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Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Introduction: In the post-Helicobacter pylori era, autoimmune gastritis (AIG) is attracting increasing attention as an origin of gastric cancer. Here, we performed clinicopathological examination of gastric cancer complicating AIG treated in our hospital., Methods: Eighty-six early gastric cancer lesions complicating AIG in 50 patients were treated by endoscopic submucosal dissection (ESD) at our hospital in 2008-2022. Their clinicopathological characteristics were compared with those of a control group comprising 2,978 early gastric cancer lesions (excluding lesions in the remnant stomach after surgery) in 2,278 patients treated by ESD during the same period., Results: Mean age was significantly higher in the AIG group than in the control group (74.7 years vs. 70.9 years; p < 0.01). In the respective groups, the occurrence rate of synchronous/metachronous lesions was 38.0% and 20.4% (p < 0.01), the ratio of longitudinal cancer locations (upper/middle/lower third [U/M/L]) was 27/32/27 and 518/993/1,467 (p < 0.01), the ratio of circumferential cancer locations (lesser curvature/greater curvature/anterior wall/posterior wall) was 25/31/12/18 and 1,259/587/475/657 (p < 0.01), the ratio of major macroscopic types (I/IIa/IIb/IIc) was 13/38/5/30 and 65/881/220/1,812 (p < 0.01). The rates of multiple gastric cancer and cancers in the U region, at the greater curvature, and of protruding types were significantly higher in the AIG group., Conclusion: The occurrence rate of multiple gastric cancer was significantly higher in gastric cancer complicating AIG (approximately 40%), and compared with the control group, the proportions of cancers at the U region, at the greater curvature, and of protruding types were significantly higher., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: We investigated the validity and safety of endoscopic submucosal dissection for gastric tumors by examining shortand long-term outcomes by tumor diameter., Materials and Methods: Endoscopic submucosal dissection for gastric tumor was performed on 4259 lesions at our hospital between January 2005 and June 2021. [Study 1] Patients were divided into 5 tumor diameter groups: 3751 lesions, ≤30 mm; 366 lesions, 31-50 mm; 106 lesions, 51-75 mm; 24 lesions, 76-100 mm; and 12 lesions, ≥101 mm. Short-term gastric endoscopic submucosal dissection outcomes were investigated. [Study 2] Long-term outcomes (delayed gastric emptying and prognosis) were investigated in 508 cases with tumor diameter ≥31 mm., Results: [Study 1] Perforation rate (%) was 1.2, 3.6, 3.8, 12.5, and 25.0 for lesions with tumor diameter ≤30 mm, in the range 31-50 mm, 51-75 mm, and 76-100 mm, and ≥101 mm, respectively. Postoperative bleeding rate (%) was 4.8, 9.0, 6.6, 20.8, and 33.3, respectively, R0 resection rate (%) was 96.8, 90.2, 89.6, 70.8, and 66.6, respectively, and curative resection rate (%) was 92.0, 61.2, 63.2, 45.8, and 8.3, respectively. [Study 2] There were 7 cases of delayed gastric emptying after wide resection, with 3 patients requiring balloon dilatation, 1 of whom subsequently underwent distal gastrectomy. Among 205 cases of noncurative resection, 110 underwent additional surgery, residual cancer was present in 11 cases, and lymph node metastasis was observed in 7 cases (1 patient died of disease). To date, 1 of the 95 patients being followed up has died of disease (mean follow-up: 2042 days)., Conclusion: Even with a tumor diameter ≥31 mm, curative resection was achieved in about 60% of cases in which intramucosal lesions were considered possible preoperatively, but the rate was low at 8.3% for tumor diameter ≥101 mm. Long-term outcomes appear favorable, with only 0.4% of the patients dying of disease but delayed gastric emptying observed in 1.7% of cases.

Outpatient nutritional counseling by a registered dietitian is often performed to prevent weight loss, but evidence supporting this practice is insufficient. In this study, we aimed to clarify the effectiveness of four-time outpatient nutritional counseling in weight-loss prevention compared with conventional intervention limited to one-time nutritional counseling. This study was designed as a retrospective cohort study. The target population was postoperative patients with stage IA and IB gastric cancer. Groups that received one-time and four-time nutritional counseling included patients who underwent gastrectomy from May 2014 to April 2017 and May 2017 to December 2019, respectively. The one-time group received counseling at discharge; the four-time group received counseling at discharge, at the first outpatient visit, and at 3 and 6 months postoperatively. There were 58 patients in the one-time group and 27 patients in the four-time group, with a significant difference in length of hospital stay (p = 0.042). Thirty-six patients (62.1%) in the one-time nutritional counseling group and 12 (44.4%) in the four-time group had a weight loss of 5% or more from hospital discharge to 6 months postoperatively. The adjusted risk ratio for the effectiveness of four counseling sessions compared with one session was 0.69 (95% confidence interval 0.35-1.34). In subgroup analysis, the effect of nutritional guidance was greater for patients with body mass index ≥23 kg/m2, but this depended on the outcome and number of cases, and there was no essential difference between the groups. In postoperative patients with stage IA and stage IB gastric cancer, four sessions of outpatient nutrition counseling may be not superior to one counseling session in preventing weight loss., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Matsushita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous studies have revealed an association between probiotic use and effectiveness of immune checkpoint inhibitors in renal and lung cancers. However, little is known regarding other cancers, including gastrointestinal cancer., Methods: To address this issue, we conducted a multicenter retrospective cohort study and the duration of nivolumab treatment for various cancers was compared between probiotic users and non-users., Results and Conclusions: In total, 488 patients who received nivolumab therapy were included. In all cancers, no significant differences in treatment duration of nivolumab were observed between probiotic users and non-users (median 62.0 vs. 56.0, hazard ratio = 1.02, p = 0.825), whereas probiotic use, compared with non-use, in patients with gastric cancer was significantly associated with a longer duration of nivolumab treatment (55.0 vs. 31.0 days, hazard ratio = 0.69, p = 0.039). In conclusion, probiotics may improve the response to nivolumab and potentially prolong progression-free survival in patients with gastric cancer., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: The objective of this study was to clarify characteristics of metachronous endoscopic curability C2 (eCura C2) cancer during post-endoscopic submucosal dissection (ESD) follow-up., Methods: Of 4,355 gastric lesions treated by ESD at our hospital during 2005-2021, 657 were metachronous. After excluding lesions found ≥2 years since the prior examination or in the gastric remnant, the remaining 515 were analyzed. Study 1: We compared 35 eCura C2 cancers and 480 eCura A-C1 cancers. Study 2: Endoscopic findings of the 35 lesions were examined to determine why they had been missed., Results: Mean tumor size was larger (34.0 mm vs. 12.1 mm, p < 0.01) and the proportions of mixed-type and poorly differentiated cancers were higher (highly:mixed:poorly, 34.3:57.1:8.6 vs. 94.2:5.0:0.8, p < 0.01) in the eCura C2 group. Study 2: At the prior examination, 4 lesions were noticed but considered benign, 2 lacked sufficient imaging, 19 were detectable on imaging but missed, and 10 were not detectable on imaging. Over half the lesions that were detectable but missed at the prior examination were in the lesser curvature, many being type IIa-IIb lesions with color similar to the background mucosa. All lesions not detectable on imaging at the prior examination were mixed-type or poorly differentiated type., Discussion: Metachronous cancer detected as eCura C2 cancers was significantly larger, and a significantly higher proportion was mixed-type or poorly differentiated cancers, compared with eCura A-C1 cancers. Possible reasons why these lesions were missed include rapid progression of mixed-type and poorly differentiated cancers, and poor recognition that lesions showing only slight color changes may be present at the lesser curvature., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background and Aim: Helicobacter pylori eradication has been shown to reduce the risk of gastric cancer (GC), with the number of eradication therapy cases on the rise. However, GC can still occur after successful treatment, and the histological differences prior to eradication in patients with and without GC are unclear. This study investigated the pre-treatment histological risk factors for GC development following eradication therapy., Methods: We retrospectively enrolled consecutive adult patients diagnosed as having H. pylori infection between April 2004 and December 2018. Atrophy and intestinal metaplasia (IM) were histologically assessed according to the updated Sydney System. The operative link on gastritis assessment and the operative link on gastric intestinal metaplasia (OLGIM) were evaluated as well., Results: Of the 247 patients analyzed in this study, 11 (4.5%) experienced GC after eradication therapy. Histological IM scores in the GC group were significantly higher at all gastric biopsy sites (p < .05), and the proportion of OLGIM III/IV stage was significantly greater in GC patients (81.8% vs. 31.8%, p < .01). For GC prediction, the area under the receiver operating characteristic curve for IM score at the lesser curvature of the corpus was the highest among all biopsy sites and not inferior to OLGIM results., Conclusions: Patients with histological IM prior to H. pylori eradication, especially at the lesser curvature of the corpus, may be at elevated risk for GC development after eradication therapy and require close surveillance., (© 2022 John Wiley & Sons Ltd.)

Helicobacter pylori (H. pylori) is an important risk factor for gastric cancer and is a recognized carcinogen. Although eradication of H. pylori reduces the incidence of gastric cancer, cases can still occur after eradication therapy. A number of such cases have been reported, and their early clinicopathological characteristics are becoming clearer. Some reports mention that endoscopic diagnosis of gastric cancer may be difficult after eradication therapy, because the cancer is covered by non-cancerous epithelium. However, there are few reports on advanced gastric cancer after eradication therapy, and its characteristics remain poorly understood. In view of the predicted increase in frequency of advanced gastric cancer after eradication therapy in the near future, it is important to be aware of these cases. In this report, we describe three cases of advanced gastric cancer detected during routine follow-up after eradication., (© 2022. Japanese Society of Gastroenterology.)

Background: Although almost all cases of gastric cancer are caused by Helicobacter pylori (HP) infection, there are some rare exceptions. Furthermore, the clinicopathological characteristics of gastric cancer may differ depending on HP infection status. This study aimed to determine the clinicopathological characteristics of undifferentiated-type gastric cancer (UD-GC) according to HP status., Methods: The study involved 83 patients with UD-GC who were selected from 1559 patients with gastric cancer who underwent endoscopic resection at our hospital and whose HP infection status was confirmed. Clinicopathological characteristics were evaluated according to HP status (eradicated, n = 28; infected, n = 32; not infected, n = 23)., Results: In patients without HP infection, UD-GCs were < 20 mm and intramucosal with no vascular invasion. In patients with eradicated HP, there was no correlation between development of UD-GC and time since eradication. Nine of twelve patients with a tumor detected ≥ 5 years after eradication had undergone yearly endoscopy. Submucosal invasion was observed in two of four patients and lymphovascular invasion in three of four patients whose UD-GC was detected ≥ 10 years after eradication. There was no significant between-group difference in the frequency of lesions with invasion into the submucosal layer or deeper (14.3%, 10.5%, and 0% in the UD-E, UD-I, and UD-U groups, respectively)., Conclusion: The clinicopathological characteristics of UD-GC were similar between HP-infected patients and HP-eradicated patients. Three of four patients with eradicated HP whose UD-GC developed ≥ 10 years after eradication were not eligible for endoscopic treatment and required additional surgery resection. In contrast, UD-GC was curable by endoscopic resection in all patients without HP infection., (© 2022. The Author(s).)

A woman in her 70s was diagnosed with a protruding mucosa-associated lymphoid tissue (MALT) lymphoma during a secondary health examination. After eradication of Helicobacter pylori, a biopsy revealed gastric follicular lymphoma (FL) and the lesion was still protruding one year later. 18 F-fluorodeoxyglucose positron emission tomography showed focal nodular hypermetabolic activity, suggesting that FL may have transformed into a diffuse large B-cell lymphoma. Upper gastrointestinal endoscopy, colonoscopy, and capsule endoscopy showed no other lesions in the gastrointestinal tract, and bone marrow biopsy showed no permeation into the marrow. Therefore, this lesion, which appeared as a submucosal tumor, was limited to the stomach. Laparoscopy and endoscopy cooperative surgery was performed, because it allows for correct pathological diagnosis while removing only a minimal portion of the stomach wall. Histological findings showed follicular structures consisting of abnormal lymphoid cells. Immunohistochemical analysis revealed that neoplastic cells were positive for CD20, CD79a, Bcl-2, CD10, and c-MYC, but negative for CD3, CD5, and cyclin D1. Finally, we diagnosed this lesion as a primary gastric FL.

Background: S-1 adjuvant chemotherapy is commonly administered postoperatively for stage II and III advanced gastric cancer., Methods: This study included 113 patients treated with S-1 adjuvant chemotherapy after surgery for stage II and III advanced gastric cancer. These patients were divided into 4 groups: group A (n = 63), who had a longer duration (≥6 months) and earlier S-1 administration (≤6 weeks) after surgery; group B (n = 16), who had a longer and later S-1 administration (>6 weeks) after surgery; group C (n = 27), who had a shorter duration (<6 months) and earlier S-1 administration after surgery; and group D (n = 7), who had a shorter and later S-1 administration after surgery., Results: The recurrence rates in groups A, B, C, and D were 15.7, 43.8, 44.4, and 57.1 %, respectively (A vs. B, p < 0.05, A vs. C and D, p < 0.01). The survival time of group A was significantly longer than that of other groups (p < 0.005). In addition, the survival time of patients with severe complications was significantly shorter than that of patients with non-severe complications (p < 0.05). An earlier S-1 administration after surgery was the only independent prognostic factor in the multivariate analysis., Conclusions: The prognosis of advanced gastric cancer was significantly related to the start of S-1 adjuvant treatment within 6 weeks after surgery.

This study is a case report on a 49-year-old woman who had a gastrectomy and lymphadenectomy for pStage IIIa gastric cancer. Shortly after a 12-month course of adjuvant chemotherapy, CT showed a nodule adjacent to the gallbladder. High (18) F-fluorodeoxyglucose accumulation was detected, with a standardized uptake value of 10. Therefore, laparoscopic excision was performed for diagnosis and treatment. The histopathological finding was suture granuloma. Suture granulomas with high standardized uptake values on PET scans are uncommon and often cause surgeons to provide an inaccurate diagnosis. Our study suggests that suture granuloma should be included in the differential diagnosis of a new or recurrent mass detected in patients with a history of prior surgery; however, surgeons must bear in mind that false-positive fluorodeoxyglucose-PET results can be observed in suture granuloma., (© 2015 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

Background and Aims: O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine (αGlcNAc) are attached to MUC6 in gastric gland mucins and serve as a tumor suppressor for gastric adenocarcinoma. Gastric atrophy is associated with risk for gastric cancer. However, the significance of αGlcNAc expression in pyloric glands of chronic atrophic gastritis remains unknown. Here, we asked whether reduced αGlcNAc expression in chronic atrophic gastritis is associated with risk for gastric cancer., Methods: We quantitatively analyzed expression of αGlcNAc relative to MUC6 in pyloric glands by immunohistochemistry in 67 patients with normal mucosa, 70 with chronic atrophic gastritis, 68 with intramucosal differentiated-type adenocarcinoma, and 11 with intramucosal undifferentiated-type adenocarcinoma. We also compared the Ki-67 labeling index in gastric epithelial cells between chronic atrophic gastritis and normal gastric mucosa with respect to αGlcNAc reduction., Results: In normal pyloric mucosa, αGlcNAc was co-expressed with MUC6. By contrast, in chronic atrophic gastritis, pyloric gland αGlcNAc expression was significantly reduced relative to MUC6. In intramucosal gastric cancer, αGlcNAc expression in pyloric glands found just beneath differentiated-type adenocarcinoma was also reduced relative to MUC6. However, pyloric glands present beneath undifferentiated-type adenocarcinoma exhibited no αGlcNAc decrease. The Ki-67 labeling index in chronic atrophic gastritis showing αGlcNAc reduction was significantly increased relative to that in normal gastric mucosa., Conclusions: Because αGlcNAc prevents the gastric cancer development, reduced αGlcNAc expression in chronic atrophic gastritis is a possible risk factor for differentiated-type adenocarcinoma of the stomach., (© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

The purpose of this study was to elucidate the prevalence and effect of Helicobacter pylori infection in Japanese teenagers. The study subjects were students ages 16 to 17 from one high school studied between 2007 and 2013. Students who tested positive on this screening examination underwent esophagogastroduodenoscopy and biopsy samples to determine their H pylori status using culture and histology. Cure of H pylori infections was determined by urea breath test. The low rate of prevalence of H pylori infection in present Japanese teenagers makes it possible and cost effective to perform examinations and carry out treatment of this infection in nationwide health screenings of high school students., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Therapeutic strategies for positive peritoneal lavage cytology [CY(+)] findings have not yet been established. The aim of the present study was to compare the effects of neoadjuvant systemic chemotherapy and surgery followed by S-1 adjuvant chemotherapy for treating gastric carcinoma in patients with CY(+) status without peritoneal metastasis., Patients and Methods: Twenty-three patients with CY(+) status without peritoneal metastasis who underwent curative surgery for gastric carcinoma between October 1999 and December 2014 were included in the study. Ten patients received neoadjuvant systemic chemotherapy followed by surgery, whereas 13 patients underwent surgery, in nine cases followed by S-1 adjuvant chemotherapy., Results: The 5-year survival in both groups was 15%, and no significant difference was observed. However, the prognosis for patients with CY(-) status after neoadjuvant systemic chemotherapy was significantly better than that of patients who were still CY(+) after neoadjuvant systemic chemotherapy (p<0.01). Among all patients, the prognosis of those with less than clinical N2 disease was significantly better than that of patients with clinical N3 (p<0.01). In multivariate analysis, clinical lymph node metastasis was the only independent prognostic factor for CY(+) patients without peritoneal metastasis (p<0.05)., Conclusion: The prognosis of gastric carcinoma with CY(+) without peritoneal metastasis is still stage IV disease and is dependent on the degree of clinical lymph node metastasis, in spite of therapeutic treatment., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: To develop a set of process-of-care quality indicators (QIs) that would cover a wide range of gastric cancer care modalities and to examine the current state of the quality of care provided by designated cancer care hospitals in Japan., Design: A retrospective medical record review., Setting: Eighteen designated cancer care hospitals throughout Japan., Participants: A total of 1685 patients diagnosed with gastric cancer in 2007., Main Outcome Measures: Provision of care to eligible patients as described in the 29 QIs, which were developed using an adaptation of the RAND/UCLA (University of California, Los Angeles) appropriateness method by a panel of nationally recognized experts in Japan., Results: Overall, the patients received 68.3% of the care processes recommended by the QIs. While 'deep venous thrombosis prophylaxis before major surgery' was performed for 99% of the cases, 'documentation before endoscopic resection' was completed for only 12% of the cases. The chemotherapy care was less likely to meet the QI standards (61%) than pre-therapeutic care (76%), surgical treatment (66%) and endoscopic resection (71%; overall difference: P < 0.001). A comparison based on the types of care showed that documentation and patient explanation were performed less frequently (60 and 53%, respectively) than were diagnostic and therapeutic processes as recommended in the QIs (85%; overall P < 0.001)., Conclusions: Although many required care processes were provided, some areas with room for improvement were revealed, especially with respect to chemotherapy, documentation and patient explanation. Continuous efforts to improve the quality and develop a system to monitor this progress would be beneficial in Japan.

Positron emission tomography (PET) is used for staging and response evaluation in primary gastric lymphoma (PGL). However, the implications of [(18)F]-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in PGL at first diagnosis have not been reported. The relationship between (18)F-FDG uptake and the expression of facilitative glucose transporters (GLUTs), hexokinase II (HK II), and Ki67, as well as malignant potential in PGL, was assessed in this study. We analyzed 23 patients with PGL [nine with diffuse large B-cell lymphoma (DLBCL); seven with high-grade mucosa-associated lymphoid tissue (MALT) lymphoma; and seven with low-grade MALT lymphoma]. The expression levels of GLUT1, GLUT3, HK II, and Ki67 were evaluated according to the percentage of positive area determined by immunohistochemistry. Standardized uptake values correlated significantly with pathological malignant potentials (low-grade/high-grade MALT lymphoma and DLBCL: p = 0.001-0.002), Ki67 (p < 0.001), and GLUT1 expression (p = 0.02). We determined that (18)F-FDG uptake is related to GLUT1 expression and tumor histological grade as well as Ki67 in PGL.

Here, we present the case of a 73-year-old woman in whom abdominal computed tomography showed an abdominal tumor (13 cm in diameter) in the backspace of the posterior gastric wall. Its feeding artery was detected to be the left gastric artery by abdominal angiography. We diagnosed it as a gastrointestinal stromal tumor (GIST) of the stomach and performed an operation. Peritoneal dissemination was observed and the tumor was connected to the gastric wall by a stalk. Histologically, the tumor consisted of spindle-shaped cells. Immunohistochemical staining showed positive c-kit and CD34 expression and negative SMA and S100 protein expression. Therefore, we diagnosed this as a case of extragastric pedunculated GIST of the stomach with peritoneal dissemination. After surgery, internal use of imatinib was started. The patient is still followed up 15 months after the operation. Combination therapy of tumor resection and imatinib chemotherapy might improve the prognosis of patients with GIST of the stomach with pedunculated growth.

Background: The purpose of this study was to clarify the surgical indications for gastrectomy combined with distal or partial pancreatectomy (GP) in patients with gastric cancer., Methods: From January 1994 to December 2009, 29 patients with primary gastric cancer surgically invading the pancreas without distant organ metastasis underwent GP for R0 resection. The patients' characteristics, surgical data, and clinicopathological features were used for the analysis of survival and prognostic factors., Results: The median disease-free survival and median survival time (MST) of all patients were 15 and 30 months, respectively. Only pN3 status (characterized by 7 or more pathologically metastatic lymph nodes) according to the Japanese Classification of Gastric Carcinoma, 14th edition, was shown to be a prognostic factor in a multivariate analysis. The MST of the patients with pN3 and the other patients were 12 and 51 months, respectively (p < 0.001)., Conclusions: We suggest that pancreas invasion should not be considered a contraindication for gastrectomy and that patients with a small number of lymph node metastases (six or fewer) might be candidates for GP in the case of gastric cancer that requires pancreatectomy for R0 resection.

Background/aims: Laparoscopic distal gastrectomy (LDG) with lymphadenectomy has been revealed to be a useful treatment for early gastric cancer but oncological adequacy is controversial., Methodology: To assess the quality of lymphadenectomy, we evaluated the number of dissected lymph nodes and the non-compliance rate (defined as an absence of nodal tissue at a node station that should have been resected) and compared the data obtained from 102 patients treated by LDG with those from 90 patients treated by open distal gastrectomy (ODG)., Results: The numbers of nodes of Categories 1 and 2, which correspond respectively to perigastric and retroperitoneal nodes, did not differ significantly between the LDG group and the ODG group. In the LDG group compared to the ODG group, there were significantly more right paracardial nodes (No. 1) but there were significantly fewer infrapyloric nodes (No. 6). However, the difference in infrapyloric nodes (No. 6) became insignificant when we re-analyzed and compared the ODG group and the patients (n=42) whose LDGs were performed by two experienced laparoscopic surgeons., Conclusions: The curability of gastric cancer on LDG was almost equivalent to that of ODG from the viewpoint of lymph node dissection, if the LDG is performed by two experienced laparoscopic surgeons. These data suggested that LDG with lymphadenectomy could possibly be adopted for advanced gastric cancer treatment under proper quality control, such as that provided by an experienced laparoscopic team.

Purpose: It has not yet been elucidated whether there are specific complications associated with totally laparoscopic distal gastrectomy (TLDG). We evaluated the complications and the risk factors associated with TLDG., Methods: A retrospective analysis was performed on 138 consecutive patients who underwent TLDG. The clinical and operative data, which included the body mass index, respiratory function, hematological data, pathological data, and the experience of surgeon, were analyzed., Results: Intraoperative and postoperative complications developed in 10 and 28 patients, respectively. A univariate analysis determined that the patient age, concurrent respiratory disease, and operation time were important risk factors. A multivariate analysis found no significant risk factors in this set, although the operation time was the most promising risk factor., Conclusions: The present data suggest that TLDG can be performed with acceptable perioperative complication rates, although a longer operation time may cause a higher frequency of postoperative complications.

A 66-year-old male was admitted to our hospital because of dyspnea in 2007. Cancerous pleural effusion and gastric cancer was diagnosed, and the chemotherapy consisted of S-1 + DOC was started for Stage IV gastric cancer. In 2009, lung cancer was found. The chemotherapy was changed to CDDP + CPT-11. This chemotherapy was effective for both lung and gastric cancers. Operation was performed for both tumors in 2010, and the pathological diagnosis revealed that gastric cancer was pStage I, Cur A, and the lung cancer was pStage IA, R0. Pathologic histology inspection of both tumors was judged to be effective for the chemotherapy prior to resection.

We report a case of patient who underwent resection for local recurrent gastric cancer at the anastomotic site curatively. The patient was a 72 years old male with a history of undergoing total gastrectomy for gastric cancer located at the gastric cardia in February 2005. The histological findings of the resected tumor showed a Type 3 advanced gastric cancer invaded into subserosa in the cardia of the stomach with positive lymphatic and venous invasion and lymph node metastasis. The histological diagnosis was moderately differentiated tubular adenocarcinoma. Both the proximal and distal margins were negative for cancer. Endoscopy, 4 years after the first operation, showed a recurrent tumor at the site of esophago-jejunal anastomosis. A resection of the tumor was carried out curatively through the left thoraco-abdominal approach in June 2009. We recommend a resection of anastomotic recurrence especially if it occurs from the first operation in the long interval.

Background: Laparoscopic gastrectomy for gastric cancer has become common due to improvement of the surgical techniques and devices for laparoscopic surgery. Although laparoscopically assisted distal gastrectomy (LADG) has several advantages over open distal gastrectomy, little has been reported about the safety and feasibility of totally laparoscopic distal gastrectomy (TLDG)., Methods: Between October 2005 and June 2007, 80 laparoscopic distal gastrectomies with regional lymphadenectomies were performed for patients with gastric cancer. After 24 patients underwent LADG and 56 patients underwent TLDG, the clinical data were compared between the two groups., Results: The groups were comparable in terms of age, gender, body mass index (BMI), tumor location, tumor size, macroscopic type, depth of invasion, histologic type, lymph node metastasis, and length of proximal margin. However, when only the patients with gastric cancer in the middle third of the stomach were compared between the two groups, the length of the proximal margin was significantly longer in the TLDG group (p < 0.05). The mean blood loss was significantly less in the TLDG group (p < 0.05). The patients in the TLDG group recovered earlier and thus had a significantly shorter postoperative hospital stay. Furthermore, the C-reactive protein level on postoperative day 7 was lower in the TLDG group than in the LADG group (p < 0.05). There was no significant difference in the postoperative complications between the two groups., Conclusion: This study demonstrated that TLDG has several advantages over LADG including smaller wounds, less invasiveness, and better feasibility of a secure ablation. The TLDG procedure yields safe anastomosis independently of the patient's constitution or the location of the cancer. Therefore, TLDG is considered to be a useful technique for patients with gastric cancer.

Combination treatment with sodium nitrite (NaNO(2)) and ascorbic acid (AsA) is well known to promote forestomach carcinogenesis in rats and weakly enhance esophageal carcinogenesis under acid reflux conditions. Nitric oxide generation and oxidative DNA damage are considered to be related to the enhancement of carcinogenesis. The purpose of the present study was to investigate whether oxidative DNA damage-associated genotoxicity and tumor initiating potential are involved in the carcinogenesis. In the bacterial reverse mutation assay using Escherichia coli deficient in the mutM gene encoding 8-hydroxydeoxyguanosine (8-OHdG) DNA glycosylase, the combination with NaNO(2) and AsA increased the mutation frequency dramatically, slight increase being evident in the parental strain. In vivo, a significant increase in 8-OHdG levels in the rat forestomach epithelium occurred at 24 h after combined treatment. Six-week-old F344 male rats were given drinking water containing 0.2% NaNO(2) and a diet supplemented with 1% AsA in combination, or the chemicals individually or basal diet alone for 12 weeks. After an interval of 2 weeks, they received 1% butylated hydroxyanisole in the diet for promotion until the end of weeks 52 and 78. Although one squamous cell carcinoma was observed in the combined group, there was no significant variation in tumor development among the groups. The study indicated that the combination of NaNO(2) with AsA induces genotoxicity due to oxidative DNA damage in vitro, and elevates 8-OHdG levels in the forestomach epithelium, but lacks initiating activity in the rat two-stage carcinogenesis model.

Aim: We investigated the clinical significance of metastasis to the lymph node (LN) along the superior mesenteric vein (14v) in gastric cancer., Methods: A retrospective study of 2,513 gastrectomy patients with a 14v dissection was done using the Ganken Igan Database., Results: The incidence of 14v metastasis correlated with tumor location, depth of tumor invasion, regional LN metastases, peritoneal metastasis, peritoneal cytology-positive, hepatic metastasis and postoperative recurrence (p < 0.01). Metastases to the infra-pyloric LN (6), supra-pyloric LN (5) and left para-cardial LN (2) were independent variables affecting 14v metastasis (p < 0.05), and the 6 status was a useful predictive factor for a 14v-negative status with a low false-negative rate (1.9%). The patients with 14v metastasis after curative surgery demonstrated a significantly lower survival rate than those without (5-year overall survival rate; 11.3 vs. 60.2%, p < 0.0001). In them, LN around the abdominal aorta (16)-positive group showed a significantly lower survival rate than the negative group (p < 0.05)., Conclusions: Advanced gastric cancer with invasion to the lower stomach often metastasizes to 14v, and the 6 status can predict 14v negative. Most patients with 14v metastasis have a poor prognosis, similar to those with systemic metastasis, although some such patients may benefit from a curative dissection.

Esophageal squamous cell carcinoma is often accompanied by intramural metastases, and it has been reported to carry a poor prognosis. Intramural metastasis from gastric cancer to the esophageal wall, however, has rarely been reported. We herein report a rare case of a 46-year-old man with an elevated esophageal lesion, resembling a 0-IIa-type esophageal cancer, which was discovered 13 months after a total gastrectomy performed for gastric cancer. The esophageal tumor, resected by endoscopic mucosal resection (EMR), was an adenocarcinoma with the same histology as the previously resected primary gastric cancer, and it showed massive lymphatic permeation. Soon after the EMR, other similar lesions emerged on the esophageal wall. We therefore considered the esophageal tumor to be a systemic expansion of the primary gastric cancer, and we administered the anticancer drug, S-1. Esophageal intramural metastases from a gastric cancer imply a systemic expansion of the gastric cancer, and portend a poor prognosis.

Background: We recently found an elevation in the pre-operative peritoneal lavage carcinoembryonic antigen (CEA) level to be associated with an earlier detection of recurrent peritoneal dissemination and a poor prognosis., Method: Two hundred and twenty-nine patients with gastric cancer were intraoperatively measured for tumor markers, CEA and CA125 based on peritoneal lavage using a chemiluminescent enzyme immunoassay., Results: The patients were divided into four groups. (A) The peritoneal lavage CEA (-) CA125 (-) group (CEA < 0.4 ng/ml, CA125 < 200 ng/ml, n = 129); (B) the peritoneal lavage CEA (-) CA125 (+) group (CEA < 0.4 ng/ml, CA125 >or= 200 ng/ml, n = 50); (C) the peritoneal lavage CEA (+) CA125 (-) group (CEA >or= 0.4 ng/ml, CA125 < 200 ng/ml, n = 18); and (D) the peritoneal lavage CEA (+) CA125 (+) group (CEA >or= 0.4 ng/ml, CA125 >or= 200 ng/ml, n = 32). The 5-year survival of the patients in groups C and D was 40 and 26%, respectively, which was lower than that of the patients in any other group (group A, B; p < 0.0001). Recurrent sites were both peritoneal dissemination and lymph node/liver in group C, while those were only peritoneal dissemination in group D., Conclusion: This combined analysis of these markers is therefore considered to be helpful method to accurately estimate the recurrent sites and prognosis for advanced gastric cancer patients.

The frequency of synchronous or metachronous multiple primary carcinomas in patients with gastrointestinal carcinoma or colorectal carcinoma (CRC) has been reported to be approximately 10%. We determined the role of hMSH2 and hMLH1 in double carcinomas with both GC and CRC. Fifty-six patients with synchronous or metachronous colorectal carcinoma with gastric carcinoma (CRC with GC), and 69 patients with CRC alone was included in our study. We investigated their clinicopathological characteristics, family history and immunohistochemical stains of hMSH2 and hMLH1 were compared between the patients with CRC alone and those with both CRC with GC. The defective protein expression of hMSH1 and/or hMLH1 in colorectal carcinomas was significantly higher in patients with both CRC with GC than in those with CRC alone (p < 0.0001). The survival rate in patients with both CRC with GC was significantly lower than that in those with CRC alone (p < 0.01), in addition, the survival rate in patients with defective protein expression of hMSH2 and/or hMLH1 was higher than in those with a positive protein expression of hMSH2 and/or hMLH1 in CRC with GC (p < 0.05). The incidence of defective protein expression of hMSH2 and/or hMLH1 in CRC with GC patients suggests that abnormalities in the function of hMSH2 and hMLH1 may play an important role in carcinogenesis. Our findings indicate that the CRC patients who demonstrate a defective protein expression of hMSH2 and/or hMLH1 have a higher risk of developing secondary carcinoma in the gastrointestinal tract.

Recurrence of early gastric cancer is rare, with an incidence of less than 10% in Japan. Using peritoneal lavage cytological examination, we detected tumor cells in the peritoneal cavity of a 73-year-old man undergoing surgery for early gastric cancer. Peritoneal dissemination of early gastric cancer is rare. Thus, we summarized the clinicopathological findings of the total 15 cases of peritoneal dissemination of early gastric cancer documented in the English medical literature, including this case. All of the patients had a tumor size >2 cm, submucosal invasion, differentiated adenocarcinoma, lymph node metastasis, and a shorter disease-free interval (average 33.1 months) than patients with other types of recurrent early gastric cancer, and the involvement of both recurrent lymph nodes and peritoneal dissemination. Based on this analysis, we conclude that patients with early gastric cancer, especially if the tumor is >2 cm with submucosal invasion, should be examined carefully for any form of recurrence.

Endoscopic mucosal resection (EMR) is a minimally invasive, standard treatment for intramucosal (early) gastric cancers, but is not standard for submucosal gastric cancers based on existing criteria. We evaluated the possibility of extending EMR as a therapy for submucosal gastric cancers by analyzing nodal micrometastasis through immunohistochemical staining in patients with apparent node-negative submucosal gastric cancer, the patients for whom EMR might be appropriate. We used anti-cytokeratin (AE1/AE3) antibody to immunohistochemically detect nodal micrometastasis that was not identified by routine pathological examination in 162 patients (total, 2048 lymph nodes) with apparent node-negative submucosal gastric cancer. The relationship between the incidence of nodal micrometastasis and clinicopathological factors was analyzed. Micrometastasis was detected in 45 of 2048 nodes (2.2%), representing 31 of 162 patients (19%). A significantly high incidence of nodal micrometastasis was found with submucosal cancers of large size (>2 cm), as well as with tumors that showed lymphatic or venous invasion and deeper submucosal invasion (p<0.0001). Nodal micrometastasis was also recognized in 2 cases of histologically well-differentiated tumors with focal submucosal invasion without venous or lymphatic invasion. Of the 162 patients, only 2 died of recurrent disease regardless of nodal involvement. Based on the present results, risk factors for nodal micrometastasis are tumor size, presence of lymphatic-vascular invasion, and depth of tumor, which are nearly the same as those established in previous pathological studies that used hematoxylin and eosin staining. We conclude that EMR is not recommended for patients with submucosal gastric cancer.

We report a case of adenosquamous carcinoma of the stomach that produced granulocyte-colony stimulating factor (G-CSF). The patient, who had an admission diagnosis of advanced gastric cancer, had marked leukocytosis without evidence of infection. After leukemia and metastatic leukemoid reaction were excluded by bone marrow examination, a G-CSF-producing cancer was suspected as the cause of the abnormally elevated serum G-CSF level. The resected stomach tumor was histologically diagnosed as adenosquamous carcinoma; positive expression of G-CSF by tumor cells was shown with immunohistochemical detection, which confirmed the preoperative diagnosis. Recurrent disease in the liver and lymph nodes, accompanied by leukocytosis and re-elevation of serum G-CSF, developed just 3 months after the curative gastrectomy and adjuvant chemotherapy. All of the recurrent disease was resected, restoring normal levels of serum G-CSF. The patient survived for almost 2 years after the initial surgery with extensive chemotherapy, including weekly treatment with paclitaxel, before finally succumbing to liver failure secondary to extensive liver metastasis.

Background: We conducted a feasibility study using S-1, a novel oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy for curatively resected gastric cancer patients., Methods: Adjuvant chemotherapy consisted of eight courses (4-week administration and 2-week withdrawal) of S-1, at 80-120 mg/body per day. Forty-one patients from 11 institutions were enrolled in this pilot study, from November 1999 to October 2000., Results: Thirty-five patients were eligible. In 7 patients, S-1 administration was discontinued due to recurrence. Among the 28 patients without recurrence, the planned eight courses of S-1 were administered to 17 patients (60.7%). In 4 patients, S-1 administration was discontinued due to subjective symptoms, such as anorexia, in the first course. Adverse reactions such as neutropenia, leukopenia, elevated total bilirubin, anorexia, general fatigue, diarrhea, nausea, and stomatitis were seen in more than half of the patients. Although grade 3 neutropenia (29.3%), leukopenia (9.8%), and diarrhea (9.8%) were observed, no grade 4 adverse effects appeared. Compared with the treatment of unresectable or recurrent gastric cancer with S-1, the incidence of adverse reactions in the adjuvant setting was slightly higher, probably due to the influence of gastrectomy., Conclusion: Except for the early development of anorexia, most likely due to adverse effects of surgery, postoperative administration of S-1 for 1 year seems feasible as adjuvant chemotherapy for gastric cancer.

Background/aims: Indications for splenectomy in patients with proximal and middle gastric cancer remain controversial. We investigated characteristic findings in patients with lymph node metastasis to the splenic hilus and the indication of splenectomy with total gastectomy for T2 and T3 advanced gastric cancer., Methodology: Two hundred and forty-one Japanese patients underwent curative operations for T2 and T3 advanced gastric cancer., Results: The mortality rates were similar, but the morbidity rate for patients who underwent pancreaticosplenectomy was higher than for patients who underwent either total gastrectomy alone or with splenectomy (p<0.007). The rates in cases of lymph node metastasis at the depth of tumor invasion within the subserosa and serosa (T3) were 1.7% and 17.5%, respectively (p<0.003). Lymph node metastasis to the splenic hilus was also evident in patients with T3 or T2 advanced gastric cancer with multiple lymph nodes metastasis (more than 7 nodes). The 10-year survival rates for patients who underwent total gastrectomy alone, with splenectomy, and with pancreaticosplenectomy in T3 advanced gastric cancers were 25%, 42% and 32%, respectively (p=0.184)., Conclusions: Based on these data, the addition of distal pancreaticosplenectomy to total gastrectomy in patients with T2 and T3 advanced gastric cancer increased the risk of complications. Nevertheless, we recommend that total gastrectomy with splenectomy should be done for patients with T3 advanced gastric cancers [and T2 advanced gastric cancer with multiple lymph nodes metastasis (more than 7 nodes)], recognizing the lymph node metastasis to the splenic hilus.

Objective: Predicting peritoneal dissemination of cancer is very difficult whatever method of examination is used. Recently, a cytological examination of peritoneal lavage has been shown to be a feasible measure to predict an early state of peritoneal seeding. The predictive value of the levels of tumor markers in peritoneal lavage for peritoneal metastasis from gastric carcinoma was thus studied., Methods: In 229 patients gastric cancer tumor markers, CEA, CA 125, and CA 19-9, in peritoneal lavage were intraoperatively evaluated using a chemiluminescent enzyme immunoassay., Results: CEA in peritoneal lavage at a cutoff level of 0.5 ng/ml showed overall a higher sensitivity of 75.8% at a specificity of 90.8% for a diagnosis of peritoneal dissemination including cytologically positive peritoneal lavage [CY(+)] than CA 125 or CA 19-9 in peritoneal lavage. The CEA level in peritoneal lavage as well as both serosal invasion and the CA 125 level in peritoneal lavage were significant factors for the prediction of peritoneal dissemination including CY(+) with a relative risk of 6.6, 14.1 and 9.4. In patients undergoing curative operations, the recurrence rate for peritoneal dissemination and liver metastasis in cases with CEA levels in peritoneal lavage of > or = 0.5 ng/ml was significantly higher than that in cases with CEA levels of < 0.5 ng/ml (p < 0.0001, p < 0.002)., Conclusions: These finding suggest that the CEA level in peritoneal lavage is thus considered to be a predictor of peritoneal dissemination including CY(+)., (Copyright 2004 S. Karger AG, Basel)

Background/aims: Primary gastric lymphoma is a relatively rare disease. As the concept of MALT (mucosa-associated lymphoid tissue) lymphoma has been acknowledged, a relation between primary gastric lymphoma and Helicobacter pylori infection seems apparent, appropriate treatment, including surgical resection, and/or chemotherapy, and/or radiotherapy has remained controversial., Methodology: Between 1974 and 1996, we treated 85 Japanese patients with histologically proven primary gastric lymphomas (stage I and II according to modified Ann Arbor staging) with surgery, and/or adjuvant chemotherapy. The clinicopathological factors, especially regarding surgical curability and survival were evaluated retrospectively., Results: Of the 85 patients (44 men, and 41 women), average age was 60.5 years. The lesion was frequently located at the middle third of the stomach, and multiple lesions were noted in 19 patients. Microscopic lymph node metastasis was positive in 37.6% (32/85), and the rate of positive metastasis increased in proportion to depth of invasion. There was a discrepancy between macro- and microscopic findings regarding lymph node metastasis. Total gastrectomy was done for 50 patients, distal gastrectomy for 31, pancreatoduodenectomy for 3, and gastrojejunostomy for 1 patient. Lymph node dissection was done at the D1,2 level for 73, and at the D3 level for 12 patients. There were no major complications except in 3 cases (subphrenic abscess), and there was 1 operative death. The overall 5-year survival and 10-year survival was 82.3% and 74.0%, respectively. In the stage I patients, the 5-year and 10-year survival rate was 97.5%, respectively. All cases of surgery were curative, and surgery alone resulted in the same survival time as the surgery plus chemotherapy group (10-year survival; 100% vs. 96.6%, no statistical difference). In the stage II patients, 5-year and 10-year survival rates were 58.6% and 44.2%, respectively. Surgery was curative in 59.3% (19/32), and palliative in 40.7% (13/32). Palliative surgery was done because of extensive lymph node metastasis in 6 patients, invasion to adjacent organ in 6, and both in 1 patient. Chemotherapy was prescribed in 71.9% of the patients (23/32), and when compared with the patients who were on chemotherapy, the survival rate showed no statistical difference regardless of palliative or curative surgery., Conclusions: Surgery for primary gastric lymphoma had low complication rate, and led to good survival rate in stage I disease. In stage II disease, surgical curability did not affect the survival, implying the necessity of the evaluation about the treatment strategy by randomized study. However, considering the stage migration before and after and possible inaccuracy of preoperative staging, the application of non-surgical treatment must be prudent.

Endoscopic mucosal resection (EMR) has been widely accepted as a minimally invasive and standard treatment for early gastric cancers without ulceration or signs of submucosal invasion and meeting the criteria for diameter, macroscopic appearance, and well- or moderately differentiated histology. However, EMR cannot be applied to some cases owing to technical difficulties relating to the intragastric location of the cancers even when the above criteria are satisfied. We report here a new approach to EMR for early cancers of the cardia located close to the esophagocardia junction that are outside the indications for ordinary EMR.

Several chemotherapy regimens used against advanced gastric cancer have been studied extensively over the decades in an attempt to further improve the prognosis of patients. To date, no standard chemotherapeutic regimens have been established worldwide. S-1 (TS-1), a combination of ftorafur and two modulators, gimestat (CDHP) and oxonic acid, in a molar ratio of 1:0.4:1, has been widely used in Japan for the treatment of advanced gastric cancer, and much attention has been paid to attempts to increase its antitumor effect by combining it with other chemotherapeutic drugs. We treated 12 patients with advanced gastric cancer with 80 mg/m2 of S-1 for 21 days and 60 mg/m2 of cisplatin (CDDP) on day 8 every 5 weeks. The treatment was continued until disease progression, unacceptable toxicity, or the patient's refusal. Eight out of 12 evaluable patients achieved a partial response (PR), with a response rate of 66.7%. The incidence of grade 3 or 4 adverse effects, including myelosuppression and gastrointestinal toxicities, was 16.6%. None of the patients treated with this regimen died of adverse effects and none required hospitalization for the toxicity. We conclude that the combination of S-1 and CDDP seems to have a high therapeutic index, enhancing the antitumor effect of S-1 while maintaining modest adverse effects, thus suggesting the possible use of this combination based at the outpatient clinic (apart from a short stay in hospital during the infusion of CDDP with hydration). Further study with a large number of patients may be needed to confirm the combination of S-1 and CDDP to be an appropriate first-line chemotherapy for gastric cancer.

A 56-year-old man presented with dysphagia, and was found to have a type 3 advanced gastric cancer with bilateral multiple lung metastases. This patient was treated with low-dose 5-FU plus CDDP chemotherapy. In the first course, CDDP (6 mg/m2/day) plus 5-FU (300 mg/m2/day) were infused for 5 successive days a week, but a tumor response was not achieved. Therefore, in the second course, CDDP (6 mg/m2/day) plus 5-FU (600 mg/m2/day) were infused every other day (3 days a week). In response to the treatment, both the gastric tumor and the lung metastases almost completely disappeared (reduction rate 95%), and PR was achieved. The CEA level markedly decreased, from 260.3 to 1.4 ng/ml and the patient's symptoms disappeared. Following this treatment, low-dose CDDP plus UFT therapy was performed and the PR was maintained for 12 months. This report shows a case of advanced gastric cancer that responded to low-dose 5-FU plus CDDP.

Background: Biological characteristics of gastric cancer depend mostly on genetic alterations in the cancer cells of individuals. To precisely predict the biological behavior and clinical outcome of individual cancer, it may be important to clarify the DNA profiles of cancer cells in each case., Methods: We have reviewed the most important results of studies on DNA ploidy of gastric cancer published in the English literature during the last 2 decades., Results: Gastric carcinoma with aneuploidy has been shown to have a high proliferative activity and a high metastatic or invasive potential, thus leading to a poor prognosis as compared to diploid tumors., Conclusion: Analyses of DNA ploidy in gastric cancer may provide clinically useful information on diagnostic, therapeutic, and prognostic aspects. Further investigations may be needed to clarify the relationship between chromosome instability and DNA ploidy.

Background: Heparanase has been reported to play an important role in tumor progression and metastasis. We examined the relationship between heparanase mRNA expression and biological factors regarding invasion and metastasis of human gastric cancer., Materials and Methods: In 63 human gastric carcinomas, 42 adjacent normal gastric tissues and four gastric cancer cell lines, heparanase mRNA expression was evaluated using reverse transcription PCR (RT-PCR). Total RNA obtained from human peripheral blood (PB) leucocyte and placenta were used as positive controls. The relationship between heparanase mRNA expression and various clinicopathological factors were analyzed., Results: The heparanase mRNA expression evaluated with RT-PCR revealed that 31 out of 63 gastric cancer tissues (49%), 11 out of 42 normal gastric tissues (26%) and 4 gastric cancer cell lines were positive. The positive rate in cancer tissues was significantly higher than that in normal tissues (p<0.05). In the heparanase mRNA-positive cancer tissues, venous invasion was frequent (p<0.05) and the histological differential grade was significantly poorer than in negative cases (p<0.01)., Conclusion: We propose that heparanase mRNA expression is involved in invasion and development of human gastric cancer and detection of this expression may be a factor related to metastasis and prognosis of such patients.

We reviewed the results of chemotherapy for gastrointestinal cancer. In Western countries, FAMTX or ECF is recognized as the standard therapy for gastric cancer. In Japan, no standard chemotherapeutic regimen has been established yet, but FP or MTX/5-FU are often used as a first line chemotherapy. There have been only a few clinical trials of adjuvant chemotherapy for gastric cancer in which this regimen was identified as having a statistically significant effect. For colon cancer, 5-FU plus LV are now used as the standard therapy. Recently, however, it has been shown that 5-FU + LV combined with CPT-11 is more active than 5-FU + LV alone. The efficacy of oral anticancer agents such as UFT + LV, S-1, and capecitabin have also been shown to be equally or more active than i.v. administration of 5-FU and LV, so that the standard therapy for colon cancer will be changed in near future.

The expression or activity of manganese superoxide dismutase (Mn-SOD) is reduced in a variety of malignant tumors and Mn-SOD may act as a new type of tumor suppressor gene. On the other hand, increased expression of Mn-SOD can diminish the cytotoxic effects of several anticancer modalities, including tumor necrosis factor alpha, ionizing radiation, certain chemotherapeutic agents and hyperthermia. Although Mn-SOD expression and its role in various cancers are intensely studied, little is known about its function in gastrointestinal carcinomas. To examine the expression level and significance of Mn-SOD in gastrointestinal carcinomas, Mn-SOD mRNA expression was examined in 53 gastric carcinoma and 38 colorectal carcinoma by reverse transcription-polymerase chain reaction and was compared with those in the corresponding normal mucosal tissues. The tumor/normal (T/N) ratio was calculated and the data were clinicopathologically analyzed. The average T/N ratios of Mn-SOD mRNA expression in gastric and colorectal carcinomas were 2.19 and 3. 72, respectively. Clinicopathologic analyses revealed positive correlation between the Mn-SOD expression level and venous invasion in both gastric and colorectal carcinomas (p<0.05 and p<0.05, respectively). Furthermore, the colorectal carcinoma with lymph node metastasis showed significantly higher Mn-SOD expression than those without it (p<0.05). Our results suggest that Mn-SOD mRNA overexpression can occur in gastric and colorectal carcinomas and may be related to increased aggressiveness.

Background: The biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) has demonstrated significantly increased response rates in comparison with the use of 5-FU alone in patients with advanced colorectal carcinoma. However, the higher response rate of LV/5-FU may occur at the expense of increased toxicity and side effects such as diarrhea, myelosuppression, and mucositis. During chemotherapy, a high incidence of hypocalcemia associated with this chemotherapy regimen was noted. This study was therefore aimed at assessing the side effects of chemotherapy using low dose LV/5-FU on calcium metabolism., Methods: Twenty-five patients with advanced gastric or colorectal carcinoma were treated with chemotherapy comprised of low dose LV administered at 20 mg/m2/ day by intravenous bolus, followed by 1-hour intravenous infusion of 5-FU at 425-600 mg/m2/day for 5 consecutive days every 28 days., Results: The toxic effects were generally mild, and included diarrhea, mucositis, leukopenia, and nausea/vomiting. Fifteen patients (65%) experienced hypocalcemia. The plasma 1,25-(OH)2D3 levels were significantly reduced on Day 5 due to the chemotherapy., Conclusions: The toxic effects of the regimen were generally mild. However, a high percentage of hypocalcemia occurred with the combination of LV/5-FU. It is therefore necessary to examine carefully the serum calcium levels of patients when using this chemotherapeutic modality.

A 62-year-old man suffering from advanced gastric cancer with multiple lung and liver metastasis was treated with FP (CDDP . 5-FU) therapy. As a result, lung metastasis disappeared completely and liver metastasis was significantly reduced in size (93%). Then, total gastrectomy, splenectomy and micro-wave-coagulation of the liver tumors were performed. Therefore, it can be said that FP therapy is an effective neoadjuvant chemotherapy.

The effect of PSK, a protein-bound polysaccharide and an immunomodulator, on lymphocytes was examined in vitro for 36 patients with gastric cancer and 26 with colorectal cancer. Cultured lymphocytes with PSK at 100 micrograms/ml increased the level of DNA synthesis, as determined by the 3H-thymidine uptake, from 0.9 to 3.0 fold, compared to the PSK non-treated cells. The increase was 1.36 +/- 0.46 fold for the gastric cancer cases and 1.37 + 0.45 fold for the colorectal cancer cases, and these levels were significantly the finding of 1.93 + 0.55 fold for a control group consisting of 15 healthy volunteers (P < 0.01). When the 1.3 fold increase of 3H-thymidine uptake was defined as the PSK-reactive group, 52.8% (19/36) of the patients with gastric cancer and 50.0% (13/26) for colorectal cancer were found in the PSK-reactive group. The PSK-reactive group demonstrated no relation to the age and sex of the patients, tissue differentiation type or tumor advancement. Our findings thus show that the in vitro activation of lymphocytes by PSK can help identify the candidates with either gastric or colorectal cancer who are the best suited to undergo immunochemotherapy including treatment with PSK.