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Objective: This study was performed to demonstrate the clinical application of duodenum-preserving pancreatic head resection (DPPHR) as a surgical treatment for pancreatic neuroendocrine tumors (PNETs) in terms of both curability and maintenance of postoperative quality of life. Methods: Seven patients diagnosed with PNETs underwent DPPHR from January 2011 to December 2021 at our institution. We investigated the clinical relevance of DPPHR based on the patients’ clinicopathological findings. Results: The median operative time was 492 min, and the median blood loss was 302 g. Postoperative complications were evaluated according to the Clavien–Dindo classification, and postoperative intra-abdominal bleeding was observed in one patient. Pathological examination revealed a World Health Organization classification of G1 in six patients and G2 in one patient. Microvascular invasion was observed in two patients (29%); however, no patients developed lymph node metastasis or recurrence during the follow-up period. A daughter lesion was observed near the primary tumor in one patient. All patients achieved curative resection, and no tumor specimens showed positive margins. Conclusions: DPPHR facilitates anatomical resection of the pancreatic head in patients with PNETs as well as detailed pathological evaluation of the resected specimen. Therefore, this surgical procedure is an acceptable alternative to pancreaticoduodenectomy or enucleation for patients with PNETs.

Abstract Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard involves time-intensive in vivo transplantation into diabetic immunodeficient mice. Given the susceptibility of isolated islets to hypoxia, we hypothesized that hypoxia present in islets before transplantation could indicate compromised islet quality, potentially leading to unfavorable outcomes. To test this hypothesis, we analyzed expression of 39 hypoxia-related genes in human islets from 85 deceased donors. We correlated gene expression profiles with transplantation outcomes in 327 diabetic mice, each receiving 1200 islet equivalents grafted into the kidney capsule. Transplantation outcome was post-transplant glycemic control based on area under the curve of blood glucose over 4 weeks. In linear regression analysis, DDIT4 (R = 0.4971, P

Abstract Background This study aimed to investigate the effect of the use of new lithotomy stirrups-2 on the pressure dispersal on lower limbs, which may lead to the prevention of well-leg compartment syndrome (WLCS) and deep venous thrombosis (DVT), which are the most commonly associated adverse events with laparoscopic and robot-assisted rectal surgery. Methods A total of 30 healthy participants were included in this study. The pressure (mmHg) applied on various lower limb muscles when using conventional lithotomy stirrups-1 and new type stirrups-2 was recorded in various lithotomy positions; 1) neutral position, 2) Trendelenburg position (15°) with a 0° right inferior tilt, and 3) Trendelenburg position (15°) with a 10° right inferior tilt. Using a special sensor pad named Palm Q®, and the average values were compared between two types of stirrups. Results The use of new lithotomy stirrups-2 significantly reduced the pressure applied on the lower limb muscles in various lithotomy positions compared with the use of lithotomy stirrups-1. The most pressured lower limb muscle when using both lithotomy stirrups was the central soleus muscle, which is the most common site for the development of WLCS and DVT. In addition, when using the conventional lithotomy stirrups-1, the pressure was predominantly applied to the proximal soleus muscle; however, when using lithotomy stirrups-2, the pressure was shifted to the more distal soleus muscle. Conclusion These results suggest that the new lithotomy stirrups-2 is useful in reducing the pressure load on leg muscles, especially on the proximal to central soleus, and may reduce the incidence of WLCS and DVT after rectal surgery performed in the lithotomy position. Further clinical studies are needed to determine whether the use of lithotomy stirrups-2 prevents these complications in various clinical settings.

Abstract This investigation examined the clinical implications of mild vertebral fractures in older community-dwelling residents. Focusing on the locomotion health of older individuals, the earlier reported Obuse study enrolled 415 randomly sampled Japanese residents aged between 50 and 89 years, 411 of whom underwent X-ray evaluations for pre-existing vertebral fractures. A blinded assessment of vertebral fractures based on Genant’s criteria was conducted on the T5-L5 spine for rating on a severity scale. Grade 1 mild fractures were not linked to age in males, but increased with aging in females. Female participants had fewer Grade 1 and 2 fractures (P = 0.003 and 0.035, respectively) but more Grade 3 fractures (P = 0.013) than did males independently of age (Grade 1, 2, and 3: 25%, 16%, and 9% in females and 40%, 22%, and 6% in males, respectively). Weak negative correlations were observed between the number of fractures and bone mineral density in females for all fracture grades (Spearman’s rho: 0.23 to 0.36, P

Abstract In this review article, we focus on recent papers on organ‐preserving pancreatectomy procedures published since 2010. When comparing central pancreatectomy (CP) and distal pancreatectomy (DP), most studies have concluded that the CP group exhibited significantly lower incidence of new‐onset diabetes or diabetes exacerbation than the DP group postoperatively. However, because of increased incidence of morbidities such as pancreatic fistula, the surgeon faces a considerable trade‐off between increased short‐term morbidity and long‐term preservation of endocrine function. When the outcomes of two types of spleen‐preserving DP (Kimura and Warshaw procedures) are compared, most studies mentioned the low incidence of postoperative gastric varices and splenic infarction with the Kimura procedure. Although there are several reports regarding the effect of spleen preservation on prevention of postoperative infections, no report on the contribution of spleen preservation to the prevention of overwhelming post‐splenectomy infection is seen. The advantages of duodenum‐preserving pancreatic head resection (DPPHR) concerning endocrine and exocrine functions continue to be subjects of discussion, mainly due to the limited number of institutions that have adopted this approach; however, DPPHR should be presented as an option for patients due to its low incidence of postoperative cholangitis. Organ‐preserving pancreatectomy requires meticulous surgical techniques, and postoperative complications may increase with this surgery compared with standard pancreatectomy, which may be influenced by the surgeon's skill and the surgical facility where the procedure is performed. Nonetheless, this technique has significant long‐term advantages in terms of endocrine and exocrine functions and its wider adoption in the future is expected.

Pancreatic islet transplantation is one of the clinical options for certain types of diabetes. However, difficulty in maintaining islets prior to transplantation limits the clinical expansion of islet transplantations. Our study introduces a dynamic culture platform developed specifically for primary human islets by mimicking the physiological microenvironment, including tissue fluidics and extracellular matrix support. We engineered the dynamic culture system by incorporating our distinctive microwell-patterned porous collagen scaffolds for loading isolated human islets, enabling vertical medium flow through the scaffolds. The dynamic culture system featured four 12 mm diameter islet culture chambers, each capable of accommodating 500 islet equivalents (IEQ) per chamber. This configuration calculates > five-fold higher seeding density than the conventional islet culture in flasks prior to the clinical transplantations (442 vs 86 IEQ/cm 2 ). We tested our culture platform with three separate batches of human islets isolated from deceased donors for an extended period of 2 weeks, exceeding the limits of conventional culture methods for preserving islet quality. Static cultures served as controls. The computational simulation revealed that the dynamic culture reduced the islet volume exposed to the lethal hypoxia (< 10 mmHg) to ~1/3 of the static culture. Dynamic culture ameliorated the morphological islet degradation in long-term culture and maintained islet viability, with reduced expressions of hypoxia markers. Furthermore, dynamic culture maintained the islet metabolism and insulin-secreting function over static culture in a long-term culture. Collectively, the physiological microenvironment-mimetic culture platform supported the viability and quality of isolated human islets at high-seeding density. Such a platform has a high potential for broad applications in cell therapies and tissue engineering, including extended islet culture prior to clinical islet transplantations and extended culture of stem cell-derived islets for maturation.

Abstract Background Left bundle branch area pacing (LBBAP) is a novel conduction system pacing technique. In this multicenter study, we aimed to evaluate the procedural success, safety, and preoperative predictors of procedural failure of LBBAP. Methods LBBAP was attempted in 285 patients with pacemaker indications for bradyarrhythmia, which were mainly atrioventricular block (AVB) (68.1%) and sick sinus syndrome (26.7%). Procedural success and electrophysiological and echocardiographic parameters were evaluated. Results LBBAP was successful in 247 (86.7%) patients. Left bundle branch (LBB) capture was confirmed in 54.7% of the population. The primary reasons for procedural failure were the inability of the pacemaker lead to penetrate deep into the septum (76.3%) and failure to achieve shortening of stimulus to left ventricular (LV) activation time in lead V6 (18.4%). Thickened interventricular septum (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.15–5.35), severe tricuspid regurgitation (OR, 8.84; 95% CI, 1.22–64.06), and intraventricular conduction delay (OR, 8.16; 95% CI, 2.32–28.75) were preoperative predictors of procedural failure. The capture threshold and ventricular amplitude remained stable, and no major complications occurred throughout the 2‐year follow‐up. In patients with ventricular pacing burden >40%, the LV ejection fraction remained high regardless of LBB capture. Conclusions Successful LBBAP was affected by abnormal cardiac anatomy and intraventricular conduction. LBBAP is feasible and safe as a primary strategy for patients with AVB, depending on ventricular pacing.

The histone H3K27 demethylase, UTX/KDM6A, plays a critical role in the early development of vertebrates, and mutations are frequently found in various cancers. Several studies on developmental and cancer biology have focused on preferential transcriptional regulation by UTX independently of its H3K27 demethylase catalytic activity. Here, we analysed gene expression profiles of wild-type (WT) UTX and a catalytic activity-defective mutant in 786-O and HCT116 cells and confirmed that catalytic activity-dependent and -independent regulation contributes to the expression of most of the target genes. Indeed, the catalytic activity-defective mutant suppressed colony formation similar to the WT in our assay system. However, the expression of several genes was significantly dependent on the catalytic activity of UTX in a cell type-specific manner, which could account for the inherent variation in the transcriptional landscape of various cancer types. The promoter/enhancer regions of the catalytic activity-dependent genes identified here were found to be preferentially modified with H3K4me1 and less with H3K27me3 than those of the independent genes. These findings, combined with previous reports, highlight not only the understanding of determinants for the catalytic activity dependency but also the development and application of pharmaceutical agents targeting the H3K27 or H3K4 modifications.

The Occipito(O)-C2 angle reflects the correct craniocervical spine alignment; however, the poor image quality of standard intraoperative fluoroscopy at times lead to inaccurate measurements. Herein, we preliminarily investigated the relationship between the O-C2 angle and the Gonion-C2 distance, which is based on the positioning of the mandible and the cervical spine. We enrolled patients who underwent cervical spine radiography in neutral, flexion, and extension positions from January 2020 to October 2020. The difference by posture changes for each parameter was defined as the Δ value, and the Spearman's rank correlation coefficient was determined. Furthermore, we determined the cutoff value of the ΔGonion-C2 distance to predict a decrease of > 10° in the ΔO-C2 angle, which is reported to be related to dysphagia and dyspnea. Seventy-four patients were included. Spearman's rank correlations for the neutral, flexion, and extension positions were 0.630 (P < 0.001), 0.471 (P < 0.001), and 0.625 (P < 0.001), respectively, while the cutoff values of the ΔGonion-C2 distance for predicting > 10° in the ΔO-C2 angle were 9.3 mm for the neutral flexion change (sensitivity: 0.435, specificity: 0.882) and 8.3 mm for the extension-neutral change (sensitivity: 0.712, specificity: 0.909). The O-C2 angle and Gonion-C2 distances correlated; however, this correlation was weaker in the flexed position. Nevertheless, the ΔGonion-C2 distance can be used as a warning sign for postoperative complications after posterior occipital bone fusion surgery, because a decrease of > 10° in the ΔO-C2 angle can be predicted with high specificity.

Abstract Myxoid liposarcoma (MLS) is a common subtype of liposarcoma. Although the prognosis is generally good, there are factors known to be associated with poor prognosis. Accurate indices are important to predict prognosis. We aimed to assess the usefulness of immunohistochemistry for phosphohistone H3 (PHH3) as a potential biomarker in comparison with Ki-67 antigen and other prognostic factors. Twenty-five patients with MLS were evaluated. Age, sex, depth of tumor, tumor size, surgical margin, oncological outcome, histological grade, presence of necrosis, proportion of round cell component (RC%), PHH3 index, and Ki-67 index were examined. Prognostic factors of the examination criteria were statistically analyzed, survival rate analyses were performed using the Kaplan–Meier method, and multivariate analysis was performed using Cox proportional-hazard regression analysis. The number of PHH3-positive tumor cells and the PHH3 and Ki-67 indices demonstrated a statistical correlation with the prognosis of MLS in univariate analysis (P

This short-term survey examined the effect of body part pain on subjective and objective handball performance in Japanese male national handball athletes. Fourteen athletes participated in this study. Assessments of pain in 10 body parts and subjective performance (concentration and satisfaction with body movement) were performed using a visual analog scale from 0 to 10 over four consecutive training days. Monitoring of heart rate and body acceleration during training was also performed to quantify the objective performance. Path analysis and linear mixed modeling were employed to assess the relationship between body pain scores and subjective/objective handball performance. Over the four days of the study period, the body part in which most athletes reported pain was the dominant shoulder (6 of 14 athletes), followed by the dominant knee, the dominant elbow, the dominant ankle joint, and the non-dominant ankle joint (3 of 14 athletes). The path analysis revealed that pain in the dominant elbow negatively correlated with concentration (standardized path coefficient = −0.644, p = 0.00), which was associated with satisfaction with body movement (standardized path coefficient = 0.704, p = 0.00). No significant effect of body pain on objective performance (heart rate and body acceleration) was found among the athletes in this study. The results suggested that the elite athletes were practicing with pain. Even if pain does not physically affect athletes’ objective performance, pain in the upper extremities, associated with the primary handball movement of throwing, may reduce the quality of practice by lowering athletes’ subjective performance.

A 51-year-old otherwise healthy woman was referred to our hospital with a fever of unknown origin, liver dysfunction, and anemia. One month prior, she had persistent and spontaneous anterior neck pain, with no exacerbation during swallowing or neck movements. Physical examination revealed no pharyngeal or tonsillar abnormalities, heart murmur, arthritis, skin rash, or lymphadenopathy, except for mild bilateral common carotid artery tenderness at the level of the thyroid cartilage. Blood tests showed nonspecific chronic inflammatory findings, anemia, and liver damage, whereas blood cultures, viral antibodies, interferon-γ release assay, and antibodies specific for any collagen disease showed negative results. Echocardiography and computed tomography without contrast of the neck, chest, abdomen, and pelvis showed no apparent abnormalities. She was subsequently diagnosed with Takayasu arteritis using positron emission tomography. Identifying a characteristic history of bilateral carotid artery tenderness and subsequent positron emission tomography can be useful for diagnosing Takayasu arteritis.

The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by O-GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated O-GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is O-GlcNAcylated on human DNMT1. Functional studies in human and mouse cells further revealed that O-GlcNAcylation of DNMT1-S878 results in an inhibition of methyltransferase activity, resulting in a general loss of DNA methylation that preferentially occurs at partially methylated domains (PMDs). This loss of methylation corresponds with an increase in DNA damage and apoptosis. These results establish O-GlcNAcylation of DNMT1 as a mechanism through which the epigenome is regulated by glucose metabolism and implicates a role for glycosylation of DNMT1 in metabolic diseases characterized by hyperglycemia.

“Firefly rats” ubiquitously express the luciferase reporter gene under the control of constitutively active ROSA26 promoter in inbred Lewis rats. Due to the minimal immunogenicity of luciferase, wide applications of Firefly rats have been reported in solid organ/cell transplantation studies for in vivo imaging, permitting quantitative and non-invasive tracking of the transplanted graft. ROSA26 is a non-coding gene and generally does not affect the expression of other endogenous genes. However, the effect of ubiquitous luciferase expression on islet morphology and function has not been thoroughly investigated, which is critical for the use of Firefly rats as islet donors in islet transplantation studies. Accordingly, in vivo glucose homeostasis (i.e., islet function in the native pancreas) was compared between age-matched luciferase-expressing Firefly rats and non-luciferase-expressing rats. In vivo assessments demonstrated no statistical difference between these rats in non-fasting blood glucose levels, intraperitoneal glucose tolerance tests, and glucose-stimulated serum C-peptide levels. Furthermore, islets were isolated from both rats to compare the morphology, function, and metabolism in vitro . Isolated islets from both rats exhibited similar in vitro characteristics in post-isolation islet yield, islet size, beta cell populations, insulin content per islet, oxygen consumption rate, and glucose-stimulated insulin secretion. In conclusion, ubiquitous luciferase expression in Firefly rats does not affect their islet morphology, metabolism, and function; this finding is critical and enables the use of isolated islets from Firefly rats for the dual assessment of islet graft function and bioluminescence imaging of islet grafts.

Abstract Aim This study aimed to compare the incidence of postoperative nonalcoholic fatty liver disease (NAFLD), postoperative cholangitis, and fibrosis‐4 (FIB)‐4 index in patients who underwent duodenum‐preserving pancreatic head resection (DPPHR) and pancreaticoduodenectomy (PD) for low‐grade malignant tumors and verify the usefulness of DPPHR in preventing the occurrence of these disorders. Methods This retrospective study included 70 patients who underwent PD (n = 39) and DPPHR (n = 31) between 2006 and 2018 for benign or low‐grade malignant tumors. The present study compared the preoperative background, cumulative incidence of postoperative NAFLD and cholangitis, and other biochemical markers, including the FIB‐4 index. Subanalysis by propensity score matching (PSM) analysis was conducted to minimize treatment selection bias. Results In terms of the cumulative incidence of NAFLD, the 5‐y incidence was significantly lower in the DPPHR group than in the PD group both before (10% vs 38%, P = .002) and after (13% vs 38%, P = .008) matching. Multivariate analyses identified DPPHR as the only independent preventive factor for postoperative NAFLD (hazard ratio: 0.160, 95% confidence intervals: 0.034–0.76, P = .021). The 5‐y cumulative incidence of postoperative cholangitis was significantly higher in the PD group than in the DPPHR group before (51% vs 3%, P

Objectives: Heterotopic ossification (HO), which occurs when bone tissue forms outside the skeleton, is extremely rare in rectal cancer. Adenocarcinoma is the histological type of all reported primary colorectal cancers with HO. However, in the present case, we observed areas of adenocarcinoma with squamous cell carcinoma-like differentiation. Here we conducted histopathological and immunohistochemical analyses to identify the mechanisms of HO development, to differentiate between adenocarcinoma and squamous cell carcinoma-like phenotypes, and to understand the associated prognostic implications. Case report: A 62-year-old woman was admitted to our hospital with symptoms of intermittent hematochezia without abdominal pain. Colonoscopy revealed stenosis with a protuberant mass in the rectum. Abdominopelvic contrast-enhanced computed tomography showed irregular wall thickness of the rectum, multiple lymph node metastases, and liver metastases. The rectal tumor exhibited calcified deposits with marked hyperintensity. We then performed Hartmann’s operation and D3 lymph node resection. The biopsy specimen revealed tubular and solid adenocarcinoma nests and squamous carcinoma-like components over a necrotic extent without secreted mucin. She received chemotherapy (mFOLFOX6 with bevacizumab) as the first option and is alive 5 months after surgery. Conclusion: To the best of our knowledge, this is the first case of heterotopic ossification in a primary rectal cancer with squamous cell carcinoma-like differentiation that was surgically resected. This case suggests that BMP-2 transformed fibroblasts and pluripotent stem cells into osteocytes. We conclude that the squamous cell carcinoma-like lesion was squamous metaplasia of adenocarcinoma.

Abstract Lethal giant larvae homolog 2 (LLGL2) and solute carrier family 7 member 5 (SLC7A5) have been reported to be involved in resistance to endocrine therapy. This study aimed to assess the effects of LLGL2/SLC7A5 co-expression in predicting prognosis and response to tamoxifen therapy in ERα-positive breast cancer patients according to LLGL2/SLC7A5 mRNA and protein expression in long-term follow-up invasive breast cancer tissues. We identified that low LLGL2/SLC7A5 mRNA co-expression (LLGL2 low/SLC7A5 low) was associated with disease-free survival (DFS) compared with other combination groups in all breast cancer patients. In ERα-positive breast cancer patients, LLGL2 low/SLC7A5 low showed longer DFS and overall survival (OS) compared with LLGL2 high/SLC7A5 high and a positive trend of longer survival compared with the other combination groups. We also observed that LLGL2 low/SLC7A5 low showed longer survival compared with LLGL2 high/SLC7A5 high in ERα-positive breast cancer patients receiving adjuvant tamoxifen therapy. Multivariate analysis demonstrated that LLGL2 low/SLC7A5 low was an independent favorable prognostic factor of both DFS and OS, not only in all breast cancer patients, but also in ERα-positive breast cancer patients. High co-expression of LLGL2 and SLC7A5 protein showed a positive trend of shorter survival. Our study showed that co-expression of LLGL2 and SLC7A5 mRNA is a promising candidate biomarker in early breast cancer patients.

Abstract Background Superior mesenteric artery (SMA) syndrome denotes a mechanical duodenal obstruction between the SMA and aorta. Total parenteral or enteral nutrition is the treatment of choice. However, surgical intervention is indicated if the patient’s condition does not improve with conservative treatment. Here, we describe a case of SMA syndrome with dysphagia treated by laparoscopic gastrojejunostomy with laparoscopic-assisted percutaneous endoscopic gastrostomy. Case presentation A 64-year-old man was admitted to another hospital because of appetite loss and vomiting. There, he was diagnosed as having superior mesenteric artery (SMA) syndrome after appropriate investigation. He had had a cerebral infarction at age 57 years, since which he had lived in social housing because of complications of that infarction. A nasogastric tube was inserted into the third portion of the duodenum beyond the constricted section. He was discharged 2 months after admission his condition having improved. He was subsequently referred to our hospital for gastrostomy because the nasogastric tube had been in place for a long time and his condition had not improved. Additionally, gastrostomy was needed as a route for enteral nutrition because he had dysphagia, which had persisted despite attempts at rehabilitation, restricting his food intake to small amounts. Computed tomography (CT) revealed compression of the third portion of the duodenum between the SMA and aorta. After obtaining informed consent, we planned an operative procedure. We performed laparoscopic gastrojejunostomy under general anesthesia, followed by laparoscopic-assisted percutaneous endoscopic gastrostomy. The operation time was 156 min and there was little blood loss. Contrast radiography on postoperative day 3 revealed no evidence of leakage or stenosis. Enteral nutrition via the gastrostomy was started. He was discharged from our hospital on the 27th postoperative day. The gastrostomy was well tolerated and there has been no evidence of recurrence of SMA syndrome during follow-up. Conclusion Gastrostomy is often performed to provide a route for administering enteral nutrition in patients with dysphagia. Development of SMA syndrome in patients with dysphagia necessitates operative management of the obstruction. Here, we describe a case of SMA syndrome with dysphagia treated by laparoscopic gastrojejunostomy with laparoscopic-assisted percutaneous endoscopic gastrostomy.

Abstract In this report, we describe a case of highly advanced hepatocellular carcinoma with tumor thrombosis extending into the main portal vein of the pancreas that was successfully treated with adjuvant lenvatinib after right hepatic resection with thrombectomy. A 70-year-old woman was referred from the clinic because of elevated hepatobiliary enzymes. The patient was positive for the hepatitis B virus antigen at our hospital. The tumor markers were highly elevated with alpha-fetoprotein (14.5 U/mL) and protein induced by vitamin K absence (PIVKAII) (1545 ng/mL), suggesting hepatocellular carcinoma. Dynamic abdominal computed tomography showed an early enhanced tumor approximately 6 cm in size and portal vein tumor thrombosis filling the main portal vein, but not extending into the splenic or superior mesenteric vein (SMV). On magnetic resonance imaging 1 week after CT, portal vein tumor thrombosis had extended to the confluence of the splenic vein with the SMV, indicating rapid tumor growth. Thus, we performed emergent right hepatectomy with tumor thrombectomy. Postoperatively, we treated the patient with lenvatinib for a tumor reduction surgery. Fortunately, the patient was alive 2 years postoperatively without recurrence. This case report suggests that a favorable outcome may be achieved with multidisciplinary treatment including resection and postoperative treatment with lenvatinib.

Abstract The natural history of intracholecystic papillary neoplasm (ICPN), especially the speed of growth from small benign to a carcinomatous lesion, is quite unrevealed. Here, we report an extremely rare case of ICPN, in which the papillary lesion was observed transforming from small and benign to malignant using abdominal ultrasound (AUS) over 2 years during routine health checks. A 44-year-old man underwent a routine health check-up. The initial AUS showed a small sessile polyp in the gallbladder, which enlarged slightly at the next AUS, a year later. In the third year, the polypoid lesion enlarged markedly, with a maximum diameter of 10 × 9 × 7 mm. Therefore, a laparoscopic cholecystectomy was performed. Microscopically, the 10 mm tumor had intracytoplasmic mucus, and a clear cytoplasm compatible with gastric-type features. Immunohistochemical analysis showed positive staining of atypical cells for MUC6 and PAS. These findings led to the diagnosis of ICPN with high-grade intraepithelial neoplasia of the gastric type. In conclusion, sessile polyps with rapid growth might be a crucial finding in the early stage of ICPN.

Despite advances in treatment options, such as corticosteroid administration and less invasive respiratory support, bronchopulmonary dysplasia (BPD) remains an important prognostic factor in preterm infants. We previously reported that furin regulates changes in lung smooth muscle cell phenotypes, suggesting that it plays a critical role in BPD pathogenesis. Therefore, in this study, we aimed to evaluate whether it regulates the alveolarization of immature lungs through activating alveolarization-driving proteins. We first examined furin expression levels, and its functions, using an established hyperoxia-induced BPD mouse model. Thereafter, we treated mice pups, as well as primary myofibroblast cell cultures, with furin inhibitors. Finally, we administered the hyperoxia-exposed mice pups with recombinant furin. Immunofluorescence revealed the co-expression of furin with alpha-smooth muscle actin. Hyperoxia exposure for 10 d decreased alveolar formation, as well as the expression of furin and its target, IGF-1R. Hexa-D-arginine administration also significantly inhibited alveolar formation. Another furin inhibitor, decanoyl-RVKR-chloromethylketone, accumulated pro-IGF-1R, and decreased IGF-1R phosphorylation in myofibroblast primary cultures. Finally, recombinant furin treatment significantly improved alveolarization in hyperoxia-exposed mice pups. Furin regulates alveolarization in immature lungs. Therefore, this study provides novel insights regarding the involvement of furin in BPD pathogenesis, and highlights a potential treatment target for ameliorating the impact of BPD.

Abstract The recent increase in the older adult population has led to a higher prevalence of cognitive impairment, which is often overlooked in routine health examinations. Citizens aged 50–89 years were targeted for this cohort survey by random sampling from the resident registry of a cooperating town in 2014. A total of 411 participants (202 male and 209 female) were enrolled. We analyzed the distribution of cognitive function test scores as determined by Montreal Cognitive Assessment and Mini-Mental State Examination tests in each age (50’s, 60’s, 70’s and 80’s) and sex group to examine whether cognitive decline could be detected by sagittal spinal balance measurement based on a radiological approach. Sagittal spinal balance was quantitatively measured as sagittal vertical axis (SVA). We observed significant associations for higher age and/or SVA anteriorization with lower cognitive function. In males, spinal balance anteriorization was associated with cognitive decline independently of age, with combinations of age and SVA also making valid cognitive decline determinations; male cases of SVA ≥ 100 mm at any age, SVA ≥ 90 mm at ≥ 70 years, and SVA ≥ 70 mm at ≥ 80 years were all more likely to have cognitive decline than cases below those values. For females, cognitive decline was more likely in cases of SVA ≥ 70 mm, regardless of age. Thus, spinal balance anteriorization can be regarded as an easily visible indicator of latent cognitive decline in community-dwelling older people.

IntroductionNon-technical skills are essential for surgical patient safety and are implemented in clinical practice. However, training for non-technical skills has not been thoroughly investigated. This study aimed to evaluate the learning curve for non-technical skill-based education in herniorrhaphy.MethodsQuality improvement initiatives, including non-technical skill-based intervention, were performed in the department of surgery. The intervention included declaring the patient safety policy, briefing and debriefing, and criterion for the switching of places of the trainee and instructor as defined by the department. Patients who underwent herniorrhaphy from April 2014 to September 2017 were included.ResultsA total of 14 trainees and nine instructors in the pre-intervention period and 14 trainees and seven instructors in the intervention period were included in this study. The median experience of each trainee was 28 and 15 cases in the pre-intervention and intervention groups, respectively. A total of 749 patients were included: 473 in the pre-intervention period and 328 in the intervention period. Demographics and hernia types were mostly similar between groups, and morbidity was not statistically different between the two groups (3.4 vs. 1.2%, p = 0.054). The nonlinear regression model showed an early decline and deep plateau phase of the learning curve in the intervention group. A significant difference was observed in the plateau operation time (61 min in the pre-intervention group and 52 min in the intervention group).ConclusionThis study demonstrated the effectiveness of non-technical skill-based intervention for surgical training. An early decline and deep plateau of the learning curve can be achieved with well-implemented quality improvement initiatives. Nonetheless, further studies are needed to establish a training program for non-technical skill-based learning.

Abstract A 30‐year‐old man was referred to our department because of repeated acute‐onset and short‐lasting fatigue attacks, which occurred from 3 months before the referral. He had no abnormal findings in blood tests, electrocardiogram (including 24‐ h monitoring), or head MRI (including angiography). His vital signs were unremarkable, and his physical examination revealed no abnormal findings. Detailed history‐taking with closed‐ended questions revealed the occurrence of tingling sensation from the right fingers as the aura before his attacks. Electroencephalography was performed, which revealed focal epilepsy. Levetiracetam resolved his symptoms. Physicians could consider non‐convulsive epilepsy as a potential cause of repeated acute‐onset and short‐lasting fatigue attacks of unknown etiology after underlying conditions, such as metabolic diseases, have been ruled out.

Abstract Background The association between pancreatic fistula (PF) after pancreaticoduodenectomy (PD) and preoperative exocrine function is yet to be elucidated. This study aimed to evaluate the association between the preoperative results of the 13C-trioctanoin breath test and the occurrence of PF, showing the clinical relevance of the breath test in predicting PF. Method A total of 80 patients who underwent 13C-trioctanoin breath tests prior to PD from 2006 to 2018 were included in this study. Univariate and multivariate analyses were conducted to reveal the preoperative predictors of PF, showing the association between 13C-trioctanoin absorption and PF incidence. Results Among 80 patients (age, 68.0 ± 11.9 years, 46 males and 34 females; 30 pancreatic ductal adenocarcinoma [PDAC]/50 non-PDAC patients), the incidence of PF was 12.5% (10/80). Logistic regression analysis results revealed that the frequency of PF increased significantly as the 13C-trioctanoin breath test value (Aa% dose/h) increased (odd’s ratio: 1.082, 95% confidence interval: 1.007–1.162, p = 0.032). Moreover, the optimal cutoff value of the preoperative fat absorption level to predict PF was 38.0 (sensitivity, 90%; specificity, 74%; area under the curve, 0.78; p = 0.005). Indeed, the incidence of PF was extremely higher in patients whose breath test value was greater than 38.0 (33%, 9/27) compared with that in patients with values less than 38.0 (1.8%, 1/53). Conclusions Favorable preoperative fat absorption evaluated using the 13C-trioctanoin breath test is a feasible and objective predictor of PF after PD.

Introduction Children’s influenza diagnosis by their guardians has been reported to be highly accurate, but clinical factors that improve the reliability of a guardian’s diagnosis are unclear. Aim To determine the accuracy of guardians’ influenza diagnosis of their children, investigate clinical factors that improve the diagnostic accuracy, and determine the additional clinical value of the guardian’s diagnosis. Methods A prospective observational study was conducted at a primary care clinic in Japan from December 2017 to April 2019. Pre-examination checklists completed by guardians accompanying children aged

Abstract Background Performing major hepatectomy for patients with marginal hepatic function is challenging. In some cases, the procedure is contraindicated owing to the threat of postoperative liver failure. In this case report, we present the first case of marginal liver function (indocyanine green clearance retention rate at 15 min [ICGR15]: 28%) successfully treated with right hepatectomy, resulting in total caudate lobe preservation. Case presentation A 71-year-old man was diagnosed with sigmoid colon cancer with three liver metastases (S5, S7, and S8). All of metastatic lesions shrunk after chemotherapy, but his ICGR15 and indocyanine green clearance rate (ICGK) were 21% and 0.12, respectively. Moreover, the remnant liver volume was only 39%. Therefore, portal venous embolism (PVE) of the right portal vein was suggested. Portography showed divergence of the considerably preserved right caudate lobe branch (PV1R) from the root of the right portal vein. The liver function was reevaluated 18 days after PVE was suggested. During this time, the ICGR15 (21–28%) and ICGK rate (0.12–0.10) deteriorated. The right caudate lobe was significantly enlarged; thus, a total caudate lobe-preserving hepatectomy (TCPRx) was performed. Patients eligible for TCPRx included those with (1) hepatocellular carcinoma or metastatic liver cancer, (2) no tumor in the caudate lobe, (3) marginal liver function (ICG Krem greater than 0.05 if TCPRx was adapted; otherwise, less than 0.05) and Child–Pugh classification category A, and (4) preserved PV1R and right caudate bile duct branch. The procedure was performed through (A) precise estimation of the remnant liver volume preoperatively, (B) repeated intraoperative cholangiography to confirm the biliary branch of the right caudate lobe (B1R) conservation, and (C) stapler division of posterior and anterior Glisson’s pedicles laterally to avoid injuries to the PV1R and B1R. Conclusions Right hepatectomy with total caudate lobe preservation, following PVE, was a safe and viable surgical technique for patients with marginal liver function.

Abstract We aimed to assess some of the potential genetic pathways for cancer development from non-malignant intraductal papillary mucinous neoplasm (IPMN) by evaluating genetic mutations and methylation. In total, 46 dissected regions in 33 IPMN cases were analyzed and compared between malignant-potential and benign cases, or between malignant-potential and benign tissue dissected regions including low-grade IPMN dissected regions accompanied by malignant-potential regions. Several gene mutations, gene methylations, and proteins were assessed by pyrosequencing and immunohistochemical analysis. RASSF1A methylation was more frequent in malignant-potential dissected regions (p = 0.0329). LINE-1 methylation was inversely correlated with GNAS mutation (r = − 0.3739, p = 0.0105). In cases with malignant-potential dissected regions, GNAS mutation was associated with less frequent perivascular invasion (p = 0.0128), perineural invasion (p = 0.0377), and lymph node metastasis (p = 0.0377) but significantly longer overall survival, compared to malignant-potential cases without GNAS mutation (p = 0.0419). The presence of concordant KRAS and GNAS mutations in the malignant-potential and benign dissected regions were more frequent among branch-duct IPMN cases than among the other types (p = 0.0319). Methylation of RASSF1A, CDKN2A, and LINE-1 and GNAS mutation may be relevant to cancer development, IPMN subtypes, and cancer prognosis.

Abstract Background Because of the coronavirus disease 2019 (COVID-19) pandemic, preoperative screenings for COVID-19 infection are often performed in many institutions. Some patients are diagnosed with COVID-19 infection by antigen tests or polymerase chain reaction (PCR) testing for COVID-19, even if they have no symptoms, such as fever or respiratory symptoms. We herein describe a patient with gastric cancer who underwent distal gastrectomy 6 weeks after recovering from COVID-19 infection diagnosed by preoperative PCR. Case presentation An 86-year-old man was transferred to our hospital because of hematemesis and melena. A hemorrhagic gastric ulcer was found in the lesser curvature of the antrum by emergency endoscopy. Endoscopic hemostasis was performed, and he was discharged after recovery. A tumor-like lesion in the lesser curvature of the antrum was found on repeat endoscopy and was diagnosed as well-differentiated adenocarcinoma by biopsy. There was no evidence of lymph node metastasis or distant metastasis; therefore, we planned radical surgery. However, he was diagnosed with COVID-19 infection by preoperative PCR screening. Although he had no symptoms, such as fever or respiratory symptoms, he was hospitalized because of his advanced age. He was discharged 10 days after admission, and repeat COVID-19 PCR was negative. We planned radical surgery for the stomach tumor 6 weeks after recovery from the COVID-19 infection. A PCR-negative COVID-19 status was confirmed again before hospitalization. Open distal gastrectomy with Billroth I reconstruction was performed. We avoided ultrasonic scalpels and used a Crystal Vision 450D surgical smoke evacuator (I.C. Medical, Inc., Phoenix, AZ, USA) to reduce intraoperative surgical smoke. The postoperative course was uneventful. Conclusion Because of the COVID-19 pandemic, some patients are diagnosed with COVID-19 infection by preoperative antigen tests or PCR, even if they have no symptoms. If possible, elective surgery should be performed 4 to 6 weeks after recovery from COVID-19 infection to maximize safety. Moreover, surgeons must consider intraoperative surgical smoke.

BackgroundTransplantation of the human pancreatic islets is a promising approach for specific types of diabetes to improve glycemic control. Although effective, there are several issues that limit the clinical expansion of this treatment, including difficulty in maintaining the quality and quantity of isolated human islets prior to transplantation. During the culture, we frequently observe the multiple islets fusing together into large constructs, in which hypoxia-induced cell damage significantly reduces their viability and mass. In this study, we introduce the microwell platform optimized for the human islets to prevent unsolicited fusion, thus maintaining their viability and mass in long-term cultures.MethodHuman islets are heterogeneous in size; therefore, two different-sized microwells were prepared in a 35 mm-dish format: 140 µm × 300 µm-microwells for 160 µm-islets. Human islets (2,000 islet equivalent) were filtered through a 160 µm-mesh to prepare two size categories for subsequent two week-cultures in each microwell dish. Conventional flat-bottomed 35 mm-dishes were used for non-filtered islets (2,000 islet equivalent/2 dishes). Post-cultured islets are collected to combine in each condition (microwells and flat) for the comparisons in viability, islet mass, morphology, function and metabolism. Islets from three donors were independently tested.ResultsThe microwell platform prevented islet fusion during culture compared to conventional flat bottom dishes, which improved human islet viability and mass. Islet viability and mass on the microwells were well-maintained and comparable to those in pre-culture, while flat bottom dishes significantly reduced islet viability and mass in two weeks. Morphology assessed by histology, insulin-secreting function and metabolism by oxygen consumption did not exhibit the statistical significance among the three different conditions.ConclusionMicrowell-bottomed dishes maintained viability and mass of human islets for two weeks, which is significantly improved when compared to the conventional flat-bottomed dishes.

A 33-year-old man was referred to our hospital with chief complaints of fever, dizziness, and headache. Although he had recurring fever and dizziness for 7 months, neurological examination, magnetic resonance imaging, computed tomography, electrocardiograms, and blood tests were normal. He was diagnosed with functional hyperthermia, cervical vertigo, and tension headache and was treated with oral medication and physical therapy. After treatment, the dizziness and headache resolved; however, the fever and anxiety did not. During follow-up, he noticed differing results from different electronic thermometers. The physician decided to use an accurate analog thermometer, a gallium thermometer, in combination with the other thermometers. The results differed significantly among the thermometers, and the electronic thermometer readings were found to be inappropriately high. The physician made a diagnosis of pseudo-fever, and the patient recognized that the gallium thermometer’s results were the most accurate reflection of his physical condition, resolving his anxiety.

A 47-year-old farm worker with diabetes mellitus, dyslipidemia, and hyperuricemia was referred to our hospital for a 3-month history of fever and malaise. He had no respiratory tract or abdominal symptoms, skin rashes, or joint pain. There was no change to his regular medication or pesticide exposure. Blood tests and echocardiography revealed no abnormalities. Whole-body computed tomography revealed a fatty liver; however, non-alcoholic steatohepatitis was excluded. We diagnosed the patient with functional hyperthermia. He had a history of snoring and weight gain, and we suspected the obstructive sleep apnea syndrome to be a stressor. Polysomnography revealed severe obstructive sleep apnea syndrome with an apnea–hypopnea index of 44.5. Continuous positive airway pressure was introduced; the axillary temperature decreased gradually and malaise was resolved. Functional hyperthermia should be considered a cause of fever with a negative inflammatory response. Obstructive sleep apnea syndrome can be a stressor for functional hyperthermia, which can be improved by interventions.

Abstract A 17‐year‐old female patient presented to our hospital with repeated transient loss of consciousness lasting less than 10 min. After regaining consciousness, she experienced no disorientation, confusion, tongue‐biting, or incontinence. Physical findings, blood tests, electrocardiogram, and echocardiogram showed no obvious abnormalities. On being asked whether she had experienced sudden rapid body movements, she answered “yes.” Therefore, we suspected juvenile myoclonic epilepsy (JME) and obtained an electroencephalogram, which showed diffuse bilateral bursts of spike‐and‐wave complexes, confirming the diagnosis. In adolescent patients with transient loss of consciousness, myoclonic jerks should be actively confirmed for the diagnosis of JME.

Abstract Raynaud's phenomenon, induced by cold stimulation and emotional stress, is also induced by whole‐body warm stimulation. A 74‐year‐old man was referred to our department because of nocturnal toe pain from 2 years prior and immediate color change of the toes from 1 year prior when submerging himself into a warm bath. Physical examination and blood tests revealed no abnormal findings suggestive of secondary Raynaud's phenomenon. Two years later, the signs and symptoms persisted. When physicians confirm Reynaud's phenomenon, they should check for the possibility of secondary Reynaud's phenomenon. Additional research on Reynaud's phenomenon induced by warm stimulation is needed.

Abstract Background Effective treatments for cancer harboring mutant RAS are lacking. In Drosophila, it was reported that PP6 suppresses tumorigenicity of mutant RAS. However, the information how PP6 regulates oncogenic RAS in mammals is limited. Methods We examined the effects of PP6 gene (Ppp6c) deficiency on tongue tumor development in K (K‐rasG12D)‐ and KP (K‐rasG12D + Trp53‐deficient)‐inducible mice. Results Mice of K and KP genotypes developed squamous cell carcinoma in situ in the tongue approximately 2 weeks after the induction of Ppp6c deficiency and was euthanized due to 20% loss of body weight. Transcriptome analysis revealed significantly different gene expressions between tissues of Ppp6c‐deficient tongues and those of Ppp6c wild type, while Trp53 deficiency had a relatively smaller effect. We then analyzed genes commonly altered by Ppp6c deficiency, with or without Trp53 deficiency, and identified a group concentrated in KEGG database pathways defined as ‘Pathways in Cancer’ and ‘Cytokine‐cytokine receptor interaction’. We then evaluated signals downstream of oncogenic RAS and those regulated by PP6 substrates and found that in the presence of K‐rasG12D, Ppp6c deletion enhanced the activation of the ERK‐ELK1‐FOS, AKT‐4EBP1, and AKT‐FOXO‐CyclinD1 axes. Ppp6c deletion combined with K‐rasG12D also enhanced DNA double‐strand break (DSB) accumulation and activated NFκB signaling, upregulating IL‐1β, COX2, and TNF.

Objective To elucidate the diagnostic accuracy of pretest probability of influenza (%) by physicians and the factors affecting the clinical diagnosis.Design Retrospective, single-centre observational study.Setting A community primary care clinic in Japan.Participants The participants were recruited from a database of studies conducted during the influenza season from December 2017 to April 2019.Primary outcome measure Sensitivity and specificity of the physician’s clinical diagnosis of influenza recorded in the medical record as pretest probability.Results A total of 335 patients (median age, 31 years; male, 66.6%) were analysed in this study. The area under the curve (AUC) of the physician’s pretest probability was 0.77. At a cut-off value of 30%, the sensitivity and negative likelihood ratio were 92.0% (95% CI 86.7 to 95.7) and 0.19 (95% CI 0.11 to 0.33), respectively. At a cut-off value of 80%, the specificity and positive likelihood ratio were 90.8% (95% CI 85.4 to 94.6) and 4.01 (95% CI 2.41 to 6.66), respectively. The AUCs of patients who had and had not taken any medications before visiting the clinic were 0.77 (95% CI 0.69 to 0.85) and 0.78 (95% CI 0.71 to 0.84), respectively. The AUCs of patients with type A and B influenza were 0.78 (95% CI 0.72 to 0.84) and 0.76 (95% CI 0.70 to 0.82), respectively. The AUCs of vaccinated and unvaccinated patients were 0.80 (95% CI 0.72 to 0.88) and 0.76 (95% CI 0.63 to 0.89), respectively. The AUC for patients less than 12 hours after onset was 0.69 (95% CI 0.51 to 0.88), and that for patients aged younger than 6 years was 0.69 (95% CI 0.49 to 0.88).Conclusions The physician’s pretest probability of influenza (%) may be useful for both definitive and exclusionary diagnoses within the limits of our study.

Abstract The aim of this study was to provide definitive reference values for bone mineral density (BMD) and bone turnover markers in the general elderly population. Registered citizens of 50 to 89 years old were targeted for this survey. After random sampling from the resident registry of Obuse town, we established eight groups based on age (50 s, 60 s, 70 s, and 80 s) and gender. A total of 411 people were enrolled. We used a dual-energy x-ray absorptiometry device to measure and evaluate BMD. The bone formation marker bone alkaline phosphatase (BAP) was measured as a bone turnover marker. Bone quality marker pentosidine, and bone resorption markers including urinary total deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), 25-hydroxyvitamin D (25[OH]D), and whole parathyroid hormone (PTH) were also measured as bone turnover markers. Sixty-three people (15.3%) were diagnosed as osteoporosis. BMD decreased with age in the femoral neck and total hip. On the other hand, there was no characteristic change with age in the lumber spine. As for bone markers, pentosidine and DPD increased with aging, although 25(OH)D, whole PTH, and BAP showed no characteristic associations with gender and aging. In terms of the relationship between low BMD and bone markers, there was a significant independent association between low BMD and TRACP-5b in females. In conclusions, hip BMD decreased with aging in men and women. However, there was no characteristic decline with aging in the lumbar spine. All bone markers showed no significant independent characteristics associated with age or gender in a multivariate analysis model, except for a significant association between low BMD and TRACP-5b in females. TRACP-5b was a potentially useful marker for the detection of low BMD.

Abstract Overall survival of patients with localized pancreatic ductal adenocarcinoma (PDAC) is extremely poor. Therefore, the establishment of multimodal treatment strategies is indispensable for PDAC patients because surgical treatment alone could not contribute to the improvement of survival. In this review article, we focus on the current topics and advancement of the treatments for localized PDAC including resectable, borderline resectable, and locally advanced PDAC in accordance with the articles mainly published from 2019 to 2020. Reviewing the articles, the recent progress of multimodal treatments notably improves the prognosis of patients with localized PDAC. For resectable PDAC, neoadjuvant chemo or chemoradiation therapy, rather than upfront surgery, plays a key role, especially in patients with a large tumor, poor performance status, high tumor marker levels, peripancreatic lymph nodes metastasis, or neural invasion suspected on preoperative imaging. For borderline resectable PDAC, neoadjuvant treatments followed by surgery is a desirable approach, and maintenance of immunonutritional status during the treatments are also important. For locally advanced disease, conversion surgery has a central role in improving a survival outcome; however, its indication should be standardized.

Abstract UTX/KDM6A encodes a major histone H3 lysine 27 (H3K27) demethylase, and is frequently mutated in various types of human cancers. Although UTX appears to play a crucial role in oncogenesis, the mechanisms involved are still largely unknown. Here we show that a specific pharmacological inhibitor of H3K27 demethylases, GSK-J4, induces the expression of transcription activating factor 4 (ATF4) protein as well as the ATF4 target genes (e.g. PCK2, CHOP, REDD1, CHAC1 and TRIB3). ATF4 induction by GSK-J4 was due to neither transcriptional nor post-translational regulation. In support of this view, the ATF4 induction was almost exclusively dependent on the heme-regulated eIF2α kinase (HRI) in mouse embryonic fibroblasts (MEFs). Gene expression profiles with UTX disruption by CRISPR-Cas9 editing and the following stable re-expression of UTX showed that UTX specifically suppresses the expression of the ATF4 target genes, suggesting that UTX inhibition is at least partially responsible for the ATF4 induction. Apoptosis induction by GSK-J4 was partially and cell-type specifically correlated with the activation of ATF4-CHOP. These findings highlight that the anti-cancer drug candidate GSK-J4 strongly induces ATF4 and its target genes via HRI activation and raise a possibility that UTX might modulate cancer formation by regulating the HRI-ATF4 axis.

Abstract While the significance of acquired genetic abnormalities in the initiation of hepatocellular carcinoma (HCC) has been established, the role of epigenetic modification remains unknown. Here we identified the pivotal role of histone methyltransferase G9a in the DNA damage-triggered initiation of HCC. Using liver-specific G9a-deficient (G9a ΔHep) mice, we revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine (DEN). In addition, pharmacological inhibition of G9a attenuated the DEN-induced initiation of HCC. After treatment with DEN, while the induction of γH2AX and p53 were comparable in the G9a ΔHep and wild-type livers, more apoptotic hepatocytes were detected in the G9a ΔHep liver. Transcriptome analysis identified Bcl-G, a pro-apoptotic Bcl-2 family member, to be markedly upregulated in the G9a ΔHep liver. In human cultured hepatoma cells, a G9a inhibitor, UNC0638, upregulated BCL-G expression and enhanced the apoptotic response after treatment with hydrogen peroxide or irradiation, suggesting an essential role of the G9a-Bcl-G axis in DNA damage response in hepatocytes. The proposed mechanism was that DNA damage stimuli recruited G9a to the p53-responsive element of the Bcl-G gene, resulting in the impaired enrichment of p53 to the region and the attenuation of Bcl-G expression. G9a deletion allowed the recruitment of p53 and upregulated Bcl-G expression. These results demonstrate that G9a allows DNA-damaged hepatocytes to escape p53-induced apoptosis by silencing Bcl-G, which may contribute to the tumor initiation. Therefore, G9a inhibition can be a novel preventive strategy for HCC.

Abstract Background An epithelial cyst in an intrapancreatic accessory spleen (ECIPAS) is rare. We report a case of ECIPAS that was treated with robot-assisted distal pancreatectomy with splenectomy. Case presentation The case was a 59-year-old woman who was referred to our hospital after a pancreatic tail tumor was found on computed tomography prior to surgery for small bowel obstruction at another hospital. A cystic lesion in the pancreatic tail was discovered and evaluated by magnetic resonance imaging and endoscopic ultrasonography. Based on clinical and radiological features, mucinous cystic neoplasm was included in the differential diagnosis. The patient underwent robot-assisted distal pancreatectomy with splenectomy. The postoperative course was uneventful. Pathological evaluation revealed a 20-mm ECIPAS in the pancreatic tail. Conclusions If a pancreatic tail tumor is present, ECIPAS should be included in the differential diagnosis. However, preoperative diagnosis is difficult, and a definitive diagnosis is often not obtained until after surgery. Surgery should be minimally invasive. Laparoscopic distal pancreatectomy has become a standard surgical procedure because it is minimally invasive. Robot-assisted surgery is not only minimally invasive, but also advantageous, because it has a stereoscopic magnifying effect and allows the forceps to move smoothly. Robot-assisted distal pancreatectomy may be a good option, when performing surgery for a pancreatic tail tumor.

Abstract Background Several inflammation-based scores are used to assess the surgical outcomes of hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the prognostic value of the prognostic nutritional index (PNI) in HCC patients who underwent hepatectomy with special attention to preoperative liver functional reserve. Methods Preoperative demographic and tumor-related factors were analyzed in 189 patients with HCC undergoing initial hepatectomy from August 2005 to May 2016 to identify significant prognostic factors. Results Multivariate analysis for overall survival (OS) revealed that female sex (p = 0.005), tumor size (p

Abstract Background Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. Methods From a Hospital‐based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow‐up periods of less than 1 month. SPSS 25 was used for statistical analysis. Results The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793‐12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782‐10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275‐9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280‐9.231). The 2‐year survival rate after hepatic metastasis was 21.7%. Conclusions The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow‐up after treatment.

Abstract Background We experienced a rare case of intraductal papillary mucinous neoplasm arising from Santorini’s duct (SD) forming a tumor protruding into the duodenum . Case presentation A 71-year-old woman was incidentally diagnosed with a 3 cm type Isp polypoid tumor in the second portion of the duodenum at another hospital. Enhanced CT and endoscopic ultrasound revealed that the origin of this protruding tumor was arising from SD and that the tumor mimicked a pedunculated duodenal tumor. Our preoperative diagnosis was a malignant pancreatic tumor arising from SD with invasion into the duodenum. She underwent a subtotal stomach-preserving pancreaticoduodenectomy, and the resected specimen showed a 25 mm tumor protruding into the duodenum with a villous surface. The pathological findings revealed that the tumor was intraductal papillary mucinous adenoma (IPMA) arising from SD. Conclusions To the best of our knowledge, this is the first case of IPMA protruding into the duodenal lumen from SD, although most of the tumors arising from SD have been reported to be malignant.

Introduction A retrocaval ureter is a rare congenital abnormality characterized by the persistence of the posterior subcardinal vein on the right, which causes the proximal ureter to deviate medially behind the inferior vena cava. The presence of retrocaval ureter is usually found because of the development of progressive hydronephrosis, but many cases are clinically silent. In addition, an urothelial malignancy associated with retrocaval ureter is very rare. Case presentation Herein we report a very rare case of a 57‐year‐old male with retrocaval ureter and carcinoma in situ diagnosed by ureteroscopy. In spite of strong adhesion in the area of the ureter behind the inferior vena cava, dissection was successfully managed by a laparoscopic procedure after cutting the ureter and separating it into two segments. Conclusion Early histopathological diagnosis and radical laparoscopic surgery based on the results of ureteroscopy may lead to a good outcome, even in retrocaval ureter cases with a carcinoma in situ.

Abstract Background Locomotive syndrome (LoS) is defined as the loss of mobility due to age-related impairment of motor organs. The purpose of this study was to evaluate the prevalence and severity of LoS, muscular strength and balancing ability, and prevalence of sarcopenia in relation to the presence of LoS according to sex and age groups ranging between 50 and 89 years. Methods Male and female participants between the ages of 50–89 were randomly selected in the resident registry of a cooperating town. Calls for participation continued until approximately 50 consenting participants were successfully recruited for each age group and sex. A total of 413 participants (203 male and 210 female) were enrolled for undergoing a LoS risk test and measuring their physical function. Physical function was compared to participants with or without LoS. Results A total of 312 patients (75.5%) were diagnosed as LoS, of which 144 (46.2%) were male and 168 (53.8%) were female. The severity of LoS for the 312 patients were 210 (67.3%) for stage 1 and 102 (32.7%) for stage 2. The prevalence of LoS in males were 37, 59, 91, and 100% in the 50s, 60s, 70s, and 80s age strata, respectively. The prevalence of LoS in females were 71, 62, 89, and 98% in the 50s, 60s, 70s, and 80s age strata, respectively. The prevalence of sarcopenia was significantly higher as the age strata in males grew higher. Knee extension strength was significantly lower for participants in their 50s and females in addition to females in their 60s with LoS. The 31 patients diagnosed as sarcopenia included 29 (93.5%) with LoS, 11 (35.4%) classified as LoS stage 1, and 18 (58.1%) classified as stage 2. Conclusions The prevalence of LoS was high in participants over 70 years of age. In males, the prevalence of sarcopenia was higher as the age strata grew higher. Patients with LoS exhibited lower knee extension strength. We believe that some measures to prevent or improve LoS may require exercise to increase the muscle strength of the lower limbs.

Abstract Background Our aim is to elucidate the true preoperative risk factors for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), making it possible to select POPF high-risk patients preoperatively regardless of intraoperative pancreatic consistency judged by the surgeon’s hand. Methods Among the 298 patients who underwent PD with pancreaticojejunostomy from 2007 to 2016, 262 patients had preoperative CT configurations that could be precisely evaluated. Risk factor analyses were conducted using various perioperative factors, including preoperative CT findings, such as CT values of the pancreas, pancreas-visceral fat CT value ratio and pancreatic outer contour. Pancreatic outer contour was further divided into smooth- (smooth interlobular) and serrated-type contours (feathery, irregular interlobular) by preoperative CT. Results In terms of the incidence of POPF, among the 262 patients, POPF grade B/C was found in 27 (10.3%): grade B in 23 (8.8%) and grade C in 4 (1.5%). According to multivariate analysis, a high pancreas-visceral fat CT value ratio (p = 0.002), serrated-type contour (p = 0.02) and no history of chemoradiotherapy (p = 0.019) were identified as independent risk factors for POPF grade B/C. Even in patients with soft pancreas, the incidence of POPF grade B/C was 0% (0/57) in patients with a pancreas-visceral fat CT value ratio of less than − 0.4 and smooth-type contour, whereas the incidence was markedly high (45.0%, 9/20) in patients with a pancreas-visceral fat CT value ratio of − 0.4 or greater and serrated-type contour, indicating that patients with soft pancreas should be categorized into POPF high-risk and low-risk groups according to preoperative CT scan results. Conclusions The pancreas-visceral fat CT value ratio and serrated-type pancreas are useful markers to preoperatively identify true POPF high-risk groups in patients undergoing PD, regardless of the pancreatic texture judged intraoperatively.

Abstract Background The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy. Methods Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1. Results Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection. Conclusion Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.

Abstract Background Portal annular pancreas (PAP) is a rare pancreatic anomaly in which the uncinate process wraps annularly around the portal vein and fuses to the body of the pancreas. PAP is highly relevant to the development of postoperative pancreatic fistula (POPF) in pancreatic surgery. Here, we describe our experience and surgical technique of laparoscopic spleen-preserving distal pancreatectomy using Warshaw’s procedure for patients with the PAP. Case presentation A 49-year-old woman with PAP was referred to our hospital for a suspicious mucinous cystic neoplasms 1.5 cm in diameter in the pancreatic tail. Laparoscopic spleen-preserving distal pancreatectomy using Warshaw’s procedure was performed. Mobilization of the pancreatic tail was first performed, and then, the splenic artery was cut. After dividing the pancreatic tail from the splenic hilum, the ventral pancreatic parenchyma was divided using a stapler. After cutting the splenic vein, complete mobilization of the pancreatic body and tail enabled easy division of the PAP. Finally, the PAP was also divided using the stapler. Although grade B POPF occurred, she was discharged on the 9th postoperative day. Conclusions Surgeons should understand the anatomical characteristics of PAP and be aware of the possibility of POPF.