Diffusion weighted imaging combining respiratory triggering and navigator echo tracking in the upper abdomen.

OBJECTIVES: To evaluate a new motion correction method, named RT + NV Track, for upper abdominal DWI that combines the respiratory triggering (RT) method using a respiration sensor and the Navigator Track (NV Track) method using navigator echoes. MATERIALS AND METHODS: To evaluate image quality acquired upper abdominal DWI and ADC images with RT, NV, and RT + NV Track in 10 healthy volunteers and 35 patients, signal-to-noise efficiency (SNRefficiency) and the coefficient of variation (CV) of ADC values were measured. Five radiologists independently performed qualitative image-analysis assessments. RESULTS: RT + NV Track showed significantly higher SNRefficiency than RT and NV (14.01 ± 4.86 vs 12.05 ± 4.65, 10.05 ± 3.18; p < 0.001, p < 0.001). RT + NV Track was superior to RT and equal or better quality than NV in CV and visual evaluation of ADC values (0.033 ± 0.018 vs 0.080 ± 0.042, 0.057 ± 0.034; p < 0.001, p < 0.001). RT + NV Track tends to acquire only expiratory data rather than NV, even in patients with relatively rapid breathing, and can correct for respiratory depth variations, a weakness of RT, thus minimizing image quality degradation. CONCLUSION: The RT + NV Track method is an efficient imaging method that combines the advantages of both RT and NV methods in upper abdominal DWI, providing stably good images in a short scan time.

PIVKA­II is associated with liver function, bone metabolism, and muscle function in patients with liver disease.

Protein induced by vitamin K (VK) absence-II (PIVKA-II) is a sensitive marker for diagnosing hepatoma but is occasionally detected in patients without hepatoma Here, the clinical significance of serum PIVKA-II levels in patients who were not administered warfarin and did not have hepatoma or liver disease were evaluated. As VK is related to muscle and bone metabolism, PIVKA-II and clinical factors related to bone and muscle were compared. A total of 441 patients with various liver diseases were evaluated. Of these, 236 patients were female. Clinical factors and anthropometric measurements were obtained for each participant during outpatient visits. Among the clinical factors, type I procollagen N-propeptide (P1NP), a low titer of undercarboxylated osteocalcin (ucOC), and 25(OH) vitamin D (VD) were used as bone metabolic markers, and SARC-F and grip strength were used as muscle-related markers. Serum PIVKA-II levels above the upper limit were associated with Child B/C (Child-Pugh score), high titers of total P1NP, and low titers of ucOC in females, and alcohol-related liver disease and low VD in males. The titer of PIVKA-II were associated with immunoglobulin (Ig) A and prothrombin time (PT)-international normalized ratio (INR) in females, and fibrosis-4-4, IgG, total bilirubin, PT-INR, and SARC-F in males. Elevated PIVKA-II levels were associated with abnormal bone physiology in females, weak muscles in males, and severe liver disease in both sexes. Assessing PIVKA-II may assist in evaluating the clinical and bone-muscle metabolic stages in liver disease. Nutrition and supplementation with fat-soluble vitamins, including VK and VD may thus serve as a potential method to alleviate or prevent bone-muscle pathophysiology in patients with liver disease.

Direct­acting antiviral treatment decreases serum undercarboxylated osteocalcin in male patients with chronic hepatitis C.

Hepatic osteodystrophy (HOD) is a common complication of chronic liver disease, including viral hepatitis. Hepatitis C virus (HCV) infection is associated with an increased risk of osteoporosis and bone mineral density (BMD) loss. Direct-acting antiviral (DAA) treatment is used to treat HCV infections; however, its effects on bone metabolism have not been reported. We compared the clinical data and bone metabolic markers at the start of DAA treatment and 1 year later in 78 patients. There were 41 female and 37 male patients. HCV was successfully treated with DAA in all patients. Bone metabolic markers included undercarboxylated osteocalcin (ucOC), 25(OH) vitamin D (VD), total type I procollagen N-propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and BMD. BMD was measured in the lumbar spine (mean, L2-L4) and femoral neck using dual-energy X-ray absorptiometry. ucOC in males decreased at 1 year after treatment initiation but not in females. In males, ucOC changes were related to alterations in proteins induced by vitamin K absence-II (PIVKA-II), hemoglobin A1c, and TRACP-5b, which contributed to P1NP and lumbar BMD at the start of DAA. Changes in ucOC among women contributed to the changes in grip strength and TRACP-5b levels. DAA treatment improved ucOC, a useful bone metabolic marker, in HCV-infected male patients. Changes in ucOC contributed to changes in PIVKA-II that likely ameliorated the vitamin K deficiency. DAA treatment has been reported to improve various extrahepatic disorders and abnormal bone metabolism, especially in HOD.

Change in tartrate-resistant acid phosphatase isoform 5b levels, a marker of bone metabolism, in patients with chronic hepatitis B treated with tenofovir alafenamide.

Hepatitis B virus (HBV) infection is associated with the risk of osteoporosis and bone mineral density (BMD) loss. Tenofovir alafenamide (TAF) is associated with a slightly lower degree of BMD loss compared with tenofovir disoproxil, without loss of the excellent anti-HBV effects. The aim of the present study was to verify the effect of bone metabolism in patients with HBV treated with TAF. A total of 87 patients were treated with TAF. Of these, 32 patients were treatment naïve, and 55 patients were treated with entecavir (ETV) for at least 1 year, after which ETV was switched to TAF. At the start of TAF and after 1 year, BMD in the lumbar and neck of the femur, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) levels as a marker of bone metabolism and serum inorganic phosphorus (P) were compared to estimate bone metabolism. Serum creatinine (Cr), cystatin C, urine protein and ß2 microglobulin levels were evaluated to estimate kidney function. Treatment with TAF for 1 year decreased TRACP-5b levels, particularly in patients with bone disease, except for a minimal significant change (MSC; decrease of 12.4%) in TRACP-5b levels. The change in rate of TRACP-5b levels were positively associated with changes in P, Cr-estimated glomerular filtration rate and TRACP-5b levels at the start of TAF. Logistic regression analysis showed that increased BMD in the lumbar region contributed to the switch from ETV to TAF. TAF induced a decrease in TRACP-5b levels in patients with HBV. Bone disease was a contributing factor for MSC. Since TRACP-5b can be used as a marker of bone metabolism and fractures, TAF may exhibit potential in preventing fractures in patients with HBV.

Comparison of calculated body muscle mass and SARC-F as methods of screening for sarcopenia in patients with chronic liver disease.

A simple method is required to screen for sarcopenia in patients with chronic liver disease. In the present study, the value of the existing SARC-F questionnaire as well as calculated body muscle mass (CBMM) approaches were assessed for screening of sarcopenia. A total of 482 patients with chronic liver disease underwent CBMM, grip strength (GS) and SARC-F score assessments. Cross-sectional computed tomography images of the third lumbar vertebrae were analyzed to determine the skeletal muscle (SM) mass in 303 patients. Cutoff CBMM values for sarcopenia were <27.903 in females and <39.731 in males. The cutoff SARC-F score for sarcopenia was ≥4 points. Sarcopenia was diagnosed using the criteria described in the Japan Society of Hepatology. GS was moderately correlated with SARC-F score (females, R=-0.578; males, -0.453) and CBMM (females, R=0.497; males, 0.548). The SM index was moderately correlated with CBMM for both sexes (females, R=0.546; males, 0.612), but not with SARC-F score in females (females, R=-0.132; males, -0.246). The area under the curve (AUC) for CBMM against sarcopenia (0.85964) was significantly larger than that for SARC-F score (0.72013) amongst males (P=0.03577) but not females. The AUCs for a modified SARC-F questionnaire (encompassing the SARC-F questionnaire, CBMM, sex and age; mSARC-F) against sarcopenia were 0.864 in males and 0.78185 in females. As a screening method, SARC-F is less useful than CBMM. However, the AUC for mSARC-F is greater than SARC-F and CBMM.

Treatment of Hepatitis C Virus Infection with Direct-acting Antiviral Agents Elevates the Serum Small-dense Low-density Lipoprotein Cholesterol Level.

Objective The low-density lipoprotein cholesterol (LDL) level is known to increase following the treatment of hepatitis C virus (HCV) infection using direct-acting antiviral agents (DAAs). This study aimed to investigate the changes in the lipid profiles, including small-dense LDL cholesterol (sdLDL), in HCV patients treated with DAAs. Patients We retrospectively assessed 67 HCV patients who achieved sustained virological response with DAA administration and were observed for more than 2 years, of whom 32 were on daclatasvir/asunaprevir, 14 were on sofosbuvir/ledipasvir, and 21 were on sofosbuvir/ribavirin. Methods We evaluated the lipid profiles, including sdLDL, every 6 months until 2 years after the start of treatment and analyzed the factors related to changes in the sdLDL level. Results The median sdLDL value at baseline was 12.8 mg/dL, which increased to 19.5 mg/dL at 6 months (p<0.001) and remained elevated at 25.4 mg/dL at 2 years later (p<0.001). The Kaplan-Meier curve indicated that patients with high values of LDL, albumin, muscle attenuation and visceral to subcutaneous adipose tissue area ratio were at increased risk for elevation of sdLDL over 35 mg/dL (log-rank test: p<0.001; p=0.008, p=0.002 and p=0.042, respectively). A multivariate analysis performed on the factors contributing to elevation of sdLDL 2 years after DAA treatment (≥35.0 mg/dL) revealed pretreatment LDL (≥91.0 mg/dL) and muscle attenuation (≥33.7 HU) as significant factors (p=0.007 and p=0.032, respectively). Conclusion SdLDL increased continuously after DAA treatment, and high LDL levels and low intramuscular fat deposition before treatment contributed to elevated sdLDL levels after treatment.

Direct-acting Antivirals Improved the Quality of Life, Ameliorated Disease-related Symptoms, and Augmented Muscle Volume Three Years Later in Patients with Hepatitis C Virus.

Objective Patient-reported outcomes (PROs) are important measures of the quality of life (QOL) and symptoms in patients with hepatitis C virus (HCV). We evaluated the PROs at the beginning of direct-acting antiviral (DAA) treatment and three years later. A low QOL in patients with chronic liver disease suggested a low muscle mass. We compared the relationship between the QOL and muscle mass. Methods DAAs were administered to 100 patients with HCV infection. The PROs included the cirrhosis-related symptom score (CSS), presence of restless legs syndrome, Pittsburg sleep quality index (PSQI) to evaluate sleep disturbance, SF-36 to measure the QOL, and calculated body muscle mass (CBMM) measured at the beginning of treatment and three years later. Computed tomography (CT) was used to screen 82 patients for hepatocellular carcinoma at the beginning of treatment and three years later. Cross-sectional CT images of the third lumbar vertebrae were analyzed to evaluate the body composition. Results The general health perception (GHN) of SF-36 was better at three years after DAA administration than at the beginning. Changes in the GHN (dGHN) were related to an improved sleep quality on the PSQI and CSS and increased CBMM. The dGHN was positively related to changes in the skeletal muscle. The sleep quality, sleep latency, fatigue, and abdominal fullness were related to dGHN. Conclusion The QOL is related to sleep disturbance and several other symptoms. Furthermore, in patients with an increased muscle volume after DAA treatment, increased muscle mass is associated with an improvement in the QOL.

[Elements that cancer peer supporters working in Japanese hospitals consider to be important in helping them perform their role].

Objectives　The purpose of this study was to identify elements that cancer peer supporters working in Japanese hospitals consider to be important in helping them perform their role.Methods　A qualitative inductive research was conducted. Introductions to potential participants were obtained from a patient association that agreed to help with the study. Interviews were conducted from July through October 2014, using an interview guide, with cancer peer supporters who consented to participate in the study. Elements they perceived as important to the performance of their role were inductively identified from interview transcripts. The analysis consisted of coding phrases in the text and organizing the codes generated into categories and subcategories.Results　The study participants consisted of 10 cancer peer supporters (2 men, 8 women), in the age range of 40 to 70 years, who provided private counseling and worked in cancer support groups in hospitals. The analysis generated 129 codes, 11 subcategories, and 5 categories. These 5 categories were: [1.Help service users determine their own paths by listening to and accepting what they say with a non-judgmental attitude]; [2.Offer a perspective distinct from that of the medical staff]; [3.Think of ways to achieve a good balance between one's personal life and cancer peer support work while maintaining a stable state of mind]; [4.Ensure that one maintains the necessary knowledge and skills, and continually improve oneself]; and [5.Build relationships of trust with medical staff and the hospital].Conclusion　Category [1] and category [2] were behaviors regarded as important when interacting with users. They were "matters regarded as important during the practice of cancer peer support working for users," and comprised the core of matters that were regarded as important. Next, as for matters regarded as important in relation to the supporters themselves, the categories were [3] and [4]. These were "matters regarded as important for continuity and qualitative improvement of cancer peer support working." Areas that call for improvement in relation to this are preparation of support systems and learning environments. Another matter regarded as important was category [5]. This was a "matter regarded as important to smoothen and facilitate cancer peer support working." Placing importance on relationships of trust with medical staff and hospitals could be considered a distinctive characteristic of cancer peer supporters working at hospitals.

Surgical treatment of Bochodalek hernia incarcerated into the extra-pleural space: A rare case report.

INTRODUCTION: Bochdalek hernias are a type of diaphragm hernia. Almost all occur in the neonatal period, only 5% of these hernias occurring in adults. We here present a rare case of adult Bochdalek hernia incarcerated in the extra-pleural space. PRESENTATION OF CASE: An asymptomatic 51-year-old man was admitted to our hospital for a detailed examination after an abnormality had been detected on a chest radiograph. Chest computed tomography (CT) examination revealed findings consistent with a left Bochdalek hernia, which we repaied surgically. Intraoperatively, retroperitoneal fatty tissue was found to be incarcerated in the extra-pleural space. Thus, surgical repair required dissection of the parietal pleura and excision of the incarcerated fatty tissues. DISCUSSION: The incarceration of the Bochdalek hernia in the extra-pleural space could not be identified on a preoperative chest CT examination. To the best of our knowledge, no reports of incarceration of a Bochdalek hernia in the extra-pleural space have been published; thus, this phenomenon is extremely rare. CONCLUSION: Surgical treatment of a Bochdalek hernia incarcerated in the extra-pleural space requires dissection of the parietal pleura and repair via a transthoracic approach.

Indices calculated by serum creatinine and cystatin C as predictors of liver damage, muscle strength and sarcopenia in liver disease.

Serum creatinine (Cr)-based glomerular filtration rate (CrGFR) is overestimated in liver disease. The present study evaluated whether the difference in CrGFR and cystatin C (CysC) GFR (dGFR) is significant in liver disease. The Cr-to-CysC ratio and sarcopenia index (SI) have been reported to correlate with muscle volume. An estimated total body muscle mass with Cr, CysC and calculated body muscle mass (CBMM) has also been reported to correlate with muscle mass. The applicability of dGFR, SI and CBMM for liver disease were evaluated. A total of 313 patients with liver damage were evaluated for Child-Pugh score, albumin-bilirubin (ALBI) score, model for end-stage liver disease, fibrosis-4, Cr, CysC, Cr-based estimated GFR (CreGFR), CysCGFR and grip strength. Of the 313 patients, 199 were evaluated using cross-sectional computed tomography (CT) of the third lumbar vertebra to determine the skeletal muscle (SM) mass. dGFR, CBMM and SI were compared to liver damage, muscle strength and muscle mass. In the 313 patients, dGFR was correlated with age, ALBI and grip strength; CBMM was correlated with body mass index (BMI) and grip strength; and SI was correlated with BMI and grip strength. In patients evaluated with CT, the correlation coefficients for CBMM and SI with SM were 0.804 and 0.293, respectively. Thus, CBMM and SI were associated with sarcopenia. The relationship between dGFR and ALBI does not differ with different grades of CrGFR-based chronic kidney disease (CKD). dGFR is a marker of liver damage and muscle strength regardless of CKD. CBMM and SI are markers for sarcopenia in liver disease.

Calculated body muscle mass as a useful screening marker for low skeletal muscle mass and sarcopenia in chronic liver disease.

AIM: Sarcopenia is a harmful condition in patients with chronic liver disease. However, the evaluation of body muscle mass requires expensive instrumentation. The sarcopenia index (SI): (creatinine / cystatin C × 100) has been reported to correlate with muscle volume. A calculated body muscle mass (CBMM) using creatinine, cystatin C, and bodyweight also correlates with muscle mass. We evaluated the applicability of using SIs and CBMMs as screening methods for sarcopenia. METHODS: Patients (n = 303) with liver damage were evaluated for creatinine, cystatin C, and grip strength (GS). All patients were evaluated using cross-sectional computed tomography images of the third lumbar vertebrae to determine their skeletal muscle (SM) mass. CBMMs and SIs were compared with SMs, GSs, and sarcopenia. RESULTS: Correlation coefficients (R) between SMI (SM / height2 [m2 ]) and CBMM, and between GS and CBMM were 0.643 and 0.723, respectively. Factors contributing to low GSs; low SM indices; and sarcopenia were age and SM; sex, age, GS, SI, and CBMM indices; and sex, bodyweight, and CBMM, respectively, in the multivariate logistic analyses. Receiver operating characteristic curve analysis between sarcopenia and CBMM showed an area under the receiver operating characteristic curve of 0.78504 in women and 0.86067 in men. Cut-off CBMM values for sarcopenia were 27.903 (sensitivity 0.73958) in women and 39.731 (sensitivity 0.7941) in men. CONCLUSIONS: CBMMs and SIs are simple and minimally invasive screening methods in which low levels are indicative of sarcopenia in patients with liver disease.

In vitro and in vivo fabrication of stable human hepatocyte tissue in combination with normal fibroblasts derived from donors of various ages.

In order to establish a minimally invasive and safe liver regenerative technology, a technique for fabricating liver tissue possessing a vascular network was developed by subcutaneously transplanting a cell sheet composed of primary human hepatocytes and normal fibroblasts. However, differences in fibroblast characteristics owing to donor age may threaten the stability of liver tissue regenerated via this technology. Herein we describe the influence of fibroblasts from multiple donors on the fabrication of engineered human hepatocyte tissues invitro and in vivo. Primary human hepatocytes were cultured with seven strains of fibroblasts derived from the skins of donors of various ages, ranging from a fetus (12 weeks) to the elderly (69 years). Engineered hepatocyte sheets were successfully harvested for all strains. At 2 weeks after the subcutaneous transplantation of the hepatocyte sheets into mice, the highest human albumin (hALB) serum concentration was noted in the mouse containing fibroblasts from a 12 year old (TIG-118). Since the platelet-derived growth factor subunit B (PDGFB) gene expression of TIG-118 cells was significantly higher than that in the other cells, PDGFB may be considered to play an important role in the initial subcutaneous engraftment of primary human hepatocytes. Even though hALB concentration exhibited a parabolic tendency with age, there was no statistically significant difference noted within 6-8 weeks after transplantation. The present study demonstrates that this technology can produce consistent and stable hepatocyte sheets that exhibit long-term survival and liver-specific functionality in vivo regardless of the fibroblast donor age.

The relationship between serum indoxyl sulfate and the renal function after catheter ablation of atrial fibrillation in patients with mild renal dysfunction.

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces renal disorders and atrial fibrillation (AF). It is well known that renal dysfunction is a risk factor for AF and radiofrequency catheter ablation (RFCA) improves the renal function. However, the improvement in the renal function after RFCA in patients with early stage chronic kidney disease (CKD) and the serial changes in the IS level have not been fully elucidated. This study aimed to investigate whether IS affects the improvement in the renal function. A total of 91 consecutive patients with mild kidney dysfunction (CKD stage I-II) who underwent RFCA and maintained sinus rhythm were prospectively enrolled. The plasma IS level and estimated glomerular filtration rate (eGFR) were determined before, 3 months, and 1 year after RFCA. The patients were divided according to the IS quartiles (Q1-4; < 0.4, 0.4-0.7, 0.7-1.2, and > 1.2 µg/ml). There was no significant difference in the eGFR among the IS quartiles. A significantly higher eGFR improvement rate was obtained for IS-Q4 than the other quartiles (p = 0.039). The IS-Q4 IS level significantly decreased at 1 year after RFCA (1.8 ± 0.8 to 1.2 ± 0.7 µg/ml, p < 0.01). The multivariable logistic model revealed that a high-IS level (IS-Q4) was an independent predictor of an eGFR improvement (OR 3.33; 95% CI 1.16-9.59; p = 0.026). A high-IS level reduction after RFCA improved the renal function in AF patients with mild kidney dysfunction.

Time-dependent structural and functional characterization of subcutaneous human liver tissue.

Subcutaneous transplantation of engineered hepatocyte/fibroblast sheets (EHFSs) is a low invasive and safe approach to construct vascularized subcutaneous human liver tissue (VSLT). However, the liver-specific structures and functionalities in the development process of VSLTs in mice remain poorly understood. Here, we describe time-dependent characteristics of the formation of the vascular network, cell-cell adhesions, liver transporters, liver-specific protein synthesis, and metabolizing activities. The EHFSs formed multilayered thick tissues by rapid neovascularization, which allows overcoming extremely difficult problems, such as the lack of oxygen supply on the formation of three-dimensional primary hepatocyte tissue under the skin. The blood vessels consisted of mouse-origin endothelial cells (ECs) (mVEGFR2) from the subcutaneous space at 1-7 days, and the following formation of the vascular network was performed by human-origin ECs (hVEGFR2). Many varieties of liver-specific gene expressions increased with the construction of the VSLTs: cell-cell adhesion molecules (CDH1, CLDN3, and CX32), transporters at basal (OATP1A1, OCT1, and NTCP) and apical membranes (MRP2, MDR1, and BSEP), blood coagulation factors (F8 and F9), urea synthesis (CPS1, OTC, and ARG1), and metabolism enzymes (CYP7A1, CYP1A2, CYP2B6, CYP3A4, and UGT1A1). Subacute hepatic failure model mice with VSLT were alive at least 7 weeks after liver damage. Thus, the ectopic liver organ offers the potential for a low invasive and safe treatment for liver diseases.

Controlled cell morphology and liver-specific function of engineered primary hepatocytes by fibroblast layer cell densities.

Engineered primary hepatocytes, including co-cultured hepatocyte sheets, are an attractive to basic scientific and clinical researchers because they maintain liver-specific functions, have reconstructed cell polarity, and have high transplantation efficiency. However, co-culture conditions regarding engineered primary hepatocytes were suboptimal in promoting these advantages. Here we report that the hepatocyte morphology and liver-specific function levels are controlled by the normal human diploid fibroblast (TIG-118 cell) layer cell density. Primary rat hepatocytes were plated onto TIG-118 cells, previously plated 3 days before at 1.04, 5.21, and 26.1×103 cells/cm2. Hepatocytes plated onto lower TIG-118 cell densities expanded better during the early culture period. The hepatocytes gathered as colonies and only exhibited small adhesion areas because of the pushing force from proliferating TIG-118 cells. The smaller areas of each hepatocyte result in the development of bile canaliculi. The highest density of TIG-118 cells downregulated albumin synthesis activity of hepatocytes. The hepatocytes may have undergone apoptosis associated with high TGF-ß1 concentration and necrosis due to a lack of oxygen. These occurrences were supported by apoptotic chromatin condensation and high expression of both proteins HIF-1a and HIF-1b. Three types of engineered hepatocyte/fibroblast sheets comprising different TIG-118 cell densities were harvested after 4 days of hepatocyte culture and showed a complete cell sheet format without any holes. Hepatocyte morphology and liver-specific function levels are controlled by TIG-118 cell density, which helps to design better engineered hepatocytes for future applications such as in vitro cell-based assays and transplantable hepatocyte tissues.

Bleeding with oral anticoagulant dabigatran is highly associated with occult cancers in atrial fibrillation patients.

AIM: The aim of this study was to examine cancer and bleeding in atrial fibrillation patients administered with dabigatran. MATERIALS & METHODS: This study enrolled 509 consecutive nonvalvular atrial fibrillation patients who received dabigatran. The mean administration period was 14.8 ± 15.7 months. We investigated the prevalence and new development of cancers. Further, the relation between cancer and adverse events was evaluated. RESULTS: In the 509 patients, major bleeding occurred in 2.6% and dyspepsia in 8.4%. Further, 16.9% patients had a history of cancer and 3.9% developed new cancers. These adverse events developed in 45% patients who developed new cancers. The cancer (hazard ratio: 6.30; p = 0.003) was a significant predictor of major bleeding. CONCLUSION: Bleeding was associated with the presence of cancer.

A rare anomaly of the right superior pulmonary vein: Report of a case.

INTRODUCTION: Although there are a lot of variations of pulmonary veins (PVs) including dangerous type that could cause serous complications during the surgery, limited information has been reported about these variations. We have experienced an extremely rare anomaly of the right superior PV. PRESENTATION OF CASE: A 74-year-old man patient with right lung cancer visited our hospital. Chest computed tomography (CT) revealed a pulmonary nodule in the right lower lobe. Contrast-enhanced three-dimensional CT (3D-CT) showed that the right superior PV ran abnormally between the right main pulmonary artery (PA) and the right main bronchus. We performed right lower lobectomy and systematic nodal dissection. The operative findings confirmed that the right superior PV ran abnormally same as 3D-CT. DISCUSSION: In most reported cases, anomalous PVs pass behind the right bronchi or into the roof of the left atrium. The anomaly reported in the present case has been reported in only one case report. This case suggests that the space between the right main PA and the right main bronchus is not always safe for dissection. CONCLUSION: Preoperative 3D-CT is useful for avoiding unexpected bleeding.

Assessment of drug-induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias.

BACKGROUND: Pilsicainide, a pure Na+ channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters. RESULTS: Among the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1 vs. 68.4±22.1 mL/min, p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61-335.0, p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6 vs. 430.7±32.6 ms, p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments. CONCLUSIONS: DIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.

Obesity Is Associated With the Development of Interstitial Pneumonia Under Long-Term Administration of Amiodarone in Refractory Atrial Fibrillation Patients.

Although oral amiodarone (AMD) has been used for the management of atrial fibrillation (AF), serious complications such as interstitial pneumonia (IP) occur very occasionally. We evaluated which factors were associated with the development of IP under the long-term administration of AMD in patients with refractory AF.This study included 122 consecutive patients (65.8 ± 11.4 years, mean body mass index [BMI] of 23.2 ± 4.3 kg/m(2)) who orally received AMD to inhibit AF between January 2004 and December 2013. Administration of AMD was begun at 400 mg daily as a loading dose, and was continued at a dosage of 50-400 mg daily after the initial loading phase, determined by the control of the arrhythmias and occurrence of side-effects. The clinical factors were compared between the patients with and without adverse effects, especially IP.During an average follow-up period of 49.2 ± 28.2 months, 53 patients (43.4%) were determined to have converted and maintained sinus rhythm. In contrast, adverse effects were detected in 46 patients (37.7%) with AMD. IP occurred in 8 patients (6.6%), thyrotoxicosis in 35 (28.7%), and others in 5 (4.1%). Four (50.0%) out of 8 patients complicated with IP had obesity (BMI > 27 kg/m(2)). Among the clinical factors, only obesity was significantly associated with the development of IP (P = 0.026).In patients with refractory AF, AMD had an antiarrhythmic effect with long-term administration, but greater adverse effects were also observed. Obesity was the most significant factor associated with the development of IP.

Efficacy of Multilayered Hepatocyte Sheet Transplantation for Radiation-Induced Liver Damage and Partial Hepatectomy in a Rat Model.

Although cell sheet technology has recently been developed for use in both animal experiments and in the clinical setting, it remains unclear whether transplanted hepatocyte sheets improve the liver function in vivo. Radiation-induced liver damage (RILD) combined with partial hepatectomy (PH) has been reported to suppress the proliferation of host hepatocytes and induce critical liver failure. The aim of this study was to improve the liver function in the above-mentioned diseased rat model (RILD + PH) using multilayered hepatocyte sheet transplantation. In this study, we used Fischer rats as a donor for primary hepatocytes and dermal fibroblast isolation. Cocultured multilayered hepatocyte sheets were generated by disseminating hepatocytes onto fibroblasts cultured beforehand on temperature-responsive culture dishes. Four cell sheets were transplanted into the recipient rats subcutaneously. Prior to transplantation, RILD (50 Gy) with 2/3PH was induced in the recipients. The same model was applied in the control group without transplantation. The serum was collected each week. The rats in both groups were sacrificed at 2 months after transplantation for the histological analysis. Consequently, the serum albumin concentrations were significantly higher in the transplant group than in the control group (54.3 ± 9.6 vs. 32.7 ± 5.7 mg/ml; p < 0.01) after 2 months and comparable to the serum albumin levels in the normal rats (58.1 ± 6.4 mg/ml). In addition, treatment with the transplanted sheets significantly improved the survival rate (57% vs. 22%, p < 0.05), and the hepatocyte sheets showed the storage of albumin, glycogen, and bile canaliculus structures. Some hepatocytes and fibroblasts were positive for Ki-67, and vascularization was observed around the cell sheets. Transplanted multilayered hepatocyte sheets can survive with additional proliferative activity, thereby maintaining the liver function in vivo for at least 2 months, providing metabolic support for rats with RILD.