Artificial intelligence-based diagnosis of upper gastrointestinal subepithelial lesions on endoscopic ultrasonography images.

BACKGROUND: Endoscopic ultrasonography (EUS) is useful for the differential diagnosis of subepithelial lesions (SELs); however, not all of them are easy to distinguish. Gastrointestinal stromal tumors (GISTs) are the commonest SELs, are considered potentially malignant, and differentiating them from benign SELs is important. Artificial intelligence (AI) using deep learning has developed remarkably in the medical field. This study aimed to investigate the efficacy of an AI system for classifying SELs on EUS images. METHODS: EUS images of pathologically confirmed upper gastrointestinal SELs (GIST, leiomyoma, schwannoma, neuroendocrine tumor [NET], and ectopic pancreas) were collected from 12 hospitals. These images were divided into development and test datasets in the ratio of 4:1 using random sampling; the development dataset was divided into training and validation datasets. The same test dataset was diagnosed by two experts and two non-experts. RESULTS: A total of 16,110 images were collected from 631 cases for the development and test datasets. The accuracy of the AI system for the five-category classification (GIST, leiomyoma, schwannoma, NET, and ectopic pancreas) was 86.1%, which was significantly higher than that of all endoscopists. The sensitivity, specificity, and accuracy of the AI system for differentiating GISTs from non-GISTs were 98.8%, 67.6%, and 89.3%, respectively. Its sensitivity and accuracy were significantly higher than those of all the endoscopists. CONCLUSION: The AI system, classifying SELs, showed higher diagnostic performance than that of the experts and may assist in improving the diagnosis of SELs in clinical practice.

Generation of magnifying endoscopic images of gastric neoplasms based on an all-in-focus algorithm.

BACKGROUND AND AIM: Magnifying endoscopy is useful for diagnosis of early gastrointestinal neoplasms by visualizing microvascular (MV) and microsurface (MS) structures of the mucosa when combined with image-enhanced endoscopy. However, precise control of the endoscope is needed because the depth of focus is narrow and the target may move. These problems may be overcome by the all-in-focus (AIF) technique, which was developed in the engineering field. The aim of the study was to evaluate magnifying endoscopic image with AIF algorithm. METHODS: Twenty gastric neoplasms were examined. Images were acquired at 80× magnification and converted to endoscopic images with an AIF algorithm (EI-AIF). The focus area and MV and MS patterns in the original image and the EI-AIF were compared on a 5-point Likert scale, where 5 indicates that the EI-AIF was superior. Intraclass correlation coefficients (ICCs) were used to assess the inter-evaluator reliability. An image quality measurement value was calculated for each image as an indicator of the degree of focus. RESULTS: The scores for focus area, MV, and MS were 4.78 ± 0.45 (ICC = 0.63), 4.12 ± 0.76 (ICC = 0.70), and 4.72 ± 0.52 (ICC = 0.45), respectively, with the EI-AIF significantly superior for all three items (P < 0.05 by Student's t-test). ICCs for the focus area and MV were > 0.60, indicating strong inter-evaluator reliability. Image quality measurement was higher for the EI-AIF compared with the original image in every case. CONCLUSIONS: Endoscopic observation with AIF algorithm gives a better image quality that allows easier evaluation of MV and MS patterns. This technique may resolve the difficulties with magnifying endoscopic observation.

[Subcutaneous continuous injection of octreotide decreased the tumor marker levels and induced cystic necrosis of the tumors in a case of pancreatic neuroendocrine tumor with multiple hepatic metastases].

For symptom alleviation, subcutaneous continuous injection of octreotide was administered to a patient with pancreatic neuroendocrine tumor (NET) accompanied by multiple hepatic metastases and ascites. The level of the tumor marker neuron-specific enolase decreased to the normal range and cystic necrosis of the tumors was confirmed. There have been some reports on the antineoplastic effects of octreotide on pancreatic NET; therefore, octreotide appears to be a valid option as a therapeutic agent in patients with highly advanced pancreatic NET, in whom administration of molecular targeted or anticancer agents is difficult because of a poor general status.

Diabetes-associated complications in Spontaneously Diabetic Torii fatty rats.

The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. The SDT-fa/fa (SDT fatty) rat shows overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with the SDT-+/+ (SDT normal) rat. However, the features of the diabetic complications in the SDT fatty rat have not been reported. In the present study, the incidence and the progression of diabetic complications in the SDT fatty rat were examined, and compared with those of the SDT normal rat. Renal function parameters, such as blood urea nitrogen, urine volume and urinary protein, increased from 4 weeks of age in the SDT fatty rat, and pathological findings in the renal tubule were observed from 8 weeks. Furthermore, cataract was observed in the SDT fatty rat from 8 weeks of age, and prolongation of peak latencies on electroretinograms was observed at 16 and 24 weeks of age. On the other hand, in the SDT normal rat, renal or ocular changes were observed from 24 weeks of age. With early incidence of diabetes mellitus, diabetes-associated complications in the SDT fatty rat were seen at younger ages than those in the SDT normal rat. In conclusion, the SDT fatty rat is expected to be a useful model for the analysis of diabetic complications and the evaluation of drugs related to metabolic diseases.

Increased fat absorption and impaired fat clearance cause postprandial hypertriglyceridemia in Spontaneously Diabetic Torii rat.

In diabetes, postprandial hyperlipidemia is recognized as a risk factor for premature atherosclerosis and following cardiovascular disease. In the present study, features of fat absorption and clearance were examined to clarify the lipid metabolism of Spontaneously Diabetic Torii (SDT) rats. Olive oil was orally administered to evaluate increase of blood triglyceride (TG) level. Mesenteric lymph chylomicron TG was also measured. mRNAs of enzymes and transfer protein related to TG metabolism and histopathological changes were evaluated. In an oil loading test, elevation of TG in plasma and lymph chylomicron was increased in SDT rats. Interestingly, SDT rats showed elevation of plasma TG after oil loading and relatively low epididymal fat lipoprotein lipase (LPL) mRNA expression even at the pre-diabetic state without increase of TG absorption from intestine. In the diabetic state, intestines of SDT rats were hypertrophic and expressed mRNAs of enzymes and transfer protein related to TG absorption highly. From these results, it seems that intestinal abnormalities related to hypoinsulinemia/hyperglycemia cause postprandial hypertriglyceridemia in SDT rats. In addition, our findings suggest that SDT rats have impaired lipid catabolism antecedent to hypoinsulinemia/hyperglycemia. These characteristics of SDT rats can be useful in studies of diabetic hypertriglyceridemia and TG metabolism.

Effect of insulin therapy on renal changes in spontaneously diabetic Torii rats.

The spontaneously diabetic Torii (SDT) rat has recently been established as an animal model of non-obese type 2 diabetes, in which ocular complications severe occur. However, the function and morphological features of the diabetic renal lesions in SDT rats have not been reported in detail. Therefore, we evaluated changes over time in renal lesions in SDT rats. In addition, SDT rats were treated with insulin to observe whether these renal complications are caused by hyperglycemia. Renal functional parameters and renal lesions were monitored in SDT rats from 8 to 68 weeks of age. Sprague-Dawley (SD) rats of similar age were used as control animals. In the insulin-treated group of SDT rats, insulin pellets were implanted at 24 weeks of age to compare the development of renal lesions. The SDT rats began to develop hyperglycemia at 20 weeks of age. In the histopathological examination of the kidney, glycogen deposition of the renal tubular epithelium and renal tubular dilation were observed from 24 weeks of age in the untreated SDT rats, and the changes in the renal tubules markedly progressed with aging. Moreover, thickening of the glomerular basement membrane was observed from 32 weeks of age. At 50 weeks of age, the glomeruli showed increase of mesangial matrix, with predominantly diffuse lesions showing by 68 weeks of age. The mesangial proliferation gradually progressed. In the SD rats, no renal lesions were present at 50 and 68 weeks of age. SDT rats with insulin treatment remained normoglycemic throughout observation and their renal functional parameters were normal. Glycemic control in SDT rats prevented the development of renal lesions. The features of SDT rats indicate their usefulness as an animal model for investigating diabetic nephropathy.

A case of postoperative hemorrhage after a hysterectomy in which a bleeding point of the left uterine artery was identified by postmortem angiography.

We report a case of fatal postoperative hemorrhage caused by failure to ligate the left uterine artery during a hysterectomy in a 42-year-old woman, as demonstrated postmortem by conventional autopsy methods and confirmed by angiography. Angiography was confirmed to be a useful adjunctive technique for postmortem diagnosis and localization of the bleeding point. In cases of suspected fatal postoperative hemorrhage, postmortem angiography may be of value to the forensic pathologist.

Acute subdural hematoma due to arteriovenous malformation primarily in dura mater: a case report.

We report a 42-year-old female with alcohol addiction who suddenly died of subdural hematoma (SDH) caused by dural arteriovenous malformation (AVM). In autopsy, there was seen a massive SDH with a total weight of 181 g that covered an entire part of the left cerebral hemisphere, although either serious external injuries of the head or any visible internal injuries of the brain were observed. SDH subsequently resulted in the tonsillar, transtentorial and subfalcial herniations with a right-sided shift of the left-lateral and third ventricles, and the left thalamus as well. Histopathological examination on the serial sections cut from the falx cerebri revealed abnormal distribution of arteries and veins with various sizes, which were comprehensively highlighted by immunohistochemical stainings with alpha-SMA and CD31. Although a very point of bleeding was not identified even by careful histological observation, we concluded that dural AVM could be critical for acute SDH in the present case. The value of ethanol concentration examined in the samples from SDH supported that the lesion could be not chronic, but acute.

A prospective stratified case-cohort study on statins and multiple adverse events in Japan.

PURPOSE: To assess the association between statins and diverse adverse events in Japanese population. METHODS: New users of statin who started statin after 6-month period of non-use were identified in 68 hospitals between January 2008 and July 2010. In addition to the random sample subcohort, we selected additional subcohort members to make the stratified sample subcohort have at least one patient in all subgroups stratified by each combination of statin and hospital. By abstraction from medical records, detailed information was obtained for all potential cases and pre-selected subcohort members. The event review committee consisting of 3 specialists judged whether possible cases met the definition of one of the adverse events of interest, and for adjudicated cases the committee further judged whether statin was a certain, probable or possible cause of the occurrence of the event. Adjusted for covariates including age, gender, status of "switcher", use of high daily dose and comorbidities at baseline, hazard ratio (HR) was estimated by the Cox proportional hazards model with Barlow's weighting method. Data were also analyzed by the method proposed by Breslow in 2009. RESULTS: A total of 6,877 new users of a statin were identified (median age: 66 years; males: 52%). The hazard ratios of increase in serum creatinine for atorvastatin and fluvastatin have wide confidence intervals, but both of the point estimates were around 2.5. Estimates of hazard ratios by the method of Barlow (1999) were similar to those by the method of Breslow (2009). CONCLUSIONS: Use of statin was not associated with a significant increased risk for renal, liver and muscle events. However, the hazard ratio of increase in serum creatinine tended to be high with atorvastatin and fluvastatin to require further studies.

Effect of food restriction on adipose tissue in spontaneously diabetic Torii fatty rats.

Spontaneously Diabetic Torii-fa/fa (SDT fatty) rat is a new model of obese type 2 diabetes. SDT fatty rat exhibits obesity associated with hyperphagia. In this study, SDT fatty rats were subjected to pair-feeding with SDT-+/+ (SDT) rats from 6 to 22 weeks of age. The ratio of visceral fat weight to subcutaneous fat weight (V/S) decreased at 12 weeks of age in the pair-feeding rats. The intraperitoneal fat weight such as epididymal and retroperitoneal fat weight decreased, whereas mesenteric fat weight had no change. Cell size of the epididymal fat in the pair-feeding rats tended to decrease. Glucose oxidation level in epididymal fat in the pair-feeding rats at 12 weeks of age was recovered to a similar level with that in SDT rats. These results indicated that SDT fatty rat is a useful model to evaluate the functional or the morphological features in adipose tissue and develop a novel drug for antiobesity.

Pancreatic function of spontaneously diabetic torii rats in pre-diabetic stage.

The Spontaneously Diabetic Torii (SDT) rat is a new model for non-obese type 2 diabetes. In the present study, we investigated changes in insulin secretion from the pancreas of male SDT rats aged 8, 16, and 24 weeks in order to analyze pancreatic function. An analysis of glucose-stimulated insulin secretion (GSIS) in isolated islets showed a marked reduction in insulin secretion in pre-diabetic 16-week-old SDT rats. When the islets were treated with tolbutamide or glucagon-like peptide-1 (7-36) amide (tGLP-1) in the presence of 11.2 mM glucose, however, insulin levels were restored to levels of normal rats. In vivo study, SDT rats exhibited a marked reduction in GSIS from 16 weeks of age. However, tolbutamide or JTP-76209, which is a novel dipeptidyl peptidase IV (DPP IV) inhibitor, increased insulin release after glucose loading and improved glucose tolerance. A marked reduction in GSIS was observed in pre-diabetic SDT rats and the reduction was improved by tolbutamide, tGLP-1, and the DPP IV inhibitor. Therefore, we concluded that the SDT rat is useful, as a model of non-obese insulin secretory disorder, for the analysis of the onset of type 2 diabetes and the development of antidiabetic agents.

Degeneration of the inferior olive in spinocerebellar ataxia 6 may depend on disease duration: report of two autopsy cases and statistical analysis of autopsy cases reported to date.

This report concerns a clinicopathological study of two autopsied patients with spinocerebellar ataxia 6 (SCA6), and a statistical analysis between neuronal loss of the inferior olive and disease duration of 15 SCA6 autopsy cases reported to date, including the two cases reported in this study. Cases 1 and 2 came from independent Japanese families. Case 1 developed gait disturbance at age 35 years and died at age 78 years; she had a CAG-repeat expansion of the SCA6 gene (25/13). Case 2 presented with gait disturbance at age 68 years and died at age 78 years; he had an expanded CAG-repeat of the SCA6 gene (22/13). Neuropathological examination of both cases disclosed not only neuronal loss of the Purkinje cells and inferior olive, but also some unnoticed features, including cactus-like expansion of the dendrite of Purkinje cells and relative preservation of Golgi cells in the granular layer of the cerebellum. Exploratory statistical analysis between 11 SCA6 autopsy cases with neuronal loss in the inferior olive (average disease duration: 27 years) and four SCA6 autopsy cases without neuronal loss in the olive (average disease duration: 14.5 years) was investigated by Kaplan-Meier estimates of survival and log-rank test, retrospectively. Kaplan-Meier estimates of survival revealed an obvious difference between the two groups. Survival of 10 years after the disease onset was 90.9% in the former 11 SCA6 autopsy cases, but was 50% in the latter four SCA6 autopsy cases. Furthermore, a log-rank test on the two groups disclosed a significant difference (P=0.0450). We postulate that the neuronal loss of the inferior olive in SCA6 may depend on disease duration.

Phase III trial of radiosensitizer PR-350 combined with intraoperative radiotherapy for the treatment of locally advanced pancreatic cancer.

A randomized, controlled trial was conducted to clarify the effect of novel radiosensitizer, PR-350, accompanied by intraoperative radiology (IOR) on locally advanced pancreatic cancer. Between July 1999 and March 2002, 48 patients were enrolled in this clinical trial and received either PR-350 or placebo. Any differences between the PR-350 group (n = 22) and control group (n = 25) were not statically significant. All patients were evaluated, and none of them showed toxicity, with the exception of 1 patient from the control group, and the PR-350 compound was considered to be safe. The efficacy of IOR with PR-350 was evaluated using CT examination. The committee responsible for evaluating efficacy reported that 47.4% of the PR-350 group showed the effective response, compared with 21.7% of the control group (P = 0.1067, Fisher analysis). At 6 months following treatment, the tumor mass reduction rate in the PR-350 group was significantly improved (P = 0.0274). By the time of the last follow-up in July 2003, 17 PR-350 patients and 24 control patients group had died of the disease. The median survival period of the PR-350 group was thus 318.5 days and that of the control group is 303.0 days. One-year survival rates of the PR-350 group and control group were 36.4% and 32.0%, respectively. Although the PR-350 group did not demonstrate significantly better survival than the control group, 4 of 22 PR-350 patients were still living more than 2 years after the end of the trial, compared with only 1 of 25 patients from the control group. The mechanism of this increased therapeutic response to radiotherapy using PR-350 must be clarified to establish more effective strategy for pancreatic cancer treatment.