Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study.

BACKGROUND & AIMS: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. METHODS: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). RESULTS: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. CONCLUSIONS: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Randomised comparison of postpolypectomy surveillance intervals following a two-round baseline colonoscopy: the Japan Polyp Study Workgroup.

OBJECTIVE: To assess whether follow-up colonoscopy after polypectomy at 3 years only, or at 1 and 3 years would effectively detect advanced neoplasia (AN), including nonpolypoid colorectal neoplasms (NP-CRNs). DESIGN: A prospective multicentre randomised controlled trial was conducted in 11 Japanese institutions. The enrolled participants underwent a two-round baseline colonoscopy (interval: 1 year) to remove all neoplastic lesions. Subsequently, they were randomly assigned to undergo follow-up colonoscopy at 1 and 3 years (2-examination group) or at 3 years only (1-examination group). The incidence of AN, defined as lesions with low-grade dysplasia ≥10 mm, high-grade dysplasia or invasive cancer, at follow-up colonoscopy was evaluated. RESULTS: A total of 3926 patients were enrolled in this study. The mean age was 57.3 (range: 40-69) years, and 2440 (62%) were male. Of these, 2166 patients were assigned to two groups (2-examination: 1087, 1-examination: 1079). Overall, we detected 29 AN in 28 patients at follow-up colonoscopy in both groups. On per-protocol analysis (701 in 2-examination vs 763 in 1-examination group), the incidence of AN was similar between the two groups (1.7% vs 2.1%, p=0.599). The results of the non-inferiority test were significant (p=0.017 in per-protocol, p=0.001 in intention-to-treat analysis). NP-CRNs composed of dominantly of the detected AN (62%, 18/29), and most of them were classified into laterally spreading tumour non-granular type (83%, 15/18). CONCLUSION: After a two-round baseline colonoscopy, follow-up colonoscopy at 3 years detected AN, including NP-CRNs, as effectively as follow-up colonoscopies performed after 1 and 3 years.

Validation study for development of the Japan NBI Expert Team classification of colorectal lesions.

BACKGROUND AND AIM: The Japan narrow-band imaging (NBI) Expert Team (JNET) was organized to unify four previous magnifying NBI classifications (the Sano, Hiroshima, Showa, and Jikei classifications). The JNET working group created criteria (referred to as the NBI scale) for evaluation of vessel pattern (VP) and surface pattern (SP). We conducted a multicenter validation study of the NBI scale to develop the JNET classification of colorectal lesions. METHODS: Twenty-five expert JNET colonoscopists read 100 still NBI images with and without magnification on the web to evaluate the NBI findings and necessity of the each criterion for the final diagnosis. RESULTS: Surface pattern in magnifying NBI images was necessary for diagnosis of polyps in more than 60% of cases, whereas VP was required in around 90%. Univariate/multivariate analysis of candidate findings in the NBI scale identified three for type 2B (variable caliber of vessels, irregular distribution of vessels, and irregular or obscure surface pattern), and three for type 3 (loose vessel area, interruption of thick vessel, and amorphous areas of surface pattern). Evaluation of the diagnostic performance for these three findings in combination showed that the sensitivity for types 2B and 3 was highest (44.9% and 54.7%, respectively), and that the specificity for type 3 was acceptable (97.4%) when any one of the three findings was evident. We found that the macroscopic type (polypoid or non-polypoid) had a minor influence on the key diagnostic performance for types 2B and 3. CONCLUSION: Based on the present data, we reached a consensus for developing the JNET classification.

Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team.

Many clinical studies on narrow-band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low-grade intramucosal neoplasia, high-grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Accuracy of using Diagnosis Procedure Combination administrative claims data for estimating the amount of opioid consumption among cancer patients in Japan.

OBJECTIVE: The state of opioid consumption among cancer patients has never been comprehensively investigated in Japan. The Diagnosis Procedure Combination claims data may be used to measure and monitor opioid consumption among cancer patients, but the accuracy of using the Diagnosis Procedure Combination data for this purpose has never been tested. METHODS: We aimed to ascertain the accuracy of using the Diagnosis Procedure Combination claims data for estimating total opioid analgesic consumption by cancer patients compared with electronic medical records at Aomori Prefectural Central Hospital. We calculated percent differences between estimates obtained from electronic medical records and Diagnosis Procedure Combination claims data by month and drug type (morphine, oxycodone, fentanyl, buprenorphine, codeine and tramadol) between 1 October 2012 and 30 September 2013, and further examined the causes of discrepancy by reviewing medical and administrative charts between April and July 2013. RESULTS: Percent differences varied by month for drug types with small prescription volumes, but less so for drugs with larger prescription volumes. Differences also tended to diminish when consumption was compared for a year instead of a month. Total percent difference between electronic medical records and Diagnosis Procedure Combination data during the study period was -0.1% (4721 mg per year per hospital), as electronic medical records as baseline. Half of the discrepancy was caused by errors in data entry. CONCLUSION: Our study showed that Diagnosis Procedure Combination claims data can be used to accurately estimate opioid consumption among a population of cancer patients, although the same conclusion cannot be made for individual estimates or when making estimates for a group of patients over a short period of time.

Clinical Features of Fecal Immunochemical Test-Negative Colorectal Lesions based on Colorectal Cancer Screening among Asymptomatic Participants in Their 50s.

OBJECTIVE: To improve the efficacy of colorectal cancer (CRC) screening, decreasing the occurrence of interval cancers is essential. Most interval CRCs develop from fecal immunochemical test (FIT)-negative CRC. This study examined the clinical characteristics of FIT-negative advanced neoplasms (AN) and sessile serrated lesions (SSL), which are main candidate precursors of FIT-negative CRC, and the eligibility criteria for total colonoscopy (TCS) screening following negative FIT. METHODS: Asymptomatic participants in their 50s were divided into two groups. The FIT-negative group underwent TCS following negative FIT, and the TCS-only group underwent TCS without FIT. One endoscopist reviewed the endoscopic images. Plausible risk factors for colorectal polyps were extracted. The clinical features of AN and SSL were compared between the groups. RESULT: Of 2,437 participants, 56.2% were included in the FIT-negative group. No between-group differences were recorded for the prevalence of different colorectal polyp types. By multivariate analysis, a significantly lower adjusted odds ratio (AOR) of AN was shown in women, and significantly higher AORs of AN were found for aging, smoking, and a family history of CRC. The AOR of SSL was higher for smokers. The proportion of AN in the right colon was higher in the FIT-negative group. No between-group differences were recorded for SSL. CONCLUSION: FIT screening was less likely to detect CRC and certain precancerous lesions in the right colon. Combining annual FIT with TCS for the high-risk population based on a scoring system, may detect FIT-negative CRC and colorectal polyps, thus, reducing interval cancer.

Successful endosocpic submucosal dissection for esophageal squamous cell carcinoma together with a lipoma.

Superficial carcinomas over submucosal tumors of the esophagus have seldom been detected. Esophageal lipomas are very rare and only a few cases have been reported. We describe the case of a 73-year-old man with superficial squamous cell carcinoma overlying a lipoma. We successfully performed en bloc resection by endoscopic submucosal dissection (ESD) using the IT-knife. Histological examination showed curative resections. In such cases, ESD may be a promising tool to perform less invasive treatment.

A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, although it is not widely used in the colorectum because of technical difficulty. OBJECTIVE: To examine the current status of colorectal ESDs at specialized endoscopic treatment centers. DESIGN AND SETTING: Multicenter cohort study using a prospectively completed database at 10 specialized institutions. PATIENTS AND INTERVENTIONS: From June 1998 to February 2008, 1111 colorectal tumors in 1090 patients were treated by ESD. MAIN OUTCOME MEASUREMENTS: Tumor size, macroscopic type, histology, procedure time, en bloc and curative resection rates and complications. RESULTS: Included in the 1111 tumors were 356 tubular adenomas, 519 intramucosal cancers, 112 superficial submucosal (SM) cancers, 101 SM deep cancers, 18 carcinoid tumors, 1 mucosa-associated lymphoid tissue lymphoma, and 4 serrated lesions. Macroscopic types included 956 laterally spreading tumors, 30 depressed, 62 protruded, 44 recurrent, and 19 SM tumors. The en bloc and curative resection rates were 88% and 89%, respectively. The mean procedure time ± standard deviation was 116 ± 88 minutes with a mean tumor size of 35 ± 18 mm. Perforations occurred in 54 cases (4.9%) with 4 cases of delayed perforation (0.4%) and 17 cases of postoperative bleeding (1.5%). Two immediate perforations with ineffective endoscopic clipping and 3 delayed perforations required emergency surgery. Tumor size of 50 mm or larger was an independent risk factor for complications, whereas a large number of ESDs performed at an institution decreased the risk of complications. LIMITATIONS: No long-term outcome data. CONCLUSIONS: ESD performed by experienced endoscopists is an effective alternative treatment to surgery, providing high en bloc and curative resection rates for large superficial colorectal tumors.

Meshed capillary vessels by use of narrow-band imaging for differential diagnosis of small colorectal polyps.

BACKGROUND: Although microvascular vessels on the surface of colorectal polyps are observed by narrow-band imaging (NBI) with magnification, its clinical usefulness is still uncertain. OBJECTIVE: Our purpose was to evaluate the usefulness of meshed capillary (MC) vessels observed by NBI magnification for differentiating between nonneoplastic and neoplastic colorectal lesions. DESIGN: Prospective polyp study. SETTING: National Cancer Center Hospital East, Chiba, Japan. PATIENTS: A total of 702 consecutive patients who underwent total colonoscopy between September and December 2004 were prospectively evaluated. Patients with polyps >10 mm and those with polyps previously evaluated by histologic examination or colonoscopy were excluded. INTERVENTION: Lesions were classified into 2 groups: polyps with invisible or faintly visible MC vessels as nonneoplastic and polyps with clearly visible MC vessels as neoplastic. Lesions judged as nonneoplastic were subjected to biopsy and those as neoplastic were removed endoscopically. Histologic analysis was performed in all lesions. MAIN OUTCOME MEASUREMENT: Visible or invisible surface MC vessels, prediction of histologic diagnosis. RESULTS: Of 92 eligible patients enrolled in this study, 150 lesions, including 39 (26%) hyperplastic polyps and 111 (74%) adenomatous polyps, were detected. Observation of MC vessels detected 107 of 111 neoplastic polyps and 36 of 39 nonneoplastic polyps. The overall diagnostic accuracy, sensitivity, and specificity were 95.3%, 96.4%, and 92.3%, respectively. LIMITATIONS: MC vessel judgment performed by a single colonoscopist with extensive experience in magnifying NBI. CONCLUSION: Observation of surface MC vessels by magnifying NBI is a useful and simple method for differentiating colorectal nonneoplastic and neoplastic polyps.

Five-year incidence of advanced neoplasia after initial colonoscopy in Japan: a multicenter retrospective cohort study.

OBJECTIVE: The National Polyp Study is used as the basis of recommendations for colonoscopic surveillance after polypectomy, establishing an interval of 3 years after removal of newly diagnosed adenomas. The aim of this retrospective cohort study was to estimate the incidence of advanced neoplasia after initial colonoscopy and compare the differences among risk groups. METHODS: Patients over 40 years who were referred for initial colonoscopy at six institutes were selected. They were classified into four groups based on the initial colonoscopy: A, patients without any adenoma; B, with adenomas of <6 mm only; C, with adenomas of >or=6 mm; D, with any intramucosal cancer. The index lesion (IL) at follow-up colonoscopy was defined as large adenoma >or=10 mm, intramucosal/invasive cancer. RESULTS: A total of 5309 patients were enrolled in this study. Overall, median follow-up period was 5.1 years. The numbers of eligible patients in the various subgroups were A, 2006; B, 1655; C, 1123; D, 525. A total of 379 ILs were newly diagnosed during follow-up colonoscopy. The cumulative incidence of ILs in each group was A, 2.6%; B, 6.7%; C, 13.4%; and D, 12.6%. CONCLUSIONS: Patients with any adenomas >6 mm or intramucosal cancer at the initial colonoscopy have a higher risk of advanced neoplasia during follow-up colonoscopy.

Relationship between MVD and meshed-capillaries using magnifying NBI colonoscopy in colorectal precursor lesions.

BACKGROUND/AIMS: To prospectively investigate differences in angiogenesis between low-grade dysplasia (LGD) and hyperplastic polyps, as well as the relationship between microvessel density (MVD) as identified by histological analysis and meshed-capillary (MC) vessels visualized using magnifying narrow band imaging (NBI) colonoscopy. METHODOLOGY: Immunohistochemical analysis of MVD was performed using monoclonal antibody against CD31. The number and thickness of vessels were investigated for 45 LGD and 25 hyperplastic polyps. In contrast, NBI colonoscopy was able to classify all lesions into either visualization or nonvisualization of MC vessels. RESULTS: No significant difference was seen in the number of thin vessels (< or =10 microm) using immunohistochemical MVD analysis between LGDand hyperplasic polyps (p = 0.36). In contrast, the number of intermediate (11-20 microm) and thick vessels (> or =21 microm) differed significantly between LGD and hyperplasic polyps, respectively (p < 0.0001, p < 0.0001). In NBI findings, the presence of MC vessels was found in 98% (44 of 45) of LGD, while MC vessels were absent in 92% (23 of 25) of hyperplasic polyps. CONCLUSIONS: We postulated that the incidence of intermediate and thick vessels (>10 microm) is related to angiogenesis occurring during carcinogenesis of colorectal mucosa. Furthermore, the appearance of visualized MC vessels during magnifying NBI colonoscopy can be used to identify angiogenesis in colorectal LGD and hyperplastic polyps.

A phase II study of sequential methotrexate and 5-fluorouracil chemotherapy in previously treated gastric cancer: a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group, JCOG 9207 trial.

OBJECTIVE: As prognosis of advanced gastric cancer is still poor, a standard regimen after first-line fluorouracil (FU)-based chemotherapy has not yet been established. Therefore, we conducted a phase II study to evaluate the efficacy and toxicity of sequential treatment with methotrexate (MTX) and also 5-FU as second-line chemotherapy in patients with advanced gastric cancer. METHODS: Treatment consisted of weekly doses of MTX (100 mg/m(2), i.v. bolus), followed by 5-FU (600 mg/m(2), i.v. bolus) 3 h after MTX administration. Leucovorin rescue therapy (six doses of 10 mg/m(2), given at 6-h intervals) was commenced 24 h after a treatment with MTX. The primary endpoint was the response rate. RESULTS: Between December 1992 and June 1995, 56 patients were registered in this study and one was ineligible. All registered patients were included in all analyses. The median age of the patients was 60 years (20-75 years). Most patients (75%) had a performance status of 0 or 1, and 51 (90%) received 5-FU-based chemotherapy as first-line treatment. The major adverse events were myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 6.3% of the patients. The overall objective response rate was 9.0% [five partial responses among 56 patients, 95% confidence interval (CI): 3.0-20%]. The median overall survival time was 237 days, and the 1-year survival proportion was 21.4%. CONCLUSIONS: Sequential MTX/5-FU therapy provides good survival outcomes with tolerable toxicity despite a limited response in patients with previously treated advanced gastric cancer. This regimen is now being evaluated in a randomized study in patients with pretreated advanced gastric cancer, by the Japan Clinical Oncology Group.

Long-term outcomes of patients with metastatic gastric cancer after initial S-1 monotherapy.

BACKGROUND: S-1, an oral fluoropyrimidine, has been shown to have excellent activity against gastric cancer in two phase II studies and is widely used in Japan. However, the long-term outcomes of patients after S-1 monotherapy for metastatic gastric cancer are unclear. The aim of this study was to investigate the long-term outcomes in metastatic gastric cancer patients who had initially received S-1 monotherapy. METHODS: Ninety-two previously untreated patients with advanced gastric cancer received S-1 monotherapy as first-line chemotherapy at the National Cancer Center Hospital East, Kashiwa, Japan, and then the long-term outcomes and characteristics of long-term survivors were analyzed retrospectively. Multivariate analysis of prognostic factors was performed by the Cox proportional hazard method. RESULTS: With a median follow-up of 3.1 years, the median progression-free survival time was 4.6 months. The median survival time was 11.9 months, with 1-, 2- and 3-year survival rates of 49.1%, 22.8%, and 9.8%, respectively. Multivariate analysis showed that good performance status (P = 0.0004) and only one metastatic site (P = 0.0048) were significant independent prognostic factors. Among 48 patients with a single metastatic site, 22 with peritoneal metastasis had longer survival times (median survival, 24 months) than patients with metastasis at other sites. Among the nine 3-year survivors, six had peritoneal metastases alone. CONCLUSIONS: The survival outcomes after S-1 monotherapy are promising, especially in patients with good performance status and a single metastatic site. Our findings suggest that, among patients with a single metastatic site, those with peritoneal metastases alone have a chance for long-term survival.

Computer-assisted analysis of biopsy specimen microvessels predicts the outcome of esophageal cancers treated with chemoradiotherapy.

PURPOSE: A computer-assisted microvessel analysis system was developed to evaluate correlations between the architecture of biopsy specimen microvessels and the outcome for patients with esophageal cancer treated with chemoradiotherapy. EXPERIMENTAL DESIGN: Biopsy specimens from 51 patients with esophageal cancer (T(2-3), any N, M0) treated with chemoradiotherapy were immunostained with an anti-CD31 antibody and quantified using computerized image analysis. We evaluated the association of several microvessel factors with overall survival, including the ratio of total microvessel perimeter to total tumor area (TP/TA), the tumor hypoxic ratio, and the ratio of total microvessel number to total tumor area (TN/TA). Results from traditional manual microvessel density (MVD) hotspot count and computerized hotspot count were compared and the relation between hotspot MVD count and survival rate was evaluated. RESULTS: The median follow-up time was 32 months. Both univariate and multivariate analyses revealed that computer-counted hotspot MVD and TN/TA and TP/TA ratios correlated significantly with the outcome of chemoradiotherapy. Kaplan-Meier survival curves showed that patients with high computer-counted hotspot MVDs and high TN/TA and TP/TA ratios had better overall survival rate than patients with low MVDs or ratios (P = 0.025, 0.008, and 0.031, respectively). Combining computer-counted MVD or TN/TA ratio with TP/TA ratio proved more predictive than any single factor. Two researcher-counted hotspot MVDs had no significant relation with outcome. CONCLUSION: Computer-assisted tumor microvessel analysis is a powerful tool in predicting the outcome for patients with esophageal cancer treated with chemoradiotherapy because intraobserver and interobserver variability is minimized.

Significance of biological markers for predicting prognosis and selecting chemotherapy regimens of advanced gastric cancer patients between continuous infusion of 5-FU and a combination of 5-FU and cisplatin.

BACKGROUND: Our previous phase II study of 5-fluorouracil (5-FU) and cisplatin (FP) for treatment of advanced gastric cancer showed that strong immunoreactivity for vascular endothelial growth factor (VEGF) is associated with chemoresponse. Patients with four or five of the favorable phenotypes, p53 (-), bcl-2 (-), gluthathione S-transferase pi (-), thymidylate synthase (-), and VEGF (+), survived longer than those with three or less of these phenotypes. The purpose of this study is to confirm our previous results and to compare the significance of those markers between continuous infusion of 5-FU (5-FUci) and FP. METHODS: Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolled to JCOG9205 were analyzed immunohistochemically for the presence of the five markers. RESULTS: Median survival times of patients treated with 5-FUci (n = 65) or FP (n = 66) were 216 and 253 days, respectively (P = 0.6953). After FP treatment, patients with four or five favorable phenotypes (n = 20) survived longer than those with three or less favorable phenotypes (n = 46) (334 days and 243 days, respectively; P = 0.0463), and the survival times of 34 and 32 patients with VEGF (-) and (+) were similar (269 days and 253 days, respectively; P = 0.6317). After 5-FUci, 30 patients with VEGF (+) survived for a shorter time than 35 patients with VEGF (-) (142 days and 302 days, respectively; P = 0.0043). CONCLUSION: The number of favorable phenotypes is prognostic for gastric cancer patients treated with FP, and VEGF has a different impact on survival between treatment with 5-FUci and FP.

Feasibility of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) for Japanese patients with unresectable metastatic colorectal cancer.

BACKGROUND: A combination of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) is one of the standard regimens for palliative and adjuvant chemotherapy for colorectal cancer. However, the feasibility of FOLFOX4 for Japanese patients has not been determined. We conducted this prospective study to evaluate the feasibility of FOLFOX4. METHODS: Previously treated or untreated patients with unresectable metastatic colorectal cancer were enrolled. The primary endpoint was the rate of completion which was defined as completion of the first 4 cycles with relative dose-intensity of oxaliplatin of 80% or higher. RESULTS: Of the 32 enrolled patients, 31 received FOLFOX4. Twenty-four patients (75%) had received prior chemotherapy. The rate of completion of the first four cycles was 87% (27/31; 95% CI, 70.2-96.4%). With the median number of cycles of nine (range, 1-26), grade 3 or 4 hematological toxicity and non-hematological toxicity were seen in 12 (39%) and 5 (16%) patients, respectively. Grade 1 or 2 sensory neuropathy was seen in 28 patients (90%), but no grade 3 or 4 neuropathy was seen. Grade 1 or 2 allergic reaction was seen in five patients (16%). One patient developed fatal interstitial pneumonitis and died of respiratory failure. Objective response rate was 28.6% (6/21; 95% CI, 11.3-52.2%) in the patients with measurable lesions. Median progression-free survival was 6.5 months (95% CI, 4.6-8.5 months) in all patients. CONCLUSIONS: The completion rate of the first four cycles was as high as expected with manageable toxicity, although fatal pneumonitis developed in one case. FOLFOX4 is feasible for Japanese patients.

Expression profiling of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy: clinical implications.

In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy (CRT) has a curative potential even in cases of locally advanced carcinoma. However, only about half of the patients benefit from CRT, and an accurate prediction of sensitivity to CRT is eagerly awaited. Using microarrays, we analyzed gene-expression patterns of pretreatment biopsy specimens from 33 patients with CRT alone including long-term survivors, more than 3 years (14 cases) and short-term survivors, less than 1 year (11 cases). The expression patterns of about 12,600 genes were used to identify genes correlated with survival terms. Fifty-seven genes correlating with short-term survival and 120 genes with long-term survival were identified. The genes involved in the immune response were characteristically upregulated in the long-term survivors, and an immunohistochemical staining confirmed an increased CD8-positive T cell number in the long-term survivors over that in the short-term survivors. In the short-term survivors, on the other hand, increased expression of the genes involved in drug resistance was observed. Our gene list should contribute to the elucidation of the mechanisms of CRT response and contains useful markers for predicting the prognosis of individual ESCC patients treated with CRT alone.

Detection and treatment of early cancer in high-risk populations.

In this paper we describe how to more efficiently detect and treat early gastric cancer (EGC) in high-risk populations. For detection, we first assess the value of known risk factors from the viewpoint of availability for cancer screening. Serum pepsinogen appears to be the most useful and realistic of the factors examined, although its adequacy needs to be assessed in high-risk populations other than those in Japan. Helicobacter pylori infection is known to be a universal risk factor (or gastric carcinogen), and several interventional studies have recently shown positive results. However, H. pylori infection can be eradicated from at-risk populations, thereby decreasing its availability for cancer screening. Smokers are thought to be at risk epidemiologically, but the efficacy of screening in this population has yet to be elucidated, and further studies are warranted. Gender and aging can be risk factors in Japanese populations; male gender and old age are predominant in the intestinal type of carcinoma which is dominant in Japan, although this is not the case in the West. As for early diagnosis of cancer, only endoscopy can be commonly used for the detection of gastritis-like EGC, seen as a faint mucosal irregularity or discoloration. To make early diagnosis more accurate, it is indispensable to carry out detailed endoscopy together with careful scrutiny of the mucosa using dye-spraying techniques. The remarkable progress of early diagnosis in Japan prompted the endoscopic treatment for less invasive EGCs. The first success was with endoscopic mucosal resection (EMR). Although convenient, its therapeutic efficacy is inadequate, particularly for larger lesions. Endoscopic submucosal dissection (ESD) has no limitation on resection size and is expected to replace surgery, although it needs a high level of skill and there are several technical problems to be solved.

Alpha-fetoprotein-producing colon cancer with atypical bulky lymph node metastasis.

Alpha-fetoprotein (AFP)-producing colorectal cancer is extremely rarely reported until now. All of the reported cases harboring synchronous hematogenous spread including liver and/or lung metastasis had a poor prognosis and died within 12 mo. We here describe a 71-year old man with AFP-producing colon cancer who presented with an unusual bulky lymph node metastasis instead of hematogenous spread. He underwent adjuvant chemotherapy in addition to curative surgical resection, which prolonged his survival.