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Biliary atresia (BA) is among the commonest indications for liver transplantation (LT) in children. We examined whether serum matrix metalloproteinase-7 (MMP-7) is useful for diagnosis of BA in Japanese infants, and whether serum MMP-7 concentrations before and after Kasai portoenterostomy (KP) predicted LT within a year.Subjects under 6 months old at eight pediatric centers in Japan were enrolled retrospectively, including patients with cholestasis and normal controls (NC) without liver disease. Patients with cholestasis were divided into groups representing BA versus cholestasis from other causes (non-BA). Serum samples were collected from patients with BA at diagnosis and 1 and 4 weeks after KP, as well as from non-BA and NC.Serum MMP-7 concentrations were significantly higher in BA at diagnosis (median, 89.1 ng/ml) than in non-BA (11.0; p 0.001) or NC (10.3; p 0.001). Receiver operating characteristic (ROC) analysis of MMP-7 for BA versus non-BA yielded an area under the ROC curve of 0.99 (95% confidence interval, 0.96-1.00). An optimal cut-off value of 18.6 ng/ml for serum MMP-7 in diagnosing BA demonstrated sensitivity and specificity of 100% and 90%, respectively. Serum MMP-7 before and 1 week and 4 weeks after KP did not differ significantly between BA requiring only KP and BA requiring LT after KP.Serum MMP-7 is a useful marker for diagnosis of BA in Japanese infants, but it could not predict LT within a year.

Phosphodiesterase 5 inhibition (PDE5i) activates cGMP-dependent protein kinase (PKG) and ameliorates heart failure; however, its impact on cardiac mitochondrial regulation has not been fully determined. Here, we investigated the role of the mitochondrial regulator peroxisome proliferator-activated receptor γ co-activator-1α (PGC1α) in the PDE5i-conferred cardioprotection, utilizing PGC1α null mice. In PGC1α(+/+) hearts exposed to 7 weeks of pressure overload by transverse aortic constriction, chronic treatment with the PDE5 inhibitor sildenafil improved cardiac function and remodeling, with improved mitochondrial respiration and upregulation of PGC1α mRNA in the myocardium. By contrast, PDE5i-elicited benefits were abrogated in PGC1α(−/−) hearts. In cultured cardiomyocytes, PKG overexpression induced PGC1α, while inhibition of the transcription factor CREB abrogated the PGC1α induction. Together, these results suggest that the PKG–PGC1α axis plays a pivotal role in the therapeutic efficacy of PDE5i in heart failure.

BACKGROUND/PURPOSE The biliary atresia (BA) inflammatory process leads to various obstructive patterns of extrahepatic biliary trees. The significance of the various BA obstructive patterns is unclear. This study aimed to determine the relationship between the anatomical patterns of the biliary tract and short- and long-term prognoses in BA. METHODS Between 1989 and 2018, 3483 patients were registered in the Japanese Biliary Atresia Registry. For this study, we selected 2649 patients who underwent Kasai portoenterostomy (KP) between the ages of 31 and 90 days to eliminate the influence of age at KP as much as possible. RESULTS Regarding the main type, there were significant differences in the jaundice clearance rate (JCR; Type I: 67.9%, Type I-cyst: 79.4%, Type II: 74.5%, Type III: 60.9%; P

To determine the outcomes of patients with cystic biliary atresia by correlating the anatomy of the hepatic ducts with the choice of biliary reconstruction surgery.The Kasai hepatoportoenterostomy (Kasai) is the initial surgical procedure offered to most patients with biliary atresia. In contrast, a hepatic-cyst-jejunostomy has been reported to be effective in patients with the cystic form of biliary atresia.We performed an international multicenter retrospective review. Two hundred eighty-seven patients were included, and 33 cases of cystic biliary atresia were identified. Outcomes were the serum total bilirubin level 3 months post-surgery and native liver survival at 2 years of age and were compared between cases who received the Kasai versus hepatic-cyst-jejunostomy in correlation to the anatomy of proximal hepatic ducts. The patients were categorized into 3 anatomical groups: patent intact hepatic ducts (n = 10), patent hypoplastic hepatic ducts (n = 13), and obliterated hepatic ducts (n = 10). All 10 patients with patent intact hepatic duct group underwent hepatic-cyst-jejunostomy, and 9 experienced bile drainage and native liver survival. Among the 13 patients with hypoplastic hepatic ducts, 11 underwent the Kasai procedure, and 9 had bile drainage, whereas 2 underwent hepatic-cyst-jejunostomy, and one survived with the native liver. All of the patients with obliterated hepatic ducts underwent the Kasai procedure; 5 established biliary drainage and survived with the native liver. Of 5 who did not drain, 3 underwent liver transplantation.In patients with cystic biliary atresia, the subset with a connection between cyst and intrahepatic bile ducts via intact proximal hepatic ducts had favorable clinical outcomes following hepatic-cyst-jejunostomy.

[Background] Ovarian teratomas are the most common ovarian tumors in children. Fertility-sparing surgery (FSS) is often recommended owing to its advantage of fertility preservation. We examined the validity of FSS in pediatric patients with ovarian teratomas. [Procedure] We retrospectively reviewed the medical records of patients who underwent initial surgery for ovarian teratomas in our department between 1972–2021. Patients were divided into two groups: oophorectomy (OVX) group and FSS group. Clinical characteristics, perioperative characteristics, and outcomes were compared between the groups. [Results] Forty-six patients underwent initial surgery (OVX: 25 patients; FSS: 21 patients). There were no differences between the groups in terms of age, pathological diagnosis, affected side, ovarian torsion, postoperative complications, recurrence rate, or length of postoperative follow-up. Regarding pathological diagnosis, immature teratomas were found only in the OVX group (p = 0.0161). The tumor size was larger in the OVX group (p = 0.0104). Regarding perioperative findings, operation time was longer in the FSS group (p = 0.0071) and bleeding volume was higher in the OVX group (p = 0.0070). The number of days until the start of oral intake and the length of hospital stay postoperatively were shorter in the FSS group (p = 0.0002 and p < 0.0001, respectively). [Conclusion] We demonstrated the advantages of FSS, including its minimally invasive approach and comparable outcomes in terms of tumor recurrence; the operation time was longer. Since both FSS and OVX are associated with a risk of tumor recurrence, long-term follow-up in anticipation of adult transition is necessary.

Objective The burden of diabetic peripheral neuropathic pain (DPNP) is poorly understood. The present study reported on the current status of DPNP in Japan, to improve our understanding of this condition among healthcare providers and inform future clinical research on its prevalence, diagnosis, and management. Methods A cross-sectional, observational study (UMIN000037023) was conducted via a web-based survey. The primary endpoints were the frequency of patients with bilateral foot symptoms, consulting a doctor, understanding DPNP, and reporting problems in daily life, as well as the treatment awareness of patients. Patients Adults ≥20 years old who were registered in the Rakuten Insight Disease Panel and receiving anti-diabetic therapy in Japan were included. Results Bilateral foot pain symptoms were reported by 1,768/7,754 (22.8%) respondents, most commonly intense numbness (13.0%). Of those with symptoms, 55.3% consulted a doctor; the most common reason for not seeking consultation was feeling that symptoms were insufficiently severe to bother their doctor (89.4%). Nearly 60% reported understanding the causes of their symptoms, with diabetes-associated neurologic deficits (58.8%) most commonly identified. About one-quarter reported daily life problems, including an inability to walk for long periods (58.3%) and feeling anxious (58.1%). Treatment awareness was reported by 18.2%; oral medications were commonly recognized (64.6%). Conclusion In Japan, 22.8% of patients with diabetes have bilateral foot pain symptoms; some experience problems in their daily life without understanding the causes of their symptoms. This supports the importance of actions to increase awareness and minimize DPNP-associated impairment of daily life in patients with diabetes.

While learning opportunities dealing with communities have been increasing in Japan in recent years, learning itself has not been subjected to significant analysis. In this study, we converted into text data the reflection sheets of a total of 1,305 students who were enrolled in the community fieldwork course required for all first-year students at Miyagi University, a public university, from 2017 to 2019, and used quantitative text analysis to analyze the data. The results suggested that the students acquired knowledge that could not be obtained from pre-learning by visiting the communities, encountering locals, and interviewing local company personnel. In particular, those who visited tsunami-affected municipalities along the coast came into contact with the realities of tsunami damage and manifested discoveries with regard to the community’s activities before and after the disaster, such as the residents’ daily lives and industries.

Aims/Introduction The prevalence of clinical polyneuropathies (ClinPNs) or nerve conduction abnormality (NCA) in the groups stratified by glucose tolerance, individual components of metabolic syndrome (metabolic syndrome [MetS] components: hypertension, dyslipidemia, obesity) and MetS defined by the International Diabetes Federation consensus was investigated in the Japanese general population. Factors associated with ClinPN and NCA were also identified. Materials and Methods A total of 625 examinees of regional medical checkup programs were recruited to this cross‐sectional study. ClinPNs were diagnosed by the Toronto Consensus. NCA was judged by at least one bilateral abnormality of sural nerve action potential amplitude or conduction velocity measured by a point‐of‐care nerve conduction device (DPNCheck). Clinical factors associated with ClinPNs or NCA were examined by multiple logistic regression analysis. Deteriorating factors of sural nerve action potential amplitude or conduction velocity values were also investigated in participants without diabetes (n = 550). Results As for glucose tolerance, ClinPNs or NCA significantly increased only in known diabetes patients compared with other groups. There was no difference between prediabetes and the normal group. The prevalence of ClinPNs and NCA was not significantly related to MetS or MetS’ components, except for frequent NCA in obesity. The factors significantly associated with both NCA and ClinPNs were smoking and known diabetes. In non‐diabetic participants, aging, tall height and hypertension were significant deteriorating factors of nerve conduction functions. Conclusions In Japan, ClinPNs and NCA were increased in known diabetes patients, but did not increase in participants with prediabetes, MetS and MetS’ components. Smoking and known diabetes were factors significantly associated with ClinPNs or NCA. Hypertension might be a modifiable deteriorating factor of nerve function.

Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors that arise from chromaffin cells. We report the case of an 11-year-old boy with no history of hypertension who presented with an abdominal mass arising from the retroperitoneum. During laparoscopic surgery, the patient developed a hypertensive crisis with a peak systolic blood pressure of over 270 mmHg, although we were able to continue to perform laparoscopic resection. Even if no concomitant symptoms due to catecholamine production are observed before surgery, as in this case, blood pressure may fluctuate during surgery. Intraoperative and postoperative management should be considered in cooperation with anesthesiologists.

Background Members of the Japanese Biliary Atresia Society (JBAS) were surveyed using questionnaires that assess their current practice regarding postoperative pharmacotherapy for outpatients with biliary atresia (BA). Methods In September 2018, questionnaires were sent to 100 member institutions of the JBAS. Questionnaires included the number of BA outpatients per institution and pharmacotherapy for outpatients with native liver. Pharmacotherapies were categorized into antibiotics, cholagogues, hepatoprotective agents, branched-chain amino acid supplement, Japanese Kampo medicine, probiotics, laxative, glycerin enema, and "others." In each category, the questionnaires asked about the medicine's details and the time of withdrawal of administration. Results Responses were collected from 58 of the 100 institutions. Fifty-four institutions (94.7%) had prescribed one or more medicines as postoperative pharmacotherapy, and three institutions (5.3%) did not prescribe any medicines. Fifty-three institutions (93.0%) had prescribed ursodeoxycholic acid (UDCA), and 32 (60.4%) of these continued prescribing UDCA as long as the condition of patients remained unchanged. Twenty-nine (50.9%) had prescribed Japanese Kampo medicines ("Inchinkoto" in all cases). Twenty-four (42.1%) had prescribed antibiotics, mainly trimethoprim-sulfamethoxazole, in 21 (87.5%). Twenty-three (40.4%) had prescribed probiotics. Conclusions There were many variations of pharmacotherapy in BA outpatients with native liver in Japan, including antibiotic, probiotic, and Inchinkoto prescriptions. Of the various drugs, the most commonly administered was UDCA.

A 10-month-old girl who had previously undergone Kasai portoenterostomy (KP) for biliary atresia was admitted because of recurrent jaundice. Intrahepatic bile duct (IHBD) dilation was observed in the lateral segment close to the umbilical portion of the portal vein on ultrasonography and computed tomography. Although percutaneous transhepatic biliary drainage by a radiologist alleviated jaundice, internal fistula formation, which was subsequently attempted, was unsuccessful due to the narrow and complicated IHBD morphology. Therefore, side-to-side cholangiojejunostomy between the dilated IHBD and jejunum of the Roux-en-Y limb was performed using intraoperative interventional radiology techniques. The patient's postoperative course was uneventful. In patients with recurrent jaundice after KP, especially that associated with solitary IHBD dilatation, a high success rate of achieving good bile flow can be expected using current techniques.

A two-year-old girl presented with an abdominal mass, abdominal pain, and fever. A quail egg-sized elastic-hard mass was palpable in the upper left abdomen. The patient's growth was impaired. Laboratory data showed an inflammatory response and elevated pancreatic enzymes. The mass showed a cystic structure adjacent to the caudal side of the bifid tail of the pancreas. A fluid collection was observed around the spleen. Surgery was planned under the diagnosis of pancreatic foregut cystic malformation (FCM) associated with a bifid pancreatic tail. However, as the inflammation worsened, parenteral nutrition (PN) was introduced and cyst drainage was performed first, obtaining 10–14 mL/day, and her symptoms subsided. Cyst drainage continued for six weeks at home. Laparoscopic surgery was performed 47 days after the initiation of drainage. Cystography showed communication between the cyst and the slightly dilated pancreatic duct of the bifid tail during surgery. A partial pancreatectomy with cystectomy was performed. The diagnosis of FCM originating from the pancreas, associated with the bifid tail, was confirmed. The postoperative course was uneventful, and the patient was discharged eight days post-surgery. Pancreatic FCM with a bifid pancreatic tail is rare, and we successfully treated it using minimally invasive surgery.

Benign retroperitoneal teratomas are relatively rare tumors that usually progress slowly and are found in newborns and young adults. Here, we report a case in which a prenatally diagnosed retroperitoneal tumor rapidly increased in diameter from 55 mm to 90 mm during the neonatal period. The tumor was removed while preserving the surrounding organs. Moreover, the patient's postoperative course was uneventful. Pathological examination revealed an immature teratoma with no malignant findings. Notably, even benign neonatal teratomas may exhibit rapid growth of their cystic components after birth.

Diabetic neuropathies are a group of heterogeneous peripheral neuropathies and are roughly classified into polyneuropathy and focal neuropathy. Diabetes-specific neuropathy is polyneuropathy, which is pathophysiologically associated with metabolic disorders due to hyperglycemia and microangiopathy. Recently, classification1,2) of the spectrum of diabetic polyneuropathy based on the different type of nerve fiber involved is growing (e.g. myelinated, unmyelinated, autonomic, somatic). Diabetic polyneuropathy (DPN) is divided into diabetic distal sensory neuropathy (DSN), diabetic small fiber neuropathy (DSFN) and diabetic autonomic neuropathy (DAN)2) .

Long-chain polyunsaturated fatty acids (LCPUFAs) are important constituents of biomembranes. Observation of blood fatty acids indicated that LCPUFA biosynthesis is affected by aging and FADS polymorphisms. This study examined the effects of aging and FADS polymorphisms on LCPUFA biosynthetic capacity via direct quantification using [U-13C]linoleic acid. Healthy young (25–34 years) and elderly (65–74 years) participants were administered [U-13C]linoleate, and its metabolites were monitored for 14 days. The time of maximum plasma concentration of 13C-arachidonic acid (ARA) was 4–5 days. The area under the curve of the 13C-ARA concentration differed by FADS1 rs174547 polymorphism (TT [100%] > TC [57%] > CC [37%]). Among C allele carriers, 13C-ARA formation was 32% lower in elderly than in young participants. This is the first report to directly demonstrate that LCPUFA biosynthetic capacity is regulated by FADS1 polymorphisms and decreased by aging in FADS1 C allele carriers.

Bronchogenic cysts are congenital malformations caused by abnormal lung buds. Almost all bronchogenic cysts are found in the thoracic cavity but rarely in the neck. We report a rare case of a cervical bronchogenic cyst diagnosed in the fetal stage. A male baby with a cervical cyst detected at 20 weeks of gestation was suspected of having a 4-cm cystic lymphatic malformation and was subsequently delivered via normal vaginal delivery at 37 weeks. At birth, no symptoms, apart from the palpable elastic tumor mass (3 cm in diameter) on the left side of the neck, were observed. He was followed-up for observation. The cyst contracted at 4 months of age. However, at one year and 4 months of age, the cyst started to grow again without symptomatic manifestations. Cystectomy was performed at 1 year and 11 months of age, and the cyst was diagnosed histologically as a bronchogenic cyst. The postoperative course was uneventful, except for transient recurrent nerve paralysis, which improved 4 months after surgery. No signs of cyst recurrence were observed at the 1-year follow-up. Our case shows that bronchogenic cysts should be considered as a differential diagnosis of cervical cystic disease found before birth. Keywords: Bronchogenic cysts, Prenatal, Cervical

Background: Multicenter study was undertaken to analyze the results of laparoscopic and open Kasai portoenterostomy. Methods: Subjects were infants with type III biliary atresia who underwent open operation (n = 106) or laparoscopic operation (n = 21) between January 2012 and December 2015. Clinical data were compared between open and laparoscopic operations (2016‐0534). Propensity score matching was performed to reduce the effect of treatment selection bias. Multivariate analyses were used to estimate the effect of the surgical approach on the jaundice clearance rate and the native liver survival rate. Results: The postoperative jaundice clearance rate and the 1‐year native liver survival rate were not significantly different between open and laparoscopic operations. Rates of cholangitis and major complications of laparoscopic operation were comparable to those of open operation. Blood loss, time to resume oral intake, time to drain removal, and duration of analgesic usage of laparoscopic operation were significantly superior to those of open operation. Similar results were observed when analysis was adjusted based on propensity score. Multivariate analyses demonstrated that only age at operation was a poor prognostic factor. Conclusion: Laparoscopic Kasai portoenterostomy was associated with several favorable perioperative outcomes compared with open Kasai portoenterostomy. The difference of surgical approach was not a significant independent predictor., ファイル公開：2020-01-24

Background We evaluated the clinical significance of follow-up data, including 99mTc-DTPA galactosyl human serum albumin (99mTc-GSA) liver scintigraphy data, as prognostic indicators for jaundice-free patients with biliary atresia (BA). Methods Of 87 patients who underwent Kasai portoenterostomy (KP) between 1991 and 2012, 45 jaundice-free patients aged 1–2 years underwent 99mTc-GSA scintigraphy and were classified into 2 groups: those who survived with a native liver (Group A, n = 34) and those who required liver transplantation (LTx) (Group B, n = 11). We compared 99mTc-GSA scintigraphy data (HH15, LHL15, and HH15/LHL15 [H/L15]) and liver function test (LFT) results between the groups. The patients underwent a second 99mTc-GSA scintigraphy at approximately 5 years of age. Results All patients survived. HH15, H/L15, total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, and alanine transaminase levels were higher in Group B than in Group A (p Conclusions Mid- and long-term prognoses may be predicted using 99mTc-GSA scintigraphy data and LFTs in patients aged 1–2 years. We recommend regular monitoring of postoperative data following KP, even in jaundice-free patients. Level of evidence III.

Diagnosis of biliary atresia (BA) can involve uncertainties. In the present prospective multicenter study, we considered whether urinary oxysterols represent a useful marker for diagnosis of BA in Japanese children. Subjects under 6 months old at 7 pediatric centers in Japan were prospectively enrolled, including patients with cholestasis and healthy controls (HC) without liver disease. Patients with cholestasis constituted 2 groups representing BA patients and others with cholestasis from other causes (non-BA). We quantitatively analyzed 7 oxysterols including 4β-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol by liquid chromatography/electrospray ionization-tandem mass spectrometry. Enrolled subjects included 14 with BA (median age 68 days; range 26–170) and 10 non-BA cholestatic controls (59; 14–162), as well as 10 HC (57; 25–120). Total urinary oxysterols were significantly greater in BA (median, 153.0 μmol/mol creatinine; range 24.1–486.7; P P P

In biliary atresia, the extrahepatic biliary tract is completely obstructed, showing various morphologic patterns of obstruction on a case-by-case basis. Hepaticoenterostomy is performed when the hepatic duct is sufficiently open for anastomosis with the intestinal tract (correctable type) in types I and II. However, such a disease type is rare, and Kasai portoenterostomy is performed in most cases. In this procedure, the extrahepatic biliary remnant containing obstructed bile ducts is transected at the appropriate level and removed. Then, the intestine is anastomosed to the liver tissue at the hepatic hilum covering the resected area of the removed remnant. We present our current techniques for open Kasai portoenterostomy.

Background This study aimed to compare the clinical outcomes of intestinal transplantation (ITX) between 2 groups by using medications for induction treatment and assess the utility of the current protocol. Methods From 2003 to 2020, 11 patients underwent ITX. Recipients were classified into 2 groups: group IL-2Ra (interleukin-2 receptor antagonist therapy, n = 6) and ATG (rabbit antithymocyte globulin therapy, n = 5). We conducted a retrospective review of patient and graft survival rates and the postoperative course. Results The 1-, 5-, and 10-year patient and graft survival rates of the 11 primary grafts in the 11 recipients were 100%, 88.9%, 62.2% and 90.0%, 78.8%, 56.3%, respectively. The median duration of follow-up for the IL-2Ra and ATG groups was 197.3 and 87.3 months, respectively. The 1-, 5-, and 10-year patient survival rates were 100%, 83.3%, 50% and 100%, 100%, 100% for the IL-2Ra and ATG groups, respectively (P = .25) and 83.3%, 66.7%, 33.3% and 100%, 100%, 100% for graft survival in the IL-2Ra and ATG groups, respectively (P = .08). The incidence of moderate and severe acute rejection was 100% and 20% in the IL-2Ra and ATG groups, respectively (P = .02). The 1- and 5-year moderate and severe rejection-free survival rates were 33.3%, 0% and 80%, 80% in the IL-2Ra and ATG groups, respectively (P = .04). Conclusions ATG significantly suppressed moderate and severe acute rejection compared with IL-2Ra, thereby showing better short- and mid-term rejection-free survival rates. Additional clinical experience is needed to determine the optimal regimen for the management of ITX recipients.

Multifactorial lifestyle intervention is known to be more effective for ameliorating cognitive decline than single factor intervention; however, the effects of combining exercise with long-chain polyunsaturated fatty acids (LCPUFA) on the elderlies' cognitive function remain unclear. We conducted a randomised, single-masked placebo-controlled trial in non-demented elderly Japanese individuals. Participants were randomly allocated to the exercise with LCPUFA, placebo, or no exercise with placebo (control) groups. Participants in the exercise groups performed 150 min of exercise per week, comprised resistance and aerobic training, for 24 weeks with supplements of either LCPUFA (docosahexaenoic acid, 300 mg/day; eicosapentaenoic acid, 100 mg/day; arachidonic acid, 120 mg/day) or placebo. Cognitive functions were evaluated by neuropsychological tests prior to and following the intervention. The per-protocol set analysis (n = 76) revealed no significant differences between the exercise and the control groups in changes of neuropsychological tests. Subgroup analysis for participants with low skeletal muscle mass index (SMI) corresponding to sarcopenia cut-off value showed changes in selective attention, while working memory in the exercise with LCPUFA group was better than in the control group. These findings suggest that exercise with LCPUFA supplementation potentially improves attention and working memory in the elderly with low SMI.

Aims/Introduction As the extensor digitorum brevis muscle is a small muscle in the most distal part of the legs, its atrophy (EDBA) might reflect symmetric polyneuropathy (SPN). We aimed to clarify the EDBA‐related factors and the usefulness of bilateral EDBA detection for diagnosing SPN, especially diabetic SPN (DSPN). Materials and Methods In 1,893 participants from the Japanese general population (investigation I) and 133 established diabetes patients (investigation II), relationships between EDBA and various factors including the traditional sitting style called “seiza’” (kneeling and sitting on one’s heels) were investigated. Analyses were carried out by univariate and multivariate analysis, and SPN or DSPN was diagnosed by the criteria of “Probable DSPN” of the Toronto Consensus. The validity of EDBA detection for diagnosing SPN/DSPN was also evaluated. Results Investigation I: EDBA was more prevalent in women than men (44% vs 20%). Significant EDBA‐related factors were aging and seiza habit regardless of sex. Male‐specific EDBA‐related factors were SPN and known diabetes. In men without seiza habit, EDBA was significantly associated with SPN regardless of diabetes, so EDBA seemed to be a useful sign for diagnosing SPN/DSPN. Investigation II: In men, DSPN was more prevalent in the EDBA group than the non‐EDBA group (71% vs 33%). Sensitivity, specificity, positive predictive value and kappa coefficient of EDBA detection for diagnosing DSPN were 44, 87, 67% and 0.323, showing fair agreement. Conclusions EDBA detection might be a useful method to screen for distal symmetric polyneuropathy, such as DSPN in men, although the exclusion of individuals with seiza habit is necessary to improve accuracy., Extensor digitorum brevis atrophy detection might be a useful method to screen for distal symmetric polyneuropathy, such as diabetic symmetric polyneuropathy in men, although the exclusion of individuals with seiza habit is necessary to improve accuracy.

Congenital hyperinsulinism is a rare disease, and the newly developed 18 fluoro-L-dihydroxyphenylalanine-positron emission tomography (18F-DOPA PET) examination can detect hyperplastic lesions. Our purpose was to report the results of a nationwide survey on surgical treatment of congenital hyperinsulinism in Japan. A questionnaire was sent to the 159 accredited and affiliated training institutes certified as pediatric surgical institutes by the Japanese Association of Pediatric Surgeons, asking if they had encountered patients who underwent surgical treatment for congenital hyperinsulinism after 18F-DOPA PET examination from 2000 to 2017. Six institutes answered that they had treated such cases, and the total number of cases was 14. 18F-DOPA PET examination detected the focal lesion in 12 of the 14 cases. 18F-DOPA PET examination could accurately determine the site of the hyperplastic lesion in the pancreas in 11 (91.7%) of the 12 cases. All cases underwent surgical resection of the hyperplastic lesion at under 2 years of age. Surgical resection of a focal hyperplastic lesion in the pancreas was a safe and effective treatment if the hyperplastic lesion was a focal lesion. However, it is necessary to check the exact distribution of the lesion by intraoperative pathologic examination of frozen sections.

Pathological stressors disrupt cellular homeostasis, causing various diseases. We report a non-glycolytic role for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the pathological growth response of the heart. In cellular and animal models for cardiac hypertrophy, nuclear translocation of GAPDH was elicited in cardiac myocytes, followed by activation of p300 histone acetyl-transferase (HAT), an inducer of heart hypertrophy gene programs. The hypertrophy was inhibited by a compound antagonizing the nuclear GAPDH cascade. In mice with selective deletion of GAPDH’s nuclear function in cardiac myocytes, the stress-induced cardiac hypertrophy and functional deficits were normalized. Nuclear GAPDH cascade plays a pivotal role in stress response/homeostatic control in the heart. GAPDH may act as a key homeostatic mediator in living organisms through its stress-responsive nuclear translation.One-sentence summaryNon-glycolytic function of GAPDH critically regulates heart homeostasis and mediates cardiac pathological hypertrophy

Owing to several therapeutic advancements, more patients with biliary atresia now survive into adulthood while retaining their native liver. However, the optimal strategy for long-term management of such patients remains unclear. Aiming to establish the current management strategies, we reviewed previous reports of long-term outcome of BA who underwent surgery at our institution as well as the relevant literature, focusing particularly on the treatment of late complications. Approximately 30–40% of long-term survivors of biliary atresia who retain their native liver exhibit late sequelae such as cholangitis and portal hypertension. Early and appropriate intervention with Kasai portoenterostomy is essential for ensuring long-term survival with good quality of life. In our hospital, the current standard for Kasai portoenterostomy involves dissecting the fibrous remnants along the porta hepatis, just on the level of the liver capsule. Cholangitis is an important late complication in biliary atresia, and the possibility of mechanical obstruction of the biliary drainage route or deformity of the intrahepatic bile ducts with or without gallstones should be thoroughly evaluated in patients with intractable cholangitis. Regarding portal hypertension, appropriate interventions such as endoscopic variceal treatment and partial splenic embolization are considered to provide good quality of life when hepatic function is preserved. Appropriate therapeutic management is strongly recommended in selected patients with late complications.

Interferon (IFN) has various side effects, including psychiatric symptoms. Event-related potentials are used as an electrophysiologic index of cognitive disorders. Auditory event-related potentials (P300) are often used in conditions in which cognitive ability is affected. In this study, we evaluated the association between P300, used to assess cognitive impairment, and neuropsychological side effects of IFN treatment in patients with chronic hepatitis C. Subjects were 20 patients with chronic hepatitis C; 13 patients were treated with peg IFN-α2b and ribavirin (riba group), and 7 patients were treated with peg IFN-α2a (alone group). P300 was performed on all patients before treatment and after 1 week, 4 weeks, 2 months, and 3 months of treatment. In addition, 10 patients of them completed the self-rating depression scale (SDS). P300 latency was significantly prolonged at all points of measurement during IFN treatment. No correlation between the change of SDS score and the change rate of P300 latency was shown. Six patients with neuropsychological symptom had a significantly increased change rate of P300 latency compared with patients without neuropsychological symptoms (P < 0.05). Based on P300 findings, this study suggests that patients with chronic hepatitis C treated with IFN may experience significant cognitive impairment.

Congenital hyperinsulinism is a rare condition, and following recent advances in diagnosis and treatment, it was considered necessary to formulate evidence-based clinical practice guidelines reflecting the most recent progress, to guide the practice of neonatologists, pediatric endocrinologists, general pediatricians, and pediatric surgeons. These guidelines cover a range of aspects, including general features of congenital hyperinsulinism, diagnostic criteria and tools for diagnosis, first- and second-line medical treatment, criteria for and details of surgical treatment, and future perspectives. These guidelines were generated as a collaborative effort between The Japanese Society for Pediatric Endocrinology and The Japanese Society of Pediatric Surgeons, and followed the official procedures of guideline generation to identify important clinical questions, perform a systematic literature review (April 2016), assess the evidence level of each paper, formulate the guidelines, and obtain public comments.

Kasai portoenterostomy (KP) is the primary procedure for biliary atresia (BA). However, due to reports of poor outcomes of KP, primary liver transplantation (LT) is preferred in selected cases. In Japan, primary LT is limited with no study reports details, particularly regarding the indications. We conducted the first nationwide survey to assess the status of primary LT in Japan. Questionnaires were sent to institutions where procedures other than KP were performed as the initial procedure for BA and registered to the Japan Biliary Atresia Registry. Parameters related to procedure selection were analyzed. Of 2895 patients registered (1989–2013), primary LT (n = 15) or exploratory laparotomy (EL) followed by LT (n = 9) without KP was performed in 24 cases (0.8%). The main reason for primary LT was late diagnosis, and for EL followed by LT, lack of fibrous tissue at the porta hepatis (ο-type). The prognoses of LT without KP was good. Non-KP initial procedures were limited. Clear criteria regarding the timing of diagnosis or patient condition could not be determined. Reasons for not initially selecting KP varied, but late diagnosis was predominant. Further study is needed to create guidelines for the initial treatment of BA patients.

Background Although cancer occurrence following surgery for biliary atresia has gradually increased, the development of cholangiocarcinoma in a native liver survivor of biliary atresia is extremely rare. Case presentation A 3-month-old female patient with the correctable type of biliary atresia underwent a cystoduodenostomy. At 16 years of age, she underwent multiple surgeries including lysis of intestinal adhesions, ileostomy, and gastrojejunostomy at another hospital. At 54 years of age, she underwent lithotomy at the porta hepatis, resection of the residual cystic bile duct with gallbladder, and hepaticojejunostomy in Roux-en-Y fashion. As she approached the age of 63, her computed tomography scan showed no liver tumors. In the following year, she developed cholangiocarcinoma at the porta hepatis and underwent chemotherapy. However, the cancer progressed, and she died before she reached the age of 64 years. Conclusions Cholangiocarcinoma is extremely rare in patients with biliary atresia. However, physicians should follow up patients with biliary atresia as closely as possible, as malignant tumors secondary to biliary atresia may increase in number in the near future because of the growing number of long-term survivors with biliary atresia.

We measured pain threshold of intra-epidermal nerve terminal (PINT) which is a simple and noninvasive method that can measure pain threshold of A delta fiber by intra-epidermal electrical stimulation. We aimed to investigate normal value, prevalence of abnormality and clinically associated factors to PINT and quantitative vibratory perception threshold (QVT). PINT and QVT were measured by a portable peripheral nerve testing device PNS-7000, and a vibration sensation meter AU 02-B in 656 Japanese regional health checkup examinees (40-75 years old; years old). Glucose tolerance; normal (N), pre-DM, newly diagnosed DM (NDM) and known DM (KDM), and neuropathic findings (pain, paresthesia, numbness in legs and reduced ATRs) were also determined. Relationship between age, glucose tolerance, neuropathic findings and PINT or QVT were investigated by simple and multivariate analyses. In 445 non-DM subjects without neuropathic findings, normal limit value of PINT (mA) was set by quantile regression method, and relationship between prevalence of PINT or QVT abnormalities and clinical factors were examined. As results, PINT was not changed under 70 years old, then somewhat elevated. QVT elevated from 50 years old. PINT was not associated with QVT. PINT was significantly elevated in NDM and KDM. QVT was elevated in diabetes and hypertension. Among the neuropathic findings, PINT was significantly associated with only pain. By multiple regression analyses, significant aggravating factors of PINT were aging and glucose intolerance. Normal values of PINT were > 0.4 (0.5 (70< years old) Prevalence of PINT abnormality were 3%, 4%, 13% and 9% in N, pre-DM, NDM and KDM, respectively. They were significantly increased with the deterioration of glucose tolerance. QVT abnormality was not significantly increased with glucose intolerance. In conclusion, PINT reflects small nerve fiber function, and associates with DM. So, PINT may be a useful for diagnosis and evaluation of small fiber neuropathy. Disclosure H. Sasaki: None. S. Kishimoto: None. K. Ogawa: None. S. Kurisu: None. K. Nanjo: None. Funding Japan Society for the Promotion of Science