Search

BACKGROUND Several factors associated with hepatocellular carcinoma (HCC) occurrence after sustained virological response (SVR) in patients with hepatitis C have been reported. However, few validation studies have been performed in the era of direct-acting anti-virals (DAAs). AIMS To develop a prediction model for HCC occurrence after DAA-mediated SVR and validate its usefulness. METHODS We analysed 2209 patients with SVR and without a history of HCC who initiated DAA treatment at 24 Japanese hospitals. These patients were divided into a training set (1473 patients) and a validation set (736 patients). RESULTS In the training set, multivariate Cox proportional hazards analysis showed that the baseline BMI (≥25.0 kg/m2 , P = 0.024), baseline fibrosis-4 (FIB-4) index (≥3.25, P = 0.001), albumin level at SVR (

Objective To compare the clinical and radiographic outcomes and complications in patients undergoing multilevel posterior cervical fusion surgery, ending at C7 or crossing the cervicothoracic junction (CTJ). Methods A total of 96 patients undergoing multilevel posterior cervical fusion surgery ending at C7, T1, or T2 were screened. The patients who fulfilled the inclusion criteria were divided into 2 groups based on the lower instrumented vertebra (LIV) level: group C7 (ending at C7) and group T1-T2 (crossing the CTJ). The radiographic and clinical outcomes were compared between the 2 groups, and the risk factors for instrument failure at LIV were investigated. Results In total, 73 patients (76%) completed at least 1 year follow-up and divided into group C7 (n = 43) and group T1-T2 (n = 30). Preoperative and postoperative radiographic parameters, the Japanese Orthopaedic Association score, and patient-reported outcomes were not significantly different between the 2 groups. Significantly longer surgical time, increased blood loss, and higher incidence rates of perioperative or postoperative complications were noted in group T1-T2. On the other hand, the incidence of instrument failures at LIV was significantly higher in group C7. Multivariate analysis showed that ending at C7, skipping screw insertion at the proximal vertebra adjacent to LIV, and a large postoperative cervical sagittal vertical axis (>40 mm) were risk factors for instrument failure at LIV. Conclusions Crossing the CTJ during multilevel posterior cervical fusion surgery reduced instrument failures at LIV, but increased the surgical invasiveness and perioperative and postoperative complications.

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

AIM In patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of patients with non-alcoholic fatty liver disease-hepatocellular carcinoma (NAFLD-HCC) without cirrhosis and on the progression of liver fibrosis. METHODS Serum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin. RESULTS The median age was 67.4 years, the median L3 skeletal muscle mass index was 44.4 cm2 /m2 , and the median body mass index was 23.4 kg/m2 . Eighty-two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men

Purpose Long-term effects on patient health-related quality of life (HRQoL) after direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) are unknown. We assessed the impact of DAA-mediated HCV clearance on HRQoL from DAA initiation to 1 year after confirmed sustained virological response at 24 weeks post-treatment (SVR24). Methods HRQoL was evaluated using the eight-item Short Form Health Survey (SF-8). Chronic HCV-infected patients were treated for 12 weeks with sofosbuvir-based DAAs. SF-8 was administered at baseline, treatment cessation, SVR24, and 1-year post-SVR24. Results A total of 109 chronic HCV-infected patients were enrolled. The average SF-8 scores were higher than the Japanese national standard values for bodily pain (BP) and mental health at baseline and for general health at 1-year post-SVR24. None of the SF-8 scores differed significantly between baseline and 1-year post-SVR24. Regarding age, sex, liver status, and treatment regimen, the SF-8 scores at 1-year post-SVR24 were affected by only age; individuals aged Conclusion Upon long-term assessment, although more factors trended higher than national standard values at 1-year post-SVR24 than at baseline, there were no significant changes within factors. As PCS tended to be associated with age, patients aged ≥ 65 years should be carefully monitored for PCS.

Spontaneous regressions of primary and/or metastatic lesions have been rarely reported in hepatocellular carcinoma (HCC). Herein, we report the case of a 71-year-old man with HCC, focusing on shape changes of lung metastases over time. Lung metastasis of HCC was histologically diagnosed by percutaneous computed tomography (CT)-guided needle biopsy after the treatment of primary HCC lesion. Lung lesions had been observed on enhanced contrast computed tomography for >3 years without any local or systemic treatment for them. During this period, treatments including surgical procedure for relapsed bladder cancer and transarterial chemoembolization for HCC were performed. Metastatic lung lesions immediately regressed after these treatments. Therefore, accumulation of such cases may help elucidate spontaneous regression mechanisms in primary HCC or its lung metastases.

Study design Multicenter retrospective observational study. Objective To determine the differences between C3 laminectomy (LN) and C3 laminoplasty (LP) in cervical LP. Summary of background data Interlaminar bony fusion after cervical LP is reported to be related to a decrease in postoperative range of motion (ROM) or neurological disorder. However, it remains uncertain whether C3 LN affects patient-reported outcomes, especially after double-door LPs. Therefore, this study aimed to investigate the effect of C3 LN compared with C3 LP in cervical double-door LP. Patients and methods Using our prospective database, consecutive patients with degenerative cervical myelopathy undergoing cervical double-door LP in 7 hospitals between April 2017 and May 2018 were enrolled. Before and 1 year after the surgeries, we collected the details of patient background data, operative factors, radiologic findings such as C2-C7 ROM angle and C2-C3 interlaminar bony fusion, the Japanese Orthopaedic Association (JOA) score, postoperative satisfaction, neck pain, and patient-reported outcomes such as Short Form-12 (SF-12), EuroQol 5 Dimension (EQ-5D), Neck Disability Index (NDI), and the Core Outcome Measures Index (COMI) for the neck. Results In all, 152 patients were enrolled, including 97 undergoing C3 LP and 55 undergoing C3 LN. There were no significant differences in patient background data, complications, and operative factors. C2-C3 interlaminar bony fusion occurred more often in the C3 LP group (22.6% vs. 5.7%). There were also no differences in the C2-C7 angle, C2-C7 ROM angle, the JOA score, patient satisfaction, neck pain, SF-12, EQ-5D, NDI, and COMI between the groups. Conclusions C2-C3 bony fusion after cervical double-door LP occurred more often in the C3 LP group than in the C3 LN group. C3 LN resulted in similar outcomes in complication rate, radiographic outcomes, and clinical outcomes compared with those of C3 LP. Level of evidence Level III.

Introduction Our previous clinical studies have demonstrated the short-term efficacy and safety of the sirolimus gel for patients with tuberous sclerosis complex (TSC). However, long-term clinical evidence is lacking. Our objective was to assess the safety and efficacy of long-term treatment with the sirolimus gel for the skin lesions of TSC patients. Methods We conducted a multicenter, open-label, uncontrolled clinical trial in 94 Japanese patients with TSC. Patients applied the 0.2% sirolimus gel on their face or head twice daily for > 52 weeks (maximum 136 weeks for safety). The safety endpoints were the rate of adverse event (AE)-caused discontinuation (primary endpoint) and the incidence of AEs. The efficacy endpoint was the response rate of angiofibromas, cephalic plaques, and hypomelanotic macules. Results Among 94 enrolled patients (mean age, 21 years; range 3–53 years), the rate of AE-caused discontinuation was 2.1% (2/94 patients). Although application site irritation and dry skin occurred relatively frequently, none of the drug-related AEs were serious; most of the drug-related AEs resolved rapidly. The major drug-related AEs (≥ 5% in incidence) were application site irritation (30.9%), dry skin (27.7%), acne (20.2%), eye irritation (8.5%), pruritus (8.5%), erythema (7.4%), dermatitis acneiform (6.4%), and dermatitis contact (5.3%). The response rates of angiofibromas, cephalic plaques, and hypomelanotic macules were 78.2% [95% confidence interval (CI) 68.0–86.3%], 66.7% (95% CI 51.1–80.0%), and 72.2% (95% CI 46.5–90.3%), respectively. Conclusions The gel was well tolerated for a long time by patients with TSC involving facial skin lesions and continued to be effective. Trial Registration ClinicalTrials.gov identifier: NCT02634931.

Background & Aims Liver inflammation has been recognized as a hallmark of hepatocarcinogenesis. Although Forkhead Box M1 (FoxM1) is a well-defined oncogenic transcription factor that is overexpressed in hepatocellular carcinoma (HCC), its role in liver inflammation has never been explored. Methods We generated hepatocyte-specific FoxM1 conditional transgenic (TG) mice by using the Cre-loxP and Tetracycline (Tet)-on systems to induce FoxM1 expression in a hepatocyte-specific and time-dependent manner. Results After treatment of Tet-derivatives doxycycline (DOX) to induce FoxM1, TG mice exhibited spontaneous development of hepatocyte death with elevated serum alanine aminotransferase levels and hepatic infiltration of macrophages. The removal of DOX in TG mice completely removed this effect, suggesting that spontaneous inflammation in TG mice occurs in a hepatocyte FoxM1-dependent manner. In addition, liver inflammation in TG mice was associated with increased levels of hepatic and serum chemokine (C-C motif) ligand 2 (CCL2). In vitro transcriptional analysis confirmed that CCL2 is a direct target of FoxM1 in murine hepatocytes. After receiving FoxM1 induction since birth, all TG mice exhibited spontaneous HCC with liver fibrosis at 12 months of age. Hepatic expression of FoxM1 was significantly increased in liver injury models. Finally, pharmacologic inhibition of FoxM1 reduced liver inflammation in models of liver injury. Conclusions Hepatocyte FoxM1 acts as a crucial regulator to orchestrate liver inflammation linking to hepatocarcinogenesis. Thus, hepatocyte FoxM1 may be a potential target not only for the treatment of liver injury but also for the prevention toward HCC., Graphical abstract

Lichen nitidus and morphea are common diseases, but an associated localization of both lesions is rare. Here, we describe the first case of lesions distributed along Blaschko's lines. A 24-year-old Japanese woman was referred to our clinic for evaluation of band-like plaques of 18-months history on the right lateral side of her abdomen. In addition, multiple milky-white papules were seen within the plaques. Histopathological examination showed there was sclerosis in the lower half of the dermis and well-circumscribed, dense, papillary dermal lymphohistiocytic aggregations showing a so-called "claw clutching a ball." Immunohistochemical analysis revealed that the morphea and lichen nitidus had similar characteristics. We speculated that unique immunologic events led to the development of lichen nitidus and morphea in our patient.

Akio Miyasaka,1,2 Yuichi Yoshida,1,2 Akiko Suzuki,1 Kei Sawara,1,3 Yasuhiro Takikawa1 1Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Shiwa-gun, Iwate, Japan; 2Department of Gastroenterology, Iwate Prefectural Ninohe Hospital, Ninohe, Iwate, Japan; 3Department of Gastroenterology, Iwate Prefectural Kamaishi Hospital, Kamaishi, Iwate, JapanCorrespondence: Akio MiyasakaDivision of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3695, JapanTel +81-19-613-7111Fax +81-19-907-7166Email akimiya@iwate-med.ac.jpPurpose: To investigate long-term incidence of hepatocellular carcinoma (HCC) and the factors associated with HCC occurrence after achieving sustained virological response (SVR) by direct-acting antiviral agent (DAA) treatment for hepatitis C virus (HCV).Methods: A total of 476 patients (male 227, female 249; median age 68) with chronic HCV infection who were treated with DAAs and achieved SVR were analyzed. The incidence of HCC and factors related to the development of HCC after HCV elimination were evaluated.Results: The median observation period was 46.4 months. During this period, 40 patients developed HCC. The incidence rates of HCC were 3.7%, 6.0%, 7.1%, 9.3%, and 10.6% at 1, 2, 3, 4, and 5 years post-SVR12, respectively. Multivariate analysis with pre-treatment factors revealed that platelet count, α-fetoprotein, fibrosis-4 (Fib-4) index, and previous HCC history were independent factors that contributed to development of HCC post-SVR following DAA treatment. Of these factors, previous HCC history was the most significant, followed by Fib-4 index. Using these two factors, a novel scoring system was established. The presence of previous HCC history was scored as 2, and then, the absence of previous HCC history was stratified by Fib-4 index (≥ 3.07, 1; < 3.07, 0). The HCC occurrence rate at 5 years was 0.4% in the 0-point group, 6.8% in the 1-point group, and 55.6% in the 2-point group, respectively.Conclusion: Fib-4 index and previous HCC history were independent predictors for development of HCC after DAA treatment. Patients with these risk factors require careful observation.Keywords: hepatocellular carcinoma, antiviral agents, sustained virological response

Background Microendoscopic laminectomy (MEL), in which a 16-mm tubular retractor with an internal scope is used, has shown excellent surgical results for patients with lumbar spinal canal stenosis. However, no reports have directly compared MEL with open laminectomy. This study aimed to elucidate patient-reported outcomes (PROs) and perioperative complications in patients undergoing MEL versus open laminectomy. Methods This is a multicenter retrospective cohort study of prospectively registered patients who underwent lumbar spinal surgery at one of the six high-volume spine centers between April 2017 and September 2018. A total of 258 patients who underwent single posterior lumbar decompression at L4/L5 were enrolled in the study. With regard to demographic data, we prospectively used chart sheets to evaluate the diagnosis, operative procedure, operation time, estimated blood loss, and complications. The follow-up period was 1-year. PROs included a numerical rating scale (NRS) for lower back pain and leg pain, the Oswestry Disability Index (ODI), EuroQol 5 Dimension (EQ-5D), and patient satisfaction with the treatment. Results Of the 258 patients enrolled, 252 (97%) completed the 1-year follow-up. Of the 252, 130 underwent MEL (MEL group) and 122 underwent open decompression (open group). The MEL group required a significantly shorter operating time and sustained lesser intraoperative blood loss compared with the open group. The MEL group showed shorter length of postoperative hospitalization than the open group. The overall complication rate was similar (8.2% in the MEL group versus 7.7% in the open group), and the revision rate did not significantly differ. As for PROs, both preoperative and postoperative values did not significantly differ between the two groups. However, the satisfaction rate was higher in the MEL group (74%) than in the open group (53%) (p = 0.02). Conclusions MEL required a significantly shorter operating time and resulted in lesser intraoperative blood loss compared with laminectomy. Postoperative PROs and complication rates were not significantly different between the procedures, although MEL demonstrated a better satisfaction rate.

Background & aims Chronic liver congestion reflecting right-sided heart failure (RHF), Budd-Chiari syndrome, or Fontan-associated liver disease (FALD) is involved in liver fibrosis and hepatocellular carcinoma (HCC). However, molecular mechanisms of fibrosis and HCC in chronic liver congestion remain poorly understood. Approach & results Here, we first demonstrated that chronic liver congestion promoted HCC and metastatic liver tumor growth using murine model of chronic liver congestion by partial inferior vena cava ligation (pIVCL). As the initial step triggering HCC promotion and fibrosis, gut-derived lipopolysaccharide (LPS) appeared to induce liver sinusoidal endothelial cells (LSECs) capillarization in mice and in vitro. LSECs capillarization was also confirmed in FALD patients. Mitogenic factor, sphingosine-1-phosphate (S1P) was increased in congestive liver and expression of sphingosine kinase 1 (SphK1), a major synthetase of S1P, was increased in capillarized LSECs after pIVCL. Inhibition of S1P receptor (S1PR)1 (Ex26) and S1PR2 (JTE013) mitigated HCC development and liver fibrosis, respectively. Antimicrobials treatment lowered portal blood LPS concentration, LSECs capillarization, and liver S1P concentration accompanied by reduction of HCC development and fibrosis in the congestive liver. Conclusions In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS-induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for RHF patients with primary or metastatic liver cancer.

Predominantly or exclusively dopamine-secreting pheochromocytoma and paraganglioma are very rare. We report a 64-year-old woman with an adrenal incidentaloma. She was normotensive and had no symptoms of catecholamine excess. The 24-hour urine catecholamine level showed normal norepinephrine (122.9 μg/day), normal epinephrine (24.3 μg/day), and markedly elevated dopamine (148 212.4 μg/day). 123I-metaiodobenzylguanidine (MIBG) scintigraphy revealed tumor uptake. After α-blockade as preoperative management, she successfully underwent laparoscopic left adrenalectomy and was finally diagnosed with an exclusively dopamine-secreting pheochromocytoma. The tumor was histologically comprised of small polygonal cells with high cellularity and was immunohistochemically positive for all 3 catecholamine-synthesizing enzymes: tyrosine hydroxylase (very weak), dopamine β-hydroxylase (heterogeneous), and phenylethanolamine N-methyltransferase (very weak). Electron microscopy revealed very few catecholamine-containing small vesicles with a few organelles, which reflected immature cells. No biochemical or imaging evidence of recurrence or metastasis were evident 1 year after the surgery. We conducted a literature search in the PubMed database. A total of 33 cases were collected. Our case had the second-highest 24-hour urinary dopamine excretion and was the first in which immunostaining for catecholamine synthase and electron microscopy were performed together. Histological findings in our case give a possible hypothesis that the mechanism underlying a dopamine-secreting pheochromocytoma is associated with immature catecholamine vesicles in which dopamine β-hydroxylase is localized, thus resulting in inhibited conversion from dopamine to norepinephrine. We also discuss the reasons for the lack of catecholamine excess symptoms, whether preoperative management of α-blockade is needed, and the association between the prognosis and genetic mutation, with an extensive literature review.

Retrospective observational study.This study examined associated factors for the improvement in spinal imbalance following decompression surgery without fusion.Several reports have suggested that decompression surgery without fusion may have a beneficial effect on sagittal balance in patients with lumbar spinal stenosis (LSS) through their postoperative course. However, few reports have examined the association between an improvement in sagittal imbalance and spinal sarcopenia.We retrospectively reviewed 92 patients with LSS and a preoperative sagittal vertical axis (SVA) more than or equal to 40 mm who underwent decompression surgery without fusion at a single institution between April 2017 and October 2018. Patients' background and radiograph parameters and the status of spinal sarcopenia, defined using the relative cross-sectional area (rCSA) of the paravertebral muscle (PVM) and psoas muscle at the L4 caudal endplate level, were assessed. We divided the patients into two groups: those with a postoperative SVA less than 40 mm (balanced group) and those with a postoperative SVA more than or equal to 40 mm (imbalanced group). We then compared the variables between the two groups.A total of 29 (31.5%) patients obtained an improved sagittal imbalance after decompression surgery. The rCSA-PVM in the balanced group was significantly higher than that in the imbalanced group (P = 0.042). The preoperative pelvic incidence (PI)-lumbar lordosis (LL) mismatch (P = 0.048) and the proportion with compression vertebral fracture (P = 0.028) in the balanced group were significantly lower than those in the imbalanced group. A multivariate logistic regression analysis identified PI-LL less than or equal to 10° and rCSA-PVM more than or equal to 2.5 as significant associated factor for the improvement in spinal imbalance following decompression surgery.A larger volume of paravertebral muscles and a lower PI-LL were associated with an improvement in sagittal balance in patients with LSS who underwent decompression surgery.Level of Evidence: 3.

The selective provocative test (SPT) under local anesthesia aids in protecting against ischemic complications during endovascular treatment. However, the use of this test under general anesthesia is not well described. Herein, we present a case of a 51-year-old man with a ruptured fusiform aneurysm in the middle cerebral artery M4 segment, which was thought to possibly supply the motor cortex. Internal trapping of the affected vessel and aneurysm by endovascular intervention was successfully performed after SPT using transcranial motor evoked potential (MEP) monitoring under general anesthesia. Transcranial MEP is suitable for neurological assessment during SPT under general anesthesia.

Overall response rates of systemic therapies against advanced hepatocellular carcinoma (HCC) remain unsatisfactory. Thus, searching for new immunotherapy targets is indispensable. NK cells are crucial effectors and regulators in the tumor microenvironment and a determinant of responsiveness to checkpoint inhibitors. We revealed the landscape of NK cell phenotypes in HCC patients to find potential immunotherapy targets. Using single cell mass cytometry, we analyzed 32 surface markers on CD56dim and CD56bright NK cells, which included Sialic acid-binding immunoglobulin-type lectins (Siglecs). We compared peripheral NK cells between HCC patients and healthy volunteers. We also compared NK cells, in terms of their localizations, on an individual patient bases between peripheral and intrahepatic NK cells from cancerous and noncancerous liver tissues. In the HCC patient periphery, CD160+CD56dim NK cells that expressed Siglec-7, NKp46, and NKp30 were reduced, while CD49a+CD56dim NK cells that expressed Siglec-10 were increased. CD160 and CD49a on CD56dim NK cells were significantly correlated to other NK-related markers in HCC patients, which suggested that CD160 and CD49a were signature molecules. CD49a+ CX3CR1+ Siglec-10+ NK cells had accumulated in HCC tissues. Considering further functional analyses, CD160, CD49a, CX3CR1, and Siglec-10 on CD56dim NK cells may be targets for immunotherapies of HCC patients.

Neurofibromatosis 1 (NF1) is a genetic disease characterized by cutaneous, neurological and osseous abnormalities. Approximately 20% of patients develop plexiform neurofibroma (PN), resulting in impaired quality of life. To evaluate distribution of diffuse PN on the body surface, a retrospective study was conducted for 354 patients with NF1 from 2007 to 2018 in Japan. We investigated a total of 40 patients with clinically apparent superficial diffuse PN. In the cases evaluated, 57.4% of the diffuse PN were located on the trunk, 19.2% the head and neck, 12.8% the lower limbs and 10.6% the upper limbs. Remarkably, 75.0% of the diffuse PN were located on the dorsal side. The frequency was significantly higher on the trunk than on the head and neck (P = 0.026). Our findings provide useful information for giving attention to the high possibility of diffuse PN on the dorsal side before progression in childhood and for future treatment in NF1.

We report a case of X-linked recessive ichthyosis with basal cell carcinoma. An 86-year-old man was referred to our department for evaluation of a 1-year history of an ulcer on his left leg. He had suffered from dry skin with scales on his entire body since childhood. Histopathological examination of the lower leg revealed intradermal proliferation of a solid nest of basaloid cells showing unclear palisading in the periphery. Marked hyperkeratosis and hypergranulosis were also seen in the adjacent dermis. Loss of the steroid sulfatase gene was found on chromosome X. Based on these finding, we made a diagnosis of X-linked recessive ichthyosis with basal cell carcinoma. To our knowledge, there has been no report of X-linked recessive ichthyosis with cutaneous malignancy. We discuss the risk of skin cancer in relation to ichthyosis.

A 44-year-old woman with chronic hepatitis C virus (HCV) infection was referred by a primary care doctor and admitted to our hospital because of worsening dyspnea on exertion and right atrial and ventricular enlargement. The patient was diagnosed with pulmonary arterial hypertension (PAH) associated with portal hypertension induced by chronic HCV infection. This diagnosis was based on a cardiological examination and findings related to liver cirrhosis with portal hypertension. After the prescription of anti-PAH medicine and a slight improvement in her respiratory symptoms, 12-week direct-acting antiviral (DAA) treatment for HCV was started. Serum HCV RNA levels rapidly decreased and HCV elimination was confirmed 24 weeks after completing DAA treatment. Before confirmation of a sustained virological response at 24 weeks after completing DAA treatment, a remarkable improvement in her cardiac markers was found in a right heart catheter study. This study was performed 6 weeks after the end of DAA administration. Therefore, we considered that HCV infection was involved in the development of PAH and that elimination of HCV by interferon-free treatment was important for this patient.

While several methods have been proposed for detecting three-dimensional (3D) objects in semi-real time by sparsely acquiring features from 3D point clouds, the detection of strongly occluded objects still poses difficulties. Herein, we propose a method of detecting strongly occluded objects by setting up virtual auxiliary point clouds in the vicinity of the target object. By generating auxiliary point clouds only in the occluded space estimated from a detected object at the front of the sensor-observed region, i.e., the occluder, the processing efficiency and accuracy are improved. Experiments are performed with various strongly occluded scenes based on real environmental data, and the results confirm that the proposed method is capable of achieving a mean processing time of 0.5 s for detecting strongly occluded objects.

Objective Since healthcare providers face an increased risk of hepatitis B virus (HBV) infection because of their work, vaccination plays a critical role in preventing HBV transmission. However, the duration for which acquired HBV surface antibodies (anti-HBs) persist remains unknown. To evaluate the primary immunologic response to HBV vaccination and its persistence in healthy Japanese adolescents. Methods In total, 690 young adults underwent HBV vaccination with a three-dose schedule. The primary response was determined by the anti-HBs titers at 1-2 months after the final dosage. Subjects with anti-HBs titers of 100 mIU/mL were classified as “non-responders,” “low-responders,” and “sufficient responders,” respectively. Anti-HB titers were re-measured at 1 or 2 years after vaccination. Results First, 95.8% and 72.8% of the subjects had anti-HBs titers of >10 and >100 mIU/mL, respectively, as a primary response. The anti-HBs titers measured at 1 and 2 years after vaccination were significantly correlated with those of the primary response (1 year: r=0.893, p100 mIU/mL at the primary response maintained an anti-HBs titer of >10 mIU/mL [1 year after vaccination, 208/209 (99.5%); 2 years after vaccination, 72/81 (90.1%)]. However, in subjects with a primary response of 10-100 mIU/mL the anti-HBs titer frequently declined; 17/38 (44.7%) and 9/10 (90.0%) subjects had a titer of

In this study, we investigated the relationships between body weight (BW), computed tomography (CT)-assessed abdominal adipose tissue, and the glycemic metabolic profile in obese Japanese patients following laparoscopic sleeve gastrectomy (LSG). This study analyzed adipose tissue compartments using CT methods before and 1 year after LSG. Thirty obese patients were studied, and variables measured included visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), density of VAT (VAT-D), and density of SAT (SAT-D). We also examined the parameters in patients according to whether they had type-2 diabetes (T2DM). LSG induced significant losses in BW, SAT, and VAT after LSG. Additionally, SAT-D and VAT-D both increased and fasting plasma glucose (FPG) and HbA1c, but not C-peptide, decreased after surgery. ΔSAT and ΔVAT were positively related, and ΔSAT-D and ΔVAT-D were negatively related to ΔBW and/or FPG. Furthermore, a multivariate regression model showed that total BW loss (TBWL) was closely related to ΔSAT (β = 0.84; p < 0.001) and ΔVAT-D (β = -0.45; p < 0.05) and improvement of FPG was related to ΔVAT (β = 0.61; p < 0.05) after LSG. Finally, ΔFPG was correlated with ΔVAT in 16 T2DM patients (r = 0.58; p < 0.05) but not in non-T2DM patients. TBWL was related to ΔSAT and ΔVAT-D, and improvement of FPG was related to ΔVAT in obese Japanese patients after LSG.

Although patients with diabetes reportedly have more back pain and worse patient-reported outcomes than those without diabetes after lumbar spine surgery, the impact of diabetes on postoperative recovery in pain or numbness in other regions is not well characterized. In this study, the authors aimed to elucidate the impact of diabetes on postoperative recovery in pain/numbness in four areas (back, buttock, leg, and sole) after lumbar spine surgery. The authors retrospectively reviewed 993 patients (152 with diabetes and 841 without) who underwent decompression and/or fixation within three levels of the lumbar spine at eight hospitals during April 2017–June 2018. Preoperative Numerical Rating Scale (NRS) scores in all four areas, Oswestry Disability Index (ODI), and Euro quality of life 5-dimension (EQ-5D) were comparable between the groups. The diabetic group showed worse ODI/EQ-5D and greater NRS scores for leg pain 1 year after surgery than the non-diabetic group. Although other postoperative NRS scores tended to be higher in the diabetic group, the between-group differences were not significant. Diabetic neuropathy caused by microvascular changes may induce irreversible nerve damage especially in leg area. Providers can use this information when counseling patients with diabetes about the expected outcomes of spine surgery.

Context Although primary aldosteronism (PA) reduces quality of life (QOL), there have been no reports on whether treatment with a mineralocorticoid receptor antagonist (MRA) improves QOL in Japanese PA patients. Objective Using the 36-Item Short-Form Health Survey (SF-36), we compared the QOL of PA patients before and after treatment and evaluated whether the effectiveness of MRAs differs by sex and serum potassium level. Methods In 50 patients diagnosed with PA (with or without hypokalemia) and treated with an MRA, the SF-36 scores, blood pressure, and clinical features were assessed before, and 3 and 6 months after treatment. Separate analyses were also conducted for males and females. Results The normative mean SF-36 score of the healthy subjects was 50. The pretreatment Role-Physical (RP) (46.7 ± 1.8, P = .019), General Health (47.1 ± 1.3, P = .042), and Role-Emotional (47.2 ± 1.7, P = .045) SF-36 subscale scores of all PA patients were significantly lower than those of healthy subjects but were improved by MRA treatment. Females with PA had a lower RP score (45.1 ± 2.2, P = .008), which was not improved by MRA treatment (46.1 ± 2.4, P = .036). In addition, PA patients with hypokalemia had a lower Mental Health SF-36 subscale score (43.2 ± 4.4, P = .041), which was improved by treatment with an MRA. Conclusion MRAs improved the QOL of Japanese PA patients, but female PA patients may be more resistant to MRAs.

Background Pathological angiogenesis is involved in the development of hepatocellular carcinoma. In patients with chronic hepatitis C (CHC), the level of angiogenic factor angiopoietin (ANGP)-2 is reported to be increased in the blood, correlating with fibrosis. In this study, we aimed to clarify whether blood ANGP-2 is useful as a biomarker for liver angiogenesis and fibrosis in CHC patients and to further reveal the relationship between such pathology in a carbon tetrachloride (CCl4)-treated liver fibrosis mouse model. Methods Plasma levels of ANGP-2, expression of a liver sinusoidal endothelial cell (LSEC) marker (CD31), collagen deposition (Sirius Red staining) in the liver, clinical fibrosis markers (Mac-2 binding protein glycosylation isomer, virtual touch quantification, and liver stiffness measurement), and liver function (albumin bilirubin score) were examined in CHC patients. To determine the effects of an anti-angiogenic agent on liver fibrosis in vivo, sorafenib was administered to the CCl4-treated mice (BALB/c male). Results The plasma levels of ANGP-2 were increased in CHC patients compared to healthy volunteers and decreased by the eradication of hepatitis C with direct-acting antivirals. In addition, plasma ANGP-2 levels were correlated with CD31 expression, collagen deposition, clinical fibrosis markers, and liver function. Sorafenib inhibited liver angiogenesis and fibrosis in the CCl4-treated mice and was accompanied by decreased ANGP-2 expression in LSECs. Conclusions ANGP-2 may serve as a useful biomarker for liver angiogenesis and fibrosis in CHC patients. In addition, angiogenesis and fibrosis may be closely related.

Study design Retrospective study using prospectively collected data. Objective This study aimed to investigate the effect of alternative antimicrobial prophylaxis agents on surgical site infections (SSIs) after spine surgery. Summary of background data Although the use of alternative antimicrobial prophylaxis agents might have a negative effect on SSI prevention, their association with SSI risk in spine surgery remains unclear. Methods We used the registry data of consecutive patients undergoing spine surgery from April 2017 to January 2020 in four institutions participating in the University of Tokyo Spine Group. Before March 2019, all institutions used cefazolin for antimicrobial prophylaxis. After March 2019, the institutions used broad-spectrum beta-lactam agents as an alternative due to a cefazolin shortage in Japan. Results Among the 3841 enrolled patients (2289 males), 2024 received cefazolin and 1117 received alternative agents. The risk of reoperation for deep SSI within 30 days of spine surgery was significantly higher in the alternative antimicrobial prophylaxis agent group (adjusted odds ratio [aOR] 1.96; 95% confidence interval [CI], 1.15-3.35; P = 0.014). In subgroup analyses, the SSI risk was significantly higher in the thoracolumbar surgery group (aOR 1.98; 95% CI, 1.06-3.73; P = 0.03). A nonsignificant consistent trend was found in all other subgroups: posterior decompression (aOR 1.91; 95% CI, 0.86-4.21; P = 0.11); posterior fixation (aOR 2.05; 95% CI, 0.99-4.24; P = 0.05); and cervical spine surgery (aOR 2.30; 95% CI, 0.82-6.46; P = 0.11). Conclusion Alternative antimicrobial prophylaxis agents increased the risk of reoperation for SSI after spine surgery compared with cefazolin. Our study supports the current practice of using first-generation cephalosporins as first-line antimicrobial prophylaxis agents in spine surgery as recommended in multiple guidelines.Level of Evidence: 3.

Background and objectives: Minimally invasive surgery has become popular for posterior lumbar interbody fusion (PLIF). Microendoscope-assisted PLIF (ME-PLIF) utilizes a microendoscope within a tubular retractor for PLIF procedures, however, there are no published reports that compare Microendoscope-assisted to open PLIF. Here we compare the surgical and clinical outcomes of ME-PLIF with those of open PLIF. Materials and Methods: A total of 155 consecutive patients who underwent single-level PLIF were registered prospectively. Of the 149 patients with a complete set of preoperative data, 72 patients underwent ME-PLIF (ME-group), and 77 underwent open PLIF (open-group). Clinical and radiographic findings collected one year after surgery were compared. Results: Of the 149 patients, 57 patients in ME-group and 58 patients in the open-group were available. The ME-PLIF procedure required a significantly shorter operating time and involved less intraoperative blood loss. Three patients in both groups reported dural tears as intraoperative complications. Three patients in ME-group experienced postoperative complications, compared to two patients in the open-group. The fusion rate in ME-group at one year was lower than that in the open group (p = 0.06). The proportion of patients who were satisfied was significantly higher in the ME-group (p = 0.02). Conclusions: ME-PLIF was associated with equivalent post-surgical outcomes and significantly higher rates of patient satisfaction than the traditional open PLIF procedure. However, the fusion rate after ME-PLIF tended to be lower than that after the traditional open method.

Background Anisakiasis is a parasitic infection caused by Anisakis worms found in raw fish. Most cases of anisakiasis occur in the stomach and rarely occur in the intestine. It is extremely rare for live larvae to break through the intestine into the mesentery and cause severe intestinal ischemia. Anisakiasis can be treated conservatively, because the larvae will die in approximately 1 week, but, sometimes, a serious condition can arise, as in this case. We report the first case of extraluminal anisakiasis in which a live Anisakis worm caused severe intestinal ischemia. Case presentation The patient was a 26-year-old woman who ate squid a week prior. She had abdominal pain and was admitted to our emergency department. On physical examination, abdominal guarding and rebound tenderness were present in her lower abdomen. Contrast-enhanced computed tomography showed ascites, the whirl sign, localized submucosal edema of the intestinal wall, and a dilated small bowel segment with edema. We suspected the strangulated small bowel obstruction based on the CT-scan findings. To rule out the strangulated small bowel obstruction, laparoscopic exploration was performed. Bloody ascites in the pouch of Douglas and severe inflammation in 20 cm of the ileum were observed. An Anisakis larva had perforated the intestinal wall and was found alive in the mesentery. The ileum had developed a high degree of ischemia, so the affected section was resected. Histopathological examination revealed that the Anisakis worm body was in the inflamed mesentery and caused a high degree of ischemia in the intestinal tract. The patient was discharged 9 days after surgery. Conclusions A living Anisakis larva punctured the mesentery of the small intestine, resulting in severe intestinal ischemia. As seen in this case, intestinal anisakiasis may cause serious symptoms, and a low threshold for performing diagnostic laparoscopy for the early diagnosis of bowel ischemia secondary to anisakiasis can be useful in determining the definite diagnosis and indications for resection.

is missing (Short communication)

Objective In the present study, we investigated the most useful confirmatory test for reflecting the severity of primary aldosteronism (PA), by evaluating 24-hour blood pressure (BP), urine albumin, left ventricular mass (LVM), and intima media thickness (IMT). Methods This study included 113 patients (80 PA and 33 non-PA hypertensive patients) who were admitted to Oita University Hospital and evaluated using ambulatory blood pressure monitoring (ABPM). First, casual blood pressure (BP) and ABPM parameters were compared between PA and non-PA patients. Second, patients were divided into PA-positive and PA-negative groups based on confirmatory tests, including the saline infusion test (SIT), captopril challenge test (CCT), and oral salt loading test (OSLT), and casual BP and ABPM parameters were compared between the 2 groups. In addition, urine albumin excretion, LVM, and maximum IMT as markers of organ damage were compared between the 2 groups. Results The ABPM parameters but not casual BP, were higher in PA patients than in non-PA patients. Nocturnal and 24-hour systolic BP (SBP) in OSLT-positive patients were significantly higher than in OSLT-negative patients. ABPM parameters in other confirmatory tests were not different between the PA-positive and PA-negative groups. Urine albumin excretion in OSLT-positive patients was significantly higher than in the OSLT-negative patients. However, in other confirmatory tests, organ damage markers were not different between the 2 groups. Conclusion The OSLT is potentially useful not only for the diagnosis of PA but also for assessment of 24-hour SBP and organ damage, as indicated by urine albumin excretion.

Background Hepatitis B surface antigen (HBsAg) loss is an ideal goal for chronic hepatitis B patients. Antiretroviral therapy (ART) in hepatitis B virus/human immunodeficiency virus-1 (HBV/HIV-1)–coinfected patients can lead to hepatic flare (HF) caused by immune reconstitution-induced inflammatory syndrome (IRIS). Here, we investigated the impact of IRIS-HF on HBsAg loss. Methods This was a retrospective study of 58 HBV/HIV-1–coinfected subjects HBsAg-positive for ≥6 months before ART initiation and followed for ≥1 year (median 9.9 years) after ART initiation. We examined humoral factors in sera from healthy volunteers, HIV-monoinfected patients, and HBV/HIV-1–coinfected patients with IRIS-HF or acute hepatitis B infection. Results During ART, HBsAg loss was observed in 20 of 58 HBV/HIV-1–coinfected patients (34.5%). Of the 58 patients, 15 (25.9%) developed IRIS-HF within 12 months of ART initiation. HBsAg loss was more frequent among patients who developed IRIS-HF (11/15, 73.3%) than those who did not (9/43, 20.9%). Multivariate analysis showed IRIS-HF was an independent predictor of subsequent HBsAg loss. Younger age and higher baseline HBV DNA titer were associated with IRIS-HF. Elevation of sCD163, not CXCL9, CXC10, CXCXL11, or CXCL13, was observed at IRIS-HF. Conclusions IRIS-HF was associated with HBsAg loss in HBV/HIV-1–coinfected patients.

is missing (Quiz)

Purpose We aimed to evaluate the safety and feasibility of the distal transradial approach (DTRA) as a novel technique for cerebral angiography based on our institutional initial experience. Methods We retrospectively analyzed our institutional database of consecutive diagnostic cerebral angiographies performed with DTRA from December 2018 to August 2019. Patient demographics and clinical and procedural data were recorded. Results In total, 51 diagnostic cerebral angiographies in 51 patients (age, 15–83 years; mean age, 59.4 years, SD 13.5; 35 (69%) females) were performed or attempted with DTRA. Ultrasound evaluation showed that the mean inner distal radial artery diameter was significantly smaller than the mean inner forearm radial artery diameter (2.19 mm vs. 2.56 mm, P Conclusion Our results demonstrate that DTRA could become a standard approach for diagnostic cerebral angiography owing to the low complication rate and the high cannulation success rate.

Liver-related diseases are the third-leading causes (9.3%) of mortality in type 2 diabetes (T2D) in Japan. T2D is closely associated with nonalcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. No pharmacotherapies are established for NASH patients with T2D. Though vitamin E is established as a first-line agent for NASH without T2D, its efficacy for NASH with T2D recently failed to be proven. The effects of pioglitazone on NASH histology with T2D have extensively been established, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and NAFLD (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin has already entered the phase 3 trial (DEAN study). A key clinical need is to determine the kinds of antidiabetic drugs that are the most appropriate for the treatment of NASH to prevent the progression of hepatic fibrosis, resulting in HCC or liver-related mortality without increasing the risk of cardiovascular or renal events. Combination therapies, such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide/GLP-1, are under development. This review focused on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2D.