Efficacy of Intrathecal MTX/Ara-C Combined with Systemic Chemotherapy in a Gastric Cancer Patient with Meningeal Carcinomatosis.

A 35-year-old man was diagnosed to have gastric cancer by endoscopic and histological examinations. Staging laparoscopy detected peritoneal metastasis. Systemic chemotherapy was started, but the patient complained of severe headache. Subsequently, a lumbar puncture demonstrated adenocarcinoma cells in the spinal fluid, suggesting the occurrence of meningeal carcinomatosis (MC) from gastric cancer. MC occurs only rarely in patients with gastric cancer, but the prognosis is invariably poor. However, this patient nevertheless survived for 12 months after receiving intrathecal MTX/Ara-C together with systemic chemotherapy. Therefore, the early detection of meningeal irritation sign and intrathecal chemotherapy might greatly improve the prognosis of gastric cancer patients with MC.

Morphological Characteristics of Early Gastric Neoplasms Detected After Helicobacter pylori Eradication.

BACKGROUND: Previous morphological studies indicated that the eradication of Helicobacter pylori (H. pylori) made gastric neoplasms endoscopically indistinct through the flattening and covering of tumors with a non-neoplastic epithelium (NE). AIM: To validate these alterations. METHODS: We reviewed and compared the endoscopic and histological findings of early gastric carcinomas and high-grade dysplasias resected endoscopically from H. pylori-infected and H. pylori-eradicated patients. The extent of NE covering a tumor was expressed as the histological length ratio of NE to the tumor. Tumor morphology was compared before and after therapies in patients who received H. pylori eradication treatments during the period from tumor discovery to endoscopic resection. RESULTS: NE-covered ratios were higher in the 59 tumors detected after the eradication of H. pylori than in the 152 tumors detected during the infection (median 8 vs. 0 %, respectively), whereas the frequency at which an elevated morphology and whitish discoloration of a tumor were observed was less (14 vs. 56 %, and 14 vs. 43 %, respectively). These were also independent characteristics for tumors detected after the eradication of H. pylori. Two elevated tumors showing whitish discoloration out of 16 tumors became endoscopically indistinct following H. pylori eradication treatments through the flattening of tumors and muting of the discoloration. CONCLUSION: The eradication of H. pylori promoted covering with NE, the flattening of tumors, and muting of the whitish discoloration, which may make a subset of tumors, potentially including whitish elevated neoplasms, indistinct.

Effects of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic treatment: analysis of molecular alterations by a randomised controlled trial.

BACKGROUND: Whether Helicobacter pylori eradication actually suppresses the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) remains controversial. The aims of this study were to clarify (1) the molecular markers related to carcinogenesis in intestinal metaplasia (IM) by a cross-sectional study, and (2) the changes of those markers by an open-label, randomised controlled trial (RCT) of H. pylori treatment. METHODS: First, we evaluated microsatellite instability (MSI), the methylation status at hMLH1, CDKN2A and APC genes, and immunoreactivity using the monoclonal antibody (mAb) Das-1 in IM in the background mucosa of 131 patients who underwent ER for gastric neoplasia and 22 chronic gastritis cases (control). Next, we performed an RCT to evaluate the changes of MSI between the H. pylori-eradicated (n=19) and non-eradicated patients (n=17) at 1 year among the H. pylori-positive patients. RESULTS: Microsatellite instability and mAb Das-1 reactivity showed significantly higher incidences in both the H. pylori-positive and -negative patients compared with the control group, thus suggesting that MSI and mAb Das-1 reactivity are associated with gastric neoplasia (OR=5.06 for MSI; OR=2.51 for mAb Das-1 reactivity). The RCT showed that H. pylori eradication did not provide significant reversals of any molecular alterations including MSI (the primary end point) and other methylation statuses and mAb Das-1 reactivity (secondary end points). CONCLUSIONS: H. pylori eradication did not produce significant changes in the molecular alterations related to carcinogenesis, suggesting that H. pylori treatment may not prevent the development of MGC in background mucosa with IM.

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

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

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

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

Occurrence of colon tumors in a 16-year-old Japanese boy after hematopoietic stem cell transplantation for Diamond Blackfan anemia at age of 4: a case report.

Diamond Blackfan anemia (DBA) is a congenital pure red cell aplasia mainly caused by a mutation in ribosomal protein genes. One of the proposed mechanisms for red cell aplasia in DBA is apoptosis caused by constitutive activation of tumor suppressor TP53 protein following defective ribosome biogenesis. Because of this close relationship between ribosome biogenesis and TP53 activation, patients with DBA are considered to be cancer-prone. The association between bone marrow failure and tumor susceptibility in DBA appears paradoxical. Also, the detailed information is lacking on malignancy occurring in patients with DBA. Here, we report a case of a 16-year-old Japanese boy suffering from multiple colon tumors during the follow-up after hematopoietic stem cell transplantation for DBA at the age of 4. Well differentiated tubular adenocarcinoma was detected at the rectum 12 years after the transplantation, followed by multiple tubular adenomas of low to high grade throughout the colon. Endoscopic submucosal dissection was performed for these tumors and the lesions were completely resected. These tumors did not show diffuse and strong TP53 positivity by immunohistochemistry, suggesting that TP53 mutation was not involved in the tumorigenesis as observed in conventional colorectal cancers. Microsatellite instability test and immunohistochemical examination of ß-catenin and MLH1 proteins of these tumors showed that WNT signaling or microsatellite instability was less likely to be involved in the present tumors as observed in conventional left-sided or right-sided colon cancers, respectively. To our knowledge, this is the first case report of colon tumors associated with DBA.

Do endoscopic features suggesting eosinophilic esophagitis represent histological eosinophilia?

BACKGROUND: Esophageal linear furrows, corrugated rings, and/or white exudates are often seen in patients with eosinophilic esophagitis (EoE); however, whether these are specific to EoE remains unclear. Endoscopic surveillance of these features was conducted to determine whether these represent esophageal eosinophilia, which is essential for the diagnosis of EoE. PATIENTS AND METHODS: Two thousand seven hundred and sixty-three patients were enrolled consecutively. Target biopsy was carried out when the above features were seen. Histological eosinophilia was defined as 24 or more eosinophils per high-power field (HPF). Associations between features and eosinophilia were analyzed statistically. RESULTS: Two thousand five hundred and forty-five patients completed the study. Linear furrows, corrugated rings and white exudates were seen in 24, 15 and 45 patients, respectively. These findings somewhat overlapped. Among 58 biopsied patients withany of the above features, these features represented eosinophilia in 14% (3/21), 23% (3/13), and 5% (2/43), respectively. None of the 199 patients who received biopsy for other features had eosinophilia. Two of five eosinophilia patients were diagnosed with EoE. Multiple comparisons revealed that eosinophil counts in linear furrows and corrugated rings but not white exudates were significantly greater than those in other features (12, 9, 1, and <1 eosinophils/HPF on average, respectively). CONCLUSIONS: An endoscopic feature suggesting EoE does not always represent esophageal eosinophilia and is non-specific for EoE, although it reminds endoscopists of the presence of EoE. The diagnostic utility of linear furrows or corrugated rings for esophageal eosinophilia is superior to that of white exudates.

Association between obesity and Barrett's esophagus in a Japanese population: a hospital-based, cross-sectional study.

BACKGROUND: The association between obesity and Barrett's esophagus (BE) in the Japanese population remains unclear. The prevalence of BE and its associated risk factors was examined. METHODS: A cross-sectional study of 1581 consecutive individuals who underwent upper gastrointestinal endoscopy was conducted. The prevalence of endoscopically suspected BE (ESBE) was evaluated. Obesity was evaluated by body mass index (BMI, ≥ 25 kg/m2) and waist circumference (WC) (males, ≥ 85 cm; females, ≥ 90 cm). Because endoscopic diagnosis of ultra-short ESBE (<1 cm in extent) is difficult and highly unreliable, this type of ESBE was excluded from the study. RESULTS: In proton pump inhibitor (PPI) non-users, the prevalence of ESBE ≥ 1 cm was 5.6%. In univariate analysis, male sex and reflux esophagitis (RE) were significantly associated with BE, but BMI, WC, and reflux symptoms were not. In multivariate logistic regression analysis, only RE (odds ratio [OR] = 3.48, 95% confidence interval [CI] 1.89-6.41, p < 0.0001) was an independent risk factor for BE; obesity and the other factors were not. In contrast, RE (OR 5.67, p = 0.0004) and large WC (OR 5.09, p = 0.0005) were significant risk factors for ESBE ≥ 1 cm in PPI users. Only male sex, but not obesity or the other risk factors, was associated with an increased risk of RE in patients not taking PPIs. CONCLUSIONS: RE, but not obesity, may have an independent association with the risk of ESBE in the Japanese population. Furthermore, obesity measures were not independent risks for RE. Interestingly, PPI-refractory RE and large WC were risk factors for ESBE ≥1 cm in patients taking PPIs.

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

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

Effect of age and correlation between esophageal visceral chemosensitivity and mechanosensitivity in healthy Japanese subjects.

BACKGROUND: The aim of this study was to examine the impact of age on esophageal sensation, and to determine whether esophageal mechanosensitivity and chemosensitivity are correlated in healthy Japanese subjects. METHODS: To evaluate chemosensitivity, a catheter was inserted and placed 10 cm above the upper border of the lower esophageal sphincter (LES), which was determined with an esophageal manometric catheter. After saline had been infused into the esophagus at a rate of 10 mL/min for 2 min, 0.1 N hydrochloric acid, instead of saline-without the subjects' knowledge-was infused for 10 min at the same rate. The acid perfusion sensitivity score (APSS) was assessed. To evaluate mechanosensitivity, a barostat test was performed, with a balloon being placed 10 cm above the upper border of the LES. The initial perception threshold (IPT), pain threshold (PT), and maximal pain were quantified. RESULTS: The APSS was significantly inversely correlated with age. IPT, PT, and mean maximal pain were significantly correlated with age. Body mass index, drinking, and smoking habits were not correlated with the esophageal perception threshold. The correlation of chemosensitivity and mechanosensitivity was also assessed, and the APSS was inversely correlated with IPT, PT, and maximal pain. CONCLUSIONS: The thresholds of esophageal visceral chemosensitivity and mechanosensitivity in same individuals were significantly correlated and both of these thresholds were inversely correlated with age.

The incidence of "silent" free air and aspiration pneumonia detected by CT after gastric endoscopic submucosal dissection.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is feasible as a treatment for early gastric cancer, it requires great skill to perform and may place patients at increased risk of a number of complications, including perforation and aspiration pneumonia. OBJECTIVE: To investigate the incidence of "silent" free air without endoscopic perforation and aspiration pneumonia detected by CT after ESD and risk factors for the development of these 2 conditions. DESIGN: Prospective cohort study. SETTING: Single academic center. PATIENTS: This study involved 87 patients with a total of 91 malignancies. INTERVENTION: All patients underwent chest and abdominal CT and blood biochemistry analysis before and 1 day after ESD. MAIN OUTCOME MEASUREMENTS: The incidence of silent free air and aspiration pneumonia after ESD and the related risk factors. RESULTS: Silent free air was identified in 37.3% of patients without perforation. Tumor location (the upper portion of the stomach), the presence of a damaged muscular layer during ESD, and procedure time, but not specimen size, were significantly associated with silent free air (P = .006, P = .04, P = .02, and P = .53, respectively). According to the receiver-operating characteristic analysis, the resulting cutoff value of the procedure time for silent free air was 105 minutes (67.7% sensitivity, 65.4% specificity). Only procedure time (≥ 105 minutes) was an independent predictor of silent free air development (odds ratio 3.23; 95% confidence interval, 1.21-8.64; P = .02). On the other hand, aspiration pneumonia was seen in 6.6% of patients. Silent free air and aspiration pneumonia did not affect hospitalization. LIMITATIONS: Single center and small number of patients. CONCLUSIONS: Silent free air is frequently observed after ESD, and longer procedure time (≥ 105 minutes) was an independent risk factor for silent free air. However, silent free air and aspiration pneumonia detected by CT are not associated with clinically significant complications.

Prospective randomized controlled trial to compare the effects of omeprazole and famotidine in preventing delayed bleeding and promoting ulcer healing after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are generally used to prevent delayed bleeding after endoscopic submucosal dissection (ESD) and to heal the artificial ulcers. However, it remains controversial whether PPIs or histamine-2 receptor antagonists (H(2) RAs) are more effective in preventing delayed bleeding after ESD. We prospectively compared the effects of omeprazole and famotidine in preventing delayed bleeding and promoting artificial ulcer healing after ESD. METHODS: A total of 158 patients (155 early gastric cancers and three adenomas) were randomly assigned to the PPI group (omeprazole 20 mg/day) or H(2) RA group (famotidine 40 mg/day) in a prospective randomized controlled trial. The primary end point was the incidence of hematemesis, melena, and/or a decrease in hemoglobin level of 2 g/dL or more requiring endoscopic hemostatic treatment. ESD-induced ulcer healing and changes in ulcer size were also compared at 6 weeks after ESD as a secondary end point. RESULTS: Of the 158 patients, two were excluded from analysis because they had been treated with a PPI before the present study. Accordingly, data from 77 PPI and 79 H(2) RA subjects were included for analysis. Delayed bleeding after ESD occurred in 6.5% of subjects (PPI group) and in 6.3% (H(2) RA group); there was no significant difference between the two groups. Likewise, the two groups were not significantly different with respect to ulcer stage or ulcer size reduction rate. CONCLUSIONS: Proton pump inhibitors are not superior to H(2) RAs for the prevention of delayed bleeding or the healing of artificially induced ulcers after ESD.

Endoscopic and clinical features of gastric ulcers in Japanese patients with or without Helicobacter pylori infection who were using NSAIDs or low-dose aspirin.

BACKGROUND: The endoscopic characteristics of gastric ulcers in patients who were using non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA) and were infected with Helicobacter pylori remain unclear. We elucidated the endoscopic characteristics of gastric ulcers that occurred in the presence or absence of H. pylori infection and were associated with the use of these drugs. METHODS: A total of 379 patients with active-stage gastric ulcer were divided into three groups: H. pylori-positive patients using neither NSAIDs nor LDA (control group, n = 216), H. pylori-positive or -negative patients using NSAIDs (NSAIDs group, n = 100), and H. pylori-positive or -negative patients using LDA (LDA group, n = 63). The differences among these groups in endoscopic characteristics of the ulcers (site, multiplicity, and morphology) were determined. The influence of an antacid drug, i.e., a proton pump inhibitor (PPI) or a histamine H(2) receptor antagonist (H(2)RA), was also investigated. RESULTS: The NSAIDs group, regardless of H. pylori infection status, had higher incidences of antral, multiple, and irregularly shaped ulcers. The LDA group had a higher incidence of antral ulcers in H. pylori-negative patients and, regardless of H. pylori infection status, a higher incidence of multiple ulcers. However, the incidence of irregularly shaped ulcers in the LDA group did not differ from that in the control group. Neither the concomitant use of an antacid nor the dosing period of NSAIDs affected the results. CONCLUSIONS: Our study elucidated the morphological characteristics of gastric ulcers in persons taking NSAIDs or LDA in the presence and absence of H. pylori infection. Our results may be clinically useful for inferring the causes of ulcers from their morphological characteristics.

Endoscopically treated Cronkhite-Canada syndrome associated with minute intramucosal gastric cancer: an analysis of molecular pathology.

There have been no reports of Cronkhite-Canada syndrome (CCS) associated gastric cancer resected with endoscopy because it is very difficult to identify small cancers that are candidates for endoscopic resection. We report a case of CCS with gastric cancer treated with endoscopic submucosal dissection, and we evaluate the molecular pathological analysis of malignant transformation in patients with CCS. A 74-year-old man had an advanced rectal cancer and gastrointestinal polyposis after presenting with hypoproteinemia, partial hair loss and atrophic nails as well as hyperpigmentation on the hands. He was diagnosed as having CCS. On upper endoscopy, a 7 mm discolored polyp with an irregular microvascular pattern revealed by magnified narrow-band imaging (NBI) was identified in gastric diffuse CCS polyposis. This lesion was treated with endoscopic submucosal dissection and diagnosed as a flat, elevated-type, mucosal well-differentiated tubular adenocarcinoma without lymphatic or venous infiltration, and with tumor-free margins. Microsatellite instability was detected in both the cancer and the surrounding CCS polyps. Mucin-histochemical analysis of the cancer area showed the complete intestinal type, and thus may have differentiated the CCS polyps from that of the common gastric hyperplastic polyps. This case illustrates that a clue to detecting small cancers may be to look for the discolored lesion among reddish CCS polyposis and thereafter to observe the irregular vascular pattern with NBI endoscopy. From the viewpoint of genetic alterations, patients with CCS polyps are considered to be at high risk for developing gastric cancer, and therefore careful follow-up examinations are necessary for the early detection of malignancies.

Morphological changes of colonic Dieulafoy's lesion: a case that could be retrospectively reviewed in a patient without treatment.

Colonic Dieulafoy's lesion (DL) is an unusual cause of lower gastrointestinal hemorrhage. We herein report the first case of DL in which the morphological changes could be retrospectively reviewed by endoscopy. A 61-year-old female, who was taking anti-thrombotics including low-dose aspirin, was admitted to our department with acute onset massive flesh bleeding per rectum. Although an emergent colonoscopy was performed, no bleeding source could be detected other than multiple diverticula in the ascending colon. A second colonoscopy after 1½ months revealed a small reddish polypoid lesion at the opposite site of the ileocecal valve, but showed no active bleeding points. After another 2 weeks, she complained of rectal bleeding again. She immediately underwent a third colonoscopy that showed pulsatile bleeding from normal overlying mucosa without a mucosal defect at the same site at the opposite site of the ileocecal valve, consistent with the DL. The lesion was successfully managed by argon plasma coagulation therapy. When reviewing initial colonoscopic images retrospectively, a telangiectasia was observed at the same site. This retrospective evaluation by endoscopy showed that the shape of the DL is changeable over a short period. It has been reported that aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of diverticular bleeding. Therefore, endoscopists should pay close attention not only to diverticular bleeding, but also to the presence of DL when performing colonoscopy on patients with rectal bleeding and taking aspirin or NSAIDs.