An Analysis of Delayed Bleeding in Cases of Colorectal Endoscopic Submucosal Dissection Due to Types of Direct Oral Anticoagulants in Japan.

BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.

Noninvasive quantitative evaluation of viable islet grafts using 111 In-exendin-4 SPECT/CT.

Islet transplantation (IT) is an effective ß-cell replacement therapy for patients with type 1 diabetes; however, the lack of methods to detect islet grafts and evaluate their ß-cell mass (BCM) has limited the further optimization of IT protocols. Therefore, the development of noninvasive ß-cell imaging is required. In this study, we investigated the utility of the 111 Indium-labeled exendin-4 probe {[Lys12(111In-BnDTPA-Ahx)] exendin-4} (111 In exendin-4) to evaluate islet graft BCM after intraportal IT. The probe was cultured with various numbers of isolated islets. Streptozotocin-induced diabetic mice were intraportally transplanted with 150 or 400 syngeneic islets. After a 6-week observation following IT, the ex-vivo liver graft uptake of 111 In-exendin-4 was compared with the liver insulin content. In addition, the in-vivo liver graft uptake of 111 In exendin-4 using SPECT/CT was compared with that of liver graft BCM measured by a histological method. As a result, probe accumulation was significantly correlated with islet numbers. The ex-vivo liver graft uptake in the 400-islet-transplanted group was significantly higher than that in the control and the 150-islet-transplanted groups, consistent with glycemic control and liver insulin content. In conclusion, in-vivo SPECT/CT displayed liver islet grafts, and uptakes were corroborated by histological liver BCM. 111 In-exendin-4 SPECT/CT can be used to visualize and evaluate liver islet grafts noninvasively after intraportal IT.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

[18F]FB(ePEG12)12-exendin-4 noninvasive imaging of insulinoma negative for insulin immunostaining on specimen from endoscopic ultrasonography-guided fine needle aspiration: a case report with review of literature.

Insulinomas are the most common functional pancreatic neuroendocrine neoplasm; when treatment is delayed, they induce hyperinsulinemic hypoglycemia, which is life-threatening. As surgical resection is the only curative treatment for insulinoma, preoperative localization is crucial; however, localization based on conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging is often inconclusive. Somatostatin receptor-targeted imaging is another option for detecting pancreatic neuroendocrine neoplasms but has low sensitivity and is not specific for insulinoma. The clinical application of other localizing approaches such as selective arterial calcium stimulation and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is limited by their being invasive and/or technically complex. Moreover, an EUS-FNA specimen of an insulinoma may be negative on insulin immunostaining. Thus, a noninvasive and clinically practical insulinoma-specific diagnostic tool to discriminate insulinomas with high accuracy is anticipated. Glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged in the effort to fulfill this need. We recently developed the novel fluorine-18-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4) for positron emission tomography (PET) imaging and reported its clinical benefit in a case of insulinoma in the pancreatic tail. We report here a case of insulinoma in the pancreatic head in which an EUS-FNA specimen was negative on insulin immunostaining while precise preoperative localization and conclusive evidence for curative enucleation was provided by 18F-exendin-4 PET/CT (Japan Registry of Clinical Trials; jRCTs051200156).

Additional 30-Second Observation of the Right-Sided Colon for Missed Polyp Detection With Texture and Color Enhancement Imaging Compared with Narrow Band Imaging: A Randomized Trial.

INTRODUCTION: The efficacy of texture and color enhancement imaging (TXI) in the novel light-emitting diode endoscopic system for polyp detection has not been examined. We aimed to evaluate the noninferiority of the additional 30-second (Add-30-s) observation of the right-sided colon (cecum/ascending colon) with TXI compared with narrow band imaging (NBI) for detecting missed polyps. METHODS: We enrolled 381 patients ≥40 years old who underwent colonoscopy from September 2021 to June 2022 in 3 institutions and randomly assigned them to either the TXI or NBI groups. The right-sided colon was first observed with white light imaging in both groups. Second, after reinsertion from hepatic flexure to the cecum, the right-sided colon was observed with Add-30-s observation of either TXI or NBI. The primary endpoint was to examine the noninferiority of TXI to NBI using the mean number of adenomas and sessile serrated lesions per patient. The secondary ones were to examine adenoma detection rate, adenoma and sessile serrated lesions detection rates, and polyp detection rates in both groups. RESULTS: The TXI and NBI groups consisted of 177 and 181 patients, respectively, and the noninferiorities of the mean number of adenomas and sessile serrated lesions per patients in the second observation were significant (TXI 0.29 [51/177] vs NBI 0.30 [54/181], P < 0.01). The change in adenoma detection rate, adenoma and sessile serrated lesions detection rate, and polyp detection rate for the right-sided colon between the TXI and NBI groups were not different (10.2%/10.5% [ P = 0.81], 13.0%/12.7% [ P = 0.71], and 15.3%/13.8% [ P = 0.71]), respectively. DISCUSSION: Regarding Add-30-s observation of the right-sided colon, TXI was noninferior to NBI.

Efficacy of antihyperglycemic therapies on cardiovascular and heart failure outcomes: an updated meta-analysis and meta-regression analysis of 35 randomized cardiovascular outcome trials.

BACKGROUND: Effects of antihyperglycemic therapies on cardiovascular and heart failure (HF) risks have varied widely across cardiovascular outcome trials (CVOTs), and underlying factors remain incompletely understood. We aimed to determine the relationships of glycated hemoglobin (HbA1c) or bodyweight changes with these outcomes in all CVOTs of antihyperglycemic therapies. METHODS: We searched PubMed and EMBASE up to 25 January 2023 for all randomized controlled CVOTs of antihyperglycemic therapies reporting both major adverse cardiovascular events (MACE) and HF outcomes in patients with type 2 diabetes or prediabetes. We performed meta-regression analyses following random-effects meta-analyses to evaluate the effects of HbA1c or bodyweight reductions on each outcome. RESULTS: Thirty-five trials comprising 256,524 patients were included. Overall, antihyperglycemic therapies reduced MACE by 9% [risk ratio (RR): 0.91; 95% confidence interval (CI) 0.88-0.94; P < 0.001; I2 = 36.5%]. In meta-regression, every 1% greater reduction in HbA1c was associated with a 14% reduction in the RR of MACE (95% CI 4-24; P = 0.010), whereas bodyweight change was not associated with the RR of MACE. The magnitude of the reduction in MACE risk associated with HbA1c reduction was greater in trials with a higher baseline prevalence of atherosclerotic cardiovascular disease. On the other hand, antihyperglycemic therapies showed no overall significant effect on HF (RR: 0.95; 95% CI 0.87-1.04; P = 0.28; I2 = 75.9%). In a subgroup analysis based on intervention type, sodium-glucose cotransporter-2 inhibitors (SGLT2i) conferred the greatest HF risk reduction (RR: 0.68; 95% CI 0.62-0.75; P < 0.001; I2 = 0.0%). In meta-regression, every 1 kg bodyweight reduction, but not HbA1c reduction, was found to reduce the RR of HF by 7% (95% CI 4-10; P < 0.001); however, significant residual heterogeneity (P < 0.001) was observed, and SGLT2i reduced HF more than could be explained by HbA1c or bodyweight reductions. CONCLUSIONS: Antihyperglycemic therapies reduce MACE in an HbA1c-dependent manner. These findings indicate that HbA1c can be a useful marker of MACE risk reduction across a wide range of antihyperglycemic therapies, including drugs with pleiotropic effects. In contrast, HF is reduced not in an HbA1c-dependent but in a bodyweight-dependent manner. Notably, SGLT2i have shown class-specific benefits for HF beyond HbA1c or bodyweight reductions.

Stabilization of kidney function and reduction in heart failure events with sodium-glucose co-transporter 2 inhibitors: A meta-analysis and meta-regression analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) events regardless of diabetes status. However, factors associated with their efficacy in HF reduction remain unknown. This study aims to identify clinically relevant markers for the efficacy of SGLT2 inhibitors in HF risk reduction. MATERIALS AND METHODS: We searched PubMed/MEDLINE and EMBASE for randomized placebo-controlled trials of SGLT2 inhibitors reporting a composite of HF hospitalization or cardiovascular death in participants with or without type 2 diabetes published until 28 February 2023. Random-effects meta-analysis and mixed-effects meta-regression were conducted to evaluate the association between the outcomes and clinical variables, including changes in glycated haemoglobin, body weight, systolic blood pressure, haematocrit and overall/chronic estimated glomerular filtration rate (eGFR) slope. RESULTS: Thirteen trials with 90 413 participants were included. SGLT2 inhibitors reduced the hazard ratio of the composite of HF hospitalization or cardiovascular death (hazard ratio 0.77; 95% confidence interval, 0.74-0.81; p < .0001). In meta-regression analysis, chronic eGFR slope (eGFR change after the initial dip) was significantly associated with the composite outcome (p = .017), and each 1 ml/min/1.73 m2 /year improvement in chronic eGFR slope led to a 14% reduction in the composite outcome. By contrast, changes in the other parameters showed no significant associations. CONCLUSIONS: Improvement in chronic eGFR slope, which reflects the stabilization of kidney function, is significantly associated with the efficacy of the SGLT2 inhibitor in HF, highlighting the cardiorenal axis role in the beneficial effects on HF. The chronic eGFR slope can be a surrogate marker of the effects of SGLT2 inhibitors on HF reduction.

Unmasked insulinoma occasioned by severe hypoglycemic coma immediately postpartum: a case report.

BACKGROUND: Insulinoma in women during pregnancy and postpartum is very rare; approximately 65% of cases are diagnosed early in pregnancy and ~ 35% immediately after delivery, few being found in middle or late pregnancy, likely due to increased insulin resistance seen after early-stage pregnancy. We successfully treated a case of insulinoma in which severe hypoglycemic coma immediately after delivery occasioned detailed investigation and diagnosis. CASE PRESENTATION: Our patient experienced hypoglycemic coma in the 3rd month of pregnancy (initially considered due to her hyperemesis gravidarum) that improved spontaneously during the gestational period. No abnormalities of plasma glucose or body weight were found in regular checkups during her pregnancy; however, recurrence of hypoglycemic coma after delivery led us to suspect insulinoma. While contrast enhanced computer tomography and endoscopic ultrasonography (EUS) initially failed to detect a tumor in the pancreas, selective arterial calcium stimulation test revealed an insulin-secreting tumor localized in the pancreatic body. She then underwent spleen-preserving distal pancreatectomy; a 10-mm tumor positive for chromogranin A, synaptophysin and insulin was identified. CONCLUSIONS: Although pregnancy can mask insulinoma-associated symptoms and make diagnosis challenging, hypoglycemic episodes during early pregnancy, which were observed in this case, are suggestive of insulinoma. Importantly, in this case, accurate preoperative localization of the tumor enabled prompt curative surgery after delivery. Thus, clinical vigilance for the occurrence of insulinoma and its localization is appropriate for pregnant women suffering severe hypoglycemia.

Standard Endoscopic Mucosal Resection vs Precutting Endoscopic Mucosal Resection Using Novel Disk-Tip Snare for Colorectal Lesions.

INTRODUCTION: SOUTEN (KANEKA Co., Tokyo, Japan) is a unique snare with a disk tip. We analyzed the efficacy of precutting endoscopic mucosal resection with SOUTEN (PEMR-S) for colorectal lesions. METHODS: We retrospectively reviewed 57 lesions of 10-30 mm treated with PEMR-S at our institution from 2017 to 2022. The indications were lesions that were difficult for standard EMR due to size, morphology, and poor elevation by injection. Various therapeutic results of PEMR-S such as en bloc resection, procedure time, and perioperative hemorrhage were analyzed, and the results of 20 lesions of 20-30 mm with PEMR-S were compared to those of lesions with standard EMR (2012-2014) using propensity score matching. Additionally, the stability of the SOUTEN disk tip was analyzed in a laboratory experiment. RESULTS: The polyp size was 16.5 ± 4.2 mm and the non-polypoid morphology rate was 80.7%. Histopathological diagnosis included 10 sessile-serrated lesions, 43 low-grade and high-grade dysplasias, and 4 T1 cancers. After matching, the en bloc resection and histopathological complete resection rates of lesions of 20-30 mm between PEMR-S and standard EMR (90.0% vs. 58.1%, p = 0.03 and 70.0% vs. 45.0%, p = 0.11). The procedure time (min) was 14.8 ± 9.7 and 9.7 ± 8.3 (p < 0.01). The en bloc resection (%) and procedure time of expert/non-expert were 89.7/85.7 (p = 0.96) and 6.1 ± 2.2/18.5 ± 7.2 (p < 0.01). The perioperative bleeding and hemostasis success rates with SOUTEN were 43.9% and 96.0%. In the experiment, the SOUTEN disk tip was fixed stably compared to other EMR snares. CONCLUSIONS: PEMR-S achieved high en bloc resection of colorectal lesions of 20-30 mm though it leaded to long procedure time.

Comparison of LED and LASER Colonoscopy About Linked Color Imaging and Blue Laser/Light Imaging of Colorectal Tumors in a Multinational Study.

INTRODUCTION: In light-emitting diode (LED) and LASER colonoscopy, linked color imaging (LCI) and blue light/laser imaging (BLI) are used for lesion detection and characterization worldwide. We analyzed the difference of LCI and BLI images of colorectal lesions between LED and LASER in a multinational study. METHODS: We prospectively observed lesions with white light imaging (WLI), LCI, and BLI using both LED and LASER colonoscopies from January 2020 to August 2021. Images were graded by 27 endoscopists from nine countries using the polyp visibility score: 4 (excellent), 3 (good), 2 (fair), and 1 (poor) and the comparison score (LED better/similar/LASER better) for WLI/LCI/BLI images of each lesion. RESULTS: Finally, 32 lesions (polyp size: 20.0 ± 15.2 mm) including 9 serrated lesions, 13 adenomas, and 10 T1 cancers were evaluated. The polyp visibility scores of LCI/WLI for international and Japan-expert endoscopists were 3.17 ± 0.73/3.17 ± 0.79 (p = 0.92) and 3.34 ± 0.78/2.84 ± 1.22 (p < 0.01) for LED and 3.30 ± 0.71/3.12 ± 0.77 (p < 0.01) and 3.31 ± 0.82/2.78 ± 1.23 (p < 0.01) for LASER. Regarding the comparison of lesion visibility about between LED and LASER colonoscopy in international endoscopists, a significant difference was achieved not for WLI, but for LCI. The rates of LED better/similar/LASER better for brightness under WLI were 54.5%/31.6%/13.9% (International) and 75.0%/21.9%/3.1% (Japan expert). Those under LCI were 39.2%/35.4%/25.3% (International) and 31.3%/53.1%/15.6% (Japan expert). There were no significant differences in the diagnostic accuracy and the comparison score of BLI images between LED and LASER. CONCLUSIONS: The differences of lesion visibility for WLI/LCI/BLI between LED and LASER in international endoscopists could be compared to those in Japanese endoscopists.

Astaxanthin attenuated the stress-induced intestinal motility disorder via altering the gut microbiota.

Gut microbiota and short-chain fatty acids (SCFAs) are recognized as key factors in the pathophysiology of irritable bowel syndrome. Astaxanthin is a carotenoid with strong antioxidant and anti-inflammatory activities. In this study, we examined the effects of astaxanthin on gut microbiota-, SCFAs-, and corticotropin-releasing factor (CRH)-induced intestinal hypermotility. Male Wistar rats (n=12 per group) were fed a diet with or without 0. 02% (w/w) astaxanthin for four weeks and CRH or saline was administered intravenously. The number of fecal pellets was counted 2 h after injection. Then the rats were sacrificed, and the cecal content were collected 3 h after injection. The number of feces was significantly increased by CRH injection in the control group (2.0 vs. 6.5; p=0.028), but not in the astaxanthin group (1.0 vs. 2.2; p=0.229) (n=6 per group). The cecal microbiota in the astaxanthin group was significantly altered compared with that in the control group. The concentrations of acetic acid (81.1 µmol/g vs. 103.9 µmol/g; p=0.015) and butyric acid (13.4 µmol/g vs. 39.2 µmol/g; p<0.001) in the astaxanthin group were significantly lower than that in the control group (n=12 per group). Astaxanthin attenuates CRH-induced intestinal hypermotility and alters the composition of gut microbiota and SCFAs.

Analysis of Texture and Color Enhancement Imaging for Improving the Visibility of Non-polypoid Colorectal Lesions.

INTRODUCTION: An endoscopic system using 5-color light-emitting diodes (LEDs) (EVIS X1; Olympus Co., Tokyo, Japan), which includes texture and color enhancement imaging (TXI), has been released. In this study, we analyzed the effects of TXI on the visibility of non-polypoid colorectal lesions and its diagnostic accuracy. METHODS: We reviewed 101 non-polypoid lesions from 26 patients observed with white light imaging (WLI), narrow band imaging (NBI), and TXI. One representative image of each mode was evaluated by 6 endoscopists using a polyp visibility score of 4 (excellent) to 1 (poor). We calculated the color difference (CD) values for each lesion in the three modes. For tumor characteristics, one representative image of TXI and NBI magnification was evaluated by 3 experts according to a NBI classification. RESULTS: The least squares means [95% confidence interval] of polyp visibility score of TXI (3.42 [3.06-3.77]) was significantly higher than that of WLI (2.85 [2.49-3.20], p < 0.001) but not that of NBI (3.33 [2.98-3.69], p = 0.258). The CD value of TXI (13.3 ± 6.3) was higher than that of WLI (9.7 ± 6.0, p < 0.001) but not that of NBI (13.1 ± 6.8, p = 0.81). For sessile serrated lesions, the CD value of TXI (11.1 ± 4.4) tended to be lower than that of NBI (12.6 ± 6.0, p = 0.07). The diagnostic accuracy and confidence level of magnification for NBI were significantly better than those for TXI (87.1 vs. 80.5%, p = 0.027, 87.5 vs. 62.7%, p < 0.001, respectively). CONCLUSION: TXI showed better visibility than WLI in terms of the endoscopist's score and CD value and may improve polyp detection.

Repeat Cold Snare Polypectomy Can Be Performed for Recurrent Benign Lesions After Cold Snare Polypectomy.

BACKGROUND AND AIMS: Recurrence after cold snare polypectomy (CSP) sometimes occurs. We assessed the feasibility of repeat CSP for recurrence after CSP. METHODS: We retrospectively reviewed recurrent lesions after CSP which were resected by repeat CSP from 2016 to 2021 in our institution and analyzed clinical outcomes of repeat CSP, comparing those of non-recurrent 454 lesions receiving standard CSP in 2016 and follow-up colonoscopy. We also analyzed the recurrent rate among cases receiving follow-up in both groups. Indication of repeat CSP was lesions diagnosed as benign tumors of ≤ 10 mm. RESULTS: We analyzed 80 lesions receiving repeat CSP. The polyp size (mean ± standard deviation: SD) was 4.1 ± 2.3 mm (range 2-10 mm). The right-sided colon and non-polypoid morphology rates were 66.3% and 43.8%, respectively. Histopathological diagnosis was 66 adenomas, 12 sessile serrated lesions (SSLs), 1 SSL with dysplasia, and 1 high-grade dysplasia. The procedure time (min, mean ± SD) of repeat CSP was 0.9 ± 0.8. Regarding the comparison of repeat CSP/ standard CSP group, the en bloc resection and histopathological complete resection rates were 78.8%/ 98.0% (p < 0.001) and 43.8%/59.6% (p = 0.007) and the rates of perioperative hemorrhage requiring endoscopic clipping were 1.3%/ 1.0% (p = 0.646). There were no postoperative hemorrhage and perforation in both groups (p = 1.0). Among lesions receiving follow-up colonoscopy, the mean recurrence rates (number, median follow-up period: interquartile) of repeat CSP and standard CSP group were 2.0% (1/50, 12 months: 12-24) versus 0.7% (3/454, 12 months: 12-24) (p = 0.862). CONCLUSIONS: Repeat CSP for benign recurrent lesions after CSP was safe and feasible.

Risk Factors of Delayed Bleeding After Cold Snare Polypectomy for Colorectal Polyps: A Multicenter Study.

BACKGROUND: Delayed bleeding (DB) rarely occurs after cold snare polypectomy (CSP) for colorectal polyps, but no large-scale studies have investigated this. The present study evaluated the rate, characteristics, and risk factors of DB of CSP. METHODS: We conducted a multicenter retrospective study at 10 Japanese institutions. A total of 18,007 patients underwent CSP for colorectal polyps ≤ 10 mm in size from March 2015 to September 2019, and cases of DB (DB group) were analyzed for the rate, antithrombotic drugs, polyp size, morphology, location, and risk factors. As a control, 269 non-bleeding cases (non-DB group) with 606 polyps who underwent CSP at the same 10 facilities in the 2-week study period were extracted. RESULTS: We analyzed 26 DB cases with 28 lesions, and the total DB rate was 0.14% (26/18,007). The DB group had significantly higher rates of using antiplatelets (42.3% vs. 13.0%, p < 0.001) and anticoagulants (19.2% vs. 2.6%, p = 0.002), and significantly higher rates of polyp size ≥ 5 mm (67.9% vs. 45.2%, p = 0.015), rectal lesion (25.0% vs. 6.6%, p = 0.003), and polypoid lesion (89.3% vs. 55.3%, p < 0.001) than the non-DB group. A multivariate analysis (odds ratio; 95% confidence interval) for patient characteristics showed antiplatelet use (4.521; 1.817-11.249, p = 0.001) and anticoagulant use (7.866; 20.63-29.988, p = 0.003) as independent risk factors for DB. Polyp size ≥ 5 mm (3.251; 1.417-7.463, p = 0.005), rectal lesion (3.674; 1.426-9.465, p = 0.007), and polypoid lesion (7.087; 20.81-24.132, p = 0.002) were also risk factors for lesion characteristics. CONCLUSIONS: The rate of DB was 0.14% and antithrombotic drug use, polyp size, location, and morphology were related to it.

Opioid-induced adrenal insufficiency in transdermal fentanyl treatment: a revisited diagnosis in clinical setting.

Opioids are widely used for treatment of acute and chronic pain. However, opioids have several well-known clinical adverse effects such as constipation, nausea, respiratory depression and drowsiness. Endocrine dysfunctions are also opioid-induced adverse effects but remain under-diagnosed in clinical settings, especially opioid-induced adrenal insufficiency (OIAI). A 46-year-old woman was treated with transdermal fentanyl at a dose of 90-120 mg daily morphine milligram equivalent for non-malignant chronic pain for four years. Fatigue, loss of appetite and decrease in vitality began about two years after starting fentanyl. Subsequently, constipation and abdominal pain appeared and became worse, which led to suspicion of adrenal insufficiency. Clinical diagnosis of OIAI was established based on laboratory findings of secondary adrenal insufficiency, including corticotropin-releasing hormone stimulation test, clinical history of long-term fentanyl use, and exclusion of other hypothalamic-pituitary diseases. Oral corticosteroid replacement therapy was unable to relieve her abdominal pain and constipation; opioid-rotation and dose-reduction of fentanyl were not feasible because of her persistent pain and severe anxiety. While her clinical course clearly suggested that long-term, relatively high-dose transdermal fentanyl treatment may have contributed to the development of secondary adrenal insufficiency, the symptoms associated with OIAI are generally non-specific and complex. Together with under-recognition of OIAI as a clinical entity, the non-specific, wide range of symptoms can impede prompt diagnosis. Thus, vigilance for early symptoms enabling treatments including corticosteroid replacement therapy is necessary for patients taking long-term and/or high dose opioid treatment.

Investigating the Influence of GABA Neurons on Dopamine Neurons in the Ventral Tegmental Area Using Optogenetic Techniques.

Dopamine (DA) is the key regulator of reward behavior. The DA neurons in the ventral tegmental area (VTA) and their projection areas, which include the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala, play a primary role in the process of reward-driven behavior induced by the drugs of addiction, including nicotine and alcohol. In our previous study, we developed a novel platform consisting of micro-LED array devices to stimulate a large area of the brain of rats and monkeys with photo-stimulation and a microdialysis probe to estimate the DA release in the PFC. Our results suggested that the platform was able to detect the increased level of dopamine in the PFC in response to the photo-stimulation of both the PFC and VTA. In this study, we used this platform to photo-stimulate the VTA neurons in both ChrimsonR-expressing (non-specific) wild and dopamine transporter (DAT)-Cre (dopamine specific) mice, and measured the dopamine release in the nucleus accumbens shell (NAcShell). We measured the DA release in the NAcShell in response to optogenetic stimulation of the VTA neurons and investigated the effect of GABAergic neurons on dopaminergic neurons by histochemical studies. Comparing the photo-stimulation frequency of 2 Hz with that of 20 Hz, the change in DA concentration at the NAcShell was greater at 20 Hz in both cases. When ChrimsonR was expressed specifically for DA, the release of DA at the NAcShell increased in response to photo-stimulation of the VTA. In contrast, when ChrimsonR was expressed non-specifically, the amount of DA released was almost unchanged upon photo-stimulation. However, for nonspecifically expressed ChrimsonR, intraperitoneal injection of bicuculline, a competitive antagonist at the GABA-binding site of the GABAA receptor, also significantly increased the release of DA at the NAcShell in response to photo-stimulation of the VTA. The results of immunochemical staining confirm that GABAergic neurons in the VTA suppress DA activation, and also indicate that alterations in GABAergic neurons may have serious downstream effects on DA activity, NAcShell release, and neural adaptation of the VTA. This study also confirms that optogenetics technology is crucial to study the relationship between the mesolimbic dopaminergic and GABAergic neurons in a neural-specific manner.

An analysis about the function of a new artificial intelligence, CAD EYE with the lesion recognition and diagnosis for colorectal polyps in clinical practice.

OBJECTIVES: Recently, CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for the lesion recognition (CADe) and the optical diagnosis (CADx) of colorectal polyps, was released. We evaluated the function of CADe and CADx of CAD EYE. METHODS: In this single-center retrospective study, we examined consecutive polyps ≤ 10 mm detected from March to April 2021 to determine whether CAD EYE could recognize them live with both normal- and high-speed observation using white-light imaging (WLI) and linked-color imaging (LCI). We then examined whether the polyps were neoplastic or hyperplastic live with magnified or non-magnified blue-laser imaging (BLI-LASER) or blue-light imaging (BLI-LED) under CAD EYE, comparing the retrospective evaluations with 5 experts and 5 trainees using still images. All polyps were histopathologically examined. RESULTS: We analyzed 100 polyps (mean size 3.9 ± 2.6 mm; 55 neoplastic and 45 hyperplastic lesions) in 25 patients. Regarding CADe, the respective detection rates of CAD EYE with normal- and high-speed observation were 85.0% and 67.0% for WLI (p = 0.002) and 89.0% and 75.0% for LCI (p = 0.009). Regarding CADx for differentiating neoplastic and hyperplastic lesions, the diagnostic accuracy values of CAD EYE with non-magnified and magnified BLI-LASER/LED were 88.8% and 87.8%. Regarding magnified BLI-LASER/LED, the diagnostic accuracy value of CAD EYE was not significantly different from that of experts (92.0%, p = 0.17), but that of trainees (79.0%, p = 0.04). We also found no significant differences in CADe or CADx between LED (53 lesions) and LASER (47 lesions). CONCLUSIONS: CAD EYE was a helpful tool for CADe and CADx in clinical practice.

Risk of lymph node metastasis after endoscopic treatment for rectal NETs 10 mm or less.

PURPOSE: For rectal neuroendocrine tumors (NETs) ≤ 10 mm, endoscopic resection is a standard treatment. However, there is no consensus whether additional surgery should be performed for patients at risk of lymph node metastasis (LNM) after endoscopic resection. The purpose of this study was to analyze the results of endoscopic resection and additional surgery of rectal NETs, thereby clarify the characteristics of cases with LNM. METHODS: This study was a multicenter retrospective cohort study conducted at 12 Japanese institutions. A total of 132 NETs ≤ 10 mm were analyzed regarding various therapeutic results. A comparative analysis was performed by dividing the cases into two groups that underwent additional surgery or not. Furthermore, the relationship between tumor size and LNM was examined. RESULTS: The endoscopic treatments were 12 endoscopic mucosal resections (EMR), 58 endoscopic submucosal resections with ligation (ESMR-L), 29 precutting EMRs, and 33 endoscopic submucosal dissections (ESD). The R0 resection rates of EMR were 41.7%, and compared to this rate, other three treatments were 86.2% (p < 0.001), 86.2% (p = 0.005), and 97.0% (p < 0.001), respectively. There were 41 non-curative cases (31.1%), and 13 had undergone additional surgery. Then, LNM was observed in 4 of the 13 patients, with an overall rate of LNM of 3.0% (4/132). The rate of positive lymphatic invasion and the rate of LNM by tumor size ≤ 6 mm and 7-10 mm were 9.7 vs. 15.4% (p = 0.375) and 0 vs. 10.3% (p = 0.007). CONCLUSIONS: A multicenter study revealed the priority of each endoscopic resection and the low rate of LNM for rectal NETs ≤ 6 mm.

Recurrence rate and lesions characteristics after cold snare polypectomy of high-grade dysplasia and T1 lesions: A multicenter analysis.

BACKGROUND AND AIM: High-grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow-up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them. METHODS: This was a multicenter retrospective-cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow-up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence. RESULTS: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow-up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow-up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non-recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P < 0.001). CONCLUSIONS: High-grade dysplasia and T1 resected by CSP were analyzed, and the local recurrence rate of them was substantially high.

Acromegaly accompanied by diabetes mellitus and polycystic kidney disease.

Acromegaly is characterized by autonomous excessive growth hormone (GH) secretion, generally due to GH-producing pituitary adenoma, and is associated with various systemic comorbidities including diabetes mellitus. Polycystic kidney disease (PKD) is characterized by the growth of numerous cysts in the kidneys that deteriorate renal function. While possible renal effects of excessive GH exposure have been a current issue in experimental medicine, only five cases of coexisting acromegaly and PKD have been reported previously, and little is known regarding the influence of acromegaly on renal disease. We treated a 50-year-old male with diabetes mellitus who showed a sudden and rapid decline of renal function along with increasing proteinuria, which led to diagnoses of PKD and acromegaly. His urinary protein levels were increased together with excessive GH secretion and worsening glycemic control. An increase of total kidney volume was also noted. Transsphenoidal surgery for the pituitary adenoma was successfully performed. Marked improvement of hyperglycemia and proteinuria were observed after the surgery, but renal function was unchanged. The patient's clinical course suggested common aspects of excessive GH secretion as an accelerating factor of the progression of diabetic nephropathy and PKD via direct and indirect pathways. Although coexisting acromegaly and PKD is clinically rare, vigilance for early diagnosis of acromegaly is appropriate in patients with diabetes and/or PKD, especially in those showing unexpected exacerbation of renal dysfunction.