Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive?

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40-50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future.

Long- vs short-segment Barrett's esophagus-derived adenocarcinoma: clinical features and outcomes of endoscopic submucosal dissection.

BACKGROUND: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. METHODS: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively. RESULTS: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). CONCLUSIONS: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

Risk stratification for synchronous/metachronous recurrence after endoscopic submucosal dissection for Barrett's esophageal adenocarcinoma using the length of Barrett's esophagus.

BACKGROUND: In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus. METHODS: We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences. RESULTS: The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively). CONCLUSIONS: Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.

Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

Effect of Helicobacter pylori eradication evaluated using magnifying endoscopy with narrow-band imaging in mixed-type early gastric Cancer.

BACKGROUND: The effect of Helicobacter pylori (H.pylori) eradication therapy on mixed-histological-type gastric cancer remains unclear. This study aimed to clarify the effect of H. pylori eradication therapy on mixed-histological-type early gastric cancer using endoscopic and histological findings. METHODS: This single-center, retrospective study included patients with mixed-histological-type gastric cancer who underwent endoscopic submucosal dissection at the Cancer Institute Hospital. We compared detailed magnifying endoscopy with narrow-band imaging findings between eradicated and non-eradicated groups of patients with differentiated-type- and undifferentiated-type-predominant cancers. Subsequently, we performed histological evaluations of the non-cancerous epithelium covering differentiated-type components. RESULTS: A total of 124 patients with mixed-type early gastric cancer were enrolled (eradicated group: 62 differentiated-type-predominant cancer patients and 8 undifferentiated-type-predominant cancer patients; non-eradication group: 40 differentiated-type-predominant cancer patients and 14 undifferentiated-type-predominant cancer patients). Regarding differentiated-type-predominant cancer, differentiated-type findings were detected in all patients in eradicated and non-eradicated groups. The difference in the detection rate of undifferentiated-type findings between both groups was not significant in differentiated-type-predominant cancer patients. In differentiated-type-predominant cancers, the percentage of non-cancerous epithelium covering differentiated-type components was higher in the eradicated group than in the non-eradicated group (median: 60% vs. 40%, p < 0.001). CONCLUSIONS: Although the pathological findings of differentiated-type-predominant cancer were affected by H. pylori eradication, eradication did not affect the diagnosis of differentiated-type-predominant early gastric cancer using magnifying endoscopy with narrow-band imaging. ME-NBI is useful for the early detection of D-MIX EGCs and diagnosis of histological types during endoscopy, regardless of whether H. pylori eradication therapy has been administered.

Prediction of the invasion depth of superficial nonampullary duodenal adenocarcinoma.

OBJECTIVES: Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial nonampullary duodenal adenocarcinoma (SNADAC); however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined. METHODS: Of 205 patients with SNADAC who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in the preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography (EUS) were retrospectively analyzed in 85 patients. RESULTS: The oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as: (i) low-risk (risk, 2%), all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla; and (ii) high-risk (risk, 23%), protruded or mixed macroscopic type on the oral side of the papilla. Based on the biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, EUS was not associated with invasion depth's diagnostic accuracy improvements. CONCLUSION: Optimal treatment indications for SNADAC can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis.

Efficacy and Safety of Self-Expandable Metallic Stent Placement for Malignant Esophageal Fistula.

Patients with malignant esophageal fistulas often experience dysphagia and infection, resulting in poor prognoses. Self-expandable metallic stent (SEMS) placement is a palliative treatment option; however, its efficacy and safety are unclear. We aimed to determine the efficacy and safety of SEMS placement for malignant esophageal fistulas. We retrospectively investigated patients who underwent SEMS placement for malignant esophageal fistulas between 2013 and 2022 at the Cancer Institute Hospital. Dysphagia scores (DSs) before and after SEMS placement, adverse events, and overall survival from SEMS placement until death were evaluated. A total of 17 patients underwent SEMS placement, including 12 and 5 patients with esophageal and lung cancers, respectively. Prior treatments included chemoradiotherapy (n = 11), radiotherapy (n = 4), and chemotherapy (n = 4); two patients underwent palliative radiotherapy after chemotherapy. All procedures were technically successful. After SEMS placement, 14 (82.4%) patients were able to consume semisolid or solid food (DS ≤ 2). Major adverse events were encountered in only one case. The median survival time after SEMS placement was 71 days (range 17-247 days). SEMS placement allowed most patients to resume oral intake with a low rate of major adverse events. SEMS placement is a reasonable palliative treatment option for patients with malignant fistulas who have poor prognoses.

Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.

Clinical outcomes of palliative treatment for gastric bleeding from incurable gastric cancer.

PURPOSE: Deciding palliative treatment for gastric bleeding from incurable gastric cancer (IGC) is worrying considering different patient situations and the lack of comprehensive assessment of palliative treatment. We evaluated the clinical outcomes and prognostic factors after palliative treatment for gastric bleeding from IGC. METHODS: We enrolled 48 consecutive patients with gastric bleeding from IGC who underwent palliative surgery (PS) or palliative radiotherapy (PRT). RESULTS: Of the 48 patients, 23 underwent PS and 25 received PRT. More patients who had an Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≥ 2 or who received chemotherapy underwent PRT than underwent PS. Severe complications were observed in 2 (8.6%) patients after PS. After PRT, 22 patients achieved hemostasis (88%), but rebleeding was found in 10 (40%). Chemotherapy was introduced after palliative treatment for 21 (91.3%) patients in the PS group and 17 (68%) patients in the PRT group. The median survival time (MST) of patients with and without chemotherapy after PS was 12.5 and 3.1 months, respectively (p ≤ 0.001), while the MST of patients with and without chemotherapy after PRT was 6.5 and 1.6 months (p < 0.001). Multivariate analyses identified ECOG-PS, tumor size, and chemotherapy after palliative treatment as independent risk factors. CONCLUSIONS: Palliative treatment strategies for gastric bleeding should be determined with consideration of the general condition, previous chemotherapy, and chemotherapy after palliative treatment.

Early Esophageal Adenocarcinoma with Non-Barrett's Columnar Epithelium Origin: Two Case Reports and a Literature Review.

We herein report two cases of early esophageal adenocarcinoma derived from non-Barrett's columnar epithelium. Both patients, a 65-year-old woman and 60-year-old man, had elevated lesions on white-light imaging. Magnifying endoscopy revealed slightly irregular surface and vessel patterns, and both patients were successfully treated with endoscopic submucosal dissection. Histopathologically, both lesions comprised of well-differentiated gastric mucin phenotype adenocarcinoma. One lesion was accompanied by ectopic gastric mucosa, but the other was speculated to be ectopic gastric mucosa according to the tumor locus at the upper thoracic esophagus. Despite its rarity, endoscopists should consider the existence of adenocarcinoma derived from non-Barrett's columnar epithelium.

Clinicopathological characteristics of advanced gastric cancer after Helicobacter pylori eradication.

Background and Aim: Helicobacter pylori (H. pylori) eradication has become popular as it prevents the development of gastric cancer. There have been no comprehensive studies on advanced gastric cancer (AGC) after eradication; thus, the clinical characteristics remain unclear. This study aimed to compare the characteristics of AGC after eradication and with current H. pylori infection and evaluate the esophagogastroduodenoscopy (EGD) follow-up after eradication. Methods: This single-center, retrospective study included 261 consecutive patients diagnosed with AGC through EGD. The patients were grouped based on their H. pylori status: eradication (n = 48) and infection (n = 213) groups. Univariate analysis was conducted to compare clinicopathological characteristics between groups. The clinical course of the eradication group was analyzed by dividing the patients into three groups according to the interval from the last EGD until AGC detection: short-interval (<1 year), intermediate-interval (2-3 years), and long-interval (4-5 years) groups. Results: The radical resection (R0) rate was higher in the eradication group. In surgical cases, the median tumor diameter was shorter in the eradication group. Analysis of EGD surveillance after eradication in 36 available cases showed that 24 (66.7%) were detected within 5 years after eradication, and 3 (8.3%) were diagnosed as AGC > 20 years after eradication. The R0 rates in the short-, intermediate-, and long-interval groups were 83.3%, 71.4%, and 60%, respectively. Conclusions: AGC after eradication was more often detected at the phase in which R0 resection was possible. EGD follow-up with tight intervals of at least 5 years after eradication is advisable.

Genomic features of Helicobacter pylori-naïve diffuse-type gastric cancer.

Helicobacter pylori (HP) is a major etiologic driver of diffuse-type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP-naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP-exposed and HP-naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP-exposed and 27 HP-naïve DGCs from sporadic, early-stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP-exposed and 17 HP-naïve samples had been preserved as fresh-frozen samples. HP infection status was determined using stringent criteria. HP-exposed DGCs exhibited an increased single nucleotide variant burden (HP-exposed DGCs; 1.97 [0.48-7.19] and HP-naïve DGCs; 1.09 [0.38-3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm-level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA-ARHGAP pathway misregulation was exclusive to HP-exposed DGCs (p = 0.0167). HP-exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP-exposed DGCs. HP-naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP-naïve and HP-exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Risk factors for lymph node metastasis and indication of local resection in duodenal neuroendocrine tumors.

Background and Aim: The risk factors for lymph node metastasis (LNM) of duodenal neuroendocrine tumors (DNETs) are not well identified, and a definitive standard of treatment for DNETs has not been established. In this study, we aimed to identify the risk factors for LNM and establish the indication of local resection for DNETs. Methods: We retrospectively reviewed 55 patients with 60 non-ampullary and nonfunctional DNETs. We evaluated the risk factors for LNM and compared the outcomes between endoscopic resection (ER) for DNETs <5 mm and laparoscopy and endoscopy cooperative surgery (LECS) for DNETs ≥5 mm. Results: LNM was present in four (8.7%) patients. Univariate analysis revealed that tumor size ≥10 mm, positive lymphovascular invasion (LVI), and 0-Is morphology were significantly associated with LNM (P = 0.008, P = 0.037, and P = 0.045, respectively). ER and LECS were performed for 18 and 11 DNETs, respectively. All lesions treated with ER or LECS were confined to the submucosal layer. The median tumor size was 3 mm in ER and 6 mm in LECS. Although there was no significant difference in the R0 (no residual tumor) resection rate, R0 resection was completely achieved in the LECS. No significant differences were observed in terms of complication rates. No recurrence was observed in any of the groups. Conclusions: Tumor size ≥10 mm, positive LVI, and 0-Is morphology were significant risk factors for LNM. We demonstrated that ER is feasible and could be safely applied for DNETs <5 mm, and LECS could be applied for DNETs 5-10 mm in size.

Sporadic non-ampullary duodenal adenoma with low-grade dysplasia: Natural history and clinical management.

Background and study aims Management strategies for sporadic non-ampullary duodenal adenoma with low-grade dysplasia (LGD) are not well established. This study aimed to analyze progression factors and determine suitable treatment strategies for LGD lesions. Patients and methods We retrospectively analyzed consecutive LGD lesions (n = 125) in patients followed up for ≥ 6 months (median, 45 months) and evaluated the changes in clinicopathological features during follow-up. All LGD lesions were classified into two groups: stable LGD (no increase or < 5 mm increase in tumor size, with unchanged histological dysplasia grade) and progressive LGD (≥ 5 mm increase in tumor size and/or progression to high-grade dysplasia or adenocarcinoma). Results Eighty-six LGD were classified as stable and 39 as progressive. Location on the oral side of the papilla of Vater, large initial tumor size ( ≥ 10 mm), macroscopically complex type, red color, and nodularity were significantly frequent in progressive LGD than in stable LGD. In multivariate analysis, large initial tumor size (odds ratio [OR], 10.2; 95 % confidence interval [CI], 3.3-32.1; P  < 0.001) and location on the oral side of the papilla of Vater (OR: 1.8, 95 % CI: 1.4-12.5; P  = 0.012) were significant factors for progression. Moreover, initial tumor size < 5 mm rarely progressed (0%-3.9 %); however, initial tumor size ≥ 20 mm and 10-19 mm located on the oral side of the papilla of Vater had a high-risk progression rate (75.0-85.7 %). Conclusions According to the risk stratification of progression factors by initial tumor size and location, we can determine suitable treatment indications for LGD lesions.

Additive effect of evaluating microsurface and microvascular patterns using magnifying endoscopy with narrow-band imaging in gastric cancer: a post-hoc analysis of a single-center observational study.

BACKGROUND: No studies have compared the performance of microvascular and microsurface patterns alone with their combination in patients undergoing magnifying endoscopy with narrow-band imaging for diagnosing gastric cancer. This study aimed to clarify the differences in diagnostic performance among these methods. METHODS: Thirty-three participating endoscopists who had received specialized training in magnifying endoscopy evaluated the microvascular and microsurface patterns of images of 106 cancerous and 106 non-cancerous lesions. If classified as "irregular," the lesion was diagnosed as gastric cancer. To evaluate diagnostic performance, we compared the diagnostic accuracy, sensitivity, and specificity of these methods. RESULTS: Performance-related items did not differ significantly between microvascular and microsurface patterns. However, the diagnostic accuracy and sensitivity were significantly higher when using a combination of these methods than when using microvascular (82.1% [76.4-86.7] vs. 76.4% [70.3-81.6] and 69.8% [60.5-77.8] vs. 63.2% [53.7-71.8]; P < 0.001 and P = 0.008, respectively) or microsurface (82.1% [76.4-86.7] vs. 73.6% [67.3-79.1] and 69.8% [60.5-77.8] vs. 52.8% [43.4‒62.1]; both, P < 0.001) patterns alone. The additive effect on diagnostic accuracy and sensitivity was 5.7‒8.6% and 6.6‒17.0%, respectively. CONCLUSIONS: We demonstrate the superiority of the combination of microvascular and microsurface patterns over microvascular or microsurface patterns alone for diagnosing gastric cancer. Our data support the use of the former method in clinical practice. Although a major limitation of this study was its retrospective, single-center design, our findings may help to improve the diagnosis of gastric cancer.

Safety and Efficacy of Self-Expandable Metallic Stent Placement Using Low Radial Force Stent for Malignant Dysphagia after Radiotherapy.

INTRODUCTION: We aimed to investigate the safety and efficacy of self-expandable metallic stent (SEMS) placement in patients with prior radiotherapy (RT) using the Niti-S stent, which is characterized by low radial force, in comparison to patients without prior RT. METHODS: A consecutive series of 83 patients who were treated by SEMS placement using Niti-S stent for severe malignant esophageal obstruction or fistula were enrolled. The adverse event rates and efficacy were retrospectively compared between patients with/without prior RT before SEMS placement (RT group [n = 32] versus non-RT group [n = 51]). RESULTS: The incidence rate of major adverse events in the RT group was 6.3% and was not significantly different from that in the non-RT group (5.9%, p = 0.95). Among the RT group, 84.4% were able to resume oral intake within a median of 2 days. Among the patients with fistula, 78.6% could resume oral intake and survive for 73 days after SEMS placement. Cox proportional hazard regression analysis identified significant factors affecting overall survival to be prior RT (hazard ratio [HR]: 1.96), low performance status (HR: 3.87), and subsequent anticancer treatment after SEMS placement (HR: 0.41). However, compared to the non-RT group, the RT group had received longer duration of anticancer treatment before SEMS placement and a lower rate of subsequent anticancer treatment after SEMS placement. CONCLUSIONS: With the Niti-S stent, the incidence of major adverse events was sufficiently low even for patients after RT. SEMS with low radial force would be an effective palliative treatment option for patients, regardless of prior RT.

Evaluation of Microvascular Patterns Alone Using Endocytoscopy with Narrow-Band Imaging for Diagnosing Gastric Cancer.

INTRODUCTION: Although endocytoscopy (EC) with narrow-band imaging (NBI) is effective in diagnosing gastric cancer, no diagnostic system has been validated. We explored a specific diagnostic system for gastric cancer using EC with NBI. METHODS: Equal numbers of images from cancerous and noncancerous areas (114 images each) were assessed by endoscopists with (development group: 33) and without (validation group: 28) specific training in magnifying endoscopy with NBI. Microvascular and microsurface patterns (MS) in each image were evaluated. Lesions were diagnosed as cancerous when patterns were deemed "irregular." The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of a diagnosis according to patterns on EC with NBI (microvascular pattern [MV] alone, MS alone, and both) were evaluated and compared between groups to determine the diagnostic performance. RESULTS: In the development and validation groups, diagnoses based on the MV alone had significantly higher accuracy (91.7% vs. 76.3%, p < 0.0001 and 92.5% vs. 67.5%, p < 0.0001, respectively) and sensitivity (88.6% vs. 68.3%, p < 0.0001 and 89.5% vs. 38.6%, p < 0.0001, respectively) than those based on the MS alone. In both groups, there were no significant differences in diagnostic accuracy between using the MV alone and both patterns. DISCUSSION/CONCLUSION: Evaluation of the MV alone is a simple and accurate diagnostic method for gastric cancer. This system could find widespread applications in clinical practice.

A novel diagnostic system for superficial nonampullary duodenal epithelial tumors sized ≤ 5 mm.

BACKGROUND: An association between specific endoscopic findings and high-grade dysplasia/carcinoma in superficial nonampullary duodenal epithelial tumors ≤ 5 mm in size has not been reported. We sought to identify the endoscopic findings associated with high-grade dysplasia/carcinoma in patients with superficial nonampullary duodenal epithelial tumors ≤ 5 mm. METHODS: We retrospectively assessed the data of 84 patients (88 lesions; low-grade dysplasia: n = 35, high-grade dysplasia/carcinoma: n = 53) with superficial nonampullary duodenal epithelial tumors who underwent initial treatment at a single center (from July 2009 to April 2021). All the patients had lesions sized ≤ 5 mm. We assumed that the endoscopic findings were independently associated with high-grade dysplasia/carcinoma and determined the accuracy, sensitivity, and specificity of a combination of independent factors for diagnosing high-grade dysplasia/carcinoma and low-grade dysplasia. RESULTS: Multivariate logistic regression of significant factors in the univariate analysis revealed that lesions with depressed morphology (odds ratio: 23.9, 95% confidence interval: 2.8-204.2; p = 0.0037) and a reddish color (odds ratio: 175.7, 95% confidence interval: 11.4-2697.1; p = 0.0002) were independently associated with high-grade dysplasia/carcinoma. McNemar's test revealed that combining the macroscopic type and color provided significantly higher sensitivity for diagnosing high-grade dysplasia/carcinoma than color alone (98.1%, 95% confidence interval: 90.1-99.7 vs. 71.7%, 95% confidence interval: 58.4-82.0; p = 0.0002). CONCLUSIONS: Reddish and depressed-type lesions before treatment were associated with high-grade dysplasia/carcinoma. Combining the macroscopic type and color can help detect high-grade dysplasia/carcinoma. These findings could help clinicians determine the best therapeutic strategy for patients with smaller (≤ 5 mm) superficial nonampullary duodenal epithelial tumors in clinical settings.

Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment.

OBJECTIVES: Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. METHODS: Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). RESULTS: In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. CONCLUSIONS: Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.