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Objective Uterine carcinosarcoma (UCS) is uncommon high-grade endometrial cancer with limited treatment options. We evaluated prognostic significance of HER2 expression and HER2 gene amplification within large cohorts of UCS, and clarify clinicopathologic characteristics of HER2-low UCS. Methods We examined HER2 protein expression in 148 patients of UCS using IVD HER2 immunohistochemistry (IHC) kits and HER2 gene amplification using FISH in 72 patients. Results HER2 IHC score was evaluated according to the latest ASCO/CAP criteria for gastric cancer, which was negative in 41 patients, low expression of 1 + was observed in 57 patients, and HER2 high expression was observed in 50 patients (2 + in 38 and 3 + in 12 patients). There was no significant statistical difference in clinicopathological characteristics based on HER2 protein expression status. HER2 negative and low expression compared to high expression revealed poor overall survival in stage I/ II. The concordance between IHC and FISH results were relatively low compared to other cancer types (HER2 IHC score 1+, 2+, and 3 + were 5%, 15%, and 50%), and combining these results was not efficient as a prognostic factor in UCS. In contrast, HER2 IHC score alone was a prognostic factor in stage I/II UCS. HER2 low group did not show specific clinicopathologic feature. Conclusions Since the HER2 IHC score low in advanced UCS is a predictive factor, stratification of UCS using HER2 IHC score for HER2 IHC score low group and developing adjuvant therapy may be proposed in the near future.

Marginal mandibulectomy is the treatment of choice when seeking to preserve mandibular continuity. In some cases, the remaining height of the mandibular body is inadequate to sustain the functional load; mandibular reinforcement with a reconstructive plate is necessary. Treatment planning prior to marginal mandibulectomy is sometimes challenging for the novice surgeon; the risk of complications, including iatrogenic fracture, is high. Additionally, intra- or pre-operative bending of the reconstructive plate on a three-dimensional (3D) model is associated with an unavoidable risk of inaccuracy. Recently, virtual planning using surgical guides and patient-specific implants has become popular. Using image manipulation and 3D design software, the surgeon can now precisely translate the preoperative plan to the operation theater. The reconstruction plate meets the patient’s needs and the surgeon’s desires. Although some limitations remain, surgeons can now work more accurately and efficiently. The patient described in the present report had recurrent ameloblastoma of the right mandibular body; marginal resection and reinforcement with a reconstruction plate were required. We present the workflow from virtual surgical planning to actual surgery. Postoperative computed tomography findings reflected concordance between the treatment plan and the surgical results.

Low-frequency noise may create specific perceptions, which might cause various health effects. The present study aimed to identify exposure–response relationships between low-frequency noise and perceptions by re-analysing an experimental study. We investigated the predominant perceptions of ‘feeling bothered’ and ‘feeling of pressure and/or vibration’ using multivariate logistic regression analysis. A significant interaction between 1/3 octave-band sound pressure level and frequency was indicated for ‘feeling bothered’ but not ‘feeling of pressure and/or vibration’, suggesting that the ‘feeling of pressure and/or vibration’ does not originate in cochlear. A mathematical model indicating resonance at approximately 50 Hz fitted the results well. A frequency weighting derived from the mathematical model could be applied to broad-band low-frequency noise to evaluate the perception and health effects. However, further investigations on the weighting for the perception are necessary because the results were obtained only from the existing study.

No studies have reported the effect of solitary living on adjuvant chemotherapy continuation in patients with gastric cancer. This study aimed to investigate the influence of solitary living on the efficacy of adjuvant chemotherapy after curative gastrectomy.We enrolled 155 patients with pathological stage II/III gastric cancer who underwent gastrectomy and adjuvant chemotherapy between January 2013 and March 2020. The patients were divided into two groups according to their living conditions, the solitary group (n = 34) versus the non-solitary group (n = 121). Clinicopathological features, predictive factors for the continuation of adjuvant chemotherapy, and long-term survival were compared between the two groups.The median body weight loss (BWL) at one month after surgery (8.9% vs. 7.0%, p = 0.01), and the rates of failure to continue six courses of chemotherapy were higher in the solitary group (41.2% vs. 14.9%, p = 0.002) than in the non-solitary group. Multivariate analysis revealed that solitary living was an independent predictive factor for discontinuing adjuvant chemotherapy (odds ratio 3.36, 95% confidence interval [CI; 1.32-8.58], p = 0.01) as well as 10% BWL at one month after surgery (odds ratio 3.99, 95% CI [1.57-10.2], p = 0.004). The relapse-free survival was significantly worse in the solitary group (p = 0.03).Solitary living may be an independent risk factor for discontinuation of adjuvant chemotherapy in patients with gastric cancer. It is necessary to examine whether social and medical support organized by medical institutes and the government improves the continuation of adjuvant chemotherapy in patients living alone.

Backgrounds : Endoscopic full-thickness resection (EFTR) without laparoscopic assistance—pure EFTR—is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been applied outside of China due to concerns about pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing regarding its procedure. This study aimed to evaluate the efficacy and safety of endoscopic resection with one port placement (EROPP) for gastric GISTs. Methods This retrospective study included 14 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2021. One camera port was inserted in the umbilicus before starting the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layer around the lesion by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect with an over-the-scope-clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety. Results All procedures were completed successfully without conversion to laparoscopic surgery. The median size of resected tumors was 23 mm (range, 10–35 mm) and the median procedure time was 37 min (range, 22–95 min). The rates of en bloc and curative resection were 100% and 86%, respectively. In two cases, another port was added to aspirate leaking fluid or to check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful and no adverse events were reported Conclusions EROPP is a safe and minimally invasive treatment for gastric GISTs and seems to be suitable as a pure EFTR procedure.

Surgery in elderly patients with esophageal cancer is challenging due to high mortality and limited survival. This study aimed to evaluate the safety and effectiveness of curative esophagectomy in elderly patients with esophageal cancer. This study included 77 and 112 patients with esophageal cancer aged ≥ 70 and 40–64 years, respectively, who underwent R0 esophagectomy between January 1998 and December 2016. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were compared. The proportions of comorbid diseases (85.7% vs. 57.1%; P

Background: To investigate patient characteristics and the risk of post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in association with fluid volume and type during ERCP. Methods: Two hundred and forty seven of 480 patients with naïve papilla undergoing therapeutic ERCP between April 2013 and March 2018 were enrolled for the study. The following patient characteristics were investigated: age, sex, body mass index, previous diseases (heart disease, renal failure, cerebrovascular disorders, coexisting malignancy and pulmonary disease), history of PEP, common bile duct diameter, diverticula and volume of fluid infused 24 hours after the procedure. All ERCP cases had naïve papilla and had undergone treatment. Results: The incidence of PEP was 8.5%. Significant differences were observed in the volume of fluid infused between patients without and with a history of heart disease (1,380 vs. 1,755 mL). The mean volume of the infused fluid was significantly lower in the PEP than non-PEP group (1,483 vs. 1,688 mL, P = 0.02). Moreover, PEP incidence differed according to a fluid infusion cutoff of 1,000 mL (7 vs. 11 cases of PEP in those with ≦1,000 mL and >1,000 mL fluid volume, respectively, P < 0.001). Conclusion: Restricted fluid volume was a newly identified risk factor for PEP, particularly in patients with heart and renal diseases as comorbidities.

Aim Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis. Methods This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio (BTR), were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios (HRs) for factors that were associated with mortality or liver transplantation. Results Among the 158 patients, baseline measurements revealed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BTR for 114 patients (72.2%). During a median follow-up of 3.0 years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis revealed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis revealed that a serum tyrosine concentration of >110 µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted HR: 1.89, 95% confidence interval: 1.15-3.11, P = 0.012). Kaplan-Meier analysis revealed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, P Conclusions Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BTR, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis. This article is protected by copyright. All rights reserved.

Direct-acting antiviral (DAA) therapy carries a potential risk of inducing hepatitis B virus (HBV) reactivation. However, the HBV kinetics during and after DAA therapy in patients co-infected with hepatitis C virus (HCV) and HBV remain unknown. We retrospectively evaluated the HBV kinetics during and after sofosbuvir/ribavirin therapy in four HBV inactive carriers co-infected with HCV. HCV was eradicated in all patients. Changes in HBV-DNA levels during treatment differed among patients. The hepatitis B surface antigen (HBsAg) levels uniformly decreased (mean -0.530 logIU/mL) by the end of treatment and returned to near the baseline in all patients. Sofosbuvir/ribavirin therapy thus demonstrated a suppressive effect on HBsAg.

A duct-to-duct-biliary-anastomosis is the preferred biliary reconstruction technique in liver transplantation; biliary complications remain the major concerns for the technique. We examined the significance of the intramural vascular network of the extrahepatic bile duct (EBD) and its relevant vessels. We microscopically examined the axial sections of the EBD with 5 mm intervals of 10 formalin-fixed deceased livers. The luminal-areas of the 3 and 9 o'clock arteries correlated significantly and positively with the distance from the bifurcation of the right and left hepatic ducts (the 3 o'clock artery

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear. Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated. Results: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1–100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141–0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. Conclusion: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.

Gaucher disease, the most prevalent metabolic storage disorder, is caused by mutations in the glucocerebrosidase gene GBA1, which lead to the accumulation of glucosylceramide (GlcCer) in affected cells. Gaucher disease type 1 (GD1), although defined as a nonneuronopathic subtype, is accompanied by an increased risk of Parkinson's disease. To gain insights into the association of progressive accumulation of GlcCer and the Parkinson's disease phenotypes, we generated dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) derived from a GD1 patient and a healthy donor control, and measured GlcCer accumulation by liquid chromatography‐mass spectrometry. We tested two DA neuron differentiation methods: a well‐established method that mimics a step‐wise developmental process from iPSCs to neural progenitor cells, and to DA neurons; and a synthetic mRNA‐based method that overexpresses a transcription factor in iPSCs. GD1‐specific accumulation of GlcCer was detected after 60 days of differentiation by the former method, whereas it was detected after only 10 days by the latter method. With this synthetic mRNA‐based rapid differentiation method, we found that the metabolic defect in GD1 patient cells can be rescued by the overexpression of wild‐type GBA1 or the treatment with an inhibitor for GlcCer synthesis. Furthermore, we detected the increased phosphorylation of α‐synuclein, a biomarker for Parkinson's disease, in DA neurons derived from a GD1 patient, which was significantly decreased by the overexpression of wild‐type GBA1. These results suggest that synthetic mRNA‐based method accelerates the analyses of the pathological mechanisms of Parkinson's disease in GD1 patients and possibly facilitates drug discovery processes., Synthetic mRNA‐based expression of transcription factors enhanced induced pluripotent stem cell differentiation and enabled early (10 days) detection of a risk factor of Parkinson's disease, i.e. the accumulation of glucosylceramide (GlcCer) in Gaucher patient neurons. This rapid differentiation method also enabled to detect the phosphorylation of α‐synuclein—a critical Parkinson's disease‐linked phenotype.

Prophylactic splenectomy for hilar lymph node (#10) dissection has shown no survival benefit for patients with proximal advanced gastric cancer that does not invade the greater curvature. However, the survival benefit of prophylactic splenectomy for proximal advanced gastric cancer invading the greater curvature side, particularly for clinically negative #10 lymph node metastasis (#10[-]) cases remains controversial.This multi-institutional retrospective study enrolled 146 consecutive patients with proximal advanced gastric cancers invading the greater curvature side with clinical #10(-) who underwent R0 total gastrectomy. For 33 of these patients, splenectomy was performed, and the remaining 113 underwent spleen-preservation gastrectomy. Short- and long-term results were compared between the splenectomy and spleen-preservation groups, with the incidence of #10 metastasis in the splenectomy group and recurrence in the spleen-preservation group compared.In the splenectomy group, longer operative time, greater blood loss, more frequent postoperative abdominal infection, and longer hospital stay were observed than in the spleen-preservation group. The two groups exhibited no differences in median relapse-free survival time (31.1 vs 59.8 months; P = 0.684) or median overall survival time (64.9 vs 65.1 months; P = 0.765). The pathologic #10 lymph node metastasis rate was 3% in the splenectomy group, and the #10 lymph node recurrence rate was 2.7% in the spleen-preservation group.Prophylactic splenectomy showed more frequent postoperative morbidities and a longer hospital stay than spleen preservation, without any long-term survival benefits.

Follow-up computed tomography revealed a 40-mm pancreatic tail cyst in a 59-year-old man with type 1 diabetes mellitus. An intraductal papillary mucinous neoplasm was suspected; mucinous cystic neoplasm (MCN) was not considered because the patient was a man. During follow-up, cyst infection occurred but was improved by conservative treatment. At the 24-month follow up examination, cyst nodules had developed, corresponding to an increase in the carbohydrate antigen 19-9 level. Mucinous cystadenocarcinoma (MCC) was diagnosed pathologically based on distal pancreatectomy. A diagnosis of male MCN/MCC is often delayed, which may lead to a poor prognosis. MCN infection is also rare and poorly recognized. We observed an atypical male case of MCN/MCC.

A 45-year-old man with steroid-dependent ulcerative pancolitis was hospitalized with frequent diarrhea, abdominal pain and distension 3 months after induction of golimumab, a tumor necrosis factor-alpha antagonist. Computed tomography showed wall thickening from the stomach to the colon and massive ascites. Peripheral blood test revealed eosinophilia. A large number of eosinophils were observed in the ascites fluid. Although esophagogastroduodenoscopy showed no abnormal findings and colonoscopy showed ulcerative colitis with a Mayo endoscopic subscore of 1, eosinophil infiltration was histologically observed. Based on these findings, we diagnosed him with eosinophilic gastroenteritis and started prednisolone. Consequently, his eosinophil counts and abdominal symptoms dramatically improved.

ObjectivesCirculating tumor DNA (ctDNA) has potential as a basis for understanding the molecular features of a tumor non-invasively and for use as a diagnostic, prognostic, and disease-monitoring marker. The aim of this study was to evaluate the clinical roles of ctDNA in patients with endometrial cancer.MethodsSince PIK3CA and KRAS are among the most common mutated genes in endometrial cancer, somatic mutations of these genes were investigated in tumor specimens and plasma collected before surgery, using droplet digital polymerase chain reaction (ddPCR). ctDNA was defined as positive when the corresponding mutation between somatic and plasma was also detected in plasma cell-free DNA (cfDNA). Relationships of the presence of ctDNA with clinicopathological features were examined.ResultsSomatic PIK3CA and/or KRAS mutations were found in 68 (34%) of 199 patients with endometrial cancer. Ten (14.7%) of 68 patients had similar mutations in cfDNA. ctDNA detected in pre-operative plasma was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.008), histology (p=0.028), and lymphovascular space invasion (p=0.002), and with shorter recurrence-free and overall survival (p=0.004 and p=0.010, respectively, by log-rank test).ConclusionTumor-related ctDNA detected in plasma before surgery was associated with poorer oncologic outcome on univariate analysis in patients with endometrial cancer harboring PIK3CA or KRAS mutations.

PurposeThis study aimed to understand better the user gaze behavior on bookshelves using eye-tracking technology.Design/methodology/approachAn eye-tracking experiment in a public library with 11 participants was performed. The impact of vertical shelf location of books on the number of times the books are looked at, the impact of horizontal location and the relationship between user behavior and location impact were examined by the findings.FindingsThe results showed that the vertical location of books has a significant impact on the number of times the books are looked at. More than 80% of the time spent looking at bookshelves was spent on books on the top to fourth rows. It was also revealed that the horizontal location of books has a little impact. Books located on the left side of shelves will be looked at significantly more often than those on the right side. No significant relationships between type of user behaviors and location impact were observed.Originality/valueThe study explored the impact of the vertical location of books on time spent looking at bookshelves using eye-tracking methodology. Few published studies do such experiments to address user gaze behavior on bookshelves. The study explored that the vertical location of books has a great impact, and horizontal location has a little impact on user gaze behavior.

BACKGROUND/AIM The purpose of this study was to evaluate the usefulness of minimally invasive esophagectomy (MIE) for stage II/III esophageal cancer (EC). PATIENTS AND METHODS We compared surgical outcomes between MIE and open esohagectomy in EC patients with pStage II/III using the propensity scoring system. RESULTS Fifty-seven patients were classified into the MIE group and 57 patients into the open esophagectomy (OE) group. The incidence of major complications was similar between the two groups. The 5-year OS was significantly better in the MIE group (69.0% vs. 35.5%; p=0.004) and no significant difference was observed in the 5-year recurrence-free survival (RFS, 52.2% vs. 29.2%; p=0.064). Multivariate analysis showed MIE was a prognostic factor of OS (p

Ovarian cancer has the highest mortality rate among gynecological cancers. Gene mutations are involved in the carcinogenesis, metastasis, and therapeutic response in ovarian cancer. However, the variety and proportion of gene mutation is not fully analyzed in Japanese ovarian cancer patients, especially, in those with recurrent tumors. In the present study, RNA-sequencing was performed for 32 clinical ovarian specimens obtained from 24 Japanese patients (24 primary cancer specimens and 8 recurrent specimens paired with corresponding primary cancer specimens). Mutations in 24 primary specimens were analyzed by comparing the sequence data mapped on RefSeq genes with those in the public online databases BRCA Exchange, COSMIC, ClinVar, and cBioportal. Mutations were observed in TP53 in 16 specimens (67%), BRCA1 in 9 (38%), BRCA2 in 13 (54%), ARID1A in 3 (13%), PIK3CA in 2 (8%), KRAS in 1 (4%), PTEN in 1 (4%), and CTNNB1 in 1 (4%), excluding synonymous mutations. Among those identified muations, 13 of 14 mutations in TP53, 10 of 11 mutations of BRCA1, 10 of 23 mutation positions of BRCA2, none of 7 mutations of ARID1A, 1 mutation of PIK3CA, and 1 mutation of CTNNB1 were consistent with those reported in the public online databases; however, the other mutations identified were novel. Comparison between matched-paired specimens of primary and recurrent tumors revealed the changes of mutational status in expressed RNAs. RNA-sequencing-based mutation analysis will be useful to reveal ethnic differences of gene mutations in ovarian cancer and to understand the contribution of gene mutations to recurrence.

Background/aim Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach. Materials and methods A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen. Results Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature.

Patients with gastric cancer who underwent laparoscopic-assisted pylorus-preserving gastrectomy (LAPPG group)or laparoscopic-assisted distal gastrectomy(LADG group)between January 2010 and December 2019 were reviewed and their postoperative nutritional status and long-term outcomes retrospectively evaluated.In total, 83 patients(LAPPG group, n=23; LADG group, n=60)were included. Weight loss rates 1, 6, 12, and 24 months postoperatively in the LAPPG and LADG groups were 5.7% and 7.1%, 6.6% and 9.6%, 5.8% and 10.1%, and 5.2% and 8.7%, respectively. The LADG group exhibited a significantly higher weight loss than the LAPPG group at 6, 12, and 24 months (p=0.007, 0.002, and 0.022, respectively). No recurrence was observed in either group within 5 years of surgery. The 5- year overall survival rate of patients with pathological Stage Ⅰ cancer( LAPPG group, n=23, LADG group, n=51) was higher in the LAPPG group than in the LADG group(100% vs 82.9%, p=0.027). There were 6 cases of death from other diseases in the LADG group(pneumonia, n=2, other cancer, n=2, postoperative bleeding, n=1, and heart failure, n=1)but none in the LAPPG group.The weight loss after LAPPG was significantly lower than that after LADG. Furthermore, the former showed a good prognosis without death from other diseases, such as pneumonia.

Pedicled flaps are used in orofacial defect reconstruction in older patients and patients with underlying diseases. The submental island flap(SIF)is one type of cervical pedicled flap; however, the modified submental island flap (MSIF), which includes mylohyoid muscle, is a simpler and safer type. Here, we report a clinical study of orofacial defect reconstruction using the MSIF following oral cancer resection.From January 2019 to December 2020, we retrospectively examined 10 cases of reconstruction using the MSIF following oral squamous cell carcinoma resection.The study population consisted of 7 men and 3 women with a mean age of 76.0(66-88)years. The primary sites were lower gingiva(n=5), tongue(n=3), and buccal mucosa in(n=2). Surgical procedures included marginal mandibulectomy( n=3), segmental mandibulectomy(n=1), partial glossectomy(n=2), hemiglossectomy(n=1), buccal mucosa resection(n=2), and combined partial glossectomy and segmental mandibulectomy(n=1). The average flap size was 61.4×36.0 mm. The average time of flap elevation was 32.4(23-50)minutes. During orofacial surgery using the MSIF, organs adjacent to the primary site could also be reconstructed. There were no complications in any patients.The MSIF is useful for orofacial defect reconstruction in older patients and patients with underlying diseases.

Introduction: The benefits of surgery in older patients with gastric cancer are controversial. This single-institution retrospective study in Japan aimed to evaluate the impact of gastrectomy in older patients with gastric cancer. Methods: A series of 234 patients aged ≥80 years with histologically confirmed gastric cancer had indications for surgical treatment at the Gastroenterological Center, Yokohama City University Medical Center, between April 2002 and December 2018. Patients who were lost to follow-up (n = 27), had tumors not eligible for surgery (n = 14), and could not achieve R0 resection (n = 7) were excluded from this retrospective study. The remaining 186 patients were included. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were evaluated. Results: The incidence of postoperative complications with Clavien–Dindo grade ≥ II was observed in 61 patients (32.8%). The 5-year relapse-free survival and overall survival (OS) rates were 84.2% and 63.4%, respectively. Multivariate analysis showed that geriatric nutritional risk index (p = 0.047), neutrophil/lymphocyte ratio (>2.36) (odds ratio, 1.94; 95% confidence interval, 1.02–3.67; p = 0.043), and total gastrectomy (TG) (odds ratio, 1.97; p = 0.042) significantly predicted postoperative complications. Moreover, TG (hazard ratio, 1.91; p = 0.036) was an independent prognostic factor of OS. Conclusions: Poor immunonutritional status and TG led to worse short-term outcomes. Moreover, TG was an independent prognostic factor of OS in older patients with gastric cancer. It is necessary to provide effective perioperative care, including nutritional support, to clarify whether short-term outcomes would be improved.

論文

Regulatory T cells (Tregs) play an important role in the antitumor immune response in epithelial ovarian cancer (EOC). To understand the immune-inhibitory networks of EOC, we addressed the association between Tregs and immune checkpoint expression on T cells in the tumor microenvironment of EOC.A total of 41 patients with stage IIIC and IV EOC were included in the analysis. We harvested cells from malignant ascites and investigated them using multi-color flow cytometry. We categorized the Tregs into 3 groups: effector-type Tregs, naïve Tregs and non-Tregs, based on the expression patterns of CD45RA and Foxp3 in CD4The median frequency of naïve Tregs, effector-type Tregs and non-Tregs were 0.2% (0-0.8), 2.0% (0-11.4) and 1.5% (0.1-6.3) in CD4These data suggest that multiple immune-inhibitory networks exist in malignant ascites from EOC patients, suggesting an approach towards combinational immunotherapies for advanced EOC patients.

INTRODUCTION: Tumor treating fields (TTFields) is an established treatment modality for glioblastoma (GBM) and is administered with the portable Optune system. Although the EF-14 phase 3 trial demonstrated the efficacy of TTFields for newly diagnosed GBM, uncertainty regarding the specific effects of this treatment has prevented its widespread clinical use. Pseudoprogression in response to chemoradiation is a known problem in GBM patients and most commonly occurs within 3 months after radiotherapy. We report 2 cases of TTFields delayed pseudoprogression. CASE REPORT: Two GBM patients being treated with TTFields showed signs of radiographic progression at 5 to 6 months after completing radiotherapy. Patient 1 was a 37-year-old woman with gliosarcoma in the right temporal lobe. Patient 2 was a 70-year-old man with wildtype-IDH GBM in the left temporal lobe. Both patients received TTFields in addition to maintenance temozolomide (TMZ) after radiotherapy (RT). Radiographic progression was noted at 5 and 6 months after RT in Patients 1 and 2, respectively. Second resections were performed, and pathology showed only the treatment effect, which ultimately led to diagnosis of pseudoprogression. DISCUSSION: Both patients had radiographic progression outside the typical pseudoprogression window. Recent studies reported that TTFields increased plasma cell membrane permeability, which could result in additional gadolinium leakage into the extracellular space. CONCLUSIONS: Better characterization of delayed pseudoprogression would improve treatment and could potentially reduce unnecessary surgeries and discontinuation of successful therapies.

Introduction Brain tumor patients suffer from psychological distress and various sequelae from the moment they are diagnosed with a brain tumor, during and after treatment. Although the number of brain tumor survivors is increasing as a result of improved treatment outcomes for brain tumors, the support system is not sufficient. We, in collaboration with the University of California San Francisco Brain Tumor Center, have established a multidisciplinary professional staff of physicians, nurses, pharmacists, rehabilitation therapists, nutritionists, and social workers to support brain tumor patients, their families, and care givers. The brain tumor survivorship program is designed to support brain tumor patients, their families, and caregivers. This report describes their efforts. Methods This program started in December 2021. We asked relevant departments in the hospital to cooperate with the program. In July 2022, the “Brain Tumor Survivorship Care Program 360” website was opened to the public. Results As of the end of August 2022, there were 9 participants, of which 7 were patients and 2 were care givers. Of these, two were patients being treated at other hospitals. Various information is provided on the website. Web meetings are also held to provide a place where participants can communicate directly with each other. When participants were asked about their requests for the program, many of them requested information on treatment, public services, and a place for communication among patients. Discussion Brain tumor patients face not only life-threatening but also painful symptoms associated with the impairment of their own physical motor and cognitive functions, which they had possessed until then. Through the survivorship program, we will continue to scientifically examine and develop a support system for the various survival-related issues that brain tumor patients and their families experience from diagnosis to the end of life.

Background Malignant gliomas have an extremely high rate of recurrence and brain invasion despite standard treatment, ultimately leading to tumor death. Tumor death is generally thought to be caused by brain herniation due to mass effect, as confirmed by studies of malignant glioma brain autopsies performed in the 1960s and 1980s. However, there have been few studies of brain autopsies of malignant gliomas after the introduction of chemotherapy with temozolomide, and the pathological characteristics of the end stage of the disease have not been clarified in recent years. In this study, we report the clinical and pathological characteristics of the end stages of malignant glioma cases treated at our hospital from the initial treatment to the confirmation of death. Methods 10 cases of malignant glioma that were treated from initial treatment to pathological autopsy at our hospital from 2007 to 2018 were included in this study. We analyzed the pathology, neuroradiological changes, and clinical course of these cases at the end stage. Results The mean age of the 10 patients was 59 (15-77) years, and the median overall survival was 16.5 months. The primary tumor sites were 2 frontal lobes, 3 parietal lobes, 3 temporal lobes, 1 cerebellum, and 1 multiple lesions. The direct cause of death in all cases was neurological death due to tumor progression. Gross findings of pathological autopsy specimens showed that tumor excision sites were cavitated or recurrent, but mass effect was poor and there were few cases of brain herniation. On the other hand, microscopic findings showed infiltration of tumor cells into the brain stem through the brain parenchyma. Conclusion This study suggests that tumor invasion into the brainstem is involved as a cause of tumor death. It is possible that the new treatment may change the recurrence pattern or alter the morphology of glioma cells.

Glucosylceramide synthase (GCS) has drawn much attention as an attractive protein target in the disease pathways of Parkinson's Disease (PD) and lysosomal storage disorders, such as Gaucher's Disease (GD). In previous our study, T-036 and its analogue, 2a, were discovered as novel GCS inhibitors. To further improve activity of this chemical series, SAR was investigated on the fused pyridyl ring core of 2a by employing a photoredox reaction that significantly reduced synthetic demand. Herein, we successfully applied the decarboxylation C-H alkylation photoredox reaction to introduce a wide variety of substituents at the 6-position of the fused pyridine core scaffold. This quick SAR acquisition facilitated the swift identification of the potent GCS inhibitors 2b (ICsub50/sub = 5.9 nM) and 2g (ICsub50/sub = 3.6 nM). Moreover, 2b exhibited superior in vivo potency to that of our previously reported lead compound, T-036.

INTRODUCTION Glioblastoma is a brain tumor with a very poor prognosis that is highly resistant to treatment. Hiba (Thujopsis dolabrata) has been used as a building material because of its insect repellent effect and refreshing fragrance. In this study, we analyzed the antitumor effects of thujopsen, which is contained in the essential oil of hiba, and investigated its antitumor aroma therapy.Methods and RESULTS We investigated the anti-tumor aroma effect of hiba essential oil on glioblastoma cells (U251, T98G), gastric cancer cells (MKN45), and breast cancer cells (MCF7). The anti-tumor effect of hiba essential oil varied depending on the carcinoma, with strong inhibition of cell proliferation observed in MKN45, U251, and T98G cells. Hinokitiol in hiba essential oil has been reported to have antitumor effects, and we isolated and identified a new antitumor factor, thujopsene, by liquid chromatography analysis. In tumor cell proliferation assays, thujopsen inhibited tumor cell proliferation more rapidly and potently than hinokitiol. Comparing the reach of the two compounds, hinokitiol showed a broader anti-tumor effect than thujopsen. The expression of caspase-3 and caspase-9 was increased by thujopsen, and DARTS analysis identified PKM2 as an intracellular binding protein of thujopsen. DISCUSSION The present study revealed that thujopsen induces apoptosis via caspase-3 and caspase-9. Furthermore, unlike hinokitiol, thujopsen was suggested to exhibit antitumor effects mediated by PKM2. CONCLUSION Thujopsen is a low molecular weight compound and easily evaporates into the air, it is expected to be applied to a new glioblastoma therapy using "aroma".