Development of Helicobacter pylori treatment: How do we manage antimicrobial resistance?

Helicobacter pylori(H. pylori) antimicrobial resistance is an urgent, global issue. In2017, the World Health Organization designated clarithromycin-resistant H.pylori as a high priority bacterium for antibiotic research and development. In addition to clarithromycin, resistance to metronidazole and fluoroquinolones has also increased worldwide. Recent international guidelines for management of H.pylori infection recommend bismuth or non-bismuth quadruple therapy for 14 d as a first-line treatment for H. pylori in areas of high clarithromycin and/or metronidazole resistance. Although these treatment regimens provide acceptable H. pylori eradication rates, the regimens used should not contribute to future resistance of H. pylori to antimicrobials. Moreover, these regimens can promote resistance, due to prolonged therapy with multiple antibiotics. A new strategy that can eradicate H. pylori as well as reduce the antibiotics used is required to prevent future antimicrobial resistance in H. pylori. Dual-therapy with vonoprazan and amoxicillin could be a breakthrough for H. pylori eradication in an era of growing antimicrobial resistance. This regimen may provide a satisfactory eradication rate of H. pylori and also minimize antimicrobial resistance due to single antibiotic use and the strong inhibitory effect of vonoprazan on gastric acid secretion.

Clinical outcomes and risk factors for perforation in gastric endoscopic submucosal dissection: A prospective pilot study

AIM: To evaluate clinical outcomes and risk factors for endoscopic perforation during endoscopic submucosal dissection (ESD) in a prospective study. METHODS: We investigated the clinical outcomes and risk factors for the development of perforation in 98 consecutive gastric neoplasms undergoing ESD regarding. Demographic and clinical parameters including patient-, tumor-, and treatment-related factors, clinical parameters, and duration of hospital stay were analyzed for risk factors for perforation. In subgroup analysis, we also compared the clinical outcomes between perforation and "silent" free air without endoscopically visible perforation detected only by computed tomography.RESULTS: Perforation was identified in 8.2% of patients. All patients were managed conservatively by the administration of antibiotics. The mean procedure time was significantly longer in patients with endoscopic perforation than in those without. According to the receiver-operating characteristic analysis, the resulting cutoff value of the procedure time for perforation was 115 min (87.5% sensitivity, 56.7% specificity). Prolonged procedure time (≥ 115 min) was associated with an increased risk of perforation (odds ratio 9.15; 95%CI: 1.08-77.54; P = 0.04). Following ESD, body temperature and C-reactive protein level were significantly higher in patients with perforation than in those without (P = 0.02), whereas there was no difference between these patient groups on the starting day of oral intake or of hospitalization. In subgroup analysis, the post-ESD clinical course was not different between endoscopic perforation and silent free air. CONCLUSION: Only prolonged procedure time (≥ 115 min) was significantly associated with perforation. The clinical outcomes of perforation are favorable and are comparable to those of patients with or without silent free air.

What types of early gastric cancer are indicated for endoscopic ultrasonography staging of invasion depth?

AIM To clarify the diagnostic efficacy and limitations of endoscopic ultrasonography(EUS) and the characteristics of early gastric cancers(EGCs) that are indications for EUS-based assessment of cancer invasion depth.METHODS We retrospectively investigated the cases of 153 EGC patients who underwent conventional endoscopy(CE) and EUS(20 MHz) before treatment.RESULTS We found that 13.7% were "inconclusive" cases with low-quality EUS images, including all nine of the cases with protruded(0-I)-type EGCs. There was no significant difference in the diagnostic accuracybetween CE and EUS. Two significant independent risk factors for misdiagnosis by EUS were identified-ulcer scarring [UL(+); odds ratio(OR) = 4.49, P = 0.003] and non-indication criteria for endoscopic resection(ER)(OR = 3.02, P = 0.03). In the subgroup analysis, 23.1% of the differentiated-type cancers exhibiting SM massive invasion(SM2) invasion(submucosal invasion ≥ 500 μm) by CE were correctly diagnosed by EUS, and 23.1% of the undifferentiated-type EGCs meeting the expanded-indication criteria for ER were correctly diagnosed by EUS.CONCLUSION There is no need to perform EUS for UL(+) EGCs or 0-I-type EGCs, but EUS may enhance the pretreatment staging of differentiated-type EGCs with SM2 invasion without UL or undifferentiated-type EGCs revealed by CE as meeting the expanded-indication criteria for ER.

Endoscopic diagnosis and treatment of superficial nonampullary duodenal tumors

The diagnostic and treatment guidelines of superficial non-ampullary duodenal tumors have not been standardized due to their low prevalence.Previous reports suggested that a superficial adenocarcinoma(SAC) should be treated via local resection because of its low risk of lymph node metastasis,whereas a highgrade adenoma(HGA) should be resected because of its high risk of progression to adenocarcinoma.Therefore,pretreatment diagnosis of SAC or HGA is important to determine the appropriate treatment strategy.There are certain endoscopic features known to be associated with SAC or HGA,and current practice prioritizes the endoscopic and biopsy diagnosis of these conditions.Surgical treatment of these duodenal lesions is often related to high risk of morbidity,and therefore endoscopic resection has become increasingly common in recent years.Endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD) are the commonly performed endoscopic resection methods.EMR is preferred due to its lower risk of adverse events;however,it has a higher risk of recurrence than ESD.Recently,a new and safer endoscopic procedure that reduces adverse events from EMR or ESD has been reported.

Histological diagnosis of gastric submucosal tumors: A pilot study of endoscopic ultrasonography-guided fine-needle aspiration biopsy vs mucosal cutting biopsy

AIM: To compare the usefulness of endoscopic ultrasonography-guided fine-needle aspiration biopsy(EUS-FNAB) without cytology and mucosal cutting biopsy(MCB) in the histological diagnosis of gastric submucosal tumor(SMT).METHODS: We prospectively compared the diagnostic yield, feasibility, and safety of EUS-FNAB and those of MCB based on endoscopic submucosal dissection. The cases of 20 consecutive patients with gastric SMT ≥1 cm in diameter. who underwent both EUS-FNAB and MCB were investigated.RESULTS: The histological diagnoses were gastrointestinal stromal tumors(n = 7), leiomyoma(n =6), schwannoma(n = 2), aberrant pancreas(n = 2), and one case each of glomus tumor, metastatic hepatocellular carcinoma, and no-diagnosis. The tumors' mean size was 23.6 mm. Histological diagnosis was made in 65.0% of the EUS-FNABs and 60.0% of the MCBs, a nonsignificant difference. There were no significant differences in the diagnostic yield concerning the tumor location or tumor size between the two methods. However, diagnostic specimens were significantly more frequently obtained in lesions with intraluminal growth than in those with extraluminal growth by the MCB method(P = 0.01). All four SMTs with extraluminal growth were diagnosed only by EUSFNAB(P = 0.03). No complications were found in either method.CONCLUSION: MCB may be chosen as an alternative diagnostic modality in tumors showing the intraluminal growth pattern regardless of tumor size, whereas EUSFNAB should be performed for SMTs with extraluminal growth.

Diagnosis of small intramucosal signet ring cell carcinoma of the stomach by non-magnifying narrow-band imaging: A pilot study

AIM: To examine the efficacy of non-magnifying narrow-band imaging(NM-NBI) imaging for small signet ring cell carcinoma(SRC).METHODS: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection(ESD) and 14 randomly selected whitish gastric ulcer scars(control). The strength and shape of the SRCs and whitish scars by NM-NBI and white-light imaging(WLI) were assessed with Image J(NIH, Bethesda).RESULTS: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index(P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle(C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs(P = 0.001). According to the receiveroperating characteristic analysis, the resulting cut-off value of the circularity index(C-index) for SRC was 0.60(85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index ≥ 0.6 was significantly more likely to be an SRC than a gastric ulcer scar(OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009).CONCLUSION: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD.

Endoscopic resection for residual lesion of metastatic gastric cancer:A case report

BACKGROUND Chemotherapy is a standard strategy for stage IV gastric cancer patients.However, some cases cannot undergo conversion surgery because of their frailty,even if the patients had response to chemotherapy. For these patients, local tumor progression is a problem. We report here the case of a patient whose residual gastric cancer was resected through endoscopic submucosal dissection(ESD)after concomitant chemotherapy for metastatic gastric cancer.CASE SUMMARY An 85-year-old male complained of difficulty swallowing, and examination revealed gastric cancer with multiple liver metastases. Although he received concomitant chemotherapy, a residual tumor was observed in the primary lesion while the metastatic lesions disappeared completely. Conversion surgery was considered optional treatment; however, he could not undergo that because of advanced age and comorbidities. Thus, we performed ESD to treat the residual tumor. As a result, we resected the residual lesion completely. The patient has been alive for 29 mo since ESD, without recurrence.CONCLUSION We achieved local control using ESD, and these findings may provide therapeutic improvements both in local control and patient survival outcomes.

Effectiveness and safety of sedation in gastrointestinal endoscopy:An opinion review

Although endoscopy is a less invasive procedure than surgery,patients can experience pain without sedation.Patients expect reduced pain during endoscopies from effective and safe sedatives.Midazolam and propofol are used for endoscopic sedation in many countries and regions.Midazolam is a widely available benzodiazepine,and many clinical trials have shown it to be an effective sedative.However,patients who are sedated with midazolam require rest in the recovery room due to its relatively long half-life,and an antagonist such as flumazenil may need to be administered in cases of deep or prolonged sedation.Propofol is a short-acting sedative with a short half-life and a quick recovery time.Therefore,the use of propofol has been increasing.However,propofol has a narrow margin of safety and often induces adverse effects such as respiratory depression.Also,propofol has no specific antagonist,and should be administered by an anesthesiologist or an endoscopist familiar with anesthesia.Remimazolam,which is a novel ultra-short-acting benzodiazepine,has recently gained attention.Remimazolam has a short half-life and an antagonist.Both effective and safe sedation is desired in accordance with the increasing need for sedative endoscopies.Therefore,in this review each sedative is summarized.

Endoscopic submucosal dissection of multiple flat adenomas in the radiated rectum

We report a case of multiple flat adenomas and cancer of the rectum that occurred 15 years after pelvic irradiation following surgery for uterine cancer.Adenoma borders were diagnosed accurately by magnifying chromoendoscopy,leading to their adequate excision using endoscopic submucosal dissection.This enabled minimal dissection of the irradiated pelvis that would have otherwise been difficult.Furthermore,our approach probably helped minimize loss of bowel function,thereby preserving the patient's quality of life as much as possible.Pathology of the resected specimens revealed thickened walls of the submucosal layer vessels,indicating chronic radiation proctitis.Pelvic irradiation of the bowel carries a high risk of causing flat adenomas and cancer.Close and long-term surveillance may be useful in such cases,using not only conventional colonoscopy but also chromoendoscopy with indigo carmine dye spray and magnifying endoscopy.

Efficacy and safety of grasping forceps-assisted endoscopic resection for gastric neoplasms:A multi-centre retrospective study

BACKGROUND Endoscopic submucosal dissection(ESD)is widely accepted for early gastric cancer(EGC)without lymph node metastasis,although ESD is challenging,even for small lesions,in the greater curvature(GC)of the upper(U)and middle(M)thirds of the stomach.Grasping forceps-assisted endoscopic resection(GF-ER)is a type of endoscopic mucosal resection that is performed via a double-channel endoscope.AIM To investigate the safety and efficacy of GF-ER vs ESD in the GC of the stomach’s U and M regions.METHODS We retrospectively reviewed the medical records of 506 patients who underwent ER of 522 EGC lesions in the stomach’s U and M regions in three institutions between January 2016 and May 2020.Nine lesions from eight patients who underwent GF-ER for EGC(the GF-ER group)were compared to 63 lesions from 63 patients who underwent ESD(the ESD group).We also performed a subgroup analysis of small lesions(≤10 mm)in 6 patients(7 lesions)from the GF-ER group and 20 patients(20 lesions)from the ESD group.RESULTS There were no statistically significant differences between the GF-ER and ESD groups in the en bloc resection rates(100%vs 100%)and the R0 resection rates(100%vs 98.4%).The median procedure time in the GF-ER group was shorter than that in the ESD group(4.0 min vs 55.0 min,P<0.01).There were no adverse events in the GF-ER group,although five perforations(8.0%)and 1 case of postoperative bleeding(1.6%)were observed in the ESD group.When we only considered lesions that were≤10 mm,the median procedure time in the GF-ER group was still shorter than that in the ESD group(4.0 min vs 35.0 min,P<0.01).There were no adverse events in the GF-ER group,although 1 case of perforation(1.6%)were observed in the ESD group.CONCLUSION These findings suggest that GF-ER may be an effective therapeutic option for small lesions in the GC of the stomach’s U and M regions.