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To determine the clinical and imaging characteristics, natural course, and surgical outcomes of pathologic myopic eyes with an extreme macular schisis simulating a retinal detachment (EMSSRD).The data of 617 highly myopic eyes with myopic traction maculopathy were studied. The diagnosis of EMSSRD in the optical coherence tomography images was made based on a high elevation of the retina (500 µ m), less obvious columnar structures, and the presence of thin remnants of outer retinal tissues above the retinal pigment epithelium.Among 617 eyes, 25 eyes had an EMSSRD. All of the eyes with an EMSSRD had macular atrophy caused by myopic macular neovascularization. In the five eyes they had progressed to MHRD, the retinal detachment started away from the macular atrophy. Among the 10 eyes which required surgery, there was no significant difference in the presurgical and postsurgical best-corrected visual acuity between the eyes operated because of a worsening of the EMSSRD and the eyes operated because of a progression to MHRD.In severely myopic eyes with macular neovascularization-related macular atrophy, a novel condition termed EMSSRD can be present. The optical coherence tomography images resemble those of a MHRD except the presence of thin remnants of the retina remaining on the retinal pigment epithelium.

Scatter plots of the diagnostic values of the constructed diagnostic model and tumor marker levels in all 191 cases.

PDF - 146KB, Scatter plots of the diagnostic values of the constructed diagnostic model and tumor marker levels in all 191 cases.

PDF - 142KB, Supplementary Table 1: Additional information of the study subjects. Supplementary Table 2: Additional information of the subjects used for the comparisons between the healthy volunteers and chronic pancreatitis patients. Supplementary Table 3: All compounds detected in the subjects� serum. Supplementary Table 4: The diagnostic performance of the metabolites as individual biomarkers for pancreatic cancer in the training set study. Supplementary Table 5: Variance inflation factors of the variables in the diagnostic model. Supplementary Table 6: Variables selected by the stepwise method. Supplementary Table 7: Serum metabolites examined in the study of chronic pancreatitis.

Additional information of the study subjects

Background: To improve the prognosis of patients with pancreatic cancer, more accurate serum diagnostic methods are required. We used serum metabolomics as a diagnostic method for pancreatic cancer.Methods: Sera from patients with pancreatic cancer, healthy volunteers, and chronic pancreatitis were collected at multiple institutions. The pancreatic cancer and healthy volunteers were randomly allocated to the training or the validation set. All of the chronic pancreatitis cases were included in the validation set. In each study, the subjects' serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS) and a data processing system using an in-house library. The diagnostic model constructed via multiple logistic regression analysis in the training set study was evaluated on the basis of its sensitivity and specificity, and the results were confirmed by the validation set study.Results: In the training set study, which included 43 patients with pancreatic cancer and 42 healthy volunteers, the model possessed high sensitivity (86.0%) and specificity (88.1%) for pancreatic cancer. The use of the model was confirmed in the validation set study, which included 42 pancreatic cancer, 41 healthy volunteers, and 23 chronic pancreatitis; that is, it displayed high sensitivity (71.4%) and specificity (78.1%); and furthermore, it displayed higher sensitivity (77.8%) in resectable pancreatic cancer and lower false-positive rate (17.4%) in chronic pancreatitis than conventional markers.Conclusions: Our model possessed higher accuracy than conventional tumor markers at detecting the resectable patients with pancreatic cancer in cohort including patients with chronic pancreatitis.Impact: It is a promising method for improving the prognosis of pancreatic cancer via its early detection and accurate discrimination from chronic pancreatitis. Cancer Epidemiol Biomarkers Prev; 22(4); 571–9. ©2013 AACR.

Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p

Carbon 11-choline positron emission tomography/computed tomography (11C-choline PET/CT) and subsequent local therapy for oligometastatic prostate cancer have been reported to be effective, but their effectiveness in castration-resistant prostate cancer (CRPC) remains unclear. Here, we evaluated the findings of 11C-choline PET/CT in CRPC patients and the efficacy of local treatments in correspondence of the pathologic choline uptake. We collected 12 cases of CRPC patients who underwent 11C-choline PET/CT between 2014 and 2016. The outcomes assessed included age, the prostate-specific antigen (PSA) value, the findings of 11C-choline PET/CT, the subsequent treatments, the PSA response following the treatments, and the progression-free survival (PFS). Seven of 12 cases (median PSA, 3.29 ng/mL) had local prostate cancer and/or one or two metastatic lesions detected by the choline PET/CT. These localized lesions were treated with radiotherapy or lymphadenectomy. PSA decreased in all the seven cases and median PSA response was 86% (range, 23–100%). Median PFS was 8.5 months (range, 2.8–25.3 months). The other five cases (median PSA, 7.41 ng/mL) had multiple metastases and systemic therapies were continued in those cases. 11C-choline PET/CT and the correspondent local treatments may play an important role in the treatment sequence of CRPC in selected patients.

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori, which causes gastric cancer (GC). We conducted a GWAS followed by regression-based prediction of GC and duodenal ulcer H. pylori strains. We identified 14 single nucleotide polymorphisms (11 amino acid changes) that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into GC pathogenesis and a basis for identifying a set of biomarkers for application in clinical settings.

Bladder tumors can be broadly divided into those of epithelial or mesodermal origin. Furthermore, 90% of bladder tumors arise from the epithelium of the bladder, and most cases of bladder cancer are histologically urothelial carcinomas. Mesodermal tumors are exceptionally rare and often benign. Of the mesenchymal tumors of the bladder, leiomyomas are the most common, and their prognosis depends on their histology. The present report describes a case of submucosal urothelial cancer in a patient with no past history of bladder cancer. To the best of our knowledge, there are no previous reports of urothelial cancer occurring in the submucosa. The present report was the first to document a case of submucosal urothelial cancer, whose diagnosis was made possible only by transurethral resection of bladder tumor. Although the precise pathomechanism of the present case was unclear, two hypotheses were considered. First, the urothelial cancer developed within a diverticulum, then the entrance of the diverticulum closed, sealing in the cancer. Second, the bladder cancer stemmed from aberrant urothelium in the submucosal tissue. If submucosal urothelial bladder carcinoma develops within the diverticular environment, its prognosis can be as poor as that of invasive bladder cancer due to the features of the diverticular environment. Even in a patient with a submucosal bladder tumor but no previous history of bladder cancer, bladder cancer should be considered in the differential diagnosis.

The present study aimed to examine the safety of a gemcitabine and cisplatin (GC) combination chemotherapy regimen with short hydration for the treatment of urothelial cancer administered on the same day (same day regimen). Patients with locally advanced or metastatic urothelial cancer received the same-day GC regimen with short hydration every 4 weeks, and their serum creatinine (Cr) level was measured to assess renal function using linear mixed model analysis. A total of 20 patients receiving the same-day regimen exhibited no significant change in their serum Cr level; nor was there any significant change in the serum Cr level between patients who received the same day regimen and those who received the drugs on different days. The present study demonstrated that the same-day regimen was safe for patients with urothelial cancer.

Central nervous system (CNS) metastasis of urothelial carcinoma (UC) is rare. Immune checkpoint inhibitors, which were developed for the treatment of patients with advanced cancer, have limited efficacy against CNS metastases due to the unique immune microenvironment of the brain. The brain is an immune-privileged organ and is protected by the blood-brain barrier. However, the management of CNS metastases of UC is crucial to improving the prognosis. The present report describes two cases of cerebral metastasis occurring in the context of systemic disease control using immunotherapy. To the best of our knowledge, the present report is the first to describe a CNS metastasis during remission induced by immunotherapy.

Collecting duct carcinoma (CDC) is a rare, extremely aggressive form of renal cancer. Recently, immune checkpoint inhibitors (ICI), anti-programmed death-1 (PD-1) antibody, and anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody were approved for use against metastatic renal cell carcinoma. We herein described two cases of metastatic renal collecting duct carcinoma treated with a combination immunotherapy consisting of nivolumab and ipilimumab. In the first case, which included a bone metastasis, the best response achieved was stable disease (SD) for one year. In the second case, which was accompanied by a lung metastasis, the best response achieved was a partial response. The outcome of these cases suggested that the combination of nivolumab and ipilimumab is effective against renal collecting duct carcinoma.

Three cases with a long-term follow-up of myopic macular neovascularization (MNV) and MNV-related macular atrophy are shown. The progression of other lesions of myopic maculopathy is also demonstrated.

Background and study aims We developed a new reporting system based on structured data entry, which selectively extracts only endoscopic findings from endoscopists’ oral statements and automatically inputs them into appropriate columns in real time during endoscopic procedures. Methods We compared the time for endoscopic procedures and report preparation (ER time) by using an esophagogastroduodenoscopy simulator in three groups: one preparing reports using a mouse after endoscopic procedures (CE group); a second group preparing reports by using voice alone during endoscopic procedures (SR group); and the final group preparing reports by operating the system with a foot switch and inputting findings using voice during endoscopic procedures (SR + FS group). For the SR and SR + FS groups, we identified the recognition rates of the speech recognition system. Results Mean ER times for cases with three findings each were 162, 130 and 119 seconds in the CE, SR and SR + FS groups, respectively. The mean ER times for cases with six findings each were 220, 144 and 128 seconds, respectively. The times in the SR and SR + FS groups were significantly shorter than that in the CE group (P Conclusion Our reporting system was demonstrated to allow an endoscopist to efficiently complete the report in real time during endoscopic procedures.

Discovery of a high-risk group for pancreatic cancer is important for prevention of pancreatic cancer. The present study was conducted as a nested case-control study including 170 pancreatic cancer cases and 340 matched controls of our population-based cohort study involving 30 239 subjects who answered a baseline questionnaire and supplied blood samples. Twelve targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated using conditional logistic regression models. Statistically significant P-value was defined as P < .05. Increasing 1,5-anhydro-d-glucitol (1,5-AG) levels were associated with a decreasing trend in pancreatic cancer risk (OR of quartile 4 [Q4], 0.50; 95% CI, 0.27-0.93; P = .02). Increasing methionine levels were also associated with an increasing trend of pancreatic cancer risk (OR of Q4, 1.79; 95% CI, 0.94-3.40: P = .03). Additional adjustment for potential confounders attenuated the observed associations of 1,5-AG and methionine (P for trend = .06 and .07, respectively). Comparing subjects diagnosed in the first 0-6 years, higher levels of 1,5-AG, asparagine, tyrosine and uric acid showed a decreasing trend for pancreatic cancer risk (P for trend = .04, .04, .04 and .02, respectively), even after adjustment for potential confounders. We found that the 12 target metabolites were not associated with pancreatic cancer risk. However, metabolic changes in the subjects diagnosed in the first 0-6 years showed a similar tendency to our previous reports. These results might suggest that these metabolites are useful for early detection but not for prediction of pancreatic cancer.

Background The feasibility and safety of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms extending to the cervical esophagus currently remain unknown because of the limited number of cases. We aimed to clarify the clinical outcomes of these cases. Methods This was a case series study conducted at a single institution that enrolled 26 consecutive patients with superficial esophageal neoplasms extending to the cervical esophagus who underwent ESD between July 2003 and December 2015. Results En bloc and complete resection rates were both 100 % and no major intraprocedural complications occurred. Thirteen patients were treated with prophylactic steroid therapy. The incidence of postoperative stricture in patients with a circumferential mucosal defect of more than three-quarters was 72.7 %. Four patients required entire circumferential resection, with perforation occurring after endoscopic balloon dilation (EBD) in two and EBD being required for more than 1 year in the other two. Conclusions ESD including the cervical esophagus is technically feasible. Circumferential resection may cause refractory postoperative stricture or post-EBD perforation, so needs to be avoided where possible.

γδT cells constitute a small proportion of lymphocytes in peripheral blood. Unlike αβT cells, the anti-tumor activities are exerted through several different pathways in a MHC-unrestricted manner. Thus, immunotherapy using γδT cells is considered to be effective for various types of cancer. Occasionally, however, ex vivo expanded cells are not as effective as expected due to cell exhaustion. To overcome the issue of T-cell exhaustion, researchers have generated induced pluripotent stem cells (iPSCs) that harbor the same T-cell receptor (TCR) genes as their original T-cells, which provide nearly limitless sources for antigen-specific cytotoxic T lymphocytes (CTLs). However, these technologies have focused on αβT cells and require a population of antigen-specific CTLs, which are purified by cell sorting with HLA-peptide multimer, as the origin of iPS cells. In the present study, we aimed to develop an efficient and convenient system for generating iPSCs that harbor rearrangements of the TCRG and TCRD gene regions (γδT-iPSCs) without cell-sorting. We stimulated human whole peripheral blood mononuclear cell (PBMC) culture using Interleukin-2 and Zoledronate to activate γδT cells. Gene transfer into those cells with the Sendai virus vector resulted in γδT cell-dominant expression of exogenous genes. The introduction of reprogramming factors into the stimulated PBMC culture allowed us to establish iPSC lines. Around 70% of the established lines carried rearrangements at the TCRG and TCRD gene locus. The γδT-iPSCs could differentiate into hematopoietic progenitors. Our technology will pave the way for new avenues toward novel immunotherapy that can be applied for various types of cancer.

Background and study aims Endoscopic submucosal dissection (ESD) for duodenal tumors results in a high delayed perforation rate due to the thinness of the duodenal wall. In most cases with perforation after duodenal ESD, additional surgery is needed due to severe peritonitis. A newly developed procedure, laparoscopic endoscopic cooperative surgery for duodenal tumors (D-LECS), may help to avoid perforation after ESD. In our institution, patients with superficial non-ampullary duodenal epithelial tumors (SNADET) smaller than 50 mm which could not have en-bloc resection by endoscopic mucosal resection were treated with D-LECS. After a laparoscopic exposure of anterior duodenal wall of second portion, ESD was performed. Laparoscopic suturing from the serosal side of ESD site was performed for reinforcement. There were neither postoperative leakage nor other complications. Therefore, D-LECS can be performed safely and prevent perforation after ESD for SNADET. D-LECS could be selected as a treatment for SNADET which can be cured by ESD.

Background Nonthermal atmospheric pressure plasma (NTAPP) has recently received attention as a novel tool in medicine. It is thought that plasma components yield plasma effects such as sterilization, blood coagulation, and wound healing. These effects are produced without thermal damage. We investigated the blood coagulation effect of NTAPP by using a multigas plasma jet. Materials and methods Multigas plasma jets can generate NTAPP by several gas species. In this study, argon, oxygen, helium, nitrogen, mock air, and carbon dioxide were used to generate NTAPP, and blood coagulation times were compared with each plasma-treated sample. The NTAPP blood coagulation effects on whole blood with four different anticoagulants were investigated. In addition, in this study, the effects of plasma treatment on porcine tissues and organs were investigated as in vivo experiment. Results A tendency to coagulate later with argon gas plasma than others was shown. There were no significant differences between oxygen, helium, nitrogen, mock air, and carbon dioxide. Whole blood with each anticoagulant demonstrated fast coagulation by NTAPP treatment. Fast control of the bleeding lesions on porcine stomach and liver by plasma treatment was observed, and no tissue damage due to the plasma treatment was detected by optical microscope. Conclusions These experiments suggest the potential of various gas NTAPPs as a novel medical device to control bleeding lesions.

AIM To investigated the hemostatic ability of the S and F1-10 methods in clinical and ex vivo studies. METHODS The hemostatic abilities of the two methods were analyzed retrospectively in all six gastric endoscopic submucosal dissection cases. The treated vessel diameter, compressed vessel frequency, and bleeding frequency after cutting the vessels were noted by the recorded videos. The coagulation mechanism of the two power settings was evaluated using the data recording program and histological examination on macro- and microscopic levels in the ex vivo experiments using porcine tissues. RESULTS F1-10 method showed a significantly better hemostatic ability for vessels ≥ 2 mm in diameter and a trend of overall better coagulation effect, evaluated by the bleeding rate after cutting the vessels. F1-10 method could sustain electrical current longer and effectively coagulate the tissue wider and deeper than the S method in the porcine model. CONCLUSION F1-10 method is suggested to achieve a stronger hemostatic effect than the S method in clinical procedures and ex vivo models.

Numerous studies of Helicobacter pylori (H. pylori) have been performed, but few studies have evaluated the effects of H. pylori infections using metabolome analysis, which involves the comprehensive study of low molecular weight metabolites. In this study, the metabolites in the stomach tissue of mice that had been infected with H. pylori SS1 for 1, 3, or 6 months were analyzed, and then evaluations of various metabolic pathways were performed to gain novel understandings of H. pylori infections. As a result, it was found that the glycolytic pathway, the tricarboxylic acid cycle, and the choline pathway tended to be upregulated at 1 month after the H. pylori SS1 infection. The urea cycle tended to be downregulated at 6 months after the infection. High levels of some amino acids were observed in the stomach tissue of the H. pylori SS1-infected mice at 1 month after the infection, whereas low levels of many amino acids were detected at 3 and 6 months after the infection. These results suggest that H. pylori infection causes various metabolic alterations at lesional sites, and these alterations might be linked to the crosstalk between H. pylori and the host leading to transition of disease conditions.

Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P

Background Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN. Methods We performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7. Results We identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors. Conclusions Marked differences in fatty acid metabolism pathways, including those related to ELOVL1 and 6, were detected between TN and EP+H-, and it was suggested that ELOVL1 and 6-related fatty acid metabolism pathways may be targets for therapies against TN. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3554-4) contains supplementary material, which is available to authorized users.

Intrahepatic cholangiocarcinomas were classified into two types based on their microscopic appearance. Tumors with histologic similarities to hilar cholangiocarcinomas (predominantly ductal adenocarcinomas with minor tubular components, if present, restricted to the invasive front) were defined as the perihilar type, whereas the others were classified as peripheral cholangiocarcinomas. Among the 47 cases examined in the present study, 26 (55%) were classified as the perihilar type, whereas 21 (45%) were the peripheral type. The perihilar type had higher pT stages and more frequently showed a periductal-infiltrating gross appearance and microscopic perineural infiltration than peripheral cholangiocarcinomas. The presence of low-grade biliary intraepithelial neoplasia in the adjacent bile ducts was only found in perihilar cholangiocarcinomas (6/21, 29%). The immunophenotype also differed between the two types with MUC5AC and MUC6 being more commonly expressed in the perihilar type. One-third of perihilar cholangiocarcinomas lacked the expression of SMAD4, suggesting SMAD4 mutations, whereas the loss of BAP1 expression and IDH1 mutations were almost restricted to the peripheral type (35 and 15%, respectively). Patients with perihilar cholangiocarcinoma had worse overall survival than those with peripheral cancer (P=0.027). A multivariate analysis identified the histologic classification as an independent prognostic factor (P=0.005, HR=3.638). Comparisons between intrahepatic and hilar cholangiocarcinomas also revealed that the molecular features and prognosis of perihilar cholangiocarcinomas were very similar to those of hilar cholangiocarcinomas. In conclusion, this histology-based classification scheme of intrahepatic cholangiocarcinomas will be useful and clinically relevant because it represents different underlying molecular features and has an independent prognostic value.