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.

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.

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.

Conversion Surgery for Patients with Advanced Gastric Cancer with Peritoneal Carcinomatosis.

BACKGROUND: Patients with advanced gastric cancer (AGC) with peritoneal carcinomatosis (PC) usually have poor outcomes and high mortality risk, even with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study analyzed the prognostic factors of AGC with PC and evaluated laparoscopic HIPEC (LHIPEC) plus neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) as a conversion surgery for AGC patients with PC with a poor initial prognosis. Patient and Methods. We retrospectively evaluated 127 patients with AGC and PC from January 1, 2012, to March 1, 2020. After the exclusion of 32 ineligible patients, the conversion group comprised 34 patients who underwent LHIPEC + NIPS as a conversion surgery followed by CRS plus HIPEC. The CRS + HIPEC group included 15 patients who underwent CRS with HIPEC alone. Additionally, the C/T group comprised 23 patients who received systemic chemotherapy, and the palliative group comprised 23 patients who received only conservative therapy or palliative gastrectomy. RESULTS: The conversion group demonstrated a significantly better mean overall survival compared to the CRS + HIPEC, C/T, and palliative groups (p < 0.001). Patients in the conversion group who underwent LHIPEC + NIPS had significantly decreased peritoneal cancer index (PCI) scores (p < 0.001) and ascites (p=0.003). Malignant ascites amount also significantly decreased after treatment in the LHIPEC + NIPS group (p < 0.001). CONCLUSIONS: LHIPEC + NIPS can significantly improve the overall survival, the PCI score, and malignant ascites amount in peritoneal cytology-positive gastric cancer with PC, and an initially high PCI score. Therefore, it may be a feasible conversion strategy for AGC patients with PC.

CRNDE-h transcript/miR-136-5p axis regulates interleukin enhancer binding factor 2 expression to promote hepatocellular carcinoma cell proliferation.

AIMS: Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte. Interleukin enhancer binding factor 2 (ILF2) plays a role in the development of HCC. However, the regulatory mechanisms of ILF2 expression in HCC remain unclear. In this study, we aimed to identify ILF2-targeting microRNAs (miRNAs) and to explore how they affect ILF2 expression in HCC. MAIN METHODS: The tissue specimens were collected from 25 HCC patients. The underlying regulatory mechanism of ILF2 expression in HCC progression was determined using luciferase reporter assay, quantitative real-time PCR, Western blotting, and BrdU incorporation assay. KEY FINDINGS: Of predicted miRNA candidates (miR-122-5p, miR-425-5p, miR-136-5p, miR-7-5p, miR-421 and miR-543), a statistically significant inverse correlation by linear correlation analysis was observed between miR-136-5p and ILF2 mRNA expressions in patients with HCC (r = -0.627, P < 0.001). Further analysis demonstrated that ILF2 was directly regulated by miR-136-5p. In addition, we showed that long noncoding RNA colorectal neoplasia differentially expressed-h (lncRNA CRNDE-h) transcript expression was significantly up-regulated in HCC, and a miR-136-5p binding site was newly found in the lncRNA CRNDE-h transcript sequence using IntaRNA tool. In terms of mechanism, highly-expressed lncRNA CRNDE-h transcript can sponge miR-136-5p, thereby preventing it from interacting with target ILF2 mRNA while promoting the proliferation of HCC cells. SIGNIFICANCE: The lncRNA CRNDE-h/miR-136-5p/ILF2 axis plays a significant regulatory role in HCC progression, which may partly explain the pathogenic mechanisms of HCC and may provide promising potential targets for the diagnosis, treatment, and prognosis of HCC.

Outcomes of Infection and Risk of Mortality in Liver Transplant Patients with Simultaneous Splenectomy.

PURPOSE: The purpose of this study was to compare the outcomes of infection between liver transplant patients with and without simultaneous splenectomy. METHODS: We retrospectively analyzed the records of 211 patients who underwent liver transplantation in the Tri-Service General Hospital from 2012 to 2017. The frequency of blood cultures obtained after liver transplantation; incidence of bacteremia, pathogens, and complications; and overall survival rates were compared between the groups. RESULTS: One hundred thirty-three of 211 patients underwent liver transplantation without simultaneous splenectomy. There were no significant differences in the frequency of blood cultures obtained after liver transplantation (non-splenectomy group and splenectomy group: 63% and 62%, respectively); incidences of bacteremia after liver transplantation (21% and 21%, respectively), repeat bacteremia (39% and 35%, respectively), cytomegalovirus infection (4% and 3%, respectively), herpes infection (6% and 7%, respectively), and fungal infection (3% and 3%, respectively); and overall survival rate between the two groups. However, there was a significant difference in infection-related deaths between the groups. Simultaneous splenectomy and episodes of antibody-related rejection were significant risk factors associated with infection-related death in multivariate analyses. CONCLUSION: Although simultaneous splenectomy does not increase the incidence of infection, simultaneous splenectomy definitely carries risks of infection-related mortality in liver transplantation.

Somatostatin Therapy in Patients with Massive Ascites After Liver Transplantation.

BACKGROUND Patients with massive ascites (MA) after liver transplantation (LT, defined here as daily ascitic drainage more than 1000 ml per day for more than 7 days after liver transplantation) are at increased risks of infection, hypoalbuminemia, graft loss, and even mortality. The aim of this retrospective cohort study was to investigate the effects of somatostatin on patients with MA after LT. MATERIAL AND METHODS Twenty-eight patients with liver cirrhosis or hepatocellular carcinoma who underwent LT complicated by MA postoperatively were included. Ten participants were receiving somatostatin therapy. The postoperative course and adverse drug effects were investigated. Daily postoperative ascitic drainage and urine output were also recorded and compared to those in the non-somatostatin group. RESULTS The somatostatin group had significantly less ascites drainage after LT compared to the non-somatostatin group (p=0.002). Urine output was significantly increased after somatostatin administration (p<0.001). No serious adverse effects influencing graft function or fatal complications occurred after somatostatin therapy. CONCLUSIONS Somatostatin treatment is beneficial for the management of MA after liver transplantation.

A Novel Strategy of Laparoscopic Insufflation Rate Improving Shoulder Pain: Prospective Randomized Study.

BACKGROUND: Laparoscopic surgery is the main trend method in a variety of surgical fields. Post-operative shoulder pain remains a bothersome issue although many surgical techniques have been applied to minimize it. A simple novel approach to reduce shoulder pain without adverse effects during and after laparoscopic surgery is desired. METHODS: This prospective randomized controlled study was conducted to enroll a total of 140 patients to evaluate the efficacy of low flow rate (1 L/min) for induction followed by high flow rate (10 L/min) for maintaining 12 mmHg pneumoperitoneum (group A, n = 70) during laparoscopic cholecystectomy (LC), compared to the continuous high flow rate group (group B, n = 70) in postoperative shoulder pain and other clinical features. The 10-visual analog scale (VAS) was applied for the severity of shoulder pain and scores were obtained at 1, 6, 12, 24, and 48 h after LC. RESULTS: There was no obvious difference in baseline characteristics as well as operative time, occurrence of bradycardia, or hospital stay between groups. The incidence of shoulder pain was not significantly different (group A 45.7% vs group B 48.6%, p = 0.866). However, the patients in group A with shoulder pain reported significantly less pain scores (p < 0.001) at 12 and 24 h after surgery, compared with those in group B. CONCLUSIONS: Applying the strategy of low flow rate to induce pneumoperitoneum followed by high flow rate to maintain the pressure provides advantages to reduce the severity of shoulder pain for patients who underwent LC and then experienced shoulder pain.

Sex-Specific Association Between Serum Uric Acid and Elevated Alanine Aminotransferase in a Military Cohort: The CHIEF Study.

AIM: The study was conducted in order to examine the sex-specific association of serum uric acid (SUA) levels with elevated serum alanine aminotransferase (ALT) in a Taiwanese military cohort. METHODS: We made a cross-sectional examination of the sex-specific relationship using 6728 men and 766 women, aged 18-50 years from a large military cohort in Taiwan. SUA levels within the reference range (<7.0 mg/dL for men and <5.7 mg/dL for women respectively) were divided into quartiles and SUA levels greater than the upper reference limits were defined as hyperuricemia. Elevated ALT levels were defined as ≥40 U/L. Multivariate logistic regression analysis was performed to determine the association between each SUA category and elevated ALT levels in men and women, respectively. RESULTS: The prevalence of hyperuricemia and elevated ALT in men were 18.7% and 12.7%, respectively, and in women were 3.3% and 2.1%, respectively. As compared with the lowest SUA quartile, hyperuricemia was associated with elevated ALT in men (odds ratios (OR): 1.62, 95% confidence intervals (CI): 1.19-2.20) after controlling for age, service specialty, body mass index, metabolic syndrome components, current cigarette smoking, alcohol intake status, and weekly exercise times, but the associations for the other SUA quartiles were null. By contrast, the associations of hyperuricemia (OR: 0.81, 95% CI: 0.10-6.64) and the other SUA quartiles with elevated ALT were null in women. CONCLUSION: Our findings suggest that the relationship between each SUA level and elevated ALT may differ by sex among military young adults. The mechanism for the sex difference requires further investigations.

Long-term outcomes in elderly patients with resectable large hepatocellular carcinoma undergoing hepatectomy.

BACKGROUND: In contrast to the feasibility of hepatectomy for resectable large hepatocellular carcinoma (HCC, >5 cm) in the younger patients, the concerns of benefits for the elderly patients remain in practice. This study aimed to evaluate the long-term outcomes and safety after hepatectomy in elderly patients with resectable large HCC compared with younger patients. METHODS: Between 2003 and 2014, a total of 2211 HCC patients were reviewed using a prospective database and 257 patients with resectable large HCC undergoing hepatectomy were included: 79 elderly patients with age ≥70 years and 178 younger patients with age <70 years. The last follow-up was assessed in December 2017. The complications, long-term outcomes and risk factors of disease-free and overall survival were analysed. RESULTS: The 1-, 3-, 5- and 7-year overall survival rates in the elderly and younger groups were 76%, 55%, 48%, and 42% and 79%, 57%, 51%, and 49%, respectively (P = 0.319). The 1-, 3-, 5-, and 7-year disease-free survival rates in the elderly and younger groups were 60%, 40%, 38%, and 27% and 54%, 36%, 32%, and 32%, respectively (P = 0.633). The analysis of post-operative outcomes of interest, including hospital stay and hospital death and hepatectomy-related complications in both groups revealed no significant difference. Serum albumin and AJCC TNM stage were independent risk factors for survival. Serum alpha-fetoprotein, tumour number and AJCC TNM stage predicted HCC recurrence. CONCLUSIONS: Our results suggested that hepatectomy can achieve comparable long-term outcomes in the selected younger and elderly patients with resectable large HCC.

Retransplant as Rescue Treatment for ABO-Compatible Living-Donor Liver Transplant Related Antibody-Mediated Rejection: A Case Report.

Antibody-mediated rejection after liver transplant, especially when the donor is not a direct relative; it is associated with additional inconvenience for patients. We encountered a case in which antibody-mediated rejection because of de novo donor specific antibodies against donor human leukocyte antigen developed 6 months after ABO-compatible living-donor liver transplant and was treated with retransplant. A 38-year-old man with hepatitis B virus-related hepatocellular carcinoma underwent living-donor liver transplant with a graft from his wife. Six months later, he experienced fatigue and jaundice. Liver biopsy revealed C4d deposits, and histologic examination showed an antibody-mediated rejection pattern. We re-evaluated recipient-donor human leukocyte antigen matching and tested the patient's blood for antihuman leukocyte antigen donor-specific antibodies against donor human leukocyte antigen. De novo auto-antibodies against human leukocyte antigen-DQ6 were identified by Luminex single antigen beads.Because exhausting all treatment options, a rescue second living-donor liver transplant was planned with the patient's stepdaughter as the donor. Pretransplant human leukocyte antigen matching was performed, and the patient was discharged without event. Two months later, hyperbilirubinemia was noted, and a residual common bile duct from the first donor with chronic fibrosis and stricture was strongly suspected. Redo hepaticojejunostomy was successfully performed, with no problems during 1-years' follow-up. Thus, liver retransplant could be a rescue treatment for antibody-mediated rejection complicated with hepatic failure.

Routine Intraoperative Neuromonitoring of the Recurrent Laryngeal Nerve to Facilitate Complete Resection and Ensure Safety in Thyroid Cancer Surgery.

Routine use of intraoperative neuromonitoring (IONM) in thyroid cancer surgery is controversial. We aimed to investigate whether it improves the completeness of thyroidectomy and ensures safety. This retrospective study included 380 thyroid cancer patients who underwent thyroidectomy, by one surgeon, between July 2006 and November 2015. Patients were grouped according to the surgeon's adaptation of IONM, as follows: none (period 1; n = 92), early (period 2; n = 141), and late (period 3; n = 147). The operative time and rates of vocal cord palsy were determined. Surgical completeness was assessed by technetium-99m imaging of the thyroid remnant and serum thyroglobulin measurement before ablation. The rate of recurrent laryngeal nerve (RLN) palsy showed a decreasing trend over time. No permanent RLN palsies occurred in nerves not invaded by tumor after routine IONM was introduced. Technetium-99m uptake (periods 1-3, 0.62 vs 0.32 vs 0.20; P < 0.01) and thyroglobulin levels (periods 1 and 2, 37.93 vs 8.98 ng/mL, respectively; P = 0.034; period 3, 9.10 ng/mL) progressively decreased. The mean thyroglobulin level dropped significantly after introduction of routine IONM. We conclude that routine IONM during thyroid cancer surgery improves surgical completeness and might prevent permanent RLN palsy over time.

High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P < 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis.

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.

HCV core inhibits hepatocellular carcinoma cell replicative senescence through downregulating microRNA-138 expression.

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HCV core protein is considered as a positive regulator of telomerase activity. In this study, we focused on the deregulated microRNA-138 (miR-138) in HCV-associated HCC. Differential expression of miR-138 was determined by TaqMan quantitative real-time PCR. The target gene of miR-138 was verified by luciferase reporter assay, quantitative real-time PCR, and Western blotting. Moreover, three assays based on telomerase activity, cell proliferation, and senescence-associated ß-galactosidase activity were performed. The correlation analysis revealed a significantly negative correlation between miR-138 and telomerase reverse transcriptase (TERT) mRNA expression in HCC. Further, we showed that mature HCV core protein of 173 amino acids, but not full-length form of 191 amino acids, suppressed miR-138 expression. TERT was verified as a direct target of miR-138 in HCC cells. Furthermore, TERT-targeting miR-138 supplementation can prevent HCV core protein from repressing HCC cell replicative senescence. Collectively, HCV core protein can enhance TERT protein expression through downregulating TERT-targeting miR-138 expression, which in turn inhibits HCC cell replicative senescence. This study may further help our understanding on the pathogenic mechanisms of HCV core protein in HCV-associated HCC development. KEY MESSAGE: miR-138 is downregulated in HCV-associated HCC. Mature HCV core protein plays a pathogenic role in suppressing miR-138 expression. Telomerase reverse transcriptase represents a direct target of miR-138 in HCC cells. miR-138 promotes HCC cell senescence, suggesting potential for HCC treatment.

Preincisional and postoperative epidural morphine, ropivacaine, ketamine, and naloxone treatment for postoperative pain management in upper abdominal surgery.

OBJECTIVE(S): Previous studies have shown that preincisional epidural morphine, bupivacaine, and ketamine combined with epidural anesthesia (EA) and general anesthesia (GA) provided pre-emptive analgesia for upper abdominal surgery. Recent studies reported that ultralow-dose naloxone enhanced the antinociceptive effect of morphine in rats. This study investigated the benefits of preincisional and postoperative epidural morphine + ropivacaine + ketamine + naloxone (M + R + K + N) treatment for achieving postoperative pain relief in upper abdominal surgery. METHODS: Eighty American Society of Anesthesiology I-II patients scheduled for major upper abdominal surgery were allocated to four groups in a randomized, single-blinded study. All patients received combined GA and EA with a continuous epidural infusion of 2% lidocaine (6-8 mL/h) 30 minutes after pain regimen. After GA induction, in Group I, an epidural pain control regimen (total 10 mL) was administered using 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg; M + R); in Group II, 1% lidocaine 8 (mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg; M + R + K); in Group III, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + naloxone (2 µg; M + R + N); and in Group IV, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg) + naloxone (2 µg; M + R + K + N), respectively. All patients received patient-controlled epidural analgesia (PCEA) with different pain regimens to control subsequent postoperative pain for 3 days following surgery. During the 3-day period following surgery, PCEA consumption (mL), numerical rating scale (NRS) score while cough/moving, and analgesic-related adverse effects were recorded. RESULTS: Total PCEA consumption for the 3-day observation period was 161.5±17.8 mL, 103.2±21.7 mL, 152.4±25.6 mL, and 74.1±16.9 mL for Groups I, II, III, and IV, respectively. (p < 0.05). The cough/moving NRS scores were significantly lower in Group IV patients than Groups I and III patients at 4 hours, 12 hours, and on Days 1 and 2 following surgery except for Group II (p < 0.05). CONCLUSION: Preincisional and postoperative epidural M + R + K + N treatment provides an ideal postoperative pain management than preincisional and postoperative epidural M + R, M + R + K, and M + R + N treatments in upper abdominal surgery.

Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan.

Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex.

Quantitative methylation analysis reveals distinct association between PAX6 methylation and clinical characteristics with different viral infections in hepatocellular carcinoma.

BACKGROUND: Related to genetic alteration, frequent promoter hypermethylation is also a contributing factor in the development of human cancers. Recently, we discovered numerous novel genes that were aberrantly methylated in hepatocellular carcinoma (HCC) by using Infinium HumanMethylation27 BeadChip array. We utilized a quantitative methylation-specific PCR (Q-MSP) system for the evaluation of PAX6 methylation in 29 normal controls and 160 paired HCC tissues and their adjacent non-tumor tissues. We verified the correlation between the methylation status of PAX6 and clinical characteristics with different viral status. RESULTS: Paired-box 6 promoter methylation was observed in 39.4 %, 15.6 %, and 3.4 % in primary HCCs, adjacent non-tumors, and normal control tissues, respectively. Methylation of the PAX6 promoter region in HCCs significantly increased compared with control tissues. PAX6 was frequently methylated in HCV-positive HCC tissues (61.3 %) and rarely methylated in HBV-positive (22.1 %) and double-negative HCC tissues (33.3 %). CONCLUSIONS: Our data suggests that promoter hypermethylation of PAX6 is a common event in HCCs and the association of PAX6 methylation in clinicopathological features is divergent with different viral status.