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Background and aim Few studies have reported on a national, population-based endoscopic retrograde cholangiopancreatography (ERCP) database. Hence, in 2015, we established a multicenter ERCP database registry, the Japan Endoscopic Database (JED) Project in preparation for a nationwide endoscopic database. The objective the present study was to evaluate this registry before the establishment of a nationwide endoscopic database. Methods From 1 January 2015 to 31 March 2017, we collected and analyzed the ERCP data of all patients who underwent ERCP in four participating centers in the JED Project based on the JED protocol. Results Four centers carried out 4104 ERCP on 2173 patients. Data entry of ERCP information (age, 100%; gender, 100%; American Society of Anesthesiologists Physical Status Classification System, 74.5%; scope, 92.7%; time to ERCP, 100%; antithrombotic drug information, 55.0%; primary selective common bile duct [CBD] cannulation methods, 73.0%; number of attempts at primary selective CBD cannulation, 67.6%; overall selective CBD cannulation methods, 68.9%; ERCP procedure time, 66.3%; fluoroscopy time, 65.1%; adverse events, 74.9%; serum amylase levels 1 day post-ERCP, 36.5%) was accurately extracted from the four centers. Success rate of CBD cannulation by level of ERCP difficulty was 98.5%, 99.0%, and 96.4% in grades 1, 2, and 3, respectively. Complication rate by overall selective CBD cannulation method was 5.6%, 7.6%, and 10.5% in the contrast-assisted technique, guidewire-assisted technique, and cross-over method, respectively. Conclusion Data from this evaluation of the JED Project, a multicenter ERCP database registry, suggest the feasibility of establishing a nationwide ERCP database and its challenges.

The aim was to investigate the current status of esophageal endoscopy, including the evaluation of smoking and alcohol consumption, in Japan. A total of 47,441 patients who underwent 69,748 sessions of esophageal endoscopy were registered in the Japan Endoscopy Database between January 2015 and March 2017. The study variables were as follows: (1) methods for monitoring the esophagus and the time required for monitoring and (2) the status of smoking and alcohol consumption in patients with esophageal cancer and head and neck cancer. Image-enhanced endoscopy was performed in 10.6%, Lugol chromoendoscopy in 4.1%, and magnifying endoscopy in 3.2%. The mean time required for gastrointestinal endoscopy was 10 min 58 s. The mean examination times in patients with or without monitoring of the head and neck were 10 min 51 s and 11 min 13 s, respectively. In 57.0% of the patients with esophageal cancer, the head and neck were monitored at the time of gastrointestinal endoscopy. The proportion of current smokers (esophageal cancer: 16.8–4.7%; head and neck cancer: 24.3–9.3%) and addicted drinkers (esophageal cancer: 52.3–40.8%; head and neck cancer: 50.2–47.3%) were lower at the second or subsequent endoscopy than at the initial endoscopy. The new strategy for esophageal endoscopy has led to an evolutionary change in Japan. The patients with esophageal cancer and head and neck cancer who underwent a second or subsequent endoscopy had lower incidences of smoking and alcohol consumption, although the incidences remained high.

Introduction Solitary Peutz-Jeghers-type polyps of the stomach are extremely rare. They are defined as unique polyps that are not associated with Peutz-Jeghers syndrome (PJS). Presentation of Case A 37-year-old woman presented at our hospital with anemia and epigastric discomfort. Esophagogastroduodenoscopy to determine the cause of anemia revealed a 5 × 6-cm pedunculated polypoid tumor at the greater curvature of the upper gastric body. Pathological examination of a biopsy specimen confirmed a Group 1 hyperplastic polyp. Computed tomography revealed neither lymph node swelling nor distant metastasis. A malignant component of the polypoid tumor was difficult to deny because of its size. The patient underwent local resection of the stomach. Her postoperative course was uneventful. A pathological examination of the surgical specimen revealed a Peutz-Jeghers-type, hamartomatous polyp containing an enlarged crypt with hyperplastic foveolar epithelium and smooth muscle proliferating into the lamina propria. No atypical cells were found in the overlying epithelium. Based on these findings, we performed colonoscopy and capsule endoscopy of the intestine. No polyps were found in the intestine or colon. She had no family history of any type of tumor and no mucocutaneous pigmentation. Discussion There were only 10 reports of solitary gastric Peutz-Jeghers polyps published to date. Although most of them did not have atypical cells, one case has proliferative component. A few reports have described relationship with malignant tumor. Conclusion Solitary gastric PJ-type polyps are rare. Careful follow-up should be recommended and further studies are needed to evaluate cancer risk of solitary gastric PJ-type polyps.

Aim: Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation. Methods: In this phase II, multicenter, double-blind, dose–response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy. Results: The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P

The results of a phase III, placebo-controlled study demonstrated that endoscopic direct spraying of L: -menthol onto the gastric mucosa effectively suppressed gastric peristalsis in the study patients. The aim of the study reported here was to determine whether the anti-peristaltic effect of an L: -menthol preparation facilitates endoscopic examinations in a clinical setting.This was a multicenter, open-label, single-arm trial in which the study cohort comprised patients in whom L: -menthol was likely to be used to facilitate endoscopic examination in clinical settings. The primary outcome was the proportion of subjects with no peristalsis (Grade 1) after treatment and at the end of endoscopy (defined as the complete suppression of gastric peristalsis). This variable was assessed according to the level of anti-Helicobacter pylori immunoglobulin G (IgG) antibody, pepsinogen test results, whether sedation was performed, and whether subjects were considered unsuitable for the use of conventional antispasmodics.Of the 119 enrolled subjects, data from 112 were included in the primary efficacy analysis. Gastric peristalsis was completely suppressed in 37.5% of the patients [42/112 patients; 95% confidence interval (CI) 28.5-47.1]. Subgroup analyses revealed that the rate of peristalsis suppression was significantly higher in patients with elevated levels of anti-H. pylori IgG antibody (26/44, 59.1%; 95% CI 43.2-73.7); P 0.001] and positive pepsinogen test results (21/35, 65.6%; 95% CI 46.8-81.4; P 0.001]. There was no significant difference according to sedation (17/52, 32.7%; 95% CI 20.3-47.1; P = 0.434) or whether subjects were considered unsuitable for use of conventional antispasmodic agents (14/28, 50.0%; 95% CI 30.6-69.4; P = 0.12].These findings are comparable to those of the phase III placebo-controlled study and provide further evidence that endoscopic direct spraying of L: -menthol effectively suppresses gastric peristalsis during upper gastrointestinal endoscopy.

GI peristalsis during GI endoscopy commonly requires intravenous or intramuscular injection of antispasmodic agents, which sometimes cause unexpected adverse reactions.Our ultimate goal was to evaluate whether the antiperistaltic effect of L-menthol-based preparations facilitates endoscopic examinations in a clinical setting.Multicenter, randomized, double-blind, placebo-controlled study.Six Japanese referral centers.A total of 87 patients scheduled to undergo upper GI endoscopy were randomly assigned to receive 160 mg of L-menthol (n=45) or placebo (n=42). Both treatments were sprayed endoscopically on the gastric mucosa. The degree of gastric peristalsis was assessed by an independent committee.The proportion of subjects with no peristalsis 90 to 135 seconds after administration and at the end of the endoscopic examination (complete suppression of gastric peristalsis). Other outcomes were the proportion of subjects with no or mild peristalsis (adequate suppression of gastric peristalsis) and the ease of intragastric observation as evaluated by the endoscopist who performed the procedure.Gastric peristalsis was completely suppressed in 35.6% (21.9, 51.2) of the L-menthol group compared with only 7.1% (1.5, 19.5) of the placebo group (P.001). In the L-menthol group, 77.8% (62.9, 88.8) (35/45 subjects) of the subjects had no or mild peristalsis at the completion of endoscopy. Minor peristalsis interfered with intragastric examination in only 1 of these 35 patients (2.9%). The incidence of adverse events did not differ significantly between the groups (P=.512).Small sample size.During upper GI endoscopy, L-menthol sprayed on the gastric mucosa significantly suppresses peristalsis with minimal adverse drug reactions compared with placebo. (NCT00742599.).

Background The main symptom of postoperative ileus (POI) is an intestinal motility disorder in which monocytes/macrophages and neutrophils play crucial roles. Prokinetic 5-hydroxytryptamine 4 receptor (5-HT 4 R) agonists and dopamine receptor antagonists are potential therapeutic agents for directly ameliorating the motility disorder associated with POI. Aim To determine the effects of the 5-HT 4 R agonists mosapride citrate (MOS) and CJ-033466 on intestinal smooth muscle contractility relative to immune reactions after POI. Methods Intestinal manipulation (IM) was applied to the rat distal ileum. Both MOS (0.3 and 1 mg/kg, s.c.) and CJ-033466 (1 mg/kg, s.c.) were administered to the animals before and after IM. At 24 h after IM, isolated intestinal smooth muscle contractile activity in vitro, gastrointestinal transit in vivo, inflammatory mediator expression and leucocyte infiltration were measured. Results After IM, ileal circular muscle contractility in vitro and gastrointestinal transit in vivo were reduced and the number of macrophages and neutrophils increased in the inflamed muscle layer, resulting in the induction of inflammatory mediators such as interleukin 1 β (IL-1β), IL-6, tumour necrosis factor α (TNFα), monocyte chemoattractant protein 1 (MCP-1) and inducible nitric oxide synthase (iNOS). Both MOS and CJ-033466 significantly attenuated not only the intestinal motility dysfunction but also the leucocyte infiltration and inflammatory mediator expression after IM. The autonomic ganglionic blocker hexamethonium (1 mg/kg, i.p.) and the α7-nicotinic acetylcholine receptor (α7nAChR) antagonist methyl lycaconitine citrate (0.087 mg/kg, i.p.) blocked MOS-mediated ameliorative actions. Immunohistochemically, α7nAChR is expressed by monocytes/macrophages but not by neutrophils in the inflamed intestine. Conclusion Stimulating the 5-HT 4 R accelerates acetyl choline (ACh) release from cholinergic myenteric neurons, which subsequently activates α7nAChR on activated monocytes/macrophages to inhibit their inflammatory reactions in the muscle layer. In addition to their gastroprokinetic action, 5-HT 4 R agonists might serve as novel therapeutic agents for POI characterised by anti-inflammatory potency.

In an attempt to improve survival of patients with locally advanced esophageal cancer, chemoradiotherapy consisting of cisplatin, 5-fluorouracil (5-FU), and irradiation has recently been used. For such patients, concurrent chemoradiotherapy using docetaxel in combination with cisplatin and 5-FU has been introduced and is under evaluation. We herein report an esophageal cancer patient with concomitant distant lymph node metastasis in whom a complete response was achieved by chemoradiation therapy. A 46-year-old man was diagnosed as having stage IV A esophageal cancer with synchronous bulky metastasis in the celiac lymph node, and concurrent chemoradiotherapy was started. Chemotherapy consisting of docetaxel (30 mg/m2 on days 1, 8), cisplatin (60 mg/m2 on day 1), and 5-FU (200 mg/m2/day, continuous infusion on days 1–14) was performed for 2 cycles. At the same time, irradiation therapy (1.8 Gy/day on 1–5 days every week for 6 weeks) was employed for both local and metastatic lesions. Although the patient experienced severe hematological toxicity throughout the course, chemoradiotherapy resulted in complete regression of both local and metastatic disease. Subsequently, he was followed as an outpatient without any maintenance therapy, and he has been free of disease for 38 months after completion of the combination therapy. Thus, concurrent chemoradiotherapy may be effective for esophageal cancer, even with visceral metastasis.

This retrospective study was conducted to compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus. Between June 2000 and May 2005, 82 consecutive patients were selected for this study in which 33 were treated with chemoradiotherapy and 49 with surgery. The patients in the chemoradiotherapy (CRT) group received 2-4 cycles of 5-fluorouracil (1000 mg/m(2)/day, day 1-4, continuous) combined with cisplatin (75 mg/m(2), day 1, bolus) plus 50.4 Gy of radiation, while those in the surgery group were treated by an esophagectomy with radical node dissection. Eighteen surgical patients received postoperative chemotherapy. The baseline clinical TNM stage was similar between the two groups. With a median follow-up period of 36 months (range: 23-84 months) with 47 survivors (57%), the 3-year overall survival rates (P = 0.22) and disease-free survival rates (P = 0.16) were 48% and 44% in the chemoradiotherapy group versus 65% and 59% in the surgery group, and lacked statistical significance. This non-randomized study on patients with resectable squamous cell carcinoma of the esophagus showed that chemoradiotherapy could result in survival comparable with conventional surgery in spite of selection bias of patients. There is a trend toward improved survival with surgery versus definitive CRT.

Background Endoscopic submucosal dissection is a novel endoluminal technique that enables resection of early stage gastrointestinal malignancies in an en bloc fashion. Aim To assess whether preceding endoscopic submucosal dissection affected the prognoses of patients who underwent additional gastrectomy with lymph node dissection due to suspicion of nodal metastasis from endoscopic submucosal dissection specimens. Patients and methods Thirty-one patients with early gastric cancer who underwent gastrectomy after endoscopic submucosal dissection were retrospectively investigated in terms of their survival and tumour recurrence. Additional gastrectomy was performed when histology of the endoscopic submucosal dissection specimens revealed that the tumours did not meet the criteria for node-negative cancers. Results Twenty-three (74%) and eight (26%) patients had undergone endoscopic submucosal dissection previously due to clinical diagnoses of node-negative cancers and possible node-positive cancers, respectively. Histology of the resected stomachs and lymph nodes revealed residual carcinoma of the stomach in two (6.5%) patients and nodal metastases in four (13%) patients. All patients remain alive without recurrence (median follow-up, 3.4 years; range, 0.6–5.2 years). Conclusions Based on the histology of endoscopic submucosal dissection specimens, preceding endoscopic submucosal dissection itself had no negative influence on a patient's prognosis when additional gastrectomy was performed. It may be permissible to resect some early gastric cancers by endoscopic submucosal dissection as a first step to prevent unnecessary gastrectomy, if technically resectable.

To detect early esophageal cancer effectively, it is important to select high-risk groups. Because we often see early esophageal cancer after gastrectomy for gastric cancer, we investigated 11 early esophageal cancers treated endoscopically in 7 patients who had undergone gastrectomy for gastric cancer. Their average age was 70.8 ± 5.2 years. Median interval between previous gastrectomy and the diagnosis of esophageal cancer was 10 years. Endoscopic examination revealed mild bile reflux into the remnant stomach and esophagitis, but there was no case of Barrett's esophagus. Histological types were all squamous cell carcinoma. Although it has been reported that cancer development is most frequent in the lower esophagus after gastrectomy, we noticed that the majority of these were located in the middle thoracic esophagus (6/11, 55%), similar to general esophageal cancer. As all cases were detected by a regular checkup, it is important to follow up patients after gastrectomy for gastric cancer.

In parathyroidectomy, it has been recognized that a shift to a minimally invasive procedure may be accompanied by a possibility of missing thyroid pathology. However, only a few findings concerning preoperative thyroid evaluation have been reported. We investigated the prevalence of concomitant thyroid pathology by preoperative neck ultrasonography (US) in patients with primary hyperparathyroidism. There were 85 patients (66 women, 19 men; mean age 57 years) in the study group. The mean preoperative calcium level was 11.2mg/dL, and the mean intact parathyroid hormone level was 206 pg/mL. All patients underwent neck US following fine-needle aspiration biopsy (FNAB). Of the 85 patients, 21 (24.7%) had thyroid nodules. Among 21 patients with thyroid nodules, 9 (10.6%) had malignant thyroid tumors, while 12 (14.1%) patients had benign thyroid nodules including multinodular goiter. Of the 9 patients with malignant thyroid nodules, 4 had papillary carcinomas with lymph node metastases. The prevalence of thyroid disease associated with hyperparathyroidism is high, and evaluation of the thyroid pathology by US enables the shift from bilateral neck exploration to the minimally invasive parathyroid surgery.

Background Pylorus-preserving gastrectomy (PPG) with extensive lymph node dissection is useful for treatment of early gastric cancer with preservation of function. This technique could be improved by using laparoscopy-assisted gastrectomy. Study design Between September 2000 and September 2004, 109 patients with T1 gastric cancer underwent surgical treatment; 72 underwent laparoscopy-assisted PPG (LAPPG) and 37 underwent conventional PPG (CPPG). Total numbers of dissected lymph nodes, retrieval at each lymph node station, intraoperative blood loss, and operation times were used as measures of the quality of lymph node dissection to compare the procedures. Continuous data are summarized as mean ± SE. Results Operation times with the LAPPG procedure (279 ± 6 minutes) were significantly, but only 20 minutes, longer than with CPPG (259 ± 8 minutes) (p = 0.047), although estimated blood loss for LAPPG patients (153 ± 13 mL) was not significantly different for those undergoing CPPG (184 ± 13 mL, p=0.13). Mean total number of dissected lymph nodes was 32.3 ± 1.6 in the LAPPG group and 28.5 ± 2.2 in the CPPG group (p = 0.16). There was no significant difference in the number of lymph nodes retrieved for any of the nodal stations between the LAPPG and CPPG procedures. Conclusions Clinical outcomes of surgical treatment were comparable for gastric cancer patients who underwent LAPPG and those treated with CPPG in terms of station-dependent lymph node dissection and estimated blood loss.

Background and Aim: Intraluminally administered peppermint oil (PO) is reportedly a safe and useful antispasmodic for gastroscopy, colonoscopy and double-contrast barium enema. The aim of this study was to examine the efficacy of oral PO for double-contrast barium meal examination (DCBM) without other antispasmodics. Methods: Two hundred and five randomly chosen subjects (PO group) and 215 sex- and age-matched controls were enrolled. All participants underwent DCBM. The PO group was orally administered PO and a barium suspension mixture at the start of DCBM. Radiographs were blindly evaluated for spasm and overlapping with barium-filled duodenal loops (scored 0–3, indicating none to severe). The quality of barium coating of the mucosa and overall diagnostic quality (scored 0–3, indicating not acceptable to excellent) were also evaluated. Results: There was no significant difference in subject acceptance between PO group and controls, and no adverse effects in either group. Scores for spasm at the esophagus, lower stomach and duodenal bulb were significantly lower in the PO than in the control group (P

Background Laparoscopic surgery of the gastrointestinal tract involves a reduced immune response compared with open surgery. The aim of this study was to assess manual handling of the gut in open procedures as the principal cause of the enhanced immune response. Methods Eighteen Landrace pigs underwent gastrectomy by three different methods: conventional open wound with bowel manipulation, laparoscopically assisted gastrectomy, and gastrectomy without manipulation using a combination of open wound and laparoscopic surgical devices. Local inflammatory changes were assessed by ascites formation, intestinal adhesion development and intestinal inflammatory gene expression. Associated systemic inflammatory changes were determined by measuring portal and systemic plasma endotoxin levels, plasma inflammatory cytokine levels, liver inflammatory gene expression and transaminase levels. Results Significantly more postoperative intra-abdominal fluid and adhesions were seen in the open group. The expression of inflammatory cytokines was significantly greater in the intestine and liver in the open group. Portal and systemic levels of endotoxin, inflammatory cytokines and transaminases were also higher. Conclusion Manual handling of organs during gastrectomy is an important contributor to the molecular and humoral inflammatory response to surgery, supporting the use of minimally invasive techniques in gastrointestinal surgery.

Pylorus-preserving gastrectomy (PPG) has been accepted as a function-preserving procedure for early gastric cancer for the prevention of postgastrectomy syndrome. In general, PPG procedures have not included suprapyloric lymph node dissection to preserve the pyloric branch of the vagal nerve and the right gastric artery. The aim of this article is to describe procedures for PPG. The technique of laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) is also introduced because PPG is an ideal application for laparoscopic surgery. Between September 2000 and September 2004, we performed 37 cases of conventional PPG and further 73 cases of LAPPG. In these patients, PPG including complete lymph node dissection around the remnant pyloric cuff was performed. For this purpose, it is recommended that the blood flow to the pyloric cuff be maintained by preserving the infrapyloric artery. All the patients showed good postoperative recovery, and no intraoperative or postoperative major complications were observed. No sign of recurrence was found in these 110 patients, and none of them demonstrated dumping syndrome. The procedures of both PPG and LAPPG are technically feasible and have an important role in the surgical management of early gastric cancer in terms of better quality of postoperative life, even with lymphadenectomy including combined suprapyloric lymph node dissection and right gastric artery division.

Mongolian gerbils infected with Helicobacter pylori (H. pylori ) develop heterotopic proliferative glands (HPGs) in the glandular stomach submucosa. To investigate the effects of H. pylori eradication on cell turnover in HPGs, three antibiotics, lansoprazole, amoxicillin and clarithromycin, were administered at 50 or 75 weeks after inoculation of H. pylori, and the stomachs were excised for histological examination at 1, 2, 4, 8 or 25 weeks thereafter. The HPGs were classified into gastric type (G-type) and others (GI + I-type), which included both pure intestinal (I-type) and gastric-and-intestinal mixed type (GI-type). Apoptosis and cell proliferation were evaluated by means of TUNEL assay and BrdU labeling, respectively. At 8 weeks post-eradication, apoptotic indices were significantly increased in the eradication group (G-type: 2.5%; GI + I-type: 7.2%) compared to the non-eradication group (G-type: 0.6%; GI + I-type: 2.1%: P < 0.01), while BrdU labeling indices were significantly decreased (G-type: 1.9%; GI + I-type: 6.8% as compared with 4.3% and 13.2%, respectively, P < 0.01 for both). At 25 weeks, the apoptotic indices were similarly higher [G-type: 0.4 (eradication group) vs. 0.2% (non-eradication group); GI + I-type: 5.8 vs. 1.1%, both P < 0.01], and the BrdU labeling indices (G-type: 0.8 vs. 2.2%, P < 0.01; GI + I-type: 5.1 vs. 11%, P < 0.05) continued to be lower in HPGs. Furthermore, there were highly significant reductions in the areas of HPGs at 8 and 25 weeks post-eradication. These findings demonstrated that eradication results in apoptosis and reduction of proliferation of HPGs in H. pylori-infected gerbils, these lesions thus being apparently reversible through regulation of cell kinetics.

The goal of this study was to elucidate whether beta-catenin gene mutations might contribute to glandular stomach carcinogenesis in Helicobacter pylori (H.pylori)-infected Mongolian gerbils. Firstly, exon 3 of gerbil beta-catenin cDNA, a mutation hot spot, was cloned and sequenced and found to have 89.3% homology with the human form and 95.5% with the rat and mouse forms. Peptide sequence in this region was shown to be 100% conserved in these mammals. Then, 45 stomach adenocarcinomas induced with N-methyl-N-nitrosourea (MNU) plus H. pylori infection and 7 induced with MNU alone were examined for beta-catenin expression by immunohistochemistry and for DNA mutations using a combination of microdissection and PCR-single strand conformation polymorphism analysis. One gastric cancer in the MNU + H. pylori group (2.2%) displayed nuclear (N) beta-catenin localization, 3 (6.7%) showed cytoplasmic (C) distribution in local regions, and 41 (91.1%) demonstrated cell membrane (M) localization. Tumors induced by MNU alone showed only membranous beta-catenin localization (7/7). Analysis of exon 3 of the beta-catenin gene dem-onstrated all tumors with membrane or cytoplasmic staining as well as surrounding normal mucosa (S) to feature wild-type beta-catenin. In contrast, the lesion with nuclear staining had a missense mutation at codon 34 [GAC (Gly) --> GAA (Glu)] in exon 3 (1/1 = 100%, N vs. M, P < 0.05; and N vs. S, P < 0.05). In conclusion, these results suggest that beta-catenin may not be a frequent target for mutation in stomach carcinogenesis in MNU + H. pylori-treated gerbils.

Many reports on the diagnostic efficacy of the [13C] urea breath test ([13C] UBT) for the detection of Helicobacter pylori in the residual stomach have shown negative results. We previously reported on the utility of [13C] UBT and conducted an evaluation to establish a standardized protocol with a shorter sampling time for [13C] UBT in partial gastrectomy patients. Sixty-two patients who had undergone partial gastrectomy were included. The [13C] UBT protocol included ingestion of 100 mg [13C] urea, use of mouthwash, and the body in a horizontal position on the left side. The sensitivity of [13C] UBT was 95.7%. Thirty minutes and a cutoff of 2.0 per thousand were found to be optimal for the test, with the body position horizontal on the left side. In the present protocol [13C] UBT appears to be a reliable and convenient tool with the same accuracy rate as other routine tests in patients with a remnant stomach.

We report a case of gastric outlet stenosis successfully diagnosed as an antral stenosis of the stomach in an 80-year-old male. Severe stenosis can be very difficult to diagnose and treat because it may be difficult to visualize the gastrointestinal tract in the area distal to the stenosis. In the present case, it had not been possible to view the area distal to the stenosis by endoscope using hyoscine-N-butylbromide (Buscopan). Peppermint oil solution is clinically inert but can inhibit gastrointestinal motility. In a recent double-blind, double-dummy controlled trial we showed that intraluminally administered peppermint oil solution was a more effective and safer antispasmodic agent than Buscopan. In the present case, where there was severe antral stenosis of the stomach, use of peppermint oil solution as an antispasmodic enabled us for the first time to successfully extend the tip of the endoscope to the duodenal bulbs in the area distal to the stenosis.

Background The mode of recurrence after esophagectomy for esophageal cancer has seldom been studied in detail from autopsy findings. Study design We reviewed the autopsy findings in 43 curatively resected cases of esophageal cancer between 1976 and 1997 at a single institution. Results Recurrent or residual esophageal cancer was identified in 27 of the 43 patients (62.8%) at autopsy. Local recurrence, lymph node metastases, hematogenous metastases, and serosal carcinomatosis were observed in 11 (25.6%), 18 (41.9%), 17 (39.5%), and 11 patients (25.6%), respectively. Metastases to the thoracic, abdominal, and cervical nodes were observed in 37.2%, 16.3%, and 11.6% of the cases at autopsy, respectively. The pulmonary hilar nodes were most frequently involved (25.6%). The frequency of local recurrence was significantly lower in cases after curative subtotal esophagectomy with two- or three-field dissection (19.4%) than in cases after lower esophagectomy (66.7%) (p = 0.032). The frequency of hematogenous metastases after curative esophagectomy after preoperative radiotherapy was significantly lower in responders (Grades 2 to 3) than in nonresponders (Grades 0 to 1) (p = 0.035). Conclusions This study showed the characteristics of recurrence after esophagectomy for esophageal cancer. Despite esophagectomy with lymph node dissection, the frequency of each mode of recurrence was remarkably high. Anatomic difficulty of complete removal of lymph nodes by surgical procedures was suggested. Hematogenous metastases and serosal carcinomatosis were beyond surgical resection. More effective multimodal therapy will be required to improve survival of esophageal cancer patients.

Histologic examination lacks the sensitivity to detect micrometastases in gastric cancer lymph nodes. In the present study, we applied a real-time RT-PCR approach to the quantitative detection of micrometastases in gastric cancer lymph nodes and compared diagnostic power with routine histology and immunohistochemistry. We studied 392 lymph nodes from 21 gastric cancer patients who underwent curative surgery. Real-time quantitative RT-PCR was performed on a LightCycler instrument using a hybridization probe for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK20) as marker genes. Immunohistochemistry with antibodies to wide-keratin was also performed in the lymph nodes to compare the sensitivity and specificity. Median (average) values of CEA mRNA in lymph nodes in patients with histology+, immunohistochemistry+/histology−, immunohistochemistry−/histology− and negative control results were 4,600 (16,000), 200 (400), 0 (9.8) and 0 (0.6), respectively. There were some false-negative results with simple CEA and CK20 real-time RT-PCR due to the presence of low gene-expressing gastric cancers as revealed by CEA and CK20 immunohistochemistry. CEA in combination with CK20 (duplex) real-time RT-PCR partially covered this weakness. Consequently, all 71 histology+ lymph nodes were positive for duplex real-time RT-PCR as well as wide-keratin immunohistochemistry. Positivity rates by histology, wide-keratin immunohistochemistry and duplex real-time RT-PCR were 18.0% (71/392), 20.9% (82/392) and 25.8% (101/392), respectively. In 2 of 8 patients with pT1N0, positive lymph nodes were observed by real-time RT-PCR but not by immunohistochemistry. These results indicate that duplex quantitative real-time RT-PCR is the most sensitive method for detecting micrometastases and useful for evaluating the prognostic significance of lymph node micrometastasis in gastric cancer patients. © 2003 Wiley-Liss, Inc.

Helicobacter pylori (H. pylori) is now well known to be associated with stomach cancer, with infection during childhood rather than as an adult considered to be more important for carcinogenesis. To evaluate the difference in susceptibility to stomach carcinogenesis in relation to age of acquisition of H. pylori infection, we designed an experiment involving inoculation of H. pylori ATCC43504 followed by N‐methyl‐N‐nitrosourea (MNU) treatment at different ages. Four‐week‐ old male Mongolian gerbils (MGs) were divided into twelve groups. H. pylori was inoculated at 4, 18 and 32 weeks of age, as representatives of early, middle and late infection, respectively. Two weeks later, the animals were treated with MNU. Groups without H. pylori and/or MNU were included as controls. The incidences of adenocarcinomas at 52 weeks after the inoculation in the early (H. pylori+MNU), middle (H. pylori+MNU), and late (H. pylori+MNU) group were 60% (12/ 20), 18.4% (2/11), and 10% (2/20), respectively. The corresponding figures were 14.8% (4/27), 0% (0/11), and 0% (0/21) in the MNU‐alone groups. A higher titer of serum IgG for H. pylori and higher gastrin level were seen in the early‐infected compared to the middle and the late groups (P

Helicobacter pylori (Hp) infection and high-salt diet administration are both considered to be important factors in gastric carcinogenesis in man. To investigate the interaction of these two factors on gastric carcinogenesis, an experimental study of the carcinogenesis model was performed. Mongolian gerbils were treated with 20 ppm of N-methyl-N-nitrosourea (MNU) in their drinking water for alternate weeks for a total of 5 weeks' exposure (groups 1, 2, 3 and 4) or were maintained as controls (groups 5, 6, 7 and 8). At week 11, the animals were inoculated with Hp (groups 1, 2, 5 and 6) or the vehicle alone (groups 3, 4, 7 and 8), and after week 12, animals were fed a 10% high salt diet (groups 1, 3, 5 and 7) or the control diet (groups 2, 4, 6 and 8). At week 50, the incidence of adenocarcinomas in group 1 (32.1%, 6 well-differentiated, 2 poorly-differentiated adenocarcinomas, and one signet-ring cell carcinoma) was significantly higher than in groups 3 (0%) (P < 0.005) and 4 (0%) (P < 0.01). The incidence of adenocarcinomas in group 2 (11.8%, one well-differentiated adenocarcinoma, and one signet-ring cell carcinoma) was also higher than in groups 3 and 4. A high-salt diet enhanced the effects of Hp infection on gastric carcinogenesis, and these two factors acted synergistically to promote the development of stomach cancers. Moreover, Hp infection promoted gastric carcinomas more than the high-salt diet.

Helicobacter pylori (Hp) infection is an important factor in human gastric disorders. Mongolian gerbils can be easily infected with Hp and represent excellent experimental models to clarify the role of Hp in chronic active gastritis, peptic ulcers, intestinal metaplasia, and gastric carcinoma. We have proved the enhancing effects of Hp infection on all histological types of gastric cancers in Mongolian gerbils exposed to chemical carcinogens. Heterotopic proliferative glands (HPGs) also frequently develop with Hp infection in the glandular stomach of infected gerbils, with a slightly dysplastic change of constituent cells. Distinguishing reversible inflammatory lesions from true neoplasms upon eradication is necessary for further biological or histochemical investigations using this model. We employed an experimental model of long‐term Hp infection and eradication in gerbils. HPGs finally developed with a phenotypic shift of intestinalization with Paneth cells. After eradication, HPGs were obviously reduced, and gastric lesions in mucosa also improved with few remnants of the former injury. This shows that reversible HPGs are frequently induced solely by Hp infection in this annual species, and are related to severe gastritis, rather than being malignant in character. Thus, distinguishing reversible lesions from true neoplasms is necessary to investigate the relationship of Hp infection and gastric carcinogenesis in this animal model.

Endotoxins (lipopolysaccharides, LPSs) are potent bacterial poisons, and they are always present in the intestine in considerable numbers. Stress, such that as a resulting from multiple injuries, burns, hypovolemia, hypoxia, intestinal ischemia, and surgery can lead to a breakdown of the gut barrier, allowing endotoxins to enter the systemic circulation via translocation. However, estimating the biological activity of translocated circulating endotoxins and identification of the mechanisms regulating their biological activities remain complex problems. CD14 has been found to exist as a soluble protein in the serum and as a glycosylphosphatidylinositol (GPI)-anchored protein of myeloid lineage cells. It plays key roles in both LPS-induced activation and in LPS internalization by cells. In this article, we outline: (i) the biological activity of circulating endotoxin; and (ii) the role of membrane and/or soluble CD14 regulating the bioactivity of circulating endotoxin in a human model of postoperative endotoxemia.

We examined the contribution of nitric oxide (NO) to the effect of ischemic preconditioning (IP) on renal function and the hemodynamics in ischemia-reperfusion (I/R) mediated kidney injury. IP was performed by using 4 minutes of ischemia followed by a 30-minute reperfusion interval. I/R treatment consisted of a 30-minute ischemia and 60-minute reperfusion interval. We measured the glomerular filtration rate (GFR), the fractional excretion of sodium (FE Na ), and the renal blood flow (RBF) in IP+I/R and I/R kidneys. Rats were pretreated with NaCl, N G -nitro-L-arginine methyl ester (L-NAME), or L-arginine. We found that IP significantly improved GFR and FE Na as compared with I/R treatment; however, this effect was completely abolished by L-NAME injection and enhanced by L-arginine treatment. L-NAME treatment significantly diminished RBF but did not alter nitrite/nitrate excretion. Furthermore, we found that IP alone does not lead to inducible NO synthase protein expression whereas I/R or IP+I/R treatment clearly did. Moreover, we observed an increased heme oxygenase-1 expression in IP+I/R kidneys as compared with I/R treated ones. Our results clearly showed that IP pretreatment protects kidneys from I/R mediated tissue injury and that these effects were partially mediated by NO. (J Lab Clin Med 2001;138:50-8)

Several studies have demonstrated that telomerase is activated and telomere length is altered in various types of tumors. In this study, we investigated telomerase activities and telomere length in 21 thyroid tumors. Telomerase activity was detected in 11 of 12 thyroid cancers and three of nine follicular adenomas. The mean telomere lengths in the cancers tissue and follicular adenomas were lower than in the respective background tissues, the differences being significant (P=0.0055 and P

BACKGROUND Neoadjuvant and postoperative chemotherapies have been widely employed for the treatment of patients with gastric carcinoma. However, to the authors' knowledge there have been no studies that focused on pharmacokinetic differences between antineoplastic agents administered before versus after gastrectomy. The influence of gastrectomy on the distribution of antineoplastic agents, especially to the regional lymph nodes, were examined. METHODS Twelve pigs were divided into 2 groups of 6 each (i.e., those with and without total gastrectomy). Under general anesthesia, 10 mg/kg of 5-fluorouracil (5-FU) was injected rapidly. Total gastrectomies were performed before these injections in the group that underwent gastrectomy. In both groups a lymph node at the root of the left gastric artery (1), a preaortic lymph node (2), and venous blood were sampled in 3 animals at 15 minutes and in another 3 animals at 60 minutes after the 5-FU injection. The 5-FU concentrations in these samples were determined by high performance liquid chromatography. RESULTS The 5-FU concentrations of 1, 2, and plasma at 15 minutes/60 minutes after injection in the nongastrectomized group were 7.75 × 103/227 ng/g, 7.58 × 103/439 ng/g, and 7.24 × 103/417 ng/mL, respectively. The corresponding concentrations in the gastrectomized group were 6.04 × 103/211 ng/g, 5.80 × 103/206 ng/g, and 5.76 × 103/229 ng/mL, respectively. There were no differences in 5-FU concentrations among any of the lymph nodes or the plasma, regardless of whether gastrectomy was performed. CONCLUSIONS No influence of gastrectomy on the distribution of 5-FU to the regional lymph nodes was observed in animal models in the current study. Cancer 2000;88:2443–6. © 2000 American Cancer Society.

BACKGROUND AND OBJECTIVES A variety of minimal invasive treatment strategies for early gastric cancer without reducing the curability have been introduced, however, the indications for the local resection of early gastric cancer have not been precisely established. METHODS Two approaches are adopted in this study to elucidate indications for local resection. One is a retrospective review of surgically resected, postoperatively histologically proven early gastric cancers between 1976 and 1996 (611 patients), and the other is the patient selection from those who underwent modified D(1) lymphadenectomy in a prospective manner between 1987 and 1996, based on the preoperative and intraoperative diagnoses of mucosal, node negative, nonpalpable gastric cancer (125 patients). In these approaches, patterns of nodal involvement in association with clinicopathological characteristics of gastric cancer were investigated. RESULTS The depressed with ulceration type and histologically high grade type were predominant characteristics of mucosal, node positive gastric cancer patients. Of these patients, after the exclusion of those who were diagnosed to have submucosal or advanced cancer preoperatively or who had palpable cancer intraoperatively, the gastric cancer < or =4 cm in maximum diameter had positive nodes confined to only one station adjacent to the cancer without simultaneous nodal involvement in the other stations. CONCLUSIONS Local resection can be performed for gastric cancers < or = 4 cm in maximum diameter that meet our criteria for modified D(1) lymphadenectomy, in association with the frozen section confirmation of cancer negative in the simultaneously dissected lymph nodes in the stations adjacent to the cancer. The adjacent lymphadenectomy and frozen section examination make the application of local resection possible for a wider segment of patients.

Background and Objectives Many combination patterns of chemotherapy and radiotherapy (chemoradiation therapy; CRT) for the treatment of esophageal cancer indicate that the optimal doses of chemotherapeutic agents and of chemotherapy and radiotherapy regimens remain unclear. The feasibility and promising outcome of our newly developed definitive CRT for nonsurgical management of esophageal cancer, essentially based on the theoretical backgrounds of the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, is investigated. Methods Six nonoperated esophageal cancer patients were treated by daily concurrent CRT, which consisted of continuous 5-fluorouracil administration with leucovorin, combined with a low dose of daily cisplatin administration before each fraction of radiation. Response to CRT and toxicities and survivals were evaluated. Results Complete and partial responses were seen in 2 patients each. Histologic examination of the biopsy specimens in the primary site showed no cancer cells in 4 patients; 1 of them survived for 31 months after CRT. The other 2 patients showed good-quality survival, having dramatic relief from dysphagia. There were no treatment-related deaths Conclusions The daily concurrent CRT is rational and promising and compares well with other series of definitive CRT. The CRT based on the theoretical background is feasible as a nonsurgical management option for esophageal cancer patients. J. Surg. Oncol. 2000;74:134–137. © 2000 Wiley-Liss, Inc.

Background: Early gastric cancer (EGC) often coexists with peptic ulcer. In this study we investigated the roles of peptic ulcer in the carcinogenesis and extension of gastric cancer. Methods: The clinicopathological characteristics of EGC and peptic ulcer and their relationship, as well as that of the background intestinal metaplasia, were compared among the following three groups: patients with peptic ulcer only inside the EGC (Contained group, 53 patients); patients with peptic ulcer only outside the EGC (Separate group, 26 patients); and patients of EGC with no peptic ulcer (Absent group, 43 patients). Results: In the Separate group, a male preponderance was observed (P = .006), and all EGCs developed in the middle or lower third of the stomach (P = .06). Most of the EGCs were an intestinal type of cancer with severe background intestinal metaplasia. Topographically, 88% of the peptic ulcers in the Separate group developed proximal to the EGC. On the other hand, in the Contained group, most EGCs developed in the middle third of the stomach with an intestinal/diffuse type ratio of 1:1. Peptic ulcers inside the EGC were significantly more shallow than those that developed outside the EGC (P = 0.008). Although the incidences of submucosal cancer were nearly the same among the three groups, the maximum cancer diameter tended to be increased in the Contained group compared to that in the Absent group, and the incidence of lymph node involvement tended to be higher in the Contained group (8%) as compared with the other two groups (4%–5%). Conclusions: These results suggest that peptic ulcer outside the EGC contributes to the development of the intestinal type of EGC, with the background of more severe intestinal metaplasia during the peptic ulcer healing processes, whereas peptic ulcer inside the EGC develops secondary to EGC and favors cancer extension and metastasis. Peptic ulcer associated with EGC can be considered to exert different biological roles in the carcinogenesis or extension of ECG according to the location of the peptic ulcer.

Background: A combination of chemotherapy and radiotherapy (chemoradiation therapy; CRT) has recently been developed to improve the survival of esophageal cancer patients. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens, remain unclear. Methods: Based on recent advances in knowledge on the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, we have recently developed concurrent CRT which consisted of continuous 5-fluorouracil (5FU) administration (600 mg/m 2/day, days 1-5) combined with a low dose of daily cisplatin administration (10 mg/m 2/day, days 1-5, and 5 or 10 mg/m 2/day, days 8-12 and 15-19) before each fraction of radiation (2 Gy each). To evaluate the efficacy and safety of our concurrent CRT, 10 esophageal cancer patients received one or one and a half courses of the CRT. Results: All patients tolerated and completed a full course of the CRT. The effectiveness of the CRT on the primary tumor included pathologically or endoscopically complete responses in three patients (30%), partial response in five (50%), no response in two (20%) and tumoral downstaging (T-c1assification) in five (50%). Grade 2 and Grade 3 toxicity, seen in six patients, did not affect surgical operation. No patients showed CRT-related deaths. Eight patients (80%) underwent resection with no operative mortality. Of these, two patients (25%) showed pathologically or endoscopically complete responses, and four (50%) showed partial response. Three patients died of cancer after resection. The two inoperable patients showed a pathologically complete response and partial response, respectively. They were relieved of their cancer-related complaints and were living without hospitalization at the time of this analysis. Conclusions: These results suggest that the concurrent CRT based on the theoretical backgrounds is effective and has acceptable toxicities with maintaining its efficacy for the treatment of esophageal cancer patients.

Primary malignant melanoma of the esophagus is a rare disease, accounting for 0.1_??_0.4% of all esophageal neoplasms. Metastases are common to the liver, mediastinum, mediastinal glands and lung. We present a case of the disease with metastases to the skin, colon and mammary gland. There have been no reported cases of colon and mamma metastasis, and skin is also a rare site for metastasis. A 78-year-old woman was reffered to our hospital for weight loss and dysphagia. She had multiple subcutaneous tumors and a solitary mammary tumor. Esophagoscopy revealed a large polypoid tumor with foci of black pigmentation in the lower esophagus. Colonoscopy disclosed a small submucosal tumor. Biopsies from these tumors were all positive for HMB-45 staining, confirming the diagnosis of malignant melanoma. Junctional activity was not found in the tissue of the esophageal tumor, but its size, characteristic polypoid figure, melanosis of the adjacent mucosa and the absence of other possible primary lesions strongly suggested the esophagus origin.

Background—Monoclonal precancerous cells undergo successive biochemical and genetic changes during the multistep process of carcinogenesis in the gastrointestinal tract. Despite a high association with intestinal-type stomach cancer (differentiated adenocarcinoma of the stomach), the role of intestinal metaplasia is unclear in stomach carcinogenesis.Aims—To study the clonality of intestinal metaplasia.Methods—The clonality of 86 single intestinal metaplastic glands isolated by EDTA treatment from gastrectomy specimens from patients with cancer were investigated. The methylation sensitive restriction enzyme HpaII and polymerase chain reaction (PCR) were used to detect a polymorphic human androgen receptor gene locus linked to an inactive X chromosome.Results—Forty one (48%) intestinal metaplastic glands were heterotypic (mixed cells of different allelic methylation) and 45 (52%) were homotypic (cell population of the same allelic methylation), while almost all the single pyloric glands were homotypic. Eleven of 13 intestinal metaplastic mucosae that were 6 mm in diameter contained glands that had originated from different cells. There were no strong relationships between clonal type and location or histological type of intestinal metaplasia.Conclusion—Intestinal metaplasia in general is not a lesion that arises or proceeds monoclonally.

BACKGROUND: The phenotypic expression of tumor cells is widely thought to resemble that of the tissue of origin. In the present study, to assess phenotypic changes that occur with disease progression, we investigated human differentiated gastric cancers at different depths of invasion for component cancer cell types.METHODS: Using a combined mucin histochemical and immunohistochemical approach, we classified surgical specimens of 301 differentiated gastric cancers into three types: gastric epithelial cell (G) type, intestinal epithelial cell (I) type and mixed gastric and intestinal (GI) type, according to the phenotypic differentiation of the component cancer cells. The relation between the phenotypic type of cancer and their depth of invasion was evaluated.RESULTS: The proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or submucosa) cases, decreasing to 22.2% in advanced (tumor invasion of muscularis propia or deeper) cases, whereas the proportion of I type cancers increased with progressive disease from 23.5% to 31.1% ( P < 0.01). Cancers invading the subserosa or deeper included more I type cases and fewer G type than cancers limited to the mucosa ( P < 0.01). In most cases of each phenotypic type, intestinal metaplasia was recognized in the surrounding background mucosa, but no clear relation was shown between the phenotype of cancers and the degree of intestinal metaplasia in the background mucosa, suggesting that intestinal metaplasia is not always a preneoplastic lesion.CONCLUSIONS: A phenotypic shift from G to I type expression was observed with the progression of human differentiated gastric cancers. Intestinalization may occur independently in cancerous and noncancerous gastric mucosa.

An animal model of stomach carcinogenesis was established using Mongolian gerbils with N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as the carcinogens. In addition, the sensitivity of these gerbils to Helicobacter pylori (H. pylori) was confirmed. One hundred and sixty specific pathogen-free male MGS/Sea animals, 7 weeks old, were treated with MNU in the drinking water (30 ppm for alternate weeks to give 10 weeks exposure, or 10 ppm or 3 ppm for 20 weeks continuous exposure), or given MNNG in the drinking water at 400 ppm or 200 ppm for 20 weeks, or orally inoculated with ATCC43504 H. pylori (1.7 x 10(8) CFUs/animal). Adenocarcinomas in the glandular stomach were found in 2 out of 12 effective animals (2/ 12) treated with 30 ppm MNU at week 20, although all were dead or moribund by week 30 due to MNU toxicity. At week 50, the incidences of gastric adenocarcinomas in groups treated with 10 ppm MNU, 3 ppm MNU, 400 ppm MNNG, and 200 ppm MNNG were 2/21 (9.5%), 1/23 (4.3%), 7/ 11 (63.6%), and 1/10 (10.0%). The lesions were generally well differentiated, although poorly differentiated adenocarcinoma was also found in a single gerbil in each of the 10 ppm MNU and 400 ppm MNNG groups. In control animals no tumors were found. In the infection study, the animals were killed at week 20, and H. pylori was detected in all cases, causing multiple erosions with marked inflammatory cell infiltration in the lamina propria and submucosa, and frequent formation of lymphoid follicles. Thus, MNU and MNNG in the drinking water induced neoplastic lesions in the glandular stomach epithelium of H. pylori-sensitive gerbils.

A 49-year-old woman was referred to our hospital with complaints of epigastric colicky pain and high fever. Abdominal computed tomography and ultrasonography showed a solid tumor in the lower abdomen. Laparotomy revealed a neoplastic mass arising in Meckel's diverticulum; therefore, a segment of the ileum, including the tumor-possessing diverticulum, was resected with a lymph node dissection. A histologic examination confirmed the lesion to be leiomyosarcoma. In the English literature, 59 cases of leiomyosarcoma in Meckel's diverticulum were reported from 1941 to 1994. The majority of patients were in their 4th decade of life, with both sexes equally affected. The most frequent symptoms associated with this disease were abdominal pain with nausea, vomiting, and melena. The majority were larger than egg-size. Although Meckel's diverticulum is difficult to diagnose preoperatively, mesenteric arteriography may at times prove useful. The standard management of this particular tumor is wide segmental resection, including the tumor and diverticulum with lymph node dissection.

1985年1月から95年11月までに当科で治療された直腸表面型早期癌41例 (m癌20病変, sm癌21病変) の治療方法, 臨床病理学的特徴, 治療成績を検討した.m癌の内視鏡切除術の適応は直径20mm以下で, 断端陽性, 合併症は見られなかった.深達度smの表面型早期癌は浸潤傾向の強い癌で, 52.4%が脈管侵襲を伴っていた.Type Bのelevated type with depressionは, 全例が脈管侵襲陽性で, D2以上の郭清をともなった手術が必要で, 肛門縁から5cmの距離があれば仙骨腹仙骨式超低位直腸切除術のよい適応である.それ以外のRbの表面型早期癌では, 術前の深達度診断に合わせて, 直腸傍リンパ節のみの郭清を直視下に行う仙骨式楔状切除術, 環状切除術を最終治療手段として行うことによって, 再発なく肛門機能温存が可能と考えられた.下部直腸表面型早期癌に対しては, 内視鏡治療と通常郭清手術の問に, 直腸傍リンパ節の郭清を行う後方アプローチを位置づけることが妥当である.

Postoperative pulmonary embolism (PPE) is a rare but extremely important complication because it is often lethal. We here report on two patients with PPE, both of who complained of an abdominal pain. Patient 1: A 60-year-old man who underwent a distal gastrectomy for an advanced gastric cancer complained of an abdominal pain and dyspnea and then fell into a state of cardiopulmonary arrest when he was walking on the second postoperative day. He was successfully resuscitated and the cause was diagnosed as PPE after examination. He eventually developed multiple organ failure and expired on the 23rd postoperative day notwithstanding full intensive care including anticoagulant therapy. Patinet 2: A 59-year-old man who underwent a distal gastrectomy for an early gastric cancer suddenly had an abdominal pain and collapsed on the first day after the operation. PPE was suspected by clinical symptoms and findings of some examinations. After the diagnosis of PPE was confirmed by a perfusion lung scintigraphy, the patient received an anticoagulant therapy and successfully recovered. We have fully realized that the prophylaxis of PPE is indispensable, and are now utilizing intermittent sequential pneumatic compression to prevent PPE.

Innervation of the gastric mucosa plays an important role in its defense mechanism. In a previous study, gastrectomy with denervation promoted tumorigenesis in the gastric body in rats after administration of a carcinogenic agent. In this study we investigated the induced gastric mucosal changes from the viewpoint of mucin histochemistry. Gastrectomy with denervation promoted the development of intestinal metaplasia, dysplasia, and carcinoma in the gastric body. Proliferating cell nuclear antigen labeling indexes as a marker for cell kinetics were significantly elevated in the denervated group. Analysis of mucin histochemistry by staining with paradoxical concanavalin A (PCA) and galactose oxidase-Schiff (GOS), which are markers for expression of the gastric phenotype, revealed that these mucins were positive in submucosal adenocystic proliferation and carcinoma at the anastomotic site. Conversely, in the gastric body these mucins disappeared with progression of dysplasia, and carcinoma cells contained neither PCA- nor GOS-positive mucins. These results suggest that there are two different processes of carcinogenesis in the gastric remnant, depending on the location, and that denervation of the remnant gastric mucosa promotes the development of cancer-related lesions in the gastric body.

In order to understand the histogenesis of precancerous and cancerous lesions, we investigated the clonality of normal single fundic gland and single pyloric gland using X-chromosome inactivation. Sixty percent of single fundic glands were cell populations methylated at the same alleles of the X-chromosome (homotypic) and 40% consisted of mixed cells methylated at different alleles of the X-chromosome (heterotypic). Among 28 fundic glands in which the clonality of the upper parts and that of the lower parts were analyzed separately, 11 glands were heterotypic in either part and 4 glands were homotypic with different allelic methylation in the upper part and in the lower part. Ninety-six percent of the single pyloric glands were homotypic and 4% were heterotypic. The results show the differences in the development of the fundic glands and the pyloric glands.

Background. Gastric mucosal blood flow, secretion of mucin, and renewal of the gastric mucosal cells are considered to be defensive factors against gastric mucosal injuries. These factors are regulated by the nervous system and neuropeptides. Gastrectomy may affect this regulation and induce gastric mucosal changes, such as atrophic gastritis and carcinoma. The effects of denervation of the gastric mucosa on tumorigenesis of the remnant stomach were investigated. Methods. Using male Wistar rats, four groups of Billroth I(B-I) gastrectomy, Billroth II(B-II) gastrectomy, and those with denervation were conducted. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after the operations, histologic examination and periodic acid-Schiff-Alcian blue (PAS-AB) staining of the gastric mucosa, analysis of cell kinetics of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen, and measurement of intragastric pH, intragastric bile acid concentration, and serum gastrin levels were performed. No carcinogenic agents were given. Results. The B-I group showed no remarkable gastric mucosal changes, but B-I with denervation showed a significant increase in the development of tumor (67%) and carcinoma (42%). In the B-II groups, the denervation induced a significant increase in tumorigenesis, from 22% to 58%. Analysis of cell kinetics revealed a significant increase of labeling index in those groups that developed tumors. PAS-AB staining showed a decrease of PAS positive mucin but an increase of acidic mucin-producing cells in the denervated groups, suggesting an increase in the number of immature cells that are more susceptible to atrophic gastritis and carcinoma. There was no close relationship between tumorigenesis and intragastric pH, intragastric bile acid concentration, or serum gastrin levels. Conclusions. After gastrectomy, not only duodenogastric reflux, but also the denervation of the gastric mucosa play an important role in the etiology of gastric remnant cancer. Cancer 1995 ; 75 :1490-6.

Spasmolytic polypeptide/trefoil family factor 2 expressing metaplasia (SPEM) is induced by oxyntic atrophy and is known as a precancerous or paracancerous lesion. We now have sought to determine whether hepatocyte growth factor (HGF) influences the development of SPEM and oxyntic atrophy. DMP-777, a parietal cell ablating reagent, was administered to HGF activator (HGFA)-deficient mice and wild-type mice. Gastric mucosal lineage changes were analyzed in the DMP-777 treatment phase and recovery phase. Both wild-type and HGFA knockout mice showed SPEM, and there was no difference in SPEM development. However, after cessation of DMP-777, HGFA-deficient mice showed delayed recovery from SPEM compared with wild-type mice. Foveolar cell hyperplasia and the increase in proliferating cells after parietal cell loss were reduced in HGFA-deficient mice. The HGFA does not affect emergence of SPEM. However, the absence of HGFA signaling causes a delay in the recovery from SPEM to normal glandular composition. HGFA also promotes foveolar cell hyperplasia and mucosal cell proliferation in acute oxyntic injury.

Technique in laparoscopic surgery using long forceps, laparoscopic coagulating shears (LCS, vessel sealing systems, and so on is absolutely different from that in open surgery. The mobility of long forceps used through ports placed at the abdominal wall is limited, and so training is required at a “dry” laboratory before addressing clinical cases. Training in an animal laboratory is much better than that in a dry laboratory, but it is often difficult to access an animal laboratory. It would be ideal to have a dry laboratory in the institution, so any young doctor can access it at any time. Everyone could then be familiar with the items used for laparoscopic surgery and hone skills of required techniques such as ligation.

The lesser sac is a potential space behind the stomach. The peritoneal covering can be traced from the anterior surface of the pancreas to the spleen. The two landmark folds are important for laparoscopic gastrectomy. The pancreaticogastric fold, which normally is covered by the left lobe of the liver, contains the left gastric artery from the retroperitoneal space to the lesser curvature of the stomach.

Peppermint oil has been shown to relax gastrointestinal smooth muscle. In this randomized, placebo-controlled study, an L-menthol preparation, NPO-11, was assessed for tolerability and pharmacokinetics (PK) during gastrointestinal endoscopy. Single doses of NPO-11, as high as 320 mg, were well tolerated. NPO-11 was rapidly absorbed, with peak concentrations reached within 1 h after administration. Approximately 70% of the administered L-menthol and its metabolites were excreted in the urine, and this amount fluctuated with no change in the dose. The principal metabolite identified in plasma and urine was menthol glucuronide. The other metabolites include mono- or di-hydroxylated menthol derivatives, most of which are excreted, in part, as glucuronic acid conjugates. The pharmacokinetic data indicated that when NPO-11 is sprayed directly onto the gastric mucosa, it is rapidly metabolized to glucuronic acid conjugates that are excreted in urine. The findings from this study provide new data on the safety and PK of NPO-11 and support further trials.