Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND AND PURPOSE: Tapering immunosuppressants is desirable in patients with well-controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction-associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody-positive MG, and to determine the factors that predict exacerbations. METHODS: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction-associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. RESULTS: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction-associated exacerbation than in those without exacerbation. The cut-off values determined in a receiver-operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. CONCLUSION: Tapering of tacrolimus was possible in most patients with well-controlled anti-acetylcholine receptor antibody-positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.

Selenium health benefit values provide a reliable index of seafood benefits vs. risks.

BACKGROUND: Methylmercury (CH3Hg) toxicity causes irreversible inhibition of selenium (Se)-dependent enzymes, including those that are required to prevent and reverse oxidative damage in the brain. Fish consumption provides numerous essential nutrients required for optimal health, but is also associated with CH3Hg exposure risks, especially during fetal development. Therefore, it is necessary to assess the amounts of both elements in seafood to evaluate relative risks or benefits. Consumption of ocean fish containing Se in molar excess of CH3Hg will prevent interruption of selenoenzyme activities, thereby alleviating Hg-exposure risks. Because dietary Se is a pivotal determinant of CH3Hg's effects, the Selenium Health Benefit Value (HBV) criterion was developed to predict risks or benefits as a result of seafood consumption. A negative HBV indicates Hg is present in molar excess of Se and may impair Se availability while a positive HBV indicates consumption will improve the Se status of the consumer, thus negating risks of Hg toxicity. OBJECTIVE: This study examined the Hg and Se contents of varieties of seafood to establish those with positive HBV's offering benefits and those having negative HBVs indicating potential consumption risks. METHODS: The Hg and Se molar concentrations in samples of meat from pilot whale, mako shark, thresher shark, swordfish, bigeye tuna, and skipjack tuna were used to determine their HBV's in relation to body weight. RESULTS: The HBVs of pilot whale, mako shark, and swordfish were typically negative and inversely related to body weight, indicating their consumption may impair Se availability. However, the HBV's of thresher shark, bigeye tuna, and skipjack tuna were uniformly positive regardless of body weights, indicating their consumption counteracts Hg-dependent risks of selenoenzyme impairment. CONCLUSIONS: The HBV criterion provides a reliable basis for differentiating seafoods whose intake should be limited during pregnancy from those that should be consumed to obtain health benefits.

Hepatectomy for hepatocellular carcinoma after perioperative management of portal hypertension.

BACKGROUND: Indications for hepatectomy in patients with hepatocellular carcinoma (HCC) who have portal hypertension (PH) have been controversial. Some studies have concluded that PH is a contraindication to hepatectomy, whereas others have suggested that perioperative prophylactic management (PPM) can help overcome complications after hepatectomy associated with PH. The objective of this retrospective study was to assess the short- and long-term outcomes after hepatectomy for HCC in patients with PH, with or without PPM. METHODS: Records were reviewed of consecutive patients who underwent hepatectomy for HCC, with or without PPM of PH, in a single institution from 1994 to 2015. Patients were divided into three groups: those who received PPM for PH (PPM group), patients who had PH but did not receive PPM (no-PPM group) and those without PH (no-PH group). RESULTS: A total of 1259 patients were enrolled, including 123 in the PPM group, 181 in the no-PPM group and 955 in the no-PH group. Three- and 5-year overall survival rates were 74·3 and 53·1 per cent respectively in the PPM group, 69·2 and 54·9 per cent in the no-PPM group, and 78·1 and 64·2 per cent in the no-PH group (P = 0·520 for PPM versus no PPM, P = 0·027 for PPM versus no PH, and P < 0·001 for no PPM versus no PH). Postoperative morbidity and mortality rates were 26·0 and 0·8 per cent respectively in the PPM group, 29·8 and 1·1 per cent in the no-PPM group, and 20·3 and 0 per cent in the no-PH group. CONCLUSION: The present study has demonstrated acceptable outcomes among patients with HCC who received appropriate management for PH in an Asian population. Enhancement of the safety of hepatic resection through use of PPM may provide a rationale for expansion of indications for hepatectomy in patients with PH.

Use of a Right Lateral Sector Graft in Living Donor Liver Transplantation Is Feasible, but Special Caution Is Needed With Respect to Liver Anatomy.

Right lateral sector (RLS) grafting has been introduced to enlarge the potential donor pool for living donor liver transplantation (LDLT); however, evidence of its feasibility is limited. Data from 437 LDLTs carried out between 2000 and 2013 were analyzed retrospectively. LDLTs using a right liver graft (n = 251) were compared with those using a RLS graft (RLSG; n = 28). No donor mortality occurred, and the major complication rates were similar between the two groups. Postoperative liver function preservation was better in the RLSG donors. Concerning the recipients, the mortality and overall survival rates were similar between the two groups. The complication rate for the recipients was higher when more than two arterial or biliary anastomoses were necessary. A systematic literature search identified four reports on LDLT using RLSGs. Among 66 LDLTs, including the present series, there were no cases of donor death, and the rates of major and minor complications in the donors were 6% and 29%, respectively. The major complication and overall mortality rates in the recipients were 29% and 6%, respectively. LDLT using an RLSG is feasible, with an acceptable survival rate among the recipients.

Response measurement of single-crystal chemical vapor deposition diamond radiation detector for intense X-rays aiming at neutron bang-time and neutron burn-history measurement on an inertial confinement fusion with fast ignition.

A neutron bang time and burn history monitor in inertial confinement fusion with fast ignition are necessary for plasma diagnostics. In the FIREX project, however, no detector attained those capabilities because high-intensity X-rays accompanied fast electrons used for plasma heating. To solve this problem, single-crystal CVD diamond was grown and fabricated into a radiation detector. The detector, which had excellent charge transportation property, was tested to obtain a response function for intense X-rays. The applicability for neutron bang time and burn history monitor was verified experimentally. Charge collection efficiency of 99.5% ± 0.8% and 97.1% ± 1.4% for holes and electrons were obtained using 5.486 MeV alpha particles. The drift velocity at electric field which saturates charge collection efficiency was 1.1 ± 0.4 × 10(7) cm/s and 1.0 ± 0.3 × 10(7) cm/s for holes and electrons. Fast response of several ns pulse width for intense X-ray was obtained at the GEKKO XII experiment, which is sufficiently fast for ToF measurements to obtain a neutron signal separately from X-rays. Based on these results, we confirmed that the single-crystal CVD diamond detector obtained neutron signal with good S/N under ion temperature 0.5-1 keV and neutron yield of more than 10(9) neutrons/shot.

Adult right living-donor liver transplantation with special reference to reconstruction of the middle hepatic vein.

Two hundred fifty-three consecutive living-donor liver transplant recipients with a right liver graft (RLG) were divided into three groups: an extended right liver graft (ERLG) group (n = 47) in which the middle hepatic vein (MHV) trunk was included in the graft, a modified right liver graft (MRLG) group (n = 114) in which the MHV tributaries were reconstructed with cryopreserved homologous veins and a simple RLG group (n = 92) in which the MHV tributaries were sacrificed. The volume of the anterior sector was significantly impaired in the RLG group compared to the other two groups, whereas the volume of the posterior sector was significantly improved in the RLG group, indicating that the impaired anterior sector regeneration by MHV deprivation was compensated by the posterior sector regeneration. The regeneration rate of the anterior sector was highest in the ERLG group (92%), moderate in the MRLG group (71%) and lowest in the RLG group (52%). The whole graft regeneration rate of the ERLG group was significantly higher than that of the other two groups. Poor regeneration, however, was not correlated with delayed functional recovery or long-term outcome. Short-term, the patency of reconstructed MHV tributaries was over 90%, but occlusion occurred frequently over the long-term, especially in V5.

A single-center experience of the use of interleukin-2 receptor antagonists for various situations in liver transplant recipients.

BACKGROUND: Interleukin-2 receptor antagonists (IL2Ra) are used mainly for (1) induction as an adjunct to conventional immunosuppression, (2) induction to facilitate calcineurin inhibitor (CNI) or steroid minimization, and (3) induction to facilitate steroid avoidance in hepatitis C virus (HCV)-positive recipients. The aim of this study was to present our strategy for IL2Ra rescue therapy and its outcome. METHODS: A total of 20 patients were treated with IL2Ra at our institute for the following indications: (1) rescue for acute rejection (n = 13), (2) CNI sparing in cases of CNI toxicity (n = 5), and (3) induction for complicated cases (n = 2). RESULTS: Rescue therapy for steroid-resistant rejection and rejection in HCV-positive recipients was successful in 11 cases, but 2 grafts were lost due to uncontrollable rejection. CNI cessation was successfully achieved with IL2Ra treatment in 3 cases with thrombotic microangiopathy and 2 cases of encephalopathy, with complete cure of these life-threatening complications of CNI. Induction with IL2Ra was successful in 2 complicated cases, 1 for CNI sparing due to renal failure and the other for adjunct immunosuppression in a case of positive lymphocytotoxic crossmatch. The overall patient/graft survival and the rate of infectious complications were comparable between those with and without IL2Ra treatment. CONCLUSIONS: IL2Ra could be safely and effectively used after liver transplantation in various situations.

Resection of segment VIII for hepatocellular carcinoma.

BACKGROUND: Anatomical resection of segment VIII (SVIII) is technically demanding. Only two small studies have published short-term outcomes. The aim of the present study was to evaluate short- and long-term outcomes after anatomical resection involving SVIII for hepatocellular carcinoma (HCC), and to compare long-term outcomes with those after non-anatomical resection of SVIII. METHODS: Outcomes after anatomical resection of SVIII or its subsegments for HCC were compared with those in patients who underwent primary non-anatomical resection of SVIII during the same period. RESULTS: A total of 154 patients underwent anatomical resection involving SVIII and 122 had non-anatomical resection. In patients undergoing anatomical resection, the preoperative indocyanine green retention rate at 15 min ranged from 2·9 to 32·2 (median 13·6) per cent, and was 10 per cent or more in 109 patients (70·8 per cent). Median duration of operation and blood loss were 378 min and 705 ml respectively. There were no postoperative deaths, but major adverse events occurred in ten patients (6·5 per cent). The cumulative 5-year recurrence-free and overall survival rates were 28·5 and 79·6 per cent, which were significantly better than rates of 19·4 and 64·8 per cent respectively after non-anatomical resection (P = 0·036 and P < 0·001). CONCLUSION: Complete resection of SVIII or its subsegments can be performed safely and the long-term outcomes seem acceptable. This can be a curative procedure for HCC, especially in patients with limited liver function reserve, in whom right hepatectomy or right paramedian sectorectomy might otherwise be needed.

Preemptive antiviral treatment for hepatitis C virus after living donor liver transplantation.

BACKGROUND: Recurrence following liver transplantation for hepatitis C virus (HCV), which is universal, affects long-term outcomes. Treatment with interferon (IFN) and ribavirin (RBV), the only widely available options at this time, have been faced with low tolerability and overall unsatisfactory results in deceased donor liver transplantation (DDLT). However, its place after living donor liver transplantation (LDLT) remains a matter of debate. Since most LDLT cases are performed in a planned manner at a lower Model for End-stage Liver Disease (MELD) score compared to DDLT, we have aggressively applied preemptive INF/RBV in our series. PATIENTS AND METHODS: We studied 122 adult recipients who underwent LDLT for HCV-related end-stage liver disease. The preemptive IFN/RBV protocol initiated treatment promptly after improvement in the patient's general condition with a low-dose IFN alpha2b and RBV (400 mg/d) followed by a gradual increase in the INFalpha2b dosage. Finally, we applied pegylated IFN (1.5 ug/kg/wk) and RBV (800 mg/d). The treatment was continued for 12 months after serum HCV-RNA became negative, which was defined as the end-of-treatment response (ETR). The response was considered to be a sustained viral response (SVR) if there were negative serologic results without antiviral treatment for another 6 months. Splenectomy was performed at the time of LDLT to improve tolerability to INF/RBV. The median age of the patients was 55 yrs (range = 23-66), with male dominance (87 males and 35 females). Median MELD score was 14 (range = 6-48). The series included 72 patients with hepatocellular carcinomas, and six with HIV coinfections. In 98 cases, HCV genotype was 1b. RESULTS: Overall survival at 5 years was 79%. Cumulative response rates under the protocol were ETR 56% and SVR 44% at 5 years. CONCLUSIONS: Preemptive IFN/RBV therapy after LDLT for HCV is feasible with acceptable outcomes.

Model for end-stage liver disease and model for end-stage liver disease-Na scores predict both before-listing and wait-list mortality.

BACKGROUND: Due to the organ shortage, many patients die without transplantation, even before completing an evaluation for candidacy. We analyzed outcomes after patient referral and factors associated with mortality both before and after listing for cadaveric donor liver transplantation. METHODS: We analyzed 132 consecutive patients who were evaluated for candidacy for cadaveric donor liver transplantation between 2003 and 2010. RESULTS: The study included 69 men and 63 women of median age 49 years (range, 1-65). Etiologies of diseases were acute hepatic failure (n=19), liver cirrhosis due to hepatitis B or C (n=36), primary biliary cirrhosis (n=19), nonviral cirrhosis (n=14), hepatocellular carcinoma (n=13), or other causes (n=31). After evaluation for candidacy, we listed 68 (52%), subjects whereas 24 (18%) died before listing. Factors affecting death before listing were the levels of albumin (P<.001), bilirubin (P<.001), sodium (P<.001), international normalized ratio (INR; P<.001), Model for End-stage Liver Disease (MELD) score (P<.001), MELD-Na score (P<.001), and Child-Pugh-Turcotte (CPT) score (P<.001). Based on multivariate Cox regression analysis, MELD score (hazard ratio [HR] 1.201, P=.017), MELD-Na score (HR 1.244, P=.014), CPT score (HR 1.468, P=.033), and INR (HR 0.491, P=.027) were independently associated with death before listing. Among 68 listed candidates, 11 (16%) underwent transplantation, whereas 29 (43%) died without transplantation. Based on multivariate Cox regression analysis, MELD score (HR 1.102, P=.001), MELD-Na score (HR 1.128, P=.001), and CPT score (HR 1.282, P=.038) independently predicted wait-list mortality. All 11 patients who underwent cadaveric liver transplantation were alive at 29 months (range, 1-55) after transplantation. CONCLUSIONS: Patients with a higher MELD, higher MELD-Na, and higher CPT score at referral were at greater risk for death without transplantation, especially before listing. Evaluation for transplantation candidacy is a time-consuming process. Therefore, earlier referral is mandatory to achieve successful listing for transplantation.

Resection of the second portion of the duodenum sacrificing the minor papilla but preserving the pancreas for a recurrent duodenal adenocarcinoma: report of a case.

Duodenal adenocarcinoma is a relatively rare malignancy and pancreaticoduodenectomy would be a standard procedure to achieve curative resection. We report a case of resection of the 2nd portion of the duodenum with nodal dissection preserving the pancreas. The patient was a 75-year-old man with right-sided paresis suffering from early cancer in the 2nd portion of the duodenum. Despite 3 times of endoscopic mucosal resections, mucosal local recurrence was found. The depth of the tumour involvement continued to be limited within the mucosal layer. We performed segmental duodenal resection with nodal dissection sacrificing the minor papilla, while preserving the pancreas and the major papilla. The pathological diagnosis was primary intramucosal adenocarcinoma; the surgical margin was negative for cancer and there was no nodal metastasis. This procedure can be an alternative to pancreaticoduodenectomy in patients with earlystage adenocarcinoma in the 2nd portion of the duodenum when the major papilla can be spared, especially in high-risk patients.

Thrombotic microangiopathy after living-donor liver transplantation.

Thrombotic microangiopathy (TMA) is an infrequent but severe life-threatening disorder in solid organ transplant recipients. Few studies of TMA in living donor liver transplant (LDLT) recipients, however, have been reported. We investigated the clinical characteristics and prognostic factors of TMA after LDLT. Among 393 adult LDLT recipients, 30 patients (7.6%) were identified to have TMA. The 1-, 3- and 5-year survival rates of these patients were lower (60.6%, 52.5% and 47.7%, respectively) than those of patients without TMA (93.0%, 89.0% and 87.3%, respectively). Multivariate analysis confirmed that reduced administration of fresh frozen plasma and sensitization against HLA are closely related with TMA (odds ratio [OR]: 2.6 and 16.1, respectively). However, a review of the cases revealed that individual responses to treatment varied considerably and the main etiologies were difficult to determine. A comparison of the clinical factors suggested that late onset (>30 days), poor response to treatment and delayed diagnosis and/or treatment are associated with a poor outcome. Because the prevention of TMA in LDLT patients is difficult, early diagnosis and initiation of intensive therapies may be crucial to improve the prognosis.

Once-daily tacrolimus in living donor liver transplant recipients.

Once-daily tacrolimus (denoted here simply as OD) is a recently developed extended release drug formulation. The purpose of the present study was to pharmacokinetically evaluate tacrolimus exposure and determine the feasibility of its de novo use in liver transplant recipients in the perioperative period. This was an open-label, single center study. Eligible patients were 18 to 65 years of age in the perioperative period after a liver transplant. Patients were initially treated with intravenous tacrolimus and then converted to the 10× milligram-for-milligram daily dose of OD administered once daily. Twenty-four hour pharmacokinetic profiles were obtained on day 7 after the conversion. Laboratory and safety parameters were also evaluated. A total of 9 patients received OD, were successfully converted, and provided pharmacokinetic profiles. Intravenous tacrolimus and OD resulted in similar areas under the curve for 24 h (AUC0-24) of tacrolimus. OD was well tolerated with a safety profile comparable to that of intravenous tacrolimus. The AUC0-24 correlated with the minimum concentration of OD (R = 0.49). Renal and liver functions remained stable. None of the patients experienced acute rejection during the observation period. OD and intravenous tacrolimus provide equivalent drug exposure, allowing conversion of selected liver transplant recipients from intravenous tacrolimus to OD in the peri-operative period.

Fusion product diagnostics planned for Large Helical Device deuterium experiment.

Deuterium experiment on the Large Helical Device (LHD) is now being planned at the National Institute for Fusion Science. The fusion product diagnostics systems currently considered for installation on LHD are described in this paper. The systems will include a time-resolved neutron yield monitor based on neutron gas counters, a time-integrated neutron yield monitor based on activation techniques, a multicollimator scintillation detector array for diagnosing spatial distribution of neutron emission rate, 2.5 MeV neutron spectrometer, 14 MeV neutron counter, and prompt γ-ray diagnostics.

Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy.

BACKGROUND: Although intraoperative cholangiography has been recommended for avoiding bile duct injury during laparoscopic cholecystectomy, radiographic cholangiography is time consuming and may itself cause injury to the bile duct. Recently, a novel fluorescent cholangiography technique using the intravenous injection of indocyanine green (ICG) has been developed. METHODS: In 52 patients undergoing laparoscopic cholecystectomy, 2.5 mg ICG was injected intravenously 30 min before the patient entered the operating room or following intubation. A fluorescent imaging system, which consisted of a xenon light source and a laparoscope with a charge-coupled device camera that could filter out light wavelengths below 810 nm, was used. Fluorescent cholangiography was performed during dissection of Calot's triangle, and its ability to delineate biliary anatomy was compared with that of preoperative cholangiography. RESULTS: Fluorescent cholangiography delineated the cystic duct in all 52 patients, and the cystic duct-common hepatic duct junction was visible before dissection of Calot's triangle in 50 patients. Fluorescent imaging also identified all accessory bile ducts that had been diagnosed before surgery in eight patients. CONCLUSION: Fluorescent cholangiography enables real-time identification of biliary anatomy during dissection of Calot's triangle. This simple technique may become standard practice for avoiding bile duct injury during laparoscopic cholecystectomy, replacing radiographic cholangiography.

Effect of annealing temperature on the structure and mechanical properties of mechanically alloyed AlMg-Nb2O5 and AlMg-ZrSi2 composites.

Mechanical alloying and hot extrusion method were used for manufacturing AlMg-based composites reinforced with addition of niobium oxide (Nb(2)O(5)) and zirconium silicide (ZrSi(2)) particles. High mechanical properties of the materials were found to result from heavily refined structure of composites. It was found that the composite structure was transformed at high temperature as a result of irreversible chemical reaction between disperse reinforcements and surrounding matrix. Chemical reaction for AlMg-Nb(2)O(5) composite results in a growth of intermetallic grains of Al(3)Nb type and very fine oxides particles of 5-20 nm in diameter. In the annealed AlMg-ZrSi(2) composite, new grains of Al(3)Zr, Mg(2)Si and Al(Mg)O are formed as a result of zirconium silicide decomposition. Hot compression tests were performed at constant true strain rate of 5.10(-3) s(-1) within the temperature range of 293-823 K. The high flow stress values are attributed to highly refined structure of the materials that essentially did not coarsen in spite of high deformation temperature.

Microstructure and mechanical properties of AA7039+20%SiC W composite.

Hot deformation tests were performed on an AA7039-matrix composite reinforced with a 20% addition of SiC whiskers. The flow stress maximum was reduced with deformation temperature from 640 MPa to approximately 8 MPa at 293 K and 823 K, respectively. TEM observations, performed on as deformed samples, revealed a highly recovered substructure of the matrix and a striated structure of the whiskers. The fringes, which are perpendicular to the whiskers' longitudinal axis, were ascribed to nano-sized twins and stacking faults formed during the crystal growth rather than to some effects of the deformation process.

Risk of parasitic worm infection from eating raw fish in Hawai'i: a physician's survey.

Public health concerns have been raised over the risk of parasitic helminth (roundworm, tapeworm and fluke) infections from eating raw fish, an increasing US consumer trend. Hawai'i consumers eat seafood at nearly 3 times the US national average rate, with a long tradition and high level of raw fish consumption. The local fish species commonly eaten raw in Hawai'i include tuna (bigeye, yellowfin, albacore and skipjack), marlin (blue and striped) and deepwater snappers (long-tailedred, pink and blue green). Forty-eight Hawai'i-based physicians (gastroenterologists, internists, general and family practitioners) were surveyed to count known cases of parasitic worm infection linked to raw fish consumption and to explore physicians' perceptions of risk associated with the consumption of fresh, never frozen local fish with an emphasis on raw tuna and skipjack. No single known case of helminth infection due to consumption of raw tuna or skipjack, or other local fish species caught in Hawai'i was reported. The majority of the physicians surveyed reported that they eat raw yellowfin and bigeye tuna, also eat raw skipjack and do not think that these fish present a significant health risk of helminthic parasites. The survey results support the conclusion that the risk of parasitic helminth infection from the consumption of Hawai'i-caught tuna, skipjack, marlin and deepwater snappers is negligible.