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.

Management and clinical outcomes of type I gastric carcinoid patients: retrospective, multicenter study in Japan.

BACKGROUND AND AIM: Type I gastric carcinoids (TIGC) are associated with chronic atrophic gastritis (CAG) with hypergastrinemia and hyperplasia of enterochromaffin-like cells. Several treatment options are currently available for these tumors including total gastrectomy, partial resection, antrectomy, endoscopic resection and endoscopic surveillance. The present study evaluated different treatment approaches and clinical outcomes of patients with TIGC in Japan. METHODS: Between 1991 and 2011, 82 patients with TIGC were identified at multicenter institutions in Japan. Patient demographics, tumor size, depth of invasion, vessel involvement, treatment approach, Helicobacter pylori infection, serum gastrin level, recurrence-free survival (RFS) and disease-specific survival (DSS) were analyzed. RESULTS: Median age of all patients at the time of diagnosis was 56 years (range, 24-79 years). There were 44 males and 38 females. Patients underwent endoscopic surveillance (n=25), endoscopic resection (n=41) or surgical resection (n=16). Intramucosal invasion was found in 19 patients, submucosal invasion in 44 patients and muscularis propria invasion in one patient. Tumor diameter was ≤ 10 mm in 71 patients, 11-20mm in five patients and ≥ 21 mm in five patients. None of the patients showed rapidly growing tumors, local recurrence or metastasis. The median (range) follow-up period was 7(0-20) years. RFS was 97.6% and DSS was 100% in all the patients. CONCLUSION: The prognosis of TIGC patients treated by different modalities in Japan is favorable regardless of the generational change of management for TIGC.

Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma.

Only a few cases of gastric adenocarcinoma of fundic gland type have been reported. Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been recently reported as a new variant of gastric adenocarcinoma. However, its clinicopathologic features are uncertain. To elucidate them, GA-CCDs exhibiting pepsinogen-I expression (10 lesions: Group A) and randomly selected gastric adenocarcinomas of differentiated type (111 lesions: Group B) were evaluated in this study. Cell differentiation by MUC2, MUC5AC, MUC6, CD10, pepsinogen-I, H+/K+-ATPase and chromogranin A, cell proliferation by Ki-67, and overexpression of p53 protein were evaluated immunohistochemically. In Group A, all GA-CCDs were located in the upper third of the stomach. Tumors were small, with the average maximum diameter ranging from 4 to 20 (average, 8.6) mm. Histologically, GA-CCDs were well-differentiated adenocarcinomas composed of pale gray-blue, basophilic columnar cells with mild nuclear atypia, resembling chief cells. Immunohistochemically, scattered positivity for H+/K+-ATPase was observed in addition to expression of pepsinogen-I and MUC6, indicating focal differentiation toward parietal cells. In Group B, pepsinogen-I was very focally expressed in 2 cases. As these 2 cases exhibited different clinicopathological and histologic features, they cannot be categorized as GA-CCD. Mild atypism, no lymphovascular invasion, low proliferative activity, no overexpression of p53, and no recurrence indicated less aggressiveness of GA-CCD. GA-CCD is rare, but it has distinct clinicopathological characteristics, especially in terms of tumor location, histologic features, phenotypic expression, and low-grade malignancy. We propose gastric adenocarcinoma of fundic gland type (chief cell predominant type) as a new entity of gastric adenocarcinoma.

Helicobacter pylori status and esophagogastroduodenal mucosal lesions in patients with end-stage renal failure on maintenance hemodialysis.

OBJECTIVES: The aim of this study was to elucidate the impact of Helicobacter pylori infection on esophagogastroduodenal mucosal lesions in patients with end-stage renal failure on maintenance hemodialysis (HD). METHODS: An upper endoscopy and the (13)C-urea breath test were performed in 198 patients on maintenance HD. Clinical features, serum pepsinogen levels and esophagogastroduodenal mucosal lesions were compared between H. pylori-positive and H. pylori-negative patients. Risk factors associated with esophagogastroduodenal mucosal lesion were determined by multivariate analyses. RESULTS: The upper endoscopy revealed that gastric erosion was the most frequent (58%) type of esophagogastroduodenal mucosal lesion, followed by duodenal erosion (18%), gastric ulcer (14%), gastroesophageal reflux disease (10%), and duodenal ulcer (7%). Of the 198 patients enrolled in the study, 81 were positive and 117 patients were negative for H. pylori infection. The time duration after the introduction of HD was significantly longer and serum pepsinogen I/II ratio was significantly higher in H. pylori-negative patients than in H. pylori-positive patients. Multivariate analyses revealed that the H. pylori infection was an independent, protective factor for gastric erosion (odds ratio 0.38; 95% confidence interval 0.21-0.70), while the infection was unrelated to other mucosal lesions. CONCLUSIONS: The most common mucosal lesion observed in our study cohort, all of whom were patients on maintenance HD, was gastric erosion. The high prevalence of this type of lesion may be explained partly by the cure of H. pylori infection during the clinical course of maintenance HD.

Linear mucosal defect may be characteristic of lansoprazole-associated collagenous colitis.

BACKGROUND: Although some cases of collagenous colitis have been induced by lansoprazole (LPZ), the clinicopathologic features of LPZ-associated collagenous colitis have not been elucidated. OBJECTIVE: To elucidate the clinical, endoscopic, and histopathologic features of LPZ-associated collagenous colitis. DESIGN: Retrospective case study. PATIENTS: The subjects were 13 patients with collagenous colitis diagnosed during a period from 2002 to 2007. MAIN OUTCOME MEASUREMENTS: The colonoscopic and histopathologic findings were compared retrospectively between 9 cases of LPZ use (LPZ group) and 4 cases without the use of LPZ (non-LPZ group). RESULTS: A colonoscopy revealed a linear mucosal defect more frequently in the LPZ group (7 of 9 cases [78%]) than in the non-LPZ group (0 of 4 cases [0%], P = .02). Friable mucosa was also noted in 4 patients (44%) in the LPZ group but none in the non-LPZ group. The colonoscopic finding in the non-LPZ group was either normal mucosa or nonspecific minimal abnormalities, whereas patients in the LPZ group had either a linear mucosal defect, mucosal bleeding, or both (P = .001). On histologic examination, the subepithelial collagen band was thicker in patients in the LPZ group than in those in the non-LPZ group (median 45 vs 26.3 mum). All patients in the LPZ group recovered from diarrhea after discontinuance of LPZ. LIMITATION: A small number of patients. CONCLUSIONS: Linear mucosal defects and friable mucosa may be characteristic colonoscopic findings in cases of LPZ-associated collagenous colitis.

Long-term remission of primary gastric T cell lymphoma associated with human T lymphotropic virus type 1: a report of two cases and review of the literature.

Two cases of primary gastric T-cell lymphoma associated with human T lymphotropic virus type 1 (HTLV-1) are presented. Case 1 was a 54-year-old man who had multiple ulcerating tumors in the lower corpus and gastric antrum. Case 2, a 60-year-old man, showed a large ulcerating tumor in the upper corpus. Both patients were positive for serum anti-HTLV-1 antibody and for the monoclonal integration of HTLV-1 proviral DNA in the tumor cells by Southern blot analysis. The patients were thus diagnosed as having primary gastric T-cell lymphoma associated with HTLV-1 of stage II(1). Case 1 underwent total gastrectomy followed by chemotherapy, while Case 2 was treated by chemotherapy and radiotherapy. Both patients have been in complete remission for more than 4 years (96 months in Case 1 and 50 months in Case 2) after the treatments. Although primary gastric T-cell lymphomas associated with HTLV-1 is characterized by an extremely poor prognosis, the present cases suggest that in the early stage, long-term survival can possibly be achieved with appropriate treatments.

Merits and faults of transanal ileus tube for obstructing colorectal cancer.

BACKGROUND: We report eight cases of obstructing colorectal cancer successfully managed by preoperative lavage using transanal ileus tube. METHODS: Decompression tube was transanally inserted into the colon proximal to the tumour under the guidance of the guide wire. Intestinal lavage with 1,500-2,000 mL of warm water was done every day until surgery. RESULTS: There were six men and two women; the mean age was 67 years (range, 50-82 years). Three cancers were in the sigmoid colon and five were in the rectum. Seven patients were treated with a one-stage operation with adequate lymph node dissection. In one patient, only sigmoidostomy was carried out for unresectable huge tumour. In all cases, no dilatation was observed at the proximal colon and no anastomotic failure developed. Four patients suffered from fever of unknown cause after the insertion of the tube. In one patient, the resected specimen showed ulcer by tube compression. In the other patient, the tube penetrated the intestinal wall, which was covered by mesentery. CONCLUSION: The transanal ileus tube is effective for the treatment of obstructing colorectal cancer. However, close observation is necessary because of possible perforation.

Probe EUS for the diagnosis of invasion depth in superficial esophageal cancer: a comparison between a jelly-filled method and a water-filled balloon method.

BACKGROUND AND OBJECTIVE: Diagnostic accuracy of probe EUS depends on the constant maintenance of luminal medium for acoustic coupling. This study compared the accuracy of probe EUS by a jelly-filled method (EUS-J) and by a water-filled balloon method (EUS-W) for the assessment of invasion depth in superficial esophageal cancer. DESIGN AND SETTING: A prospective, single-center study. PATIENTS: Forty superficial esophageal cancers in 38 patients. INTERVENTIONS: Patients were alternately assigned to EUS-J or EUS-W. The depth of invasion was classified into epithelium or lamina propria mucosae (D1), muscularis mucosae or superficial layer of the submucosa (D2), and deep portion of the submucosa (D3). Depiction rate, interobserver variation between 2 observers, and accuracy for the determination of invasion depth were compared between EUS-J and EUS-W. MAIN OUTCOME MEASUREMENTS AND RESULTS: Eighteen cancers were examined by EUS-J, and 22 cancers were examined by EUS-W. The actual depth of invasion was D1 in 21 cancers, D2 in 9 cancers, and D3 in 10 cancers. Depiction rate (94.4% vs 77.2%, P = .14) and interobserver agreement of EUS determination (82.3% vs 58.8%, P = .13) was higher in EUS-J than in EUS-W. The overall accuracy for the diagnosis of invasion depth was 77.8% in EUS-J and 59.1% in EUS-W (P = .18). The sensitivity for the diagnosis of D1 cancer was significantly higher in EUS-J than in EUS-W (100% vs 50%, P = .03), while the specificity was not different between the 2 procedures (81.8% vs 87.5%). CONCLUSIONS: EUS-J is superior to EUS-W for the assessment of invasion depth in superficial esophageal cancer, especially for intramucosal cancer.

GI involvement in Henoch-Schönlein purpura.

BACKGROUND: The diagnosis of Henoch-Schönlein purpura is difficult, especially when abdominal symptoms precede cutaneous lesions. The aim of this study was to determine the distribution of GI involvement in Henoch-Schönlein purpura. METHODS: Endoscopic or radiographic findings throughout the entire GI tract were retrospectively reviewed for 7 patients with Henoch-Schönlein purpura. Histopathologic findings were analyzed and correlated with findings at EGD and colonoscopy. OBSERVATIONS: The duodenum and small intestine were most frequently involved (6 patients, each site). Contrast radiography of the small intestine demonstrated thickened mucosal folds or small barium flecks. Findings at EGD were multiple irregular ulcers, mucosal redness and petechiae in the duodenum. In 4 patients, the second part of the duodenum was predominantly affected. Ulcerating lesions accompanied by hematoma-like protrusions were detected in 4 patients in whom leukocytoclastic vasculitis was proven histopathologically. CONCLUSIONS: EGD appears to have the greatest diagnostic utility in patients suspected to have Henoch-Schönlein purpura with GI involvement.

Comparison of EUS and magnifying colonoscopy for assessment of small colorectal cancers.

BACKGROUND: Prediction of invasion depth and lymph node metastasis is mandatory when local treatment is considered for small colorectal cancer. The aim of this study was to compare the accuracy of EUS with a catheter probe (probe-EUS) and magnifying colonoscopy for prediction of invasion depth and lymph node metastasis for small colorectal cancer. METHODS: Small colorectal cancers were imaged by both probe-EUS and magnifying colonoscopy. Invasion depth by probe-EUS was determined by the presence or absence of distortion of the third sonographic layer. Findings by magnifying colonoscopy were divided into regular, distorted, and amorphous patterns. Histopathologically, depth of invasion was classified as intramucosa/slight or deep invasion. Findings by probe-EUS and magnifying colonoscopy were compared with respect to deep invasion and lymph node metastasis. RESULTS: There were 22 small colorectal cancers with intramucosa/slight invasion and 28 with deep invasion. Four of 30 cancers had associated lymph node metastasis. Accuracy for depth of invasion was 91.8% for probe-EUS and 63.3% in magnifying colonoscopy, the difference being statistically significant (p = 0.0013). Negative predictive value of probe-EUS for deep invasion was higher than that for magnifying colonoscopy (respectively, 90.9% vs. 54.1%) in the population studied (prevalence deep invasion 56%). The accuracy for lymph node metastasis was 24.1% for probe-EUS and 72.4% for magnifying colonoscopy, the difference being statistically significant (p < 0.001). Positive predictive value for lymph node metastasis was higher when the amorphous pattern was noted by magnifying colonoscopy compared with the positive predictive value for deep invasion by probe-EUS (respectively, 33.3% vs. 8.7%) in the population studied (prevalence lymph node metastasis 13.3%). CONCLUSIONS: Probe-EUS is superior to magnifying colonoscopy for determination of invasion depth in small colorectal cancer. Magnifying colonoscopy may be predictive of lymph node metastasis, thereby suggesting that the procedures provide complementary information with respect to the decision for local versus surgical therapy.