare mesenchymal neoplasms, and have been found in various organs such as the liver, kidney, falciform ligament, uterus, uterine cervix, and both the small and large bowel. However, only 3 cases of mesenteric PEComa have been described in the literature so far. The treatment and prognosis of malignant mesenteric PEComas are discussed. CASE REPORT: We report the case of a 59-year-old man diagnosed with PEComa. He underwent segmental resection of the jejunum and tumor resection. Malignant mesenteric PEComa was confirmed on the basis of clinicopathological features. Tumor resection was followed by concurrent chemoradiotherapy. CONCLUSION: Besides surgery, no effective treatment for malignant PEComa has been established thus far because of the rarity of this tumor. Here, we report our experience of treating a malignant mesenteric PEComa using surgery and subsequent adjuvant therapy, which effectively controlled disease progression and prevented local recurrence.

Liver transplantation with simultaneous splenectomy increases risk of cancer development and mortality in hepatocellular carcinoma patients.

BACKGROUND: Splenectomy has previously been found to increase the risk of cancer development, including lung, non-melanoma skin cancer, leukemia, lymphoma, Hodgkin's lymphoma, and ovarian cancer. The risk of cancer development in liver transplantation (LT) with simultaneous splenectomy remains unclear. AIM: To compare hepatocellular carcinoma (HCC) recurrence and de novo malignancy between patients undergoing LT with and without simultaneous splenectomy. METHODS: We retrospectively analyzed the outcomes of 120 patients with HCC within the University of California San Francisco criteria who received LT with (n = 35) and without (n = 85) simultaneous splenectomy in the Tri-Service General Hospital. Univariate and multivariate Cox regression analyses for cancer-free survival and mortality were established. The comparison of the group survival status and group cancer-free status was done by generating Kaplan-Meier survival curves and log-rank tests. RESULTS: The splenectomy group had more hepatitis C virus infection, lower platelet count, higher -fetoprotein level, and longer operating time. Splenectomy and age were both positive independent factors for prediction of cancer development [hazard ratio (HR): 2.560 and 1.057, respectively, P < 0.05]. Splenectomy and hypertension were positive independent factors for prediction of mortality. (HR: 2.791 and 2.813 respectively, P < 0.05). The splenectomy group had a significantly worse cancer-free survival (CFS) and overall survival (OS) curve compared to the non-splenectomy group (5-year CFS rates: 53.4% vs 76.5%, P = 0.003; 5-year OS rate: 68.1 vs 89.3, P = 0.002). CONCLUSION: Our study suggests that simultaneous splenectomy should be avoided as much as possible in HCC patients who have undergone LT.

Effect of the Nintendo Ring Fit Adventure Exergame on Running Completion Time and Psychological Factors Among University Students Engaging in Distance Learning During the COVID-19 Pandemic: Randomized Controlled Trial.

BACKGROUND: The COVID-19 outbreak has not only changed the lifestyles of people globally but has also resulted in other challenges, such as the requirement of self-isolation and distance learning. Moreover, people are unable to venture out to exercise, leading to reduced movement, and therefore, the demand for exercise at home has increased. OBJECTIVE: We intended to investigate the relationships between a Nintendo Ring Fit Adventure (RFA) intervention and improvements in running time, cardiac force index (CFI), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index score), and mood disorders (5-item Brief Symptom Rating Scale score). METHODS: This was a randomized prospective study and included 80 students who were required to complete a 1600-meter outdoor run before and after the intervention, the completion times of which were recorded in seconds. They were also required to fill out a lifestyle questionnaire. During the study, 40 participants (16 males and 24 females, with an average age of 23.75 years) were assigned to the RFA group and were required to exercise for 30 minutes 3 times per week (in the adventure mode) over 4 weeks. The exercise intensity was set according to the instructions given by the virtual coach during the first game. The remaining 40 participants (30 males and 10 females, with an average age of 22.65 years) were assigned to the control group and maintained their regular habits during the study period. RESULTS: The study was completed by 80 participants aged 20 to 36 years (mean 23.20, SD 2.96 years). The results showed that the running time in the RFA group was significantly reduced. After 4 weeks of physical training, it took females in the RFA group 19.79 seconds (P=.03) and males 22.56 seconds (P=.03) less than the baseline to complete the 1600-meter run. In contrast, there were no significant differences in the performance of the control group in the run before and after the fourth week of intervention. In terms of mood disorders, the average score of the RFA group increased from 1.81 to 3.31 for males (difference=1.50, P=.04) and from 3.17 to 4.54 for females (difference=1.38, P=.06). In addition, no significant differences between the RFA and control groups were observed for the CFI peak acceleration (CFIPA)_walk, CFIPA_run, or sleep quality. CONCLUSIONS: RFA could either maintain or improve an individual's physical fitness, thereby providing a good solution for people involved in distance learning or those who have not exercised for an extended period. TRIAL REGISTRATION: ClinicalTrials.gov NCT05227040; https://clinicaltrials.gov/ct2/show/NCT05227040.

Locoregional therapy-induced tumor necrosis as a predictor of recurrence after liver transplant in patients with hepatocellular carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy. METHODS: We conducted a hospital-based retrospective analysis of 100 patients with HCC who received a liver transplant, 86 of whom had received pretransplant locoregional therapy. We evaluated various patient- and tumor-related parameters to determine the risk factors for recurrence. Furthermore, we grouped patients by the degree of tumor necrosis after locoregional therapy and identified the factors that were associated with a favorable tumor response. RESULTS: Initial tumor extent beyond the University of San Francisco (UCSF) criteria, microvascular invasion, and attainment of less than 90% tumor necrosis after locoregional therapy were independent risk factors for tumor recurrence. In addition, there was a significant correlation between the tumor necrosis percentage and disease-specific survival rate. Among patients whose tumors initially exceeded the UCSF criteria, those with extensive locoregional therapy-induced tumor necrosis had lower recurrence rates. All recurrences after transplant occurred within 3 years, and recurrence rates in patients with extensive tumor necrosis at 1, 2, and 3 years were 3%, 6%, and 10%, respectively. Female gender and a solitary tumor were independently associated with extensive tumor necrosis. CONCLUSIONS: In HCC patients who are transplant candidates and undergo pretransplant locoregional therapy, the degree of induced tumor necrosis affects both tumor recurrence and survival rate.

Use of a totally implantable access port through the external jugular vein when the cephalic vein approach is not feasible.

BACKGROUND: We report our experience of using a totally implantable access port (TIAP) through the external jugular vein (EJV) when the cephalic vein (CV) approach is not feasible. METHODS: We reviewed 197 cases involving TIAP implantation through the EJV in a single medical center between January 1995 and January 2009. All the ports were implanted after the CV approach was found unfeasible. Patient characteristics, operating time, and early and late complications were recorded. RESULTS: The mean patient age was 50 years (range: 33-75). The mean operating time was 54.5 ± 7.5 minutes. Early complications within the first 30 postoperative days included port hematoma (2%) and catheter migration (2%). The late postoperative complications included catheter occlusion (2.5%), venous thrombosis (2%), and port infection (1.5%). There were no complications associated with TIAP disconnection. CONCLUSIONS: The EJV approach is an easy and safe alternative method for TIAP implantation when the CV approach is not feasible. This method can avoid conversion to percutaneous puncture of the subclavian vein, which could result in life-threatening complications such as pneumothorax and hemothorax. In patients with breast cancer or those who are contraindicated for TIAP implantation on the opposite side, the EJV cutdown approach provides an alternative route with comfortable and satisfactory results as complications with this approach are rare.