Results of the interim analysis of a prospective, multicenter, observational study of small subepithelial lesions in the stomach.

OBJECTIVES: Long-term outcomes of gastric subepithelial lesions have not been elucidated. To reveal the natural history, we initiated a prospective, 10-year follow-up of patients with small (≤20 mm) gastric subepithelial lesions in September 2014. Here, we report the results of an interim analysis of a prospective observational study. METHODS: In total, 567 patients with 610 lesions were prospectively registered between September 2014 and August 2016. The location, size, morphology, and number of subepithelial lesions were recorded on a web-based case report form. This study has been conducted as an Academic Committee Working Group of the Japan Gastroenterological Endoscopy Society. RESULTS: The endoscopic follow-up period was 4.60 ± 1.73 years (mean ± standard deviation), and survival data were investigated for 5.28 ± 1.68 years. This interim analysis revealed that the estimated cumulative incidence of a size increase ≥5 mm, after accounting for patients' death and resection of the tumor as competing risk events, was 4.5% at 5 years. In addition, the estimated cumulative incidence of lesion size increase ≥5 mm or resection of lesions was 7.9% at 5 years, and that of size increase ≥10 mm or resection of lesions was 4.5% at 5 years. CONCLUSION: These results indicate that approximately one in 13 patients with small (≤20 mm) gastric subepithelial lesions may require resection or further investigation for increased tumor size (≥5 mm) within 5 years.

Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis.

To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant.

Nonrecurrence Rate of Underwater EMR for ≤20-mm Nonampullary Duodenal Adenomas: A Multicenter Prospective Study (D-UEMR Study).

BACKGROUND AND AIMS: Endoscopic resection of nonampullary duodenal adenoma is often challenging, and its technique has not yet been standardized. To overcome the practical difficulty of conventional endoscopic mucosal resection, underwater endoscopic mucosal resection (UEMR) was recently developed; therefore, we investigated the effectiveness and safety of UEMR for nonampullary duodenal adenoma. METHODS: A multicenter, prospective cohort study was conducted at 21 institutions in Japan. We enrolled patients with no more than 2 nonampullary duodenal adenomas ≤20 mm in size, who were planned to undergo UEMR. After UEMR, follow-up endoscopies were scheduled at 2 and 12 months after the procedure, and biopsy specimens were taken from the post-UEMR scars. The primary endpoint was the proportion of patients with histologically proven nonrecurrence at follow-up endoscopy and biopsy. RESULTS: A total of 155 patients with 166 lesions underwent UEMR. One patient with a non-neoplastic lesion in the resected specimen and 10 patients with 10 lesions who were lost to follow-up were excluded. Finally, 144 patients with 155 lesions who received all follow-up endoscopies were analyzed for the primary endpoint. The proportion of patients with proven nonrecurrence was 97.2% (n = 140 of 144; 95% confidence interval, 92.8%-99.1%) which exceeded the predefined threshold value (92%). Two cases of delayed bleeding (1.2%) occurred and they were successfully managed by clips. All recurrences were successfully treated by additional endoscopic treatment. CONCLUSIONS: This multicenter, prospective cohort study demonstrated effectiveness and safety of UEMR for nonampullary duodenal adenomas ≤20 mm in size. (University Hospital Medical Network Clinical Trials Registry, Number: UMIN000030414).

Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: a retrospective observational study.

BACKGROUND: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection. METHODS: We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group). RESULTS: The average age was older in the Hp group than in the uninfected group (68.1 ± 8.1 vs. 63.4 ± 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%). CONCLUSIONS: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection.

Perioperative Clinical Course Variables Associated with Length of Hospital Stay after Primary Intracranial Meningioma Resection.

The relationship between perioperative clinical course variables and postoperative length of hospital stay (LOS) in patients undergoing primary intracranial meningioma resection has not been fully elucidated. We therefore aimed to identify the perioperative clinical course variables that predict postoperative LOS in such patients. We retrospectively collected data concerning demographics, tumor characteristics, and perioperative clinical course variables in 76 patients who underwent primary intracranial meningioma resection between January 2010 and December 2019, and tested for associations with postoperative LOS. Univariate analyses showed that younger age, fewer days to postoperative initiation of standing/walking, preoperative independence in activities of daily living (ADL), and ADL independence one week after surgery were associated with shorter postoperative LOS. Multiple regression analyses with these factors identified that days to stand/walk initiation and ADL independence one week after surgery were associated with postoperative LOS. Based on these results, we conclude that rehabilitation programs that promote early mobilization and the early acquisition of independence may reduce postoperative LOS in patients who undergo primary intracranial meningioma resection.

A Case of Dual-pathology Hepatocellular Carcinoma (HCC) and Cholangiolocellular Carcinoma (CoCC) after Eradication of Hepatitis C Virus (HCV) Infection.

A 75-year-old Japanese man visited our hospital for further examination of liver tumors. He had a history of successful hepatitis C virus (HCV) eradication and therapy for hepatocellular carcinoma (HCC) at another hospital. Magnetic resonance imaging (MRI) revealed two tumors in the liver. He underwent anterior inferior (S5) and posterior inferior (S6) subsegmentectomy of the liver. Microscopic examination found that one tumor was HCC while the other was cholangiolocellular carcinoma (CoCC). We experienced a rare case of liver cancer with two synchronous pathologies, HCC and CoCC.

Long-term outcomes of endoscopic versus surgical resection for MM-SM1 esophageal squamous cell carcinoma using propensity score analysis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) confined to the muscularis mucosae (MM) or up to 200 µm of the submucosa (SM1) confers the risk for lymph node metastasis, and is defined as relative indication for endoscopic submucosal dissection (ESD) by the Japan Esophageal Society guidelines. Although additional surgical treatment after ESD is recommended, long-term outcomes of ESD compared with those of surgery have not been clarified. This study aimed to evaluate the long-term outcomes of ESD and surgery for cN0M0 relative indication lesions of ESCC. METHODS: Between 2006 and 2016, patients with relative indication lesions of ESCC who underwent ESD or surgery at nine participating hospitals were examined retrospectively. Using propensity score matching, we evaluated survival curves for and hazard ratios associated with endoscopic submucosal dissection and surgery. RESULTS: In total, 155 lesions in the ESD group and 106 lesions in the surgery group met the pathological criteria of relative indication for endoscopic resection. After matching, 50 matched pairs of patients who underwent ESD or surgery were selected. The 5-year overall survival rates were 84.5% [95% confidence interval (CI) 68-93] in the ESD group and 79% [95% CI 60-90] in the surgery group. The hazard ratio of mortality for ESD compared with that for surgery estimated by Cox regression analysis was 0.79 (95% CI 0.3-2.06, p = 0.63). CONCLUSIONS: Compared with surgery, ESD does not compromise long-term outcomes. ESD alone or ESD with chemotherapy and/or radiotherapy may be an option for the treatment of MM and SM1 ESCC.

Importance of Second-look Endoscopy on an Empty Stomach for Finding Gastric Bezoars in Patients with Gastric Ulcers.

　Most gastric bezoars can be treated with endoscopic fragmentation combined with or without cola dissolution, whereas laparotomy or laparoscopic surgery is generally inevitable for small intestinal bezoars because they cause small bowel obstruction. Therefore, early diagnosis and management of gastric bezoars are necessary to prevent bezoar-induced ileus. To investigate the incidence of overlooked gastric bezoars during the initial esophagogastroduodenoscopy, we retrospectively reviewed the cases of 27 patients diagnosed with gastrointestinal bezoars. The bezoars were diagnosed using esophagogastroduodenoscopy (n=25), abdominal ultrasonography (n=1), and barium follow-through examination (n=1). Bezoars were overlooked in 9/25 patients (36.0%) during the initial endoscopy examination because the bezoars were covered with debris in the stomach. Of the 9 patients, 8 had concomitant gastric ulcers, and the other patient had gastric lymphoma. Although a computed tomography (CT) scan was performed before the second-look endoscopy in 8 of the 9 patients, the bezoars were mistaken as food debris on CT findings and were overlooked in these patients. In conclusion, gastric bezoars may not be discovered during the initial esophagogastroduodenoscopy and CT scan. In cases with debris in the stomach, second-look endoscopy is essential to detect bezoars.

Lesion size, elevated morphology, and non or closed-type atrophy are predictive factors for gastric adenocarcinoma of the fundic gland type rather than oxyntic gland adenoma.

Background: An oxyntic gland neoplasm confined to the mucosal layer (T1a) is classified as an oxyntic gland adenoma, whereas that with submucosal invasion (T1b) is defined as gastric adenocarcinoma of the fundic gland type (GA-FG). Methods: To reveal the differences in clinical features between them, we retrospectively investigated 136 patients with 150 oxyntic gland adenoma and GA-FG lesions. Results: The univariate analysis revealed that the mean size (GA-FG vs. oxyntic gland adenoma, 7.7±5.4 vs. 5.5±3.1 mm), the prevalence of elevated morphology (79.1% vs. 51.8%), black pigmentation within the lesion (23.9% vs. 9.6%), and non or closed-type atrophy (81.2% vs. 65.1%) were different between the two groups. A multivariate logistic regression analysis revealed that ≥5 mm lesion size (odds ratio, 2.96; 95% confidence interval: 1.21-7.23), elevated morphology (odds ratio, 2.40; 95% confidence interval: 1.06-5.45), and no or closed-type atrophy (odds ratio, 2.49; 95% confidence interval: 1.07-5.80) were factors in distinguishing GA-FG from oxyntic gland adenoma. When oxyntic gland neoplasms with no or one feature were judged as oxyntic gland adenomas and those with two or three features were judged as GA-FG, the sensitivity and specificity were 85.1% and 43.4% for GA-FG, respectively. Conclusions: We identified three possible distinctive features of GA-FG compared to oxyntic gland adenoma: lesion size ≥5 mm, elevated morphology, and no or closed-type atrophy.

Long-term outcomes of patients with primary intestinal follicular lymphoma managed with watch-and-wait strategy.

Patients with primary intestinal follicular lymphoma are often followed-up without a specific treatment, and this approach is called the "watch-and-wait approach." However, the long-term outcomes of this patient group have not been sufficiently investigated. We enrolled patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed with the watch-and-wait approach in 20 institutions. We retrospectively investigated the overall, disease-specific, and event-free survival rates as well as the rate of spontaneous regression. Among the 248 patients with follicular lymphoma with gastrointestinal involvement, 124 had localized disease (stage I or II1). We analyzed the data of 73 patients who were managed using the watch-and-wait approach. During the mean follow-up period of 8.3 years, the follicular lymphoma had spontaneously resolved in 16.4% of the patients. The 5-year and 10-year overall survival rates were 92.9% and 87.1%, respectively. With disease progression (n = 7), initiation of therapy (n = 7), and histologic transformation to aggressive lymphoma (n = 0) defined as events, the 5-year and 10-year event-free survival rates were 91.1% and 86.9%, respectively. No patient died of progressive lymphoma. Thus, both 5-year and 10-year disease-specific survival rates were 100%. In conclusion, an indolent long-term clinical course was confirmed in the patients with primary intestinal follicular lymphoma. The watch-and-wait strategy is a reasonable approach for the initial management of these patients.

Resection depth for small colorectal polyps comparing cold snare polypectomy, hot snare polypectomy and underwater endoscopic mucosal resection.

Background and study aims Small colorectal polyps are removed by various methods, including cold snare polypectomy (CSP), hot snare polypectomy (HSP), and underwater endoscopic mucosal resection (UEMR), but the indications for using these methods are unclear. We retrospectively assessed the efficacy of CSP, HSP, and UEMR for small polyps, focusing on the depth of the resected specimens. Patients and methods Outpatients with non-pedunculated small polyps (endoscopically diagnosed as 6 to 9 mm), resected by two endoscopists between July 2019 and September 2020, were enrolled. We histologically evaluated the specimens resected via CSP, HSP, and UEMR. The main outcome was the containment rate of the muscularis mucosa (MM) and submucosa (SM) tissues. Results Forty polyps resected via CSP (n = 14), HSP (n = 12), or UEMR (n = 14) were enrolled after excluding 13 polyps with resection depths that were difficult to determine. The rates of specimens containing MM and SM tissue differed significantly (57 % and 29 % for CSP, 92 % and 83 % for HSP, and 100 % and 100 % for UEMR, respectively ( P  = 0.005 for MM and P  < 0.001 for SM tissue). Multiple logistic regression analysis showed UEMR was an independent factor relating to the containment of SM tissue. The thickness of SM tissue by CSP, HSP, and UEMR were 52 µm, 623 µm, and 1119 µm, respectively ( P  < 0.001). The thickness by CSP was significantly less than those by HSP and UEMR ( P  < 0.001, Bonferroni correction). Conclusions UEMR could be the best method to contain SM tissue without injection. Further studies are needed to evaluate the indication of UEMR for small polyps.

Strategy for Removing an Impacted Enterolith using Double-Balloon Enteroscopy in Crohn's Disease.

An enterolith in Crohn's disease is an uncommon but serious condition because it can cause intestinal obstruction. Endoscopic treatment to remove the enterolith is attempted first, but is sometimes difficult owing to poor accessibility of the endoscope. In such cases, surgical treatment is inevitable. We successfully overcame poor accessibility and removed an enterolith using double-balloon enteroscopy. We describe our method below and suggest several helpful techniques. LEARNING POINTS: Patients with Crohn's disease sometimes have a history of intestinal stricture, which can cause intestinal obstruction by enterolith-related impaction.Endoscopic treatment is the first choice to remove an enterolith, but is sometimes difficult.We successfully removed an enterolith using double-balloon enteroscopy and employing several helpful techniques.

Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma or gastric adenocarcinoma of the fundic gland type.

The aim of this study was to reveal the histological features of oxyntic gland adenomas and gastric adenocarcinoma of the fundic-gland type (GA-FG). We retrospectively examined the histological features of 126 lesions of oxyntic gland adenoma and/or GA-FG in 116 patients. The prevalence of oxyntic gland adenomas and GA-FG was approximately equal. The majority of the lesions were resected by endoscopic mucosal resection using a diathermic snare (EMR, n = 42) or endoscopic submucosal dissection (ESD, n = 72). Histologically, there were no lesions with invasion at the level of the muscularis propria or deeper, and lymphovascular invasion was present in 1.6%. Of the ESD and EMR specimens, there were no lesions that were positive for vertical margins. Among the eight GA-FG patients with deep (≥ 500 µm) submucosal invasion, six were treated with endoscopic resection alone, and no recurrence was documented. No patients died of the disease during the median follow-up period of 14.5 months. In conclusion, all lesions were confined to the mucosa or submucosa and were negative for vertical margins. Lymphovascular invasion was present in only 1.6% of the patients. Thus, we believe that endoscopic resection is a suitable initial treatment method for oxyntic gland adenoma and GA-FG.

Diagnostic Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Gastric Mesenchymal Tumors.

There have been no comparative studies investigating the results of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with gastric mesenchymal tumors, including leiomyomas, leiomyosarcomas, schwannomas, and gastrointestinal stromal tumors (GISTs). We retrospectively reviewed the data of 142 patients with pathologically diagnosed gastric mesenchymal tumors treated at 11 institutions. We analyzed the correlation between the maximum standardized uptake value (SUVmax) evaluated using fluorodeoxyglucose-positron emission tomography (FDG-PET) and the tumor size. The correlation between the SUVmax and mitotic index was also investigated in GISTs. The SUVmax (mean ± standard deviation) was 0.5 ± 0.6 in very low-risk GISTs (n = 42), 2.1 ± 0.7 in low-risk GISTs (n = 26), 4.9 ± 0.8 in intermediate-risk GISTs (n = 22), 12.3 ± 0.8 in high-risk GISTs (n = 20), 1.0 ± 1.0 in leiomyomas (n = 15), 6.9 ± 1.2 in schwannomas (n = 10), and 3.5 in a leiomyosarcoma (n = 1). The SUVmax of GISTs with an undetermined risk classification was 4.2 ± 1.3 (n = 8). Linear associations were observed between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax of GISTs with a high mitotic index was significantly higher than that of GISTs with a low mitotic index (9.6 ± 7.6 vs. 2.4 ± 4.2). In conclusion, we observed positive correlations between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax also positively correlated with the mitotic index and risk grade in GISTs. Schwannomas showed a higher FDG uptake than GISTs and leiomyomas.

Two cases of primary small cell carcinoma of the stomach.

We report 2 cases of small cell carcinoma (SmCC) of the stomach with distant metastasis that were treated with the same chemotherapeutic regimens as used to treat small cell lung cancer. Although the mean survival of patients with SmCC of the stomach is reported to be only 7 months, our patients survived for 15 and 14 months, respectively. In our experience, these chemotherapeutic regimens might provide a survival benefit for patients with SmCC of the stomach, although they demonstrated no remarkable antitumor effects.

Endoscopic mucosal resection of primary anorectal malignant melanoma: a case report.

Anorectal melanoma is a rare malignant tumor with a poor prognosis. However, several studies have reported cases of long-term survival. In this report, we present a patient with anorectal melanoma who has survived for 9 years after endoscopic mucosal resection. An 85-year-old man was referred to our hospital for further examination and treatment of an anal tumor 2 cm in size. Endoscopic ultrasonography revealed that the depth of tumor invasion was confined to the submucosal layer. Endoscopic mucosal resection was performed, and the tumor was diagnosed as a malignant melanoma. The patient was followed without any additional treatment, which was per his wishes. Although melanoma recurred 4 times thereafter, endoscopic mucosal resection was performed for each recurrent lesion. Thus, he has been alive for 9 years since the first endoscopic mucosal resection without distant metastases. If the depth of tumor invasion is shallow, endoscopic mucosal resection is a useful option among other therapeutic modalities.

Gastric ulcer after prophylactic balloon-occluded retrograde transvenous obliteration.

A 74-year-old man with compensated hepatitis C virus-related liver cirrhosis was admitted for the treatment of small hepatocellular carcinoma (HCC) by radiofrequency ablation therapy (RFA). As a routine pretreatment examination, gastrointestinal endoscopy was performed, and large nodular varices were observed in the gastric fornix, with telangiectasia on top of the varices. As soon as the RFA was completed, prophylactic balloon-occluded retrograde transvenous obliteration (B-RTO) was performed. Seven days after the B-RTO, the patient complicated of upper abdominal pain. Gastrointestinal endoscopy was performed, and a deep ulcer, located at the top of the tumor-shaped gastric varices, was found. The ulcer showed rapid healing after 1-week administration of a proton pump inhibitor (PPI). A severe ulcer after a B-RTO procedure, is extremely rare, because sclerosing agents rarely flow into the gastric mucosa. The ulcer in this patient was deep and large, and it may have been due to direct mucosal damage caused by the sclerosing agent, because mucosal telangiectasia on top of the varices was observed before the B-RTO. It is likely that, in this patient, the mucosal vessels communicated with the submucosal large varices, and ethanolamine oleate (EOI) flowed into the gastric mucosa via this communication. Based on our experience, we recommend periodic follow-up endoscopy.

[A case of mixed duct-islet cell tumor of the pancreas].

A 30-year-old woman was referred to us because of hypoglycemic attack. The tumor on the pancreatic body of 22 mm size was revealed by close inspection, and was diagnosed as insulinoma. Surgical resection was performed, but curative resection was impossible because the component of adenocarcinoma infiltrating into surrounding tissue coexisted with insulinoma. Postoperatively, we make a diagnosis of combined tumor of the pancreas, i.e. mixed duct-islet cell carcinoma. In this paper, we discuss this rare disorder and summarize 33 cases reported in the Japanese literature.

Clinical impact of sarcopenia and relevance of nutritional intake in patients before and after allogeneic hematopoietic stem cell transplantation.

PURPOSE: We conducted a retrospective study to evaluate the effect of rehabilitation on minimizing sarcopenia during hematopoietic stem cell transplantation (HSCT) therapy. METHODS: We developed a protocol to test for retention of physical function during HSCT. Muscle strength, muscle circumference, and muscle function before and after HSCT were measured. Consecutive patients with hematological malignancies who underwent HSCT treatment were recruited in this research. RESULTS: We included 34 patients (16 females, 18 males; median age, 51.5 years). Bodyweight significantly decreased after HSCT (p < 0.001). Nine females and three males had sarcopenia prior to allogeneic HSCT. After HSCT, bilateral hand grip strength and bilateral knee extensor strength decreased significantly. The total caloric intakes for pre-conditioning, during preparation regimen, and after transplant were 1709, 1024, and 1445 kcal, respectively, and were significantly attenuated in the post-transplant period. Serum albumin was significantly decreased in the final period. Conversely, C-reactive protein was slightly but significantly increased across the transplantation process. Multivariate regression analysis revealed that oral caloric intake after the transplantation period and sex were significantly related to muscle weakness (p = 0.033 and 0.036, respectively). CONCLUSIONS: Sarcopenia during HSCT was affected by oral caloric intake during the preparation regimen and after transplantation. Physical therapy in conjunction with nutritional therapy may help prevent weakness in HSCT recipients.