Artificial intelligence in detection of small bowel lesions and their bleeding risk:A new step forward

The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate.The development of artificial intelligence(AI)in CE could simplify physicians’tasks.The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk,and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

Device-assisted enteroscopy: Are we ready to dismiss the spiral?

Motorized spiral enteroscopy(MSE)is the latest advance in device-assisted enteroscopy.Adverse events related to MSE were discussed in a recent large systematic review and meta-analysis and were directly compared with those of balloon enteroscopy in a case-matched study and a randomized controlled trial.Following the real-life application of MSE,an unexpected safety issue emerged regarding esophageal injury and the technique has been withdrawn from the global market,despite encouraging results in terms of diagnostic and therapeutic yield.We conducted an Italian multicenter real-life prospective study,which was prematurely terminated after the withdrawal of MSE from the market.The primary goals were the evaluation of MSE performance(both diagnostic and therapeutic)and its safety in routine endoscopic practice,particularly in the early phase of introduction in the endoscopic unit.A subanalysis,which involved patients who underwent MSE after unsuccessful balloon enteroscopy,demonstrated,for the first time,the promising performance of MSE as a rescue procedure.Given its remarkable performance in clinical practice and its potential role as a backup technique following a previously failed enteroscopy,it may be more appropriate to refine and enhance MSE in the future rather than completely abandoning it.

Extravasated contrast volumetric assessment on computed tomography angiography in gastrointestinal bleeding:A useful predictor of positive angiographic findings

BACKGROUND Gastrointestinal bleeding(GIB)is a severe and potentially life-threatening condition,especially in cases of delayed treatment.Computed tomography angiography(CTA)plays a pivotal role in the early identification of upper and lower GIB and in the prompt treatment of the haemorrhage.AIM To determine whether a volumetric estimation of the extravasated contrast at CTA in GIB may be a predictor of subsequent positive angiographic findings.METHODS In this retrospective single-centre study,35 patients(22 men;median age 69 years;range 16-92 years)admitted to our institution for active GIB detected at CTA and further submitted to catheter angiography between January 2018 and February 2022 were enrolled.Twenty-three(65.7%)patients underwent endoscopy before CTA.Bleeding volumetry was evaluated in both arterial and venous phases via a semi-automated dedicated software.Bleeding rate was obtained from volume change between the two phases and standardised for unit time.Patients were divided into two groups,according to the angiographic signs and their concordance with CTA.RESULTS Upper bleeding accounted for 42.9%and lower GIB for 57.1%.Mean haemoglobin value at the admission was 7.7 g/dL.A concordance between positive CTA and direct angiographic bleeding signs was found in 19(54.3%)cases.Despite no significant differences in terms of bleeding volume in the arterial phase(0.55 mL vs 0.33 mL,P=0.35),a statistically significant volume increase in the venous phase was identified in the group of patients with positive angiography(2.06 mL vs 0.9 mL,P=0.02).In the latter patient group,a significant increase in bleeding rate was also detected(2.18 mL/min vs 0.19 mL/min,P=0.02).CONCLUSION In GIB of any origin,extravasated contrast volumetric analysis at CTA could be a predictor of positive angiography and may help in avoiding further unnecessary procedures.

Post-trans-arterial chemoembolization hepatic necrosis and biliary stenosis: Clinical charateristics and endoscopic approach

Liver cancer is the fifth most common tumor and the second highest death-related cancer in the world.Hepatocarcinoma(HCC)represents 90%of liver cancers.According to the Barcelona Clinic Liver Cancer group,different treatment options could be offered to patients in consideration of tumor burden,liver function,pa-tient performance status and biochemical marker serum concentration such as alpha-fetoprotein.Trans-arterial chemoembolization(TACE)is the treatment of choice in patients with diagnosis of unresectable HCC not eligible for liver trans-plantation,and preserved arterial supply.TACE is known to be safe and its com-plications are generally mild such as post-TACE syndrome,a self-resolving adverse event that occurs in about 90%of patients after the procedure.However,albeit rarely,more severe adverse events such as biloma,sepsis,hepatic failure,chemoagents induced toxicities,and post-TACE liver necrosis can occur.A prompt diagnosis of these clinical conditions is fundamental to prevent further complications.As a result,biliary stenosis could be a rare post-TACE necrosis complication and can be difficult to manage.Complications from untreated biliary strictures include recurring infections,jaundice,chronic cholestasis,and secon-dary biliary cirrhosis.

Femoral artery blowout syndrome after inguinal lymphadenectomy for penile cancer

Dear Editor,Inguinal lymphadenectomy represents a crucial step in both staging and treatment of penile cancer and can be curative in some patients.Nevertheless,severe morbidity can be high in up to 50%of cases.The most-reported complications are skin necrosis,wound infection,lymphoedema,and lymphocele[1].In this setting,artery blowout syndrome(ABS)is a complication rarely described,presenting with vessels exposure through wound dehiscence,leading to arterial wall rupture with potentially life-threatening bleeding(Type III ABS).Reports have been described following radiation treatment of the groins or the neck[2,3].We present the first case of femoral artery wall rupture with severe hemorrhage after iliac and inguinal lymphadenectomy for penile cancer in a patient without previous radiation treatment.Written consent for case publication was obtained.

A型肉毒毒素额部除皱后引起皮脂分泌改变的实验研究

目的：观察比较两种不同注射剂量的A型肉毒毒素（BTX-A）行额部注射除皱术后，引起局部皮脂分泌改变的情况，并研究其剂量和功效之间的关联。方法20例额部皱纹患者（中度至重度）随机分为注射总量10 U或20 U的两个治疗组。注射药物为宝妥适（BOTOX, BOTOX Cosmetic；Allergan, Irvine, CA），使用肌肉内注射标准五点法。评价注射后2周、4周、8周、16周患者额部注射区域（注射点外围半径0.5 cm区域、注射点外围半径0.6～1.5 cm环形区域、注射点外围半径1.6～2.5 cm环形区域）皮肤油脂分泌水平。结果两种不同剂量注射2周、4周、8周后额部注射点外围半径0.5 cm区域平均皮脂分泌水平较注射前显著下降（P＜0.05），注射16周后注射点外围半径0.5 cm区域平均油脂分泌水平于注射前相比没有显著差异。注射2周、4周、8周、16周后，注射点外围半径1.6～2.5 cm环形区域皮肤的平均油脂分泌水平显著高于注射前平均皮肤油脂分泌水平（P＜0.05），注射点外围半径1.6～2.5 cm环形区域皮肤的平均油脂分泌水平与注射前水平相比没有显著的统计学差异。结论10 U及20 U肌肉内BTX-A注射2周、4周及8周后，能显著减少注射点外围半径0.5 cm区域的皮脂分泌，并引起注射点外围半径1.6～2.5 cm环形区域皮肤的皮脂分泌增高。

乳房体积测量方法的比较研究

目的比较各类乳房体积测量方法,为临床应用提供参考。方法以"breast volume"、"breast measurement"和"breast volumetry"为关键词,检索Pubmed和万方数据库,筛选出以乳房体积测量为主题的文献。回顾、整理各类乳房体积测量方法,并分析其原理,比较其准确性、经济性和操作可行性。结果自1970年7月至2013年5月,总共有46篇以乳房体积测量的文章符合入选标准。目前已被报道的乳房体积测量方法共有9种,可以根据其测量原理分为三类:影像法,包括MRI、超声和CT测量;自然法,包括3D建模、排水体积法和胸模法;几何法,包括Grossman-Roudner、人体测量计算和X线摄片。结论 9种测量方法中,3D建模和MRI测量法,因准确性较高,又没有明显的副作用,可以用来为术前计划提供参考;Grossman-Roudner模具测量法和人体测量法虽可靠性有所降低,但经济简便,可以使用在较大样本量的临床研究中。

Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks (sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ (PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stress-associated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients.

From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting

Fecal calprotectin(FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases(IBD). Many different methods of assessment have been developed and different cutoffs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome(IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn's disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.

Digital subtraction angiography for the analysis of supraaortic vessels: What is its role nowadays?

For about 50 years, angiography represented the only imaging method for studying carotid arteries in order to detect the presence of pathological stenosis due to atherosclerotic plaque. Recently, thanks to the use of non-invasive methods, physicians are able to study and quantify the presence of carotid atherosclerosis in vivo These procedures have enabled the introduction of new concepts: (1) the degree of carotid stenosis is approxi- mate to the volume and extension of carotid plaque; and (2) a set of parameters, easily identifiable by com- puted tomography angiography, magnetic resonance angiogram and ultra-sound echo-color Doppler, are closely linked to the development of ischemic symptoms and can significantly increase the risk of stroke regard- less of the degree of stenosis. In light of these findings vulnerable plaques should be identified early, and the role of Digital Subtraction Angiography which is a purely technical luminal technique should be determined.

Locally advanced rectal cancer:The importance of a multidisciplinary approach

Rectal cancer accounts for a relevant part of colorectal cancer cases,with a mortality of 4-10/100000 per year.The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients.In the last two decades,new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival.Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates.The employment of neoadjuvant treatment,delivered before surgery,also achieved an improved local control and an increasedsphincter preservation rate in low-lying tumors,with an acceptable acute and late toxicity.This review describes the multidisciplinary management of rectal cancer,focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

Endoscopic ultrasound-guided ethanol ablation ofpancreatic neuroendocrine tumours:A case study andliterature review

Here we offer a review of the literature regarding endoscopic ultrasound-guided ethanol ablation for pancreatic neuroendocrine tumours and describe the case of a cystic tumour completely ablated after a multisession procedure. A total of 35 PubM ed indexed cases of treated functioning and non-functioning pancreatic neuroendocrine tumours resulted from our search, 29 of which are well-documented and summarised. Endoscopic ultrasound-guided ethanol ablation appears as a local, minimally invasive treatment of pancreatic neuroendocrine tumours, suitable for selected patients. This technique appears feasible, relatively safe and efficient, especially when applied to symptom relief in functioning tumours, aiming at loss of endocrine secretion. For non-functioning tumours, where the goal is complete tissue ablation, eus guided ethanol ablation can provide good results for patients who are unfit for surgery or for those who refuse surgical resection. Its role in "fit for surgery" patients requires assessment through further studies.

颈动脉壁厚度与脑缺血症状:多层CT血管成像的评价

本研究的目的是用多层CT血管成像(MDCTA)探讨颈动脉壁厚度(CAWT)是否能成为预测脑卒中风险增加的一种有效参数。

Gut microbiota and immune system in liver cancer:Promising therapeutic implication from development to treatment

Liver cancer is a leading cause of death worldwide,and hepatocellular carcinoma(HCC)is the most frequent primary liver tumour,followed by cholangiocarcinoma.Notably,secondary tumours represent up to 90% of liver tumours.Chronic liver disease is a recognised risk factor for liver cancer development.Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration.The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota,its metabolites and the liver through the portal flow.The interplay between the immune system and gut microbiota is also well-known.Although primarily resulting from experiments in animal models and on HCC,growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours.Despite the curative intent of“traditional”treatments,tumour recurrence remains high.Therefore,microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment.Furthermore,microbiota could represent a non-invasive biomarker for early liver cancer diagnosis.This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development,focusing on the potential therapeutic implications.

Clinical significance of glycated hemoglobin in the acute phase of ST elevation myocardial infarction

In population-based studies,including diabetic and nondiabetic cohorts,glycated hemoglobin A1c(HbA1c) has been reported as an independent predictor of allcause and cardiovascular disease mortality.Data on the prognostic role of HbA1c in patients with acute myocardial infarction(MI) are not univocal since they stem from studies which mainly differ in patients' selection criteria,therapy(thrombolysis vs mechanical revascularization) and number consistency.The present review is focused on available evidence on the prognostic significance of HbA1c measured in the acute phase in patients with ST-elevation myocardial infarction(STEMI) submitted to primary percutaneous coronary intervention(PCI).We furthermore highlighted the role of HbA1c as a screening tool for glucose intolerance in patients with STEMI.According to available evidence,in contemporary cohorts of STEMI patients submitted to mechanical revascularization,HbA1c does not seem to be associated with short and long term mortality rates.However,HbA1c may represent a screening tool for glucose intolerance from the early phase on in STEMI patients.On a pragmatic ground,an HbA1c testhas several advantages over fasting plasma glucose or an oral glucose tolerance test in an acute setting.The test can be performed in the non-fasting state and reflects average glucose concentration over the preceding 2-3 mo.We therefore proposed an algorithm based on pragmatic grounds which could be applied in STEMI patients without known diabetes in order to detect glucose intolerance abnormalities from the early phase.The main advantage of this algorithm is that it may help in tailoring the follow-up program,by helping in identifying patients at risk for the development of glucose intolerance after MI.Further validation of this algorithm in prospective studies may be required in the contemporary STEMI population to resolve some of these uncertainties around HbA1c screening cutoff points.

Colonoscopic evaluation of hematochezia in low and average risk patients for colorectal cancer:A prospective study

AIM: To relate the endoscopic findings in patients with hematochezia with regard to age in “low and average risk” for colorectal cancer (CRC) and to localize signifi cant lesions in order to identify patients who need sigmoidoscopy or total colonoscopy. METHODS: This prospective study was performed in an open access GI endoscopy unit. Out of 4322 consecutive patients undergoing colonoscopy, 918 reported hema- tochezia. The fi nal study group comprized 180 patients aged below 45 and 237 over 45. Main exclusion criteria were a 1st-degree family history of colorectal carcinoma, patients reporting blood mixed with stools and/or pro- gressive colonic symptoms, or patients who had under- gone colon surgery for neoplastic lesions. RESULTS: Total colonoscopy could be performed in 96% of patients. Abnormal findings were observed in 34.3% of the younger and in 65.7% of the older ones. Findings were the presence of polyps in the distal colon (n = 2) and IBD in the proximal colon (n = 29) in the group of the younger patients, and polyps (n = 15), IBD (n = 13), and carcinoma (n = 6, 4 of the lesions were located proximal to the splenic flexure) in the elderly. Our f indings suggest that the diagnostic potential of total colonoscopy in patients younger than 45 referring scant hematochezia, is not mandatory. By exploring only the distal tract of the colon we have misdiagnosed two cases of IBD located in the ascending colon. In this group of patients additional risk factors must be identifi ed before performing a total colonoscopy. Regarding the patients older than 45 yr, the exploration of the distal colon would have led to our overlooking a carcinoma, two neoplastic polyps and one IBD located in the proximal colon. CONCLUSION: Young patients with scant hematochezia but without risk factors for neoplasia do not need a totalcolonoscopy, whereas is mandatory performing a total colonoscopy in older patients even in the presence of anal pathology.

Markers of systemic inflammation and colorectal adenoma risk: Meta-analysis of observational studies

To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODSPubMed and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers, including: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and risk of colorectal adenoma. Random-effects models were used to calculate summary odds ratios (ORs) with 95%CIs for the highest vs lowest category of exposure. Heterogeneity was assessed by using the Q test and I2 statistic. Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTSA total of 14 case-control studies were included. Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary (OR = 1.23, 95%CI: 0.98-1.54; I2 = 54%, Pheterogeneity = 0.01) in the general analysis, but significant increased odds when considering only advanced adenoma (OR = 1.59, 95%CI: 1.09-2.32; I2 = 44%, Pheterogeneity = 0.15). Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma. Five studies examined the association between circulating levels of TNF-α and colorectal adenoma risk, including a total of 1,568 cases and 2,832 controls. The summary OR for the highest vs the lowest category of exposure was 1.00 (95%CI: 0.77-1.29). The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls. The summary OR for the highest vs the lowest category of exposure was 1.19 (95%CI: 0.92-1.55).CONCLUSIONSummary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk. The role of potential confounding factors should be further evaluated.

Novel endoscopic over-the-scope clip system

This paper reports our experience with a new overthe-scope clip in the setting of recurrent bleeding and oesophageal fistula. We treated five patients with the over-the-scope Padlock Clip?. It is a nitinol ring, with six inner needles preassembled on an applicator cap, thumb press displaced by the Lock-It? delivery system. The trigger wire is located alongside the shaft of the endoscope, and does not require the working channel. Three patients had recurrent bleeding lesions(bleeding rectal ulcer, post polypectomy delayed bleeding and duodenal Dieulafoy's lesion) and two patients had a persistent respiratory-esophageal fistula. In all patients a previous endoscopic attempt with standard techniques had been useless. All procedures were conducted under conscious sedation but for one patient that required general anaesthesia due to multiple comorbidities. We used one Padlock Clip? for each patient in a single session. Simple suction was enough in all of our patients to obtain tissue adhesion to the instrument tip. A remarkably short application time was recorded for all cases(mean duration of the procedure: 8 min). We obtained technical and immediate clinical success for every patient. No major immediate, early or late(within 24 h, 7 d or 4 wk) adverse events were observed, over follow-up durations lasting a mean of 109.4 d. One patient, treated for duodenal bulb bleeding from a Dieulafoy's lesion, developed signs of mild pancreatitis 24 h after the procedure. The new over-the-scope Padlock Clip? seems to be simple to use and effective in different clinical settings, particularly in "difficult" scenarios, like recurrent bleeding and respiratory-oesophageal fistulas.

Vitamin E for the treatment of children with hepatitis B e antigen-positive chronic hepatitis:a systematic review and meta-analysis

AIM To assess vitamin E efficacy,defined as its ability to induce hepatitis B e antigen(HBeAg) seroconversion,in children with HBeAg-positive persistent hepatitis.METHODS In July 2016,we extracted articles published in MEDLINE and the Cochrane Library using the following search terms:"chronic hepatitis B","children","childhood","therapy","treatment","vitamin E","tocopherols","tocotrienols".Only randomized controlled trials(RCTs) published in English language were collected.RESULTS Three RCTs met inclusion criteria and were considered in the present meta-analysis.Overall,23/122 children in the treatment group underwent HBeAg seroconversion vs 3/74 in the control group(OR=3.96,95%CI:1.18-13.25,P=0.025).CONCLUSION Although our meta-analysis has several limits,including the very small number of available studies and enrolled children with HBeAg positivity-related hepatitis,it suggests that vitamin E use may enhance the probability to induce HBeAg seroconversion in these patients.Further well designed and adequately sized trials are required to confirm or deny these very preliminary results.