Advancements in hemostatic strategies for managing upper gastrointestinal bleeding: A comprehensive review

Upper gastrointestinal(GI)hemorrhage presents a substantial clinical challenge.Initial management typically involves resuscitation and endoscopy within 24 h,although the benefit of very early endoscopy(<12 h)for high-risk patients is debated.Treatment goals include stopping acute bleeding,preventing rebleeding,and using a multimodal approach encompassing endoscopic,pharmacological,angiographic,and surgical methods.Pharmacological agents such as vasopressin,prostaglandins,and proton pump inhibitors are effective,but the increase in antithrombotic use has increased GI bleeding morbidity.Endoscopic hemostasis,particularly for nonvariceal bleeding,employs techniques such as electrocoagu-lation and heater probes,with concerns over tissue injury from monopolar electrocoagulation.Novel methods such as Hemospray and Endoclot show promise in creating mechanical tamponades but have limitations.Currently,the first-line therapy includes thermal probes and hemoclips,with over-the-scope clips emerging for larger ulcer bleeding.The gold probe,combining bipolar electrocoagulation and injection,offers targeted coagulation but has faced device-related issues.Future advancements involve combining techniques and improving endoscopic imaging,with studies exploring combined approaches showing promise.Ongoing research is crucial for developing standardized and effective hemorrhage management strategies.

Clinical diagnostic advances in intestinal anastomotic techniques:Hand suturing,stapling,and compression devices

The development of intestinal anastomosis techniques,including hand suturing,stapling,and compression anastomoses,has been a significant advancement in surgical practice.These methods aim to prevent leakage and minimize tissue fibrosis,which can lead to stricture formation.The healing process involves various phases:hemostasis and inflammation,proliferation,and remodeling.Mechanical staplers and sutures can cause inflammation and fibrosis due to the release of profibrotic chemokines.Compression anastomosis devices,including those made of nickel-titanium alloy,offer a minimally invasive option for various surgical challenges and have shown safety and efficacy.However,despite advancements,anastomotic techniques are evaluated based on leakage risk,with complications being a primary concern.Newer devices like Magnamosis use magnetic rings for compression anastomosis,demonstrating greater strength and patency compared to stapling.Magnetic technology is also being explored for other medical treatments.While there are promising results,particularly in animal models,the realworld application in humans is limited,and further research is needed to assess their safety and practicality.

Long-term result of endoscopic Histoacryl （N-butyl-2-cyanoacrylate）injection for treatment of gastric varices

AIM:To evaluate the long-term efficacy and safety of endoscopic obliteration with Histoacryl  for treatment of gastric variceal bleeding and prophylaxis.METHODS:Between January 1994 and March 2010 at SoonChunHyang University Hospital,a total of 127 patients with gastric varices received Histoacryl  injections endoscopically.One hundred patients underwent endoscopic Histoacryl  injections because of variceal bleeding,the other 27 patients received such injections as a prophylactic procedure.RESULTS:According to Sarin classification,56 patients were GOV1,61 patients were GOV2 and 10 patients were IGV.Most of the varices were large(F2 or F3,111 patients).The average volume of Histoacryl  per each session was 1.7±1.3 cc and mean number of sessions was 1.3±0.6.(1 session-98 patients,2 sessions-25 patients,≥3 sessions-4 patients).Twenty-seven patients with high risk of bleeding(large or fundal or RCS+or Child C) received Histoacryl  injection as a primary prophylactic procedure.In these patients,hepatitis B virus was the major etiology of cirrhosis,25 patients showed GOV1 or 2(92.6%)and F2 or F3 accounted for 88.9%(n=24).The rate of initial hemostasis was 98.4%and recurrent bleeding within one year occurred in 18.1%of patients.Successful hemostasis during episodes of rebleeding was achieved in 73.9%of cases.Median survival was 50 mo (95%CI 30.5-69.5).Major complications occurred in 4 patients(3.1%).The rebleeding rate in patients with hepatocellular carcinoma or GOV2 was higher than in those with other conditions.None of the 27 subjects who were treated prophylactically experienced treatment-related complications.Cumulative survival rates of the 127 patients at 6 mo,1,3,and 5 years were 92.1%,84.2%,64.2%,and 45.3%,respectively.The 6 mo cumulative survival rate of the 27 patients treated prophylactically was 75%.CONCLUSION:Histoacryl  injection therapy is an effective treatment for gastric varices and also an effective prophylactic treatment of gastric varices which carry high risk of bleeding.

Efficacy and safety of 0.4 percent sodium hyaluronate for endoscopic submucosal dissection of gastric neoplasms

AIM:To evaluate the efficacy and safety of sodium hyaluronate solution(SH) in endoscopic submucosal dissection(ESD) of gastric neoplasms.METHODS:A prospective multicenter randomized,double blind,controlled trial was designed and utilized in this study.A total of 76 patients with 5-20 mm sized gastric neoplasms were enrolled at three academic hospitals in South Korea from June 2011 to October 2011.Patients were randomly assigned to the 0.4% sodium hyaluronate or control groups.All lesions underwent endoscopic ESD.ESD was performed with 0.4%SH and normal saline(NS) solution for submucosal injection.Efficacy was assessed using en bloc resection and the number of additional injections.Secondary evaluation variables were the volume of injection material,steepness of mucosal elevation,bleeding rate,procedural time and operator satisfaction.Finally,the safety was assessed by analyzing adverse events during the study.RESULTS:The usefulness rate in the 0.4%SH group and the controlled group had statistically significant difference under intention to treat(ITT) analysis(90.91% vs 61.11% P = 0.0041).Under per protocol(PP),the usefulness rate is statistically significant different(93.10% vs 61.76%,P = 0.0036).The difference in volume of the solution injected between 0.4%SH group and the controlled group and NS group was also statistically significant under intention to treat and per protocol analysis(ITT:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0003,PP:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0004).Satisfaction above the grade good was significantly higher in the SH group under intention to treat and per protocol analysis(ITT:90.91% vs 61.11%,P = 0.0041,PP = 93.11% vs 61.77%,P = 0.0022).Adverse events above grade 3 were not noticed in either group.All adverse events were treated and were judged as not associated with the submucosal injection solutions.CONCLUSION:0.4%SH solution is a safe and effective agent that doesn't cause any significant adverse events and is useful for submucosal injection during ESD.

Ever-changing endoscopic treatment for early gastric cancer:Yesterday-today-tomorrow

Endoscopic resection has been an optimal treatment for selected patients with early gastric cancer(EGC) based on advances in endoscopic instruments and techniques. As endoscopic submucosal dissection(ESD) has been widely used for treatment of EGC along with expanding ESD indication, concerns have been asked to achieve curative resection for EGC while guaranteeing precise prediction of lymph node metastasis(LNM). Recently, new techniques including ESD or endoscopic full-thickness resection combined with sentinel node navigation enable minimal tumor resection and a laparoscopic lymphadenectomy in cases of EGC with high risk of LNM. This review covers the development and challenges of endoscopic treatment for EGC. Moreover, a new microscopic imaging and endoscopic techniques for precise endoscopic diagnosis and minimally invasive treatment of EGC are introduced.

Plasma levels of acylated ghrelin in patients with functional dyspepsia

AIM:To investigate the relationship between plasma acylated ghrelin levels and the pathophysiology of functional dyspepsia.METHODS:Twenty-two female patients with functional dyspepsia and twelve healthy volunteers were recruited for the study.The functional dyspepsia patients were each diagnosed based on the Rome Ⅲ criteria.Eligible patients completed a questionnaire concerning the severity of 10 symptoms.Plasma acylated ghrelin levels before and after a meal were determined in the study participants using a commercial human acylated enzyme immunoassay kit;electrogastrograms were performed for 50 min before and after a standardized 10-min meal containing 265 kcal.RESULTS:There were no significant differences in plasma acylated ghrelin levels between healthy volunteers and patients with functional dyspepsia.However,in patients with functional dyspepsia,there was a negative correlation between fasting plasma acylated ghrelin levels and the sum score of epigastric pain(r =-0.427,P = 0.047) and a positive correlation between the postprandial/fasting plasma acylated ghrelin ratio and the sum score of early satiety(r = 0.428,P =0.047).Additionally,there was a negative correlation between fasting acylated ghrelin plasma levels and fasting normogastria(%)(r =-0.522,P = 0.013).Interestingly,two functional dyspepsia patients showed paradoxically elevated plasma acylated ghrelin levels after the meal.CONCLUSION:Abnormal plasma acylated ghrelin levels before or after a meal may be related to several of the dyspeptic symptoms seen in patients with functional dyspepsia.

Does immunohistochemical staining have a clinical impact in early gastric cancer conducted endoscopic submucosal dissection?

AIM: To evaluate clinicopathologic parameters and the clinical significance related lymphovascular invasion (LVI) by immunohistochemical staining (IHCS) in endoscopic submucosal dissection (ESD). METHODS: Between May 2005 and May 2010, a total of 348 lesions from 321 patients (mean age 63 ± 10 years, men 74.6%) with early gastric cancer (EGC) who met indication criteria after ESD were analyzed retrospectively. The 348 lesions were divided into the absolute (n = 100, differentiated mucosal cancer without ulcer ≤ 20 mm) and expanded (n = 248) indica-tion groups after ESD. The 248 lesions were divided into four subgroups according to the expanded ESD indication. The presence of LVI was determined by factor Ⅷ-related antigen and D2-40 assessment. We compared LVI IHCS-negative group with LVI IHCSpositive in each group. RESULTS: LVI by hematoxylin-eosin staining (HES) and IHCS were all negative in the absolute group, while was observed in only the expanded groups. The positive rate of LVI by IHCS was higher than that of LVI by HES (n = 1, 0.4% vs n = 11, 4.4%, P = 0.044). LVI IHCS-positivity was observed when the cancer invaded to the mucosa 3 (M3) or submucosa 1 (SM1) levels, with a predominance of 63.6% in the subgroup that included only SM1 cancer (P < 0.01). In a univariate analysis, M3 or SM1 invasion by the tumor was significantly associated with a higher rate of LVI by IHCS, but no factor was significant in a multivariate analysis. There were no cases of tumor recurrence or metastasis during the median 26 mo follow-up. CONCLUSION: EGCs of the absolute group are immunohistochemically stable. The presence of LVI may be carefully examined by IHCS in an ESD expanded indication group with an invasion depth of M3 or greater.

Endoscopic submucosal dissection for early gastric cancer:Quo vadis?

The diagnosis of early gastric cancer(EGC) is of great interest because its endoscopic and surgical treatment presents the best chance for a cure.With technical development,endoscopic submucosal dissection(ESD) has been widely performed for the curative treatment of EGC in Korea.Multinational studies of ESD for EGC will be the next missions that overcome these limitations and global guidelines will be processed for ESD for EGC.

A novel device for endoscopic submucosal dissection,the Fork knife

瞄准：用一台新奇设备介绍并且评估功效和内视镜的粘膜下层解剖(ESD ) 的技术方面，叉刀。方法：从 2004 年 3 月到 2008 年 4 月， ESD 在一个单个第三级的工作分派中心用 Flexknife (组 B ) 在使用一把叉刀(Endo FSregister )( 组 A ) 的 265 胃的损害上并且在 72 胃的损害上被执行。我们回顾地比较了 resected 标本的肿瘤，病理检查所见，和尺寸的内视镜的特征。我们也比较了在二个组之间的整块切除术率，完全的切除术率，复杂并发症，和过程时间。结果：resected 标本的吝啬的尺寸是 4.27 +/- 在组 A 和 4.29 +/- 的 1.26 厘米在组 B 的 1.48 厘米。整块切除术率是 95.8%(254/265 损害) 在组 A 并且 93.1%(67/72 ) 在组 B。没有 resected 边缘的肿瘤房间侵略的完全的 ESD 在 81.1% 被获得(215/265 ) 组 A 并且在 73.6%(53/72 ) 组 B。穿孔率是 0.8%(2/265 ) 在组 A 并且 1.4%(1/72 ) 在组 B。吝啬的过程时间是 59.63 +/- 在组 A 和 76.65 +/- 的 56.12 min 在组 B 的 70.75 min (P 【 0.05 ) 。结论：叉刀(Endo FSregister ) 为临床的实践是有用的并且有的优点减少过程时间。

A case of intussuscepted Meckel’s diverticulum

We report colonoscopic features of an intussuscepted Meckel's diverticulum, presenting with hematochezia. A 35-year-old woman presented to the emergency room with acute onset, transient, sharp, severe epi-gastric pain that began 6 h earlier. Colonoscopy re-vealed a reddish, soft, fi st-sized polypoid lesion in the terminal ileum. The lesion was misinterpreted as a hematoma by an inexperienced endoscopist. The pa-tient began to complain of intermittent, severe peri-umbilical pain following the colonoscopic examination. Subsequent computed tomography showed an enteric intussusception. An exploratory laparotomy revealed an intussuscepted Meckel's diverticulum, with trans-mural infarction. Colonoscopy was of little use in as-sessing the intussusception. However, colonoscopic examination may be performed initially, especially in an intussuscepted Meckel's diverticulum present-ing with hematochezia. Endoscopists should note the endoscopic features of an intussuscepted Meckel's diverticulum.

Usefulness of magnifying endoscopy for iodine-unstained lesions in a high-risk esophageal cancer population

AIM: To investigate the usefulness of magnified observations of iodine-unstained esophageal lesions in the histological diagnosis of esophageal mucosa abnormalities, in high-risk esophageal cancer groups. METHODS: The subjects included 38 patients who had at least one of the four criteria known to be highrisk factors for esophageal cancer. Following endoscopic observation, magnified observations were performed on iodine-unstained lesions of the esophagus. The total number of lesions was 43. These lesions were classified as type A (clear papilla), type B (fused papilla), and type C (non-visible papilla) according to the findings. Tissue biopsy was then carried out. Finally the histological findings were graded in terms of histological factors, and their relationships were compared. RESULTS: Of the 43 lesions, 11 were type A, 17 were type B, and 15 were type C under magnifying endoscopy. Histological findings such as inflammatory cell infiltration and basal cell hyperplasia were significantly increased in type B and type C lesions compared with type A lesions (P < 0.05). Low-grade esophageal dysplasia was apparent in 1 (9%) of 11 type A lesions, in 3 (18%) of 17 type B lesions, and in 6 (40%) of 15 type C lesions, with the highest rate in type C. CONCLUSION: Magnified observations of the esophagus, classified by papillary aspects using magnifying endoscopy of iodine-unstained lesions in high-risk esophageal cancer groups, are considered useful in estimating dysplasia and inflammation of esophageal mucosa.

Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett's esophagus

AIM:To determine whether magnified observation of short-segment Barrett’s esophagus(BE)is useful for the detection of specialized intestinal metaplasia(SIM).METHODS:Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to×80.The magnified images were analyzed with respect to their pit-patterns,which were simultaneously classified into five epithelial types[Ⅰ(small round),Ⅱ(straight),Ⅲ(long oval),Ⅳ(tubular),Ⅴ(villous)]by Endo’s classification.Then,a 0.5%solution of methylene blue(MB)was sprayed over columnar mucosa.The patterns of the magnified image and MB staining were analyzed.Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy.RESULTS:Three of five patients with a typeⅤ(villous)epithelial pattern had SIM,whereas 21 patients with a non-typeⅤepithelial patterns did not have SIM.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of pit-patterns in detecting SIM were 100%,91.3%,92.3%,60%and100%,respectively(P=0.004).Three of the 12 patients with positive MB staining had SIM,whereas 14patients with negative MB staining did not have SIM.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of MB staining in detecting SIM were 100%,60.9%,65.4%,25%and100%,respectively(P=0.085).The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemar’s test(P=0.0391).CONCLUSION:The magnified observation of a shortsegment BE according to the mucosal pattern and its classification can be predictive of SIM.