Search

Objectives The Japan Endoscopy Database Project was initiated to develop the world's largest endoscopy data repository. This study describes the first phase of the colonoscopy project in Japan. Methods Data were aggregated offline by integrating information from the endoscopy database software from January 2015 through March 2017. The study population included all patients who underwent colonoscopy at eight centers. Results A total of 31,395 patients who underwent 38,497 colonoscopy procedures were registered. The majority of procedures were performed for screening (n = 14,156), followed by fecal immunochemical test positivity (n = 3960), abdominal symptoms (n = 3864), post-colorectal surgery surveillance (n = 3431), post-endoscopic treatment surveillance (n = 3757), thorough pre-treatment examination (n = 2822), and therapeutic purposes (n = 6507). In the screening group, advanced cancers, early cancers, and adenomas were diagnosed endoscopically in 2.1%, 1.3%, and 28.7% of cases, respectively, while in the fecal immunochemical test-positive group, they were diagnosed in 2.5%, 1.9%, and 41.6% of cases, respectively. The incidence of complications was 0.177% and 0.152% in the screening and fecal immunochemical test-positive groups, respectively. The therapeutic procedures included 1446 cold forceps polypectomy procedures, 4770 cold snare polypectomy procedures, 368 hot biopsies, 2998 hot snare polypectomy procedures, 9775 endoscopic or piecemeal endoscopic mucosal resections, and 1660 endoscopic submucosal dissections. A total of 173 procedure-related complications (0.82%) occurred in 21,017 therapeutic procedures performed in 15,744 patients. Conclusions The first phase of the Japan Endoscopy Database Project established the proportions of the diagnostic and therapeutic colonoscopy procedures, and complication rates in real-world settings.

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 Endoscopic intragastric balloon (IGB) placement has been performed in Japan since 2004. The nationwide surveys were repeatedly carried out to confirm the effectiveness and safety of IGB in Japan. We herein present the accumulated results. Methods Twenty-six Japanese endoscopists personally imported products of the BioEnterics Intragastric Balloon (BIB)/Orbera system after completing the training courses in Japan. Mail surveys were posted to them every 2 years from 2010. This study included the accumulated data of the six surveys, and excluded data from non-Japanese patients and the Orbera365 data. Results Between 2004 and 2019, 399 obese Japanese patients underwent IGB treatment using the BIB/Orbera system. The incidence rates of early removal of IGB within 1 week and complications due to IGB were 4.8% and 6.1%, respectively. The average percent excess weight loss (%EWL) and percent total weight loss (%TWL) at IGB removal were 46.6% and 11.5%, and successful weight loss, defined as %EWL ≥ 25% or %TWL ≥ 10%, was achieved in 65.6% or 54.5% of the patients, respectively. Multivariate analyses revealed that older age and larger saline filling volume were independent predictors of successful weight loss. At 1 year after IGB removal, successful weight loss defined by the %EWL and %TWL was maintained in 44.7% and 34.1% of the patients, respectively. Conclusion IGB therapy using the BIB/Orbera system has been safely and effectively performed in Japan. The successful weight loss may be associated with older age and larger saline filling volume.

Aim: To clarify whether antithrombotic drugs affect diagnosis using the immunochemical faecal occult blood test ­(iFOBT) of colorectal neoplasia. Methods: Using the Japan Endoscopy Database from 8 centres between 2015 and 2017, we analyzed data about patients who were iFOBT positive and had received direct oral anticoagulants (DOAC), warfarin, aspirin or thienopyridine. One-to-one matching-analogue propensity score weighted analyses were performed to compare the positive predictive value (PPV) of all neoplasms, invasive and non-invasive colorectal cancers and adenomas between drug users and non-users. All neoplasms included invasive and non-invasive colorectal cancer, and adenomas. Results: We analyzed 197 DOAC users and 196 non-users, 153 warfarin users and 153 non-users, 408 aspirin users and 415 non-users, and 97 thienopyridine users and 97 non-users. No significant differences were observed in the PPV for all neoplasms (56.67 vs. 50.43%), invasive cancer (4.32 vs. 3.53%), non-invasive cancer (15.58 vs. 15.56%) or adenoma (53.13 vs. 48.09%) between the DOAC user and non-user groups. No significant differences were observed in the PPV for all neoplasia, invasive and non-invasive cancer, or adenoma between warfarin, aspirin and thienopyridine use and non-users. Conclusions: DOAC, warfarin, aspirin and thienopyridine use did not decrease the PPVs of the iFOBT used to evaluate all colorectal neoplasia.

The advent of electronic medical records brought image filing systems to many hospitals, as well as electronic endoscopic medical records. However, data integration among multiple different vendors has not yet been accomplished. We start the Japan Endoscopic Database (JED) Project endorsed by Japan Gastroenterological Endoscopy Society (JGES) from January 2015. The purposes of this project are as follows: (i) developing the world's largest endoscopic database generated from daily use of the reporting system; (ii) capturing the actual performance of endoscopic practice in Japan; and (iii) standardizing the terminology and fundamental items for registry of clinical studies. Moreover, the JED project has the potential to automatically collect data about adverse events, competency and evaluation of residents, and actual numbers of procedures on a nationwide scale, certification for the specialty board system, and so on. We believe that this design paper will be helpful not only for future nationwide research but also for international research (UMIN000016093).

Background and Aim The Japan Endoscopy Database (JED) Project was started to develop the world's largest endoscopic database, capture the actual performance of endoscopic practice, and standardize the terminology and fundamental items needed for a clinical and research registry. This paper presents a progress report on the first phase of this project undertaken at eight endoscopic centers in Japan. Methods The list of data items to be collected was drafted by the MSED-J (Minimal Standard Endoscopic Database) subcommittee. These items were aggregated offline by integrating data from two endoscopic filing systems between July 2015 and December 2015. The study population included all patients who underwent esophagogastroduodenoscopy or colonoscopy at all eight centers, patients who underwent enteroscopy at five of the eight centers, and patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) at four of the eight centers. Results Data collected in this phase included 61 070 endoscopic procedures, of which 40 475 were esophagogastroduodenoscopies, 215 were enteroscopies, 19 204 were colonoscopies, and 1176 were ERCPs. Frequencies of complications were 0.68% for esophagogastroduodenoscopy, 0% for enteroscopy, 0.43% for colonoscopy, and 13.34% for ERCP. In addition, we obtained various data including Helicobacter pylori infection status, past history of endoscopy in patients who underwent enteroscopy or colonoscopy, and degree of difficulty of ERCP, although the frequencies of reporting were sometimes low, with some items

Background and Aims: Esophageal adenocarcinoma develops in the setting of gastroesophageal reflux and columnar metaplasia in distal esophagus. Columnar metaplasia arising in gastroesophageal reflux models has developed in rat; however, gastroesophageal reflux models in mice have not been well-characterized. Methods: One hundred thirty-five C57Bl/6J mice aged 8 weeks old were divided into the following operations: esophagogastrojejunostomy (side-to-side) (EGJ), esophageal separation and esophagojejunostomy (end-to-side) (EJ), and EJ and gastrectomy (end-to-side) (EJ/TG). The animals were euthanized after 40 weeks and the histology of the junction was examined. Immunohistochemistry for p53, PDX-1, and CDX-2 was performed. Results: Metaplasia developed in 15/33 (45.5%) of EGJ, 0/38 (0%) of EJ, and 6/39 (15.4%) of EJ/TG (P < .05) and dysplasia developed 7/33 (21.2%) of EGJ, 0% of EJ, and 1/39 (2.6%) of EJ/TG. p53 was positive in all of the dysplastic regions, 12/15 (80%) metaplasias in the EGJ model, and 1/6 (16.7%) metaplasia in the EJ/TG model. CDX-2 was positive in all cases of metaplasias, but decreased in some cases of dysplasia. PDX-1 was positive in 7/8 (88%) cases of dysplasia and in 15/21 (71%) cases of metaplasia (P < .05). Conclusions: The EGJ model, which causes reflux of gastric acid and duodenal content, developed metaplasia and dysplasia most frequently. No metaplasia developed in the EJ model in which gastric juice and duodenal content mixed before reflux. Thus, duodenal contents alone can induce columnar metaplasia and dysplasia; however, the combination of gastric acid with duodenal content reflux can cause metaplasia and dysplasia more efficiently. Keywords: GERD, Esophageal Reflux, Barrettâs Esophagus, Esophageal Adenocarcinoma

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.

Highlights • Non-parasitic hepatic cysts with biliary communication are extremely rare. • Overlooking of the communication site may lead to postoperative bile leakage. • Air leak test was useful for the detection of the small biliary communication., Introduction Symptomatic non-parasitic hepatic cysts with biliary communication are rare and no standard treatment has been established yet. Careful attention should be paid to avoidance of postoperative bile leakage during surgical treatment. Presentation of case We report the case of a 74-year-old man who visited our department complaining of right upper abdominal pain and elevated serum levels of the liver enzymes. Computed tomography revealed hepatic cysts including a large one measuring 16 cm in diameter in Segments IV and VIII. Percutaneous drainage of the cyst revealed bile-staining of the cyst fluid. Endoscopic retrograde cholangiography demonstrated the presence of a cyst–biliary communication. We performed open deroofing of the cyst. During the operation, the biliary fistula was invisible, however, air injection into the bile duct through the stump of the cystic duct caused release of air bubbles from the cyst cavity, which allowed us to detect the small biliary orifice and repair it successfully by suture. Discussion We utilized the intraoperative air leak test, which has previously been reported to be effective for preventing postoperative bile leakage in patients undergoing hepatectomy to detect of a small cyst–biliary communication in a case undergoing non-parasitic hepatic cyst surgery. Conclusion An intraoperative air leak test may be a useful test during surgical treatment of non-parasitic hepatic cysts with biliary communication.

Objective To compare radical surgery with definitive chemoradiation (CRT) for esophageal squamous cell carcinoma using propensity score (PS) matching at our single institution. Materials and methods A total of 386 consecutive, surgically treated and 243 CRT-treated cases between 2001 and 2014 were analyzed. PS was calculated using multivariable analysis (logistic regression) for pairs of variables such as treatment time, age, sex, primary tumor location, clinical stage, and clinical T- and N-stage for patients after excluding clinical T4 and M1 cases. According to PS, 133 surgically-treated and 134 CRT-treated cases were selected randomly by software. Results The patients’ median age was 68 years in the CRT group and 71 years in the surgery group. Clinical stage II-III, T3, N0 (according to the 7th American Joint Committee on Cancer-2009), and upper plus middle thoracic esophageal disease were seen in 68%, 44%, 54%, and 59%, respectively, in the CRT group and 64%, 47%, 55%, and 64%, respectively, in the surgery group. The 3- and 5-year overall survival was 47.1% and 34.0% in the CRT group and 68.3% and 54.4% in the surgery group (p = 0.0019). The 3- and 5-year progression-free survival was 45.3% and 38.8% in the CRT group and 61.1% and 54.4% in the surgery group (p = 0.022). Conclusion CRT may be inferior to surgery in survival, although a selection bias for patients selected for a non-operative approach cannot be excluded, especially since surgery is the standard of care at this institution. A prospective randomized clinical trial will be necessary to draw a definite conclusion.

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

The topical antispasmodic agent l-menthol is useful for inhibiting gastric peristalsis during diagnostic upper gastrointestinal endoscopy. However, it remains unclear whether l-menthol is similarly effective during therapeutic endoscopy, thereby improving treatment outcomes in a clinical setting.A total of 83 patients scheduled to undergo endoscopic treatment at 8 Japanese referral centers were randomly assigned to receive l-menthol or placebo. The degree of gastric peristalsis (peristaltic score: grade 1-5) was assessed by an independent committee. The primary outcome was the proportion of subjects in whom no or mild peristalsis (grade 1 or 2) was maintained throughout endoscopic treatment. Secondary outcomes were the duration of sustained response and the incidence of adverse drug reactions.The proportion of patients with no or mild peristalsis was significantly higher in the l-menthol group (85.4 %, 95 % confidence intervals 70.8-94.4: 35/41 subjects) than in the placebo group (39.0 %, 24.2-55: 16/41; P0.001). The sustained response rates in the l-menthol and the placebo were, respectively, 90.0 and 39.6 % 30 min post-dose, and 79.9 and 35.7 % at the completion of the resection. The sustained response rates were significantly higher in the l-menthol group than in the placebo group (P0.001, log-rank test). The incidence of adverse drug reactions did not differ significantly between the two groups (P = 1.000).During gastric endoscopic submucosal dissection, spraying l-menthol on the gastric mucosa significantly suppressed peristalsis, with minimal adverse drug reactions as compared with placebo. l-menthol solution might be useful for therapeutic endoscopy.

Background The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008. Methods From 208 participating hospitals, 53 items including surgical procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed. Results The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed. Conclusions Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.

The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registry in 2008. Approximately 50 data items, including surgical procedures, pathological diagnoses, and survival outcomes, for 12004 patients with primary gastric cancer treated in 2001 were collected retrospectively from 187 participating hospitals. Data were entered into the JGCA database according to the JGCA Classification of gastric carcinoma, 13th edition and the International Union Against Cancer (UICC) TNM Classification of malignant tumors, 5th edition by using an electronic data collecting system. Finally, data of 11261 patients with gastric resection were analyzed. The 5-year follow-up rate was 83.5%. The direct death rate was 0.6%. TNM 5-year survival rates (5YSRs)/JGCA 5YSRs were 91.8/91.9% for stage IA, 84.6/85.1% for stage IB, 70.5/73.1% for stage II, 46.6/51.0% for stage IIIA, 29.9/33.4% for stage IIIB, and 16.6/15.8% for stage IV. The proportion of patients more than 80 years old was 7.0%, and their 5YSR was 48.7%. Compared to the JGCA archived data, though the follow-up rate needs to be improved, these data suggest that the postoperative results of patients with primary gastric carcinoma have improved in those with advanced disease and in the aged population in Japan.

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.).

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.

症例は63歳の男性で, 2002年7月にMtUtLt T3-4, N2, cStageIIIの高分化型扁平上皮癌 (以下, SCC) を指摘された. 気管支浸潤も疑われ, 根治的放射線化学療法を施行された. 2002年12月, 腫瘍はCR, リンパ節はPRの評価であった. 2003年9月, 門歯より40～45cmに全周性の粘膜不整像, ルゴール不染があり, 食道癌と診断された. 別照射野にて再度放射線化学療法50Gyを施行されたがNCであり, 2004年に内視鏡的粘膜下層切除術を追加施行された.m1, ly0, v0のSCCであった. さらに, 2004年8月, 下咽頭癌 (SCC, T1 N0 M0) の診断にて下咽頭部分切除術を施行された. 2006年1月, 胃噴門部に径2cmの粘膜下腫瘍様隆起が出現した. 超音波内視鏡下針生検にてSCCと診断され2006年4月噴門側胃切除術を施行した. 病理組織学的検査所見は中分化型SCCであり高度の静脈侵襲を伴い, 最初に診断された食道癌の血行性転移の可能性が示唆された.

近年, 虚血性心疾患に対して行われる冠動脈ステント治療において免疫抑制剤や抗癌剤を表面に塗布し徐放化させる薬剤溶出性ステント (drug-eluting coronary stent; 以下, DES) が多用されている. DESは従来の金属露出型ステントより再狭窄率が低いという重要な長所を持つが, 留置後1か月以降に遅発性血栓症が起こるリスクを有しており, 使用患者はアスピリンの終生投与およびチクロピジンの最低3か月以上の投与が必須とされている. DES留置後に消化器癌が指摘されると, 出血リスクを避けるために周術期に抗血小板薬の休止が必要となるが, ヘパリン点滴持続静脈投与への変更などによる抗凝固療法による代替の安全性に関するエビデンスは乏しい. 我々はDES留置後に胃癌が発見された3症例を経験したため文献的考察を含めて検討し, 指針を考案した.

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.

An endo-cytoscopy system allows acquisition of optical biopsies that are quite similar to conventional histology. To simplify discrimination between normal and malignant tissue in the oesophagus using endo-cytoscopy system, we analysed the nuclear (dark staining) area in the obtained images with the goal of an accurate, automatic diagnosis.Ex vivo endo-cytoscopic observation was performed using endoscopically or surgically resected oesophagus from 10 enrolled patients. Oesophageal tissues were stained using 1% methylene blue, and endo-cytoscopic images were obtained at normal and malignant areas (two areas of each) in each oesophagus. The centre of each image (4x10(-2) mm(2)) was processed by computer, and the area occupied by the total nuclei in each selected field and its ratio to the entire field were calculated.The mean area of the total nuclei was 0.10x10(-2)+/-0.03x10(-2) mm(2) (range 0.05x10(-2) to 0.18x10(-2) mm(2)) in the normal group and 0.40x10(-2)+/-0.06x10(-2) mm(2) (range 0.33x10(-2) to 0.55x10(-2) mm(2)) in the malignant group (P0.001). The mean ratio of total nuclei to the entire selected field was 6.4+/-1.9% (range 3.1-11.3%) in the normal tissues and 25.3+/-3.8% (range 20.5-34.5%) in the malignant samples (P0.001).Endo-cytoscopy system allowed automatic differentiation of normal and malignant tissues in the oesophagus, which could simplify endo-cytoscopic diagnosis. Further study will elucidate whether such analysis is applicable to inflammatory or pre-malignant epithelia in the oesophagus or other gastrointestinal organs.

Peritoneal cytology is an important prognostic factor of gastric cancer. However, peritoneal cytology requires great skill, which may explain its low prevalence. A reverse transcriptase–polymerase chain reaction–based assay with multiple marker genes or immunocytochemistry was assessed as an alternative method of gathering the same kind of data as cytology. Peritoneal washings from 179 patients with gastric cancer were analyzed by multiplex reverse transcriptase–polymerase chain reaction with 10 marker genes and subsequent hybridization to a customized oligo-nucleotide array. Results with this assay were either validated as a prognostic factor or confirmed by demonstrating the presence of cancer cells by immunocytochemical cytology. Only 1 (2.2%) of 44 disease-free cases was shown to be positive by the microarray assay, whereas 13 (93%) of 14 conventional cytology–positive cases were found to be positive. This assay further detected approximately one-third of cytology-negative patients either with peritoneal recurrence (7 of 20, 35%) or with non-peritoneal recurrence (6 of 22, 27%). A high concordance between the microarray assay and immunocytochemical cytology with five antibodies against CK20, FABP1, MUC2, TFF1, and MASPIN was confirmed. The clinical outcome of the microarray assay–positive cases was poor, as was that of the cytology-positive cases. Our assay, though time-consuming and requiring special equipment, demonstrated a specificity and sensitivity equal to or better than cytology in our institutes. The minimal free peritoneal cancer cells detected by the microarray assay may provide the same clinical information as larger amounts of cancer cells for patients with gastric cancer. An anti-MASPIN antibody may be helpful in peritoneal cytology of 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.

We present a rare case of invasive right breast carcinoma in a 72-year-old woman with Behçet's disease (BD). A radical modified right mastectomy and axillary lymphadenectomy were performed and postoperative hormonal therapy with the aromatase inhibitor anastrozole was administered for adjuvant therapy. At 10 months follow-up the patient remains disease free. Malignancies associated with BD are very uncommon. The pathological findings showed small vessel vasculitis and lobulitis of the breast in association with invasive carcinoma.

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.

To evaluate the treatment outcome of preoperative neoadjuvant radiotherapy combined with chemotherapy (CTx) for 17 esophageal cancer patients. Between 1992 and 2004, patients with locally advanced esophageal cancer (stage III or IV) before curative-intent surgery received radiotherapy (RT) combined with CTx (Cisplatin: 75 mg/m2, bolus infusion, and 5-fluorouracil (5-FU): 1,000 mg/m2/24 h, continuous infusion for 4 days) at a median total dose of 30 Gy (n=17). The median survival period was 13.8 months. The overall survival rates at 1, 2, and 3 years were 75%, 40%, and 20%, respectively. According to univariate analysis, no factor of worse prognosis was found. Pathological markedly (Grade 3) or moderately (Grade 2) effects were observed in 4 patients (24%) and 8 patients (47%), respectively. These results indicate that, although this regimen was effective in terms of pathological effect, it is unclear whether it made a contribution to the improvement of survival rate.

We designed an outpatient regimen consisting of fractional cisplatin in combination with S-1, a novel oral fluoropyrimidine derivative for the treatment of recurrent or advanced gastric cancer and conducted a phase I study to determine the dose limiting toxicities (DLTs) and recommended dose (RD).Escalating dosages of cisplatin (15, 20, and 25 mg/m(2), as levels 1, 2, and 3, respectively) were administered over 2 h on days 1, 8, and 15, with a fixed dose of S-1 for 3 consecutive weeks (days 1-21), repeated every 5 weeks. National Cancer Institute common toxicity criteria(NCI-CTC) grade 2 toxicities required treatment delay. Primary first cycle DLTs were defined as NCI-CTC grade 3 or 4 toxicities (except for hemoglobin levels, nausea, and vomiting).Nine patients were initially enrolled, and DLTs did not appear; however, one level-3 patient experienced grade 3 anemia. An additional three patients were enrolled in level 3 to confirm the toxicity profiles, and none experienced DLTs. Toxicity evaluations throughout a total of 62 cycles revealed that grade 1 or 2 hematological toxicities were common, although mostly transient, with recovery without specific treatment. One patient each in levels 1 and 3 required hospitalization due to grade 3 toxicities in the later cycles. Mean dose intensities for S-1 and cisplatin were both more than 91%. There were no treatment-related deaths. The preliminary response rate was 44%.It was concluded that the RD of cisplatin in this regimen was 25 mg/m(2) (level 3). S-1 in combination with fractional cisplatin is a promising regimen that allows repeated drug administration, in an outpatient setting, for advanced or recurrent gastric cancers. A phase II study of the RD is now under way.

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.

In the present study, we aimed to establish an additional standardized protocol with a higher H. pylori eradication rate in the remnant stomach. Fifty-five H. pylori-positive patients were randomly allocated to one of three regimens: LAC--lansoprazole, amoxicillin, and clarithromycin b.i.d. for 7 days (n = 17); LAC+CET--LAC b.i.d. plus cetraxate q.i.d. for 7 days (n = 20); and LEFT--LAC for 7 days in a horizontal body position on the left side for 30 min (n = 18). Patient compliance and side effects were checked via interviews. H. pylori eradication was successful in 75, 72, and 41% in LAC+CET, LEFT, and LAC, respectively. The eradication rate was significantly higher in LAC+CET than in LAC (P = 0.024) but not in LEFT (P = 0.058). Adverse events that occurred in each group were almost all mild ones. Cetraxate plus LAC for 1 week is a safe and effective regime for the eradication of H. pylori in patients after partial gastrectomy.

Gastric cancer is still the second leading cause of cancer death worldwide, although the incidence of this disease has been gradually decreasing. The diversity of gastric cancer is well known. However, the mechanism underlying this diversity is still unknown. We have performed experimental and clinical studies on gastric carcinogenesis. These results suggest that the variety in the type and extent of inflammation in the stomach, and the different response to inflammation are responsible for the diversity in gastric carcinogenesis. This concept is supported by clinical and experimental evidence that eradication of Helicobacter pylori diminishes the incidence of gastric cancer and that PPAR gamma ligand, a modulator of inflammation and cell differentiation, prevents gastric carcinogenesis.

Cushing症候群として発症した左副腎皮質癌の1切除例を報告する.症例は52歳,男性.平成14年1月より顔面のむくみを自覚.平成15年5月,腰背部痛にて近医受診し,諸検査にて巨大な左後腹膜腔腫瘍が疑われたため当院紹介入院となった.満月様顔貌,耐糖能異常,骨密度低下とともにCTにて左後腹膜腔に径約20cmの腫瘍を認め,血中CA19-9濃度の上昇およびcortisol過剰産生を認めたため,副腎皮質癌と診断し,平成15年6月,外科的切除を施行した.術中傍大動脈リンパ節の転移を認めたため,腫瘍とともに可及的にリンパ節を摘出したが,術1カ月後に多発肝転移が出現. TAEの後TS-1, CDDPおよびop'-DDDの投与を行うも, 6カ月後,腫瘍塞栓の遊離による肺硬塞と思われる症状にて急死した.以上,内分泌活性を持つ大きな副腎皮質癌症例を報告した.

Background. Postoperative small bowel obstruction following abdominal procedures is more common in patients who have undergone laparotomy. However, little is known about the influence of climate on the incidence of postoperative small bowel obstruction. Methods. To evaluate whether seasonal climatic variations are a risk factor for postoperative small bowel obstruction, hospital-based, retrospective case series was designed from medical records of 230 patients suffering from postoperative small bowel obstruction admitted to the Tokyo University Branch Hospital. Detailed analysis of weather charts from the Japanese Meteorological Agency and review of medical records for selected patients who were diagnosed with postoperative small bowel obstruction. The obstruction was diagnosed by abdominal X-ray imaging, clinical examination, and patient interviews. Results. A total of 233 patients diagnosed with postoperative small bowel obstruction were identified. Analysis of the medical records of these 233 patients revealed that the variables associated with an increased risk of postoperative small bowel obstruction included low ambient temperatures of 5–10 °C, an increase in air humidity by 40–50% and air pressure of 1010–1015 hPa. Conclusion. The typical winter weather in Tokyo is characterised by low temperatures, low humidity and moderate air pressure. These winter climate conditions could be correlated with an increased incidence of postoperative small bowel obstruction in Tokyo during our observation period.

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.

Background: Irinotecan hydrochloride (CPT-11) in combination with cisplatin has emerged as a new therapeutic option for the treatment of advanced gastric cancer. So far, very few combination trials have been reported, and a relatively high frequency of grade 3/4 toxicities in previous trials has been a major problem. The purpose of this study was to elucidate the efficacy and safety of a low dose, fractional administration of CPT-11 and cisplatin that is principally based on recently acquired knowledge of the synergistic antitumor activities between these two agents. Methods: Five relapsed gastric cancer patients were treated every 2 weeks with a starting dose of CPT-11 (30 mg/m2) and a fixed dose of cisplatin (30 mg/m2). All patients were of performance status 0 and had received prior chemotherapy. Dose escalation of CPT-11 to 40 mg/m2 or to 50 mg/m2 was performed whenever possible. Responses, toxicities, and at-home ratio during chemotherapy were evaluated. Results: The response rate reached 40%. Toxicities were grade 1/2, and no grade 3/4 hematological toxicities or diarrhea were observed. Repeated subsequent treatments could be performed in an outpatient setting without treatment delay or cancellations, which resulted in an 83%–92% at-home ratio in four patients receiving five or more cycles of treatment. There were no treatment-related deaths. Conclusion: A low dose, fractional administration of CPT-11 and cisplatin seems rational, encouraging, and safe, and compares well with other trials of the combination. Outpatient administration provides the patients with a better quality of life, suggesting a meaningful therapeutic option for relapsed gastric cancer patients in particular.