Endoscopic optical diagnosis provides high diagnostic accuracy of esophageal squamous cell carcinoma.

BACKGROUND: Recent technological advances have stimulated the development of endoscopic optical biopsy technologies. This study compared the accuracy of endoscopic diagnosis using magnifying narrow-band imaging (NBI) and histologic diagnosis of esophageal squamous lesions. METHODS: Patients at high risk for esophageal squamous cell carcinoma were examined with endoscopy and subsequent biopsy. The lesions diagnosed as cancer on NBI and the lesions diagnosed as cancer on biopsy were resected endoscopically or surgically. Histological diagnoses of resected specimens, the reference standards in this study, were made by a pathologist who was blind to both the endoscopic and biopsy diagnoses. The primary outcome was the accuracy of endoscopic and biopsy diagnosis. A noninferiority trial design with a noninferiority margin of -10% was chosen to investigate the accuracy of endoscopic diagnosis using magnifying NBI. RESULTS: Between November 2010 and October 2012, a total of 111 lesions in 85 patients were included in the analysis. The accuracy of endoscopic diagnosis and biopsy diagnosis for all lesions was 91.0% (101/111) and 85.6% (95/111), respectively. The difference in diagnostic accuracy was 5.4% (95% confidence interval: -2.9%-13.7%). The accuracy of endoscopic diagnosis and biopsy diagnosis of invasive cancers was 94.9% (74/78) and 84.6% (66/78), respectively. The difference was 10.3% (95% confidence interval: 1.6%-19.0%) for invasive cancers. The lower bound of the 95% confidence interval was above the prestated -10% in both cases. CONCLUSION: Noninferiority of endoscopic diagnosis by magnifying NBI to histologic diagnosis by biopsy was established in this study (p = 0.0001). TRIAL REGISTRATION: The study was registered on 9th November 2010 in the University Hospital Medical Network Clinical Trials Registry as number: UMIN000004529.

Delayed perforation: a hazardous complication of endoscopic resection for non-ampullary duodenal neoplasm.

BACKGROUND: Perforation is a major complication of endoscopic resection for gastrointestinal neoplasms. However, little is known about delayed perforation after endoscopic resection for non-ampullary duodenal neoplasm. The aim of the present study was to investigate the clinical features of delayed perforation after endoscopic resection for non-ampullary duodenal neoplasm. PATIENTS AND METHODS: This was a retrospective cohort study conducted in a referral cancer center. A total of 63 patients (41 with adenomas and 22 with carcinomas) underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) from January 1993 to December 2011. Incidence, outcome, and factors associated with occurrence of delayed perforation were investigated. RESULTS: Delayed perforation occurred in four patients (6.3%). All lesions were located distal to Vater's ampulla. Three of four delayed perforations occurred within 36 h after endoscopic resection. All patients developed retroperitonitis, and two also had retroperitoneal abscesses. Although three patients were cured with conservative management, a long hospital stay was required (28-, 80-, and 81-day hospital stay, respectively). One patient required emergency surgery as a result of panperitonitis. There was, fortunately, no mortality in this series. The significant predictors of delayed perforation were location (distal to Vater's ampulla, P = 0.007) and resection method (ESD and piecemeal EMR, P = 0.003). CONCLUSION: Endoscopic resection for non-ampullary duodenal neoplasms has a possible risk of morbid complication i.e. delayed perforation, especially in patients with lesions located on the side distal from the ampulla and who are treated with piecemeal EMR or ESD.

Randomized study of two endo-knives for endoscopic submucosal dissection of esophageal cancer.

OBJECTIVES: Settings for endoscopic submucosal dissection (ESD) of esophageal cancer have not been standardized, and no studies have directly compared ESD devices in humans. METHODS: We conducted a randomized study to compare the performances of two different endo-knives, the Flush knife and Mucosectom, for esophageal ESD in 48 lesions. All procedures were initiated by two endoscopists, who were assisted by senior endoscopists with verbal advice. In the Flush-knife group, mucosal incision with a 2-mm Flush knife was followed by submucosal dissection using a 1-mm Flush knife. In the Mucosectom group, mucosal incision with a 2-mm Flush knife was followed by submucosal dissection with a Mucosectom. The primary outcome variable was the procedure time required for submucosal dissection. The secondary outcome variables were total procedure time, self-completion rates, and adverse events. RESULTS: Total procedure time in the Mucosectom group was significantly shorter than in the Flush-knife group (57±21 vs. 83±27 min, respectively; P<0.001). The submucosal-dissection time in the Mucosectom group was significantly shorter than in the Flush-knife group (40±18 vs. 61±23 min, respectively; P<0.001). The self-completion rate in the Mucosectom group was slightly higher than in the Flush-knife group, but the difference was not significant (91.7% vs. 75%, respectively; P=0.25). One perforation and one postoperative bleeding occurred in the Flush-knife group, both of which were treated successfully by endoscopic treatment. CONCLUSIONS: The Mucosectom reduced the procedure and submucosal-dissection times of esophageal ESD, without increasing adverse events.

Comprehensive investigation of areae gastricae pattern in gastric corpus using magnifying narrow band imaging endoscopy in patients with chronic atrophic fundic gastritis.

BACKGROUND: Barium radiographic studies have suggested the importance of evaluating areae gastricae pattern for the diagnosis of gastritis. Significance of endoscopic appearance of areae gastricae in the diagnosis of chronic atrophic fundic gastritis (CAFG) was investigated by image-enhanced endoscopy. MATERIALS AND METHODS: Endoscopic images of the corpus lesser curvature were studied in 50 patients with CAFG. Extent of CAFG was evaluated with autofluorescence imaging endoscopy. The areae gastricae pattern was evaluated with 0.2% indigo carmine chromoendoscopy. Micro-mucosal structure was examined with magnifying chromoendoscopy and narrow band imaging. RESULTS: In patients with small extent of CAFG, polygonal areae gastricae separated by a narrow intervening part of areae gastricae was observed, whereas in patients with wide extent of CAFG, the size of the areae gastricae decreased and the width of the intervening part of areae gastricae increased (p < 0.001). Most areae gastricae showed a foveola-type micro-mucosal structure (82.7%), while intervening part of areae gastricae had a groove-type structure (98.0%, p < 0.001). Groove-type mucosa had a higher grade of atrophy (p < 0.001) and intestinal metaplasia (p < 0.001) compared with foveola type. CONCLUSIONS: As extent of CAFG widened, multifocal groove-type mucosa that had high-grade atrophy and intestinal metaplasia developed among areae gastricae and increased along the intervening part of areae gastricae. Our observations facilitate our understanding of the development and progression of CAFG.

A water-jet videoendoscope may reduce operation time of endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: One of the problems with endoscopic submucosal dissection (ESD) for early gastric cancer is that it prolongs procedure time considerably. AIM: The purpose of this study was to investigate whether a videoendoscope with water-jet function shortened the time of ESD for early gastric cancer. METHODS: A total of 82 early gastric cancers that were intramucosal, differentiated-type adenocarcinoma ≤2 cm, without ulcer or scar, in 75 consecutive patients were investigated. Three supervised resident endoscopists participated as operators. After stratification by the operator and tumor location, the lesions were randomly assigned to the water-jet videoendoscope or a conventional videoendoscope groups. An insulated tipped knife was used for the ESD procedure. Total operation time was evaluated as a primary endpoint. RESULTS: The median (25-75th percentile) total operation time for the water-jet videoendoscope group was 51 (33-87) minutes, which was shorter than the 62 (43-88) minutes for the conventional videoendoscope, but it did not reach significance (P = 0.201). Multivariate analysis revealed that the water-jet videoendoscope (OR 3.0, P = 0.046), tumor size ≤14 mm (OR 3.2, P = 0.040) and antral tumor (OR 4.5, P = 0.046) were significantly associated with short (≤60 min) operation time. CONCLUSIONS: The water-jet videoendoscope may reduce operation time of ESD for early gastric cancer, compared with conventional videoendoscope. A large-scale multicenter trial is warranted to clarify the efficacy of the water-jet videoendoscope for gastric ESD.

Risk factors of chest pain after endoscopic resection of early esophageal cancer.

BACKGROUND/AIMS: Although endoscopic resection is sometimes associated with chest pain, the risk factors for this complication have not been investigated. METHODOLOGY: From January 2003 to December 2007, 241 patients were treated by endoscopic resection and 139 patients who met our criteria were analyzed. The case group was 40 patients who took an analgesic after endoscopic resection because of chest pain. The controls were 79 patients who did not experience chest pain after endoscopic resection. Twenty patients experienced chest pain, but did not take any analgesics. RESULTS: Although, 60 patients (43%) experienced chest pain, this was treatable by a common analgesic. Univariate analysis revealed that female gender had significant association and resection of posterior wall mucosa had marginal association with chest pain and analgesic use. No significant association with chest pain and analgesic use was found for age, resection method, use of acid suppressing drugs, lesion size and site. Logistic-regression analysis showed that significant risk factors for chest pain and analgesic use were female gender (odds ratio 3.45) and resection of posterior wall mucosa (odds ratio 3.13). CONCLUSIONS: Female gender and resection of posterior wall mucosa were associated with chest pain and analgesic use after endoscopic resection.

Efficacy of an endo-knife with a water-jet function (Flushknife) for endoscopic submucosal dissection of superficial colorectal neoplasms.

OBJECTIVES: Endoscopic submucosal dissection (ESD) is currently not a common treatment for colorectal neoplasms because it is time consuming and technically difficult. Flushknife--an electrosurgical endo-knife with a water-jet function--is expected to reduce the difficulty of colorectal ESD. The objective of this study was to investigate the efficacy of a water-jet function for colorectal ESD. METHODS: This study was a prospective randomized controlled trial, which was conducted at a cancer referral center. A total of 49 patients, with a total of 51 superficial colorectal neoplasms (median tumor size of 30 mm), were enrolled and randomly assigned to undergo ESD using either the Flexknife (electrosurgical endo-knife without a water-jet function) or the Flushknife. Tumors were resected by ESD using each endo-knife. The procedures were conducted by two endoscopists. Operation time was defined as the main outcome measure. RESULTS: En bloc resection was achieved in 23 out of 26 (88%) lesions in the Flexknife group and in 24 out of 24 (100%) lesions in the Flushknife group. The mean operation time (95% confidence interval) was 87.3 (71.3-103.4) min in the Flexknife group and 61.0 (49.3-72.7) min in the Flushknife group (P=0.02). The Flushknife reduced the number of endoscopic device changes (P=0.001), the number of submucosal injections (P=0.001), and the mean amount of injected hyaluronate sodium (P=0.001) compared with the Flexknife. No severe adverse events were observed in either group. CONCLUSIONS: Without increasing adverse events, the endo-knife with a water-jet function efficiently reduced the operation time of colorectal ESD in patients with large superficial colorectal neoplasms. (University hospital Medical Information Network Clinical Trials Registry number UMIN000001302).

Autofluorescence imaging with a transparent hood for detection of colorectal neoplasms: a prospective, randomized trial.

BACKGROUND: Colonoscopy is one of the most reliable methods for detection of colorectal neoplasms, but conventional colonoscopy can miss some lesions. OBJECTIVE: To evaluate the efficacy of autofluorescence imaging (AFI) with a transparent hood (TH) for detection of colorectal neoplasms. DESIGN: A 2 × 2 factorial designed, prospective, randomized, controlled trial. SETTING: This study was conducted at the Osaka Medical Center for Cancer and Cardiovascular Diseases, a tertiary cancer center. PATIENTS: A total of 561 patients. INTERVENTIONS: Patients were allocated to 1 of 4 groups: (1) white light imaging (WLI) alone--colonoscopy using WLI without a TH; (2) WLI+TH--colonoscopy using WLI with a TH; (3) AFI alone--colonoscopy using AFI without a TH; and (4) AFI+TH--colonoscopy using AFI with a TH. Eight colonoscopists used each allocated method. MAIN OUTCOME MEASUREMENT: The difference in neoplasm detection rate (number of detected neoplasms per patient) between the WLI alone and AFI+TH groups. RESULTS: Neoplasm detection rate (95% confidence interval) in the AFI+TH group was significantly higher than in the WLI alone group (1.96 [1.50-2.43] vs 1.19 [0.93-1.44]; P = .023, Tukey-Kramer multiple comparison test). Relative detection ratios (95% confidence interval) for polypoid neoplasms based on Poisson regression model were significantly increased by mounting a TH (1.69 [1.34-2.12], P < .001), and relative detection ratios for flat neoplasms were significantly increased by AFI observation (1.83 [1.24-2.71], P = .002). LIMITATIONS: Open trial performed in single cancer referral center. CONCLUSION: AFI colonoscopy with a TH detected significantly more colorectal neoplasms than did conventional WLI colonoscopy without a TH.

Endoscopic Doppler US for the prevention of ulcer bleeding after endoscopic submucosal dissection for early gastric cancer: a preliminary study (with video).

BACKGROUND: After endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), delayed bleeding occurs in 1.7% to 38% of cases. Routine coagulation of all nonbleeding visible vessels (NBVVs) in post-ESD ulcers is currently performed as standard practice, but it cannot eliminate bleeding. An endoscopic Doppler US (DOP-US) probe system has possible benefits for the prediction of recurrent bleeding in peptic ulcer hemorrhage. OBJECTIVE: To establish optimum use and evaluate feasibility of DOP-US for post-ESD ulcers. DESIGN: Case series study. SETTING: Cancer referral center. PATIENTS: Eight patients with mucosal EGC larger than 2 cm without ulceration or scarring and 2 patients with EGC less than 3 cm with scarring. INTERVENTIONS: We searched for a positive DOP-US signal (DOP-US+), which was defined as pulsatile sound at a depth of 1.5 mm, and NBVVs or areas with DOP-US+ were coagulated with hemostatic forceps. A multibending, double-channel videoendoscope that was fitted with a transparent hood was used. MAIN OUTCOME MEASUREMENTS: Detectability of DOP-US signals in post-ESD ulcers. RESULTS: One of 13 oozing bleeding sites, 24 (18%) of 136 NBVVs, and 7 areas without any bleeding stigmata had DOP-US+ and were coagulated until the signal became silent. One hundred twelve NBVVs (82%) and 8 adherent clots without DOP-US signals were left untreated. No delayed bleeding was experienced at 30 days. Median time required for Doppler examination was 34 minutes, but it improved to 18 and 19 minutes in patients 9 and 10, respectively. CONCLUSIONS: DOP-US might be helpful in the endoscopic management of post-ESD ulcers in EGC. Our setting and maneuver warrant further investigation to clarify whether DOP-US can reduce delayed bleeding and avoid unnecessary coagulation for NBVVs in post-ESD ulcers.

Autofluorescence imaging for predicting development of metachronous gastric cancer after Helicobacter pylori eradication.

BACKGROUND AND AIMS: Although Helicobacter pylori eradication decreases the incidence of metachronous gastric cancer after endoscopic treatment for early gastric cancer (EGC), metachronous cancer still develops after successful eradication, particularly in patients with severe corpus gastritis. We investigated whether the extent of atrophic fundic gastritis diagnosed by autofluorescence imaging (AFI) videoendoscopy is predictive of development of metachronous gastric cancer after H. pylori eradication in patients treated with endoscopic submucosal dissection (ESD) for EGC. PATIENTS AND METHODS: A total of 82 patients who underwent ESD for EGC from 2003 to 2006, who received eradication therapy participated in this study. The extent of chronic atrophic fundic gastritis was evaluated by AFI and categorized into closed and open type. The main outcome was the incidence of metachronous gastric cancer detected by annual surveillance endoscopy. RESULTS: During a median observation period of 55 months, metachronous gastric cancer developed in 12 of 82 patients (14.6%). Multivariate Cox's proportional hazard analysis revealed that open-type, atrophic fundic gastritis diagnosed by AFI was significantly associated with development of metachronous gastric cancer (hazard ratio: 4.88, 95% confidence interval [CI]: 1.32-18.2, P = 0.018) after adjustment for age, sex, histological intestinal metaplasia, serum pepsinogen level, and H. pylori status. CONCLUSIONS: Metachronous EGC developed after successful H. pylori eradication, and extensive atrophic fundic gastritis diagnosed by AFI was a significant predictor, thus it could identify patients undergoing ESD for EGC who still required intensive surveillance after eradication.

Significance of each narrow-band imaging finding in diagnosing squamous mucosal high-grade neoplasia of the esophagus.

BACKGROUND AND AIM: Although narrow-band imaging (NBI) is used increasingly in clinical situations, the significance of each NBI finding has not been investigated. The primary endpoint of the present study was to identify the significant NBI findings to diagnose esophageal mucosal high-grade neoplasia. METHODS: Between August 2007 and January 2009, we detected 59 new superficial esophageal lesions. The video images of NBI were recorded digitally. NBI findings such as brownish dots (dilated intra-epithelial papillary capillary loop [IPCL]), tortuous IPCL, elongated IPCL, caliber change in IPCL, variety in IPCL shapes, demarcation line, brownish epithelium, and protrusion or depression were evaluated using the video images. The association between each NBI finding and diagnosis of mucosal high-grade neoplasia, and intra- and interobserver agreement was evaluated. RESULTS: In univariate analysis, brownish epithelium, brownish dots, tortuous IPCL, variety in IPCL shapes and demarcation line were associated significantly with diagnosis of mucosal high-grade neoplasia. In multivariate analysis, brownish epithelium and brownish dots were confirmed to be independent factors. Odds ratios were 25.5 (95% confidence interval [CI]: 2.4-268) for brownish epithelium and 19.3 (95% CI: 1.8-207.7) for brownish dots. Intraobserver agreement was substantial for brownish epithelium and brownish dots. Interobserver agreement was moderate in brownish epithelium and brownish dots. CONCLUSIONS: Brownish epithelium and brownish dots were confirmed to be significant and reproducible NBI findings in the diagnosis of squamous mucosal high-grade neoplasia of the esophagus. Initial assessment of esophageal lesions should be done based on these findings.

Prospective evaluation of narrow-band imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia in experienced and less experienced endoscopists.

Narrow-band imaging (NBI) is a novel, noninvasive optical technique that uses reflected light to visualize the organ surface. However, few prospective studies that examine the efficacy of NBI screening for esophageal cancer have been reported. To compare the diagnostic yield of NBI endoscopy for screening of squamous mucosal high-grade neoplasia of the esophagus between experienced and less experienced endoscopists. Patients with a history of esophageal neoplasia or head and neck cancer received NBI endoscopic screening for esophageal neoplasia followed by chromoendoscopy using iodine staining. Biopsy specimens were taken from iodine-unstained lesions and the histological results of mucosal high-grade neoplasias served as the reference standard. The primary outcome was the sensitivity of NBI for detecting new lesions. The secondary outcome was the positive predictive value of NBI and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of NBI in a per lesion basis. A total of 350 patients (170 by experienced endoscopists and 180 by less experienced endoscopists) underwent endoscopic examination. A total of 42 new mucosal high-grade neoplastic lesions (25 in the experienced endoscopist group and 17 in the less experienced endoscopist group) were detected. In the per-lesion-based analysis, the sensitivity was significantly higher in the experienced endoscopist group (100%; 25/25) compared with the less experienced endoscopist group (53%; 9/17) (P < 0.001). The positive predictive value of NBI was higher in the experienced endoscopist group than in the less experienced endoscopist group (45%, 25/55 vs. 35%, 9/26), although the difference was not significant (P = 0.50). The sensitivity of NBI in the less experienced endoscopist group was 43% in the former half of patients, and increased to 60% in the latter half of patients. In the per-patient-based analysis, the sensitivity of NBI was significantly higher in the experienced endoscopist group (100%) than in the less experienced endoscopist group (100 vs. 69%, respectively; P = 0.04). The positive predictive values of the experienced endoscopist group and the less experienced endoscopist group were similar, and were 48 and 47%, respectively. In conclusion, compared with the gold standard of chromoendoscopy with iodine staining, the sensitivity of NBI for screening of mucosal high-grade neoplasia was 100% with the experienced endoscopists but was low with the less experienced endoscopists. Electronic chromoendoscopy with NBI is a promising screening tool in these high-risk patients with esophageal mucosal high-grade neoplasia, particularly when performed by endoscopists with experience of using NBI.

Quantitative analysis of the color change after iodine staining for diagnosing esophageal high-grade intraepithelial neoplasia and invasive cancer.

BACKGROUND: Despite its high sensitivity for detecting esophageal cancer, chromoendoscopy with iodine staining has low specificity and requires many biopsy specimens, which is undesirable. Dramatic color change after iodine staining (initially whitish yellow and then pink 2 to 3 minutes later) has come to be recognized as the pink-color sign in cancerous lesions. OBJECTIVE: The aim of the present study was to verify the accuracy of the pink-color sign for diagnosing esophageal squamous neoplasms by a quantitative analysis. DESIGN: A quantitative analysis of endoscopic images was performed by using prospectively pooled data. SETTING: A cancer referral center. PATIENTS: From December 2003 to September 2005, consecutive patients who underwent a procedure by an experienced endoscopist and had iodine-unstained lesions measuring 5 to 20 mm in diameter without obvious protrusions or ulcers were prospectively enrolled. MAIN OUTCOME MEASUREMENTS: The diagnostic ability of the quantitative assessment of the color change at 2 minutes after iodine staining (late phase) was investigated by using a receiver operating characteristic analysis. RESULTS: A total of 45 iodine-unstained lesions in 32 patients were included in the study. Among these, 22 of 23 pink-color-positive lesions were diagnosed as high-grade intraepithelial neoplasias or invasive cancers, whereas 19 of 22 pink-color-negative lesions were diagnosed as nonneoplastic lesions or low-grade intraepithelial neoplasias. The area under the receiver operating characteristic curve was 0.94, indicating excellent validity of the test. A sensitivity of 88% and specificity of 95% were obtained. LIMITATIONS: Single-center retrospective analysis. CONCLUSIONS: We verified the accuracy of the pink-color sign for diagnosing esophageal squamous neoplasms by a quantitative analysis.

Analysis of the color patterns of early gastric cancer using an autofluorescence imaging video endoscopy system.

BACKGROUND: Using a novel autofluorescence imaging video endoscopy system (AFI), tumors in the esophagus and the colon appeared purple in a green background, but the color patterns of early gastric cancer (EGC) were found to vary. Factors associated with these patterns remain unknown. The aims of the present study were to classify the color patterns of EGCs and to investigate the correlation between the patterns and clinicopathological features. METHODS: A total of 107 EGCs that had been evaluated by AFI endoscopy, prior to endoscopic or surgical resection, were included. The color patterns of EGCs in AFI images and the association between tumor color and clinicopathological factors were evaluated. These factors included tumor morphology, location, size, background color, histological type, depth of invasion, lymphatic or vessel permeation, and ulceration. RESULTS: The color patterns of EGCs were classified into the following four groups: purple tumors in a green background (52%); green tumors with a purple margin in a green background (21%); green tumors in a purple background (17%); and purple tumors in a purple background (10%). Univariate analysis showed that macroscopic type, histological type, ulceration, and background AFI color were significantly associated with tumor color, whereas multivariate analysis revealed that macroscopic type was the only independent contributor to tumor color. CONCLUSION: The present study has enabled a clearer understanding of the significance of tumor color in relation to the AFI imaging of EGCs. Recognition of the color patterns in AFI images should help in the diagnosis of EGCs.

[The effectiveness of S-1 based sequential chemotherapy as second-line treatment for advanced/recurrent gastric cancer].

BACKGROUND: We conducted this study to evaluate the efficacy of S-1 combination chemotherapy as second-line treatment for advanced/recurrent gastric cancer that was resistant to S-1 based chemotherapy as first-line treatment. PATIENTS AND METHODS: We evaluated patients included in phase II.III clinical trials, that is SPIRITS trial(S-1 vs CDDP +S-1), GC0301/TOP-002(S-1 vs CPT-11+S-1), OGSG0002(S-1+CPT-11)and OGSG0105(S-1+paclitaxel). Eligibility criteria at first-line included; pathologically proven gastric cancer, adequate bone marrow, hepatic, and renal functions, PS 0-2, no prior therapy, life expectancy estimated > or =12 weeks, age 20-75 years and written informed consent. Endpoints were as follows; )PFS in first-line and second-line, )Time to Second Progression(TSP), 3) OS. RESULTS: Sixty-six patients were evaluable in this study. We classified these patients into 4 groups according to the protocol. A)S-1 alone in first-line and S-1 combination in second-line(n=7), B)S-1 alone in first-line and other drugs in second-line(n=13), C)S-1 combination in first-line and another S-1 combination in second-line(n=33), D) S-1 combination in first-line and other drugs in second-line(n=13). We compared S-1 combination group(A+C)to other drugs group(B+D)in second-line. In first-line, PFS was 157.5 days in group(A+C)and 130 days in group(B +D)(p=0.2749). In second-line, PFS, TSP and OS were as follows; 72.5, 256.5, 473 days in group(A+C)and 56, 201.5, 398.5 days(PFS; p=0.0806, TSP: p=0.0718, OS: p=0.0204)in group(B+D), respectively. With regards to adverse events, group(A+C)in first-line showed higher frequency in grade 3/4 leukopenia(10%), febrile neutropenia(5%)and grade 3 diarrhea(10%)than group(B+D). In second-line, group(B+D)showed grade 3/4 leukopenia (12%)and neutropenia(8%)than group(A+C). There were no treatment-related deaths. CONCLUSION: These results indicate that S-1 combination chemotherapy is efficient as second-line for advanced/recurrent gastric cancer that got resistant to S-1 based chemotherapy as first-line.

Comparison of EMR and endoscopic submucosal dissection for en bloc resection of early esophageal cancers in Japan.

BACKGROUND: EMR and endoscopic submucosal dissection (ESD) are now being increasingly used for the treatment of esophageal cancers. However, their efficacies in smaller lesions have not been compared. OBJECTIVE: For effective use of these methods, we compared the results of ESD and 2 major EMR methods for treating esophageal cancers of

Infrared endoscopic system for bleeding-point detection after flushing with indocyanine green solution (with videos).

BACKGROUND: Infrared endoscopy is used to visualize vessels in the GI tract. By applying this system, we developed a new method to visualize a bleeding point during endoscopic resection. OBJECTIVE: This study aimed to evaluate the ability of infrared endoscopy to detect a bleeding point during endoscopic resection and to elucidate the mechanism required for clear visualization of a bleeding point by in vitro color analysis. DESIGN: Observational case series. SETTING: A cancer-referral center. PATIENTS AND INTERVENTIONS: A total of 10 bleeding sites were observed during endoscopic resection of upper-GI cancers by infrared endoscopy after flushing with indocyanine green (ICG) solution (0.125 mg/mL water). MAIN OUTCOME MEASUREMENTS: Detection of bleeding points. RESULTS: Bleeding points were identified in all bleeding sites by infrared endoscopic viewing. Bleeding points were displayed in white, whereas, an ulcer bed was in blue and pooled blood was a blue-to-gray color. By in vitro color analysis, blood was white, blood twice diluted with ICG solution was dark blue, and blood 4-times diluted with ICG solution was light blue on infrared endoscopic views. Color differences with blood dilution were more obvious in an infrared endoscopic view compared with a conventional endoscopic view. Blood thickness, movement, and clotting did not influence the color differences. LIMITATIONS: Uncontrolled study. CONCLUSIONS: We reported a flushing method by which we could detect all bleeding points during endoscopic resection. Clear visualization of bleeding points comes from differences in blood and ICG concentration between spurting and pooled blood.

[A case of gastric carcinoid with type A gastritis].

A 40-year-old man was admitted to our hospital for treatment of gastric carcinoid of 7-mm in diameter associated with type A gastritis. Endoscopic mucosal resection was performed and histological examination revealed a gastric carcinoid with submucosal invasion (2500microm). Three months after the resection, the other carcinoid of 3-mm lesion was found, but no recurrence of resected portion. Neither local recurrence nor distant metastasis has been observed during 1-year follow-up period. These findings revealed that gastric carcinoid with type A gastritis, when smaller than 1-cm in diameter, could be cured with endoscopic procedure.

Cross talk between apoptosis and invasion signaling in cancer cells through caspase-3 activation.

In solid tumors, cancer cells are exposed to various microenvironmental stresses such as hypoxia, nutritional depletion, and low pH. Cancer cells adapt to these stresses and circumvent cell death. When the antiapoptotic signals overcome the stress, cancer cells might acquire physiologic functions, such as invasiveness, instead of cell death. Here, we report that tumor cells acquire an invasive capacity from apoptotic signals through caspase activation. We treated rat ascites hepatoma MM1 cells with an apoptosis-inducing drug, etoposide, or hypoxia, and assessed the invasion capacity with an in vitro bioassay. Although MM1 cells hardly showed invasiveness in serum-free medium, under stress conditions, invasive capacity accompanied with morphologic change was induced with caspase-3 activation. Such stress-induced invasion as well as morphologic change was suppressed by blocking caspase-3 activity with caspase inhibitors or by RNA interference of caspase-3. In contrast, lysophosphatidic acid-induced invasiveness was not affected by caspase-3 inhibition. These results suggest that caspase-3 activation contributes to the stress-induced invasive capacity of these cancer cells.

Inhibition of transendothelial migration and invasion of human breast cancer cells by preventing geranylgeranylation of Rho.

Rho family GTPases are frequently overexpressed in breast cancers, which regulate cancer cell migration and invasion. They require prenylation, a lipid post-translational modification, for full biological functions. We examined the effects of 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (fluvastatin), a selective farnesyltransferase inhibitor (FTI-277) and a selective geranylgeranyltransferase type I inhibitor (GGTI-298) on in vitro invasive capacity of MDA-MB-231 human breast cancer cells into the endothelial cell monolayer in a transendothelial migration assay. Although, at a maximal dose of 5 microM, fluvastatin did not affect the integrity of endothelial cell monolayer, the transendothelial migration of MDA-MB-231 cells was inhibited potently by fluvastatin in a dose-dependent manner. The transendothelial migration of MDA-MB-231 cells was also inhibited potently by GGTI-298 in a dose-dependent manner but weakly by FTI-277. The inhibitory effects of fluvastatin, GGTI-298 and FTI-277 on MDA-MB-231 cell invasion were shown to correlate well with inhibition of the membrane localization of RhoA and RhoC, but not with Ras. These results suggest that geranylgeranylation step of RhoA and RhoC could be a good therapeutic target for the prevention of invasion and metastasis of breast cancer cells.