Optimal interval of endoscopic screening based on stage distributions of detected gastric cancers.

BACKGROUND: Although Korea and Japan have a national gastric cancer screening program, their screening intervals are different. The optimal screening interval of endoscopic screening in Japan was investigated based on the stage distributions of screen-detected gastric cancers. METHODS: Patients with gastric cancer detected by endoscopic and radiographic screenings were selected from the Niigata City Medical Association database. The stage distributions of the detected gastric cancers were compared among patients with different screening histories in both groups. Gastric cancer specific survival rates were analyzed using the Kaplan-Meier method with the log-rank test. RESULTS: There were 1585 and 462 subjects in the endoscopic and radiographic screening groups, respectively. In the endoscopic screening group, the stage IV proportion was lower in patients with screening history 1 and 2 years before diagnosis than in patients without screening history. Stage IV development was significantly related to the absence of screening history (p < 0.001); however, there were no differences between patients who had endoscopic screening history 2 and 3 years before diagnosis. The survival rates were not significantly different between patients with endoscopic screening 1 and 2 years previously (p = 0.7763). The survival rates were significantly higher in patients with endoscopic screening history 1 and 2 years before diagnosis than in patients without screening history (p < 0.001), and in patients with endoscopic screaming 3 years before diagnosis (P < 0.0069). CONCLUSION: The endoscopic screening interval for gastric cancer can be expanded to at least 2 years based on the stage distributions of detected cancers and the patient survival rates.

The relationship between iron deficiency in patients with Helicobacter pylori-infected nodular gastritis and the serum prohepcidin level.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) is recognized as a causative agent for unexplained iron-deficiency anemia (IDA). We evaluated many background factors influencing an iron-deficiency state in adult patients with various H. pylori-infected upper gastrointestinal tract diseases. METHOD: Study 1: H. pylori-infected 121 patients (nodular gastritis (NG) (n = 19), duodenal ulcer (DU) (n = 30), or gastric ulcer (GU) (n = 47), or gastric hyperplastic polyp (GHP) (n = 25)) were enrolled. The RBC count and hemoglobin, iron, ferritin, pepsinogen (PG) I, PG II, gastrin, and anti-H. pylori antibody (Ab) levels in the serum were measured. Study 2: H. pylori-infected 105 patients (NG, n = 19; DU, n = 43; GU, n = 32; GHP, n = 11) and non-H. pylori-infected individuals (n = 35) were examined for the levels of prohepcidin, ferritin, and iron in the serum. In addition, we measured the data before and after the H. pylori eradication. RESULTS: In the patients with GHP and NG, hypoferritinemia was observed in comparison with the GU and DU patients. In the GHP patients, low levels of PG I, a decreased PG I/II ratio, and hypergastrinemia were observed. The levels of serum prohepcidin in the patients with H. pylori-associated disease were higher than those in the uninfected adults. In the patients with NG, the serum prohepcidin levels were higher than those in the other H. pylori-infected patient groups and decreased after the eradication. CONCLUSION: H. pylori-related iron-deficiency state might be associated with several factors, such as hypochlorhydria and hepcidin, in patients with GHP or NG.

Usefulness of endoscopic submucosal dissection for type I gastric carcinoid tumors compared with endoscopic mucosal resection.

BACKGROUND/AIMS: Gastric carcinoid tumors (GCTs) often extends into the submucosa, and are therefore difficult to resect completely by using conventional endoscopic mucosal resection (EMR). Endoscopic submucosal dissection (ESD) allows en bloc resection of submucosal gastrointestinal lesions. Therefore, ESD may be a feasible method for complete resection of GCT. Our purpose is to clarify the usefulness of ESD for treatment of type I GCT. METHODOLOGY: Between 1998 and 2011, EMR or ESD was performed for 13 lesions in 12 patients with type I GCTs. Among the 13 GCTs, 6 were resected using EMR, and 7 were removed using ESD. RESULTS: All lesions were histologically classified as Grade 1. The depth of invasion was the mucosa for 1 lesion and the submucosa for 12 lesions. The horizontal margins of excision were negative for all lesions; however, the vertical margins were positive in 4 lesions (66.7%) in the EMR group and no lesions (0%) in the ESD group. CONCLUSIONS: The results of this study suggest that ESD for small type I GCT is better to achieve complete resection than conventional EMR. ESD would be an effective technique for the treatment of small type I GCT.

Familial juvenile polyposis syndrome with a novel SMAD4 germline mutation.

Juvenile polyposis syndrome (JPS) is a dominantly inherited disorder characterized by the development of numerous juvenile polyps (JPs) of the gastrointestinal tract, and associated with a mutation of the SMAD4 or BMPR1A gene. Here, we report a mother-daughter case of familial JPS. A 29-year-old female patient with severe iron deficiency anemia and hypoproteinemia had numerous polyps in the stomach and a few polyps in the ileum and colon that were detected endoscopically. Biopsy specimens from the gastric polyps were diagnosed as JPs. The patient underwent a laparoscopy-assisted total gastrectomy, and her anemia and hypoproteinemia improved. Her mother also had multiple JPs in the stomach, duodenum, jejunum, and colon. We then diagnosed them as having familial JPS. Moreover, germline mutation analysis of the 2 patients presented a novel pathogenic SMAD4 variant.

Contributing factors to gastric ulcer healing after endoscopic submucosal dissection including the promoting effect of rebamipide.

BACKGROUND: The healing process for artificial ulcers resulting from endoscopic submucosal dissection (ESD) for gastric cancer is not understood. AIM: To clarify factors that promote healing and the additional healing effects of rebamipide, we conducted a randomized controlled trial to compare proton pump inhibitor (PPI) and combination PPI plus rebamipide treatments. METHODS: One hundred and seventy patients with early gastric cancers that had undergone ESD were enrolled. Follow-up endoscopy was scheduled at 4-6 weeks after ESD. We assessed marginal healing and basal healing independently by endoscopic observation. Marginal healing was determined by a regenerating epithelium and/or converging folds around the periphery of the ulcer. Basal healing was declared when the ulcer was covered by white coat thinning such that basal granulation could be seen. The sizes of the artificial ulcers were divided into normal size (area <1,200 mm(2)) or large size (area ≥ 1,200 mm(2)). RESULTS: Initial ulcer size and duration after ESD were significantly correlated with both marginal and basal healing rates by univariate analysis. The marginal healing rate of antral lesions was higher than that of body lesions. Multivariate analysis showed a large-sized ulcer was the only significant predictor of delayed healing, with delayed healing defined as no observed marginal or basal healing (p < 0.0001). Subgroup analysis for the effect of rebamipide on large-sized ulcers showed a significantly higher rate of basal healing in the combination PPI and rebamipide group (p = 0.015). CONCLUSIONS: Healing in ESD-induced ulcers was dependent on the initial ulcer size. In large-sized ulcers, rebamipide promotes basal healing.

The efficacy of endoscopic triamcinolone injection for the prevention of esophageal stricture after endoscopic submucosal dissection.

BACKGROUND: Use of endoscopic submucosal dissection (ESD) for management of widespread superficial esophageal carcinomas may be complicated by the development of severe strictures, which may require serial treatment with endoscopic balloon dilatation (EBD). OBJECTIVE: The goal of this study was to determine the efficacy of endoscopic triamcinolone injection (ETI) for the prevention of stricture formation after ESD. DESIGN: Case series. SETTING: Tertiary-care referral center. PATIENTS: A total of 41 consecutive patients who had a semi-circumferential mucosal defect that arose after ESD for superficial esophageal squamous cell carcinomas were enrolled in this study. INTERVENTIONS: EBD and ETI. MAIN OUTCOME MEASUREMENTS: Incidence of stricture and frequency of required EBD. RESULTS: ETI was performed in one group of patients (study group, n = 21) but not in the other (control group, n = 20). The incidence of stricture was significantly lower in the study group (19.0%) than in the control group (75.0%; P < .001). The number of required EBDs was also lower in the study group (mean, 1.7; range, 0-15) than in the control group (mean, 6.6; range 0-20). There were no side effects or complications associated with ETI. LIMITATIONS: Nonrandomized study design and small number of patients in a single endoscopic center. CONCLUSIONS: This study suggests that ETI is safe and effective for the prevention of esophageal stricture in patients undergoing ESD for superficial esophageal squamous cell carcinomas.

Capnographic monitoring during endoscopic submucosal dissection with patients under deep sedation: a prospective, crossover trial of air and carbon dioxide insufflations.

BACKGROUND AND AIMS: The safety of carbon dioxide (CO(2)) insufflation has not been fully established for esophageal and gastric endoscopic submucosal dissection (ESD) under deep sedation, because CO(2) retention is not only caused by CO(2) insufflation but also by the sedation level and the patient's respiratory status. To clarify the clinical safety of CO(2) insufflation, we conducted a crossover trial of air and CO(2) insufflations. METHODS: A total of 60 patients with early esophageal or gastric cancers underwent ESD during which insufflation was switched from CO(2) to air or from air to CO(2); transcutaneous partial pressure CO(2) (PtcCO(2)) was monitored in all patients. We also assessed respiratory function, arterial blood gas analysis, and smoking history. RESULTS: Although significant increases in PtcCO(2) from baseline were observed, there were no significant differences in PtcCO(2) levels during CO(2) insufflation compared with levels during air insufflation in groups that received CO(2) preceding air or air preceding CO(2). All patients underwent ESD safely without adverse events, including 20 patients with subclinical respiratory dysfunction. The sedation protocol was the only significant predictor of CO(2) retention, independent of CO(2) insufflation. CONCLUSIONS: CO(2) insufflation can be used as safely as air insufflation during ESD under deep sedation.

Mucin phenotype and narrow-band imaging with magnifying endoscopy for differentiated-type mucosal gastric cancer.

BACKGROUND: Several studies have described the surface glandular structure in differentiated early gastric cancer observed by narrow-band imaging with magnifying endoscopy (NBI-ME) in two main patterns, i.e., a papillary or granular structure in an intralobular loop pattern (ILL) and a pit structure in a fine network pattern (FNP). However, it is uncertain why the NBI-ME findings of differentiated-type carcinomas are divided into two main patterns. We investigated the significance of the mucin phenotype in the morphogenetic difference between ILL and FNP. METHODS: We evaluated 120 intramucosal, well- or predominantly well-differentiated tubular adenocarcinomas. In each lesion, one area that showed the predominant pattern of microsurface structures and microvessels was selected and marked by electrocoagulation for a strict comparative study by NBI-ME and pathological investigation. NBI-ME findings were classified into three patterns: ILL, FNP, and intermediate. Mucin phenotypes were judged as gastric, intestinal, or gastrointestinal type by immunohistochemistry. RESULTS: The mucin phenotype was gastric or gastrointestinal type in 24 (92.3%) of 26 ILL lesions. Intestinal phenotype was observed in 22 (84.6%) of 26 FNP lesions. The gastrointestinal phenotype was observed in 50 (73.5%) of 68 intermediate pattern lesions. The mucin phenotype and NBI-ME results were significantly correlated (P < 0.001). CONCLUSIONS: The mucin phenotype of differentiated early gastric cancer might be involved in morphogenetic differences between the papillary and pit structures visualized by NBI-ME.

Usefulness of magnifying narrow band imaging for assessing lateral tumor extent of early gastric cancer: a case report.

Narrow band imaging with magnifying endoscopy (NBI-ME) is a novel technology that enhances vascular architecture and surface structure of the superficial mucosa of the gastric cancer. We report a case in which the lateral extent of slightly elevated tumor was clearly defined based on the presence of irregular microvessel pattern and irregular microsurface pattern using NBI-ME. This lesion was diagnosed as well-differentiated adenocarcinoma confined to the mucosa because of granular/papillary surface structure containing loop-like microvessels.

Self-limiting risk of metachronous gastric cancers after endoscopic resection.

BACKGROUND: Since endoscopic resection (ER) has been established as a treatment for early gastric cancer, metachronous multiple cancers have become a problem. It is unclear whether the risk of metachronous cancer is self-limiting or permanent. The aim of this study was to evaluate the incidence of multiple cancers after ER during a long-term follow-up study. PATIENTS AND METHODS: A total of 234 patients who received initial ER for early gastric cancers were evaluated retrospectively. ER included endoscopic mucosal resection and endoscopic submucosal dissection. Patients were followed up with endoscopy for 3.0-19.6 years (median, 5.0 years), including 40 patients surveyed for more than 10 years. Accessory cancers detected after ER, but which could be retrospectively viewed in pre-ER pictures, were evaluated in the metachronous group. RESULTS: Thirty patients (12.8%) developed 36 metachronous multiple cancers. The median interval between the discovery of metachronous cancer and the initial ER was 3.2 years; the longest interval was 9.7 years. Eight (22.2%) of the 36 metachronous cancers could be detected retrospectively in the picture record from pre-ER. The Kaplan-Meier curve of cumulative incidence of metachronous cancers stopped increasing after 10 years of follow up. CONCLUSIONS: Although the residual gastric mucosa after ER is thought to be a high-risk environment, the high risk may only be the result of occult synchronous cancers. It is probable that the high risk of metachronous cancers is not continuous after 10 years.

A primary follicular lymphoma of the duodenum treated successfully with radiation therapy.

A 48-year-old man was admitted to our hospital because of repeated episodes of epigastralgia. Endoscopy showed multiple whitish granules extending from the 2nd to 3rd portion of the duodenum. Biopsy specimens showed well circumscribed follicles with a monotonous population of predominantly small cleaved cells that were positive for CD20, CD10 and BCL2, but negative for CD5. A full staging study showed no abnormalities. The tumor was finally diagnosed according to the WHO classification as a stage I follicular lymphoma (FL), grade 1, of the duodenum and subsequently received irradiation to the involved area. After 3 years of followup, he is still in complete remission. Because FL arising in the duodenum has recently reported with increasing frequency, patients with multiple granules in the duodenum should be examined carefully.

Advanced gastric cancer and a concomitant pregnancy associated with disseminated intravascular coagulation.

Gastric cancer associated with pregnancy is extremely rare and the prognosis is generally grave. A 31-year-old Japanese women, 41 weeks pregnant, displayed disseminated intravascular coagulation (DIC), although clinical symptoms and diagnostic examinations did not indicate an obstetrical cause. She went into labor spontaneously and vaginally delivered a 3248-g normal female infant, after receiving a blood transfusion. On the day 5 postpartum, a gastroduodenal fiberscope examination indicated advanced gastric cancer. She was also diagnosed with bilateral chronic subdural hematoma and underwent an operation to allow drainage. It was not possible to treat her curatively, so she was treated conservatively for DIC. She died on day 13 postpartum. Necropsy of the iliac bone indicated bone marrow metastasis of adenocarcinoma. This is the first known case of a pregnant woman with DIC occurring as the first manifestation of advanced gastric cancer.

Prophylactic clip application does not decrease delayed bleeding after colonoscopic polypectomy.

BACKGROUND: The most common major complication of colonoscopic polypectomy is postpolypectomy hemorrhage. Although several factors have been implicated in the occurrence of hemorrhage, accurate prediction of delayed bleeding remains difficult. This randomized controlled trial evaluated the efficacy of prophylactic clip application for prevention of delayed postpolypectomy bleeding. METHODS: Postpolypectomy ulcers created by colonoscopic removal of polyps (mean size 7.8 [4.0] mm) with the endoscopic mucosal resection technique were randomly assigned to prophylactic clip placement (n = 205) or no clip (n = 208). Baseline characteristics of the patients and polyps excised were comparable between the groups. Delayed bleeding was defined as the postprocedure passage of bloody stool or massive hematochezia. The site of delayed bleeding was identified at emergent colonoscopy. RESULTS: Delayed bleeding was identified from 2 ulcers in each group from 1 to 4 days after resection (mean 2.3 days). Delayed bleeding occurred from 0.98% of ulcers in the clip group and 0.96% in the non-clip group (p > 0.9999). No patient with delayed bleeding required transfusion or surgery. CONCLUSIONS: Prophylactic clip placement did not decrease the occurrence of delayed bleeding after colonoscopic polypectomy.

What is an appropriate indication for endoscopic papillary balloon dilation?

OBJECTIVE: There are a number of views on the indication for endoscopic papillary balloon dilation (EPBD) in the management of bile duct stones. In this study, we have evaluated the efficacy and safety of EPBD compared with endoscopic sphincterotomy (EST). DESIGN: Prospective randomized trial. SETTING: One university hospital and one general hospital. PARTICIPANTS AND MAIN OUTCOME MEASURES: One hundred and forty patients were randomly allocated to EPBD or EST. Outcomes and complications were observed for a median period of 30 months. RESULTS: Both treatment approaches finally achieved similar success rates and needed similar numbers of treatment sessions for patients with stones less than 10 mm in diameter. However, for patients with stones of 10 mm or more, EPBD required a significantly greater mean number of treatment sessions than EST (2.4 vs 1.6, P < 0.01). Early complications occurred in seven EPBD (four pancreatitis, two cholangitis and one basket impaction) and eight EST (three pancreatitis, two bleeding and three cholangitis) patients. Late complications occurred in four EPBD (three recurrent bile duct stones and one cholecystitis) and six EST (three recurrent stones and three cholecystitis) patients. CONCLUSIONS: EPBD has little risk of bleeding. The technique removed small bile duct stones just as easily as did EST. These two procedures had approximately the same risk of pancreatitis and incidence of recurrent bile duct stones. Therefore, both procedures appear to be appropriate treatments for small bile duct stones. Whether or not EPBD becomes an established treatment will depend on further long-term studies.

Gastric carcinoid tumors without autoimmune gastritis in Japan: a relationship with Helicobacter pylori infection.

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.