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This case involved an 82-year-old man with a history of diabetes mellitus and myocardial infarction. He was undergoing treatment with 2 oral antiplatelet agents. The patient presented to our hospital for carcinomatous pyloric stenosis caused by type 4 advanced gastric cancer. Although distal gastrectomy was planned, preoperative coronary angiography revealed triple- vessel coronary artery disease. Therefore, surgery was performed under management of intra-aortic balloon pumping (IABP)therapy. The patient's hemodynamics at the time of the operation were stable, and no perioperative cardiovascular complications occurred. However, the patient was not able to start an oral diet because of impaired swallowing function. Although he underwent daily swallowing rehabilitation, he died of aspiration pneumonia 40 days postoperatively. There are many reports of cancer resection under IABP management for patients with severe heart disease. Because the perioperative hemodynamics were stable in all 21 reported cases of digestive malignant tumor resections in Japan, an IABP is suggested to be very effective for patients with severe heart disease. However, early death has also occurred, as in the present case. Close attention to the indications for IABP therapy is needed, especially in elderly patients, in consideration of not only cancer and heart disease but also preoperative activities of daily living.

There is no known recommended chemotherapy after radical surgery for gastric cancer for patients who have non-curative disease. We defined positive peritoneal cytology(CY1), resection margin involvement, pathological peritoneal metastasis (pP1)and pN3b as clinical non-curative factors and administered adjuvant chemotherapy with S-1 and docetaxel(DOC) (80 mg/m2 day 1-14 of S-1 for 2 weeks with 40 mg/m2 of DOC on day 1, every 3 weeks). This regimen lasted for 1 year; however, if chemotherapy could be continued after this period, we used S-1 only. We reported the results of 11 cases who received this treatment., Patients: There were 6 total gastrectomies and 5 distal gastrectomies. Clinical non-curative factors were 5 pP1, 5 pN3b, 3 CY1 and 1 resection margin involvement., Results: At the end of adjuvant therapy there were 6 completions, 4 recurrences, and 1 patient with side effects. The main adverse event of Grade 3 or greater was neutropenia (46%). The recurrence rate was 63.6%. Types of relapse included 6 disseminations and 1 patient with lymph node involvement. One-, 3-, and 5-year survival rates were 100%, 72.7% and 72.7%, respectively, and the RFS was 64.0 months., Conclusion: S-1 and DOC adjuvant chemotherapy produced good results and may serve as a therapy of choice for patients with advanced gastric cancer with non-curative factors after a relatively curative resection.

Background: Capecitabine plus cisplatin (XP) is a standard global regimen, while S-1 plus cisplatin (SP) is a Japanese standard for first-line treatment of advanced gastric cancer (AGC). We conducted a phase II trial comparing XP with SP for patients with AGC to confirm whether these regimens can be used as controls in a phase III study and to explore whether histological subtypes favour XP or SP., Patients and Methods: Eligible patients were randomised to receive either S-1 40 mg/m 2 for 21 days plus cisplatin 60 mg/m 2 (q5w) or capecitabine 1000 mg/m 2 for 14 days plus cisplatin 80 mg/m 2 (q3w). The primary end-point was progression-free survival (PFS). The secondary end-points were overall survival (OS), overall response rate (ORR) and safety., Results: In 110 eligible patients, 24-week PFS was higher in both groups (SP 50.9%, XP 43.5%) than the protocol-specified threshold of 40%. The median PFS for SP versus XP was 5.6 and 5.1 months (hazard ratio [HR], 1.126; p = 0.5626); OS was 13.5 and 12.6 months (HR, 0.942; p = 0.7769) and the ORR was 42.4% and 69.4% (p = 0.0237), respectively. The most common grade ≥3 adverse events with SP/XP were anaemia (16%/20%), neutropenia (9%/18%) and anorexia (18%/13%). Subgroup analysis by histological classification showed no statistical difference between treatments., Conclusions: XP and SP are comparable and can be recommended as control arms in a phase III study for AGC. Histological subtypes were not sensitive markers for the selection of XP or SP., Clinical Trial Registration: NCT00140624., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results., Methods: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival., Results: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed., Conclusions: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Lentinan (LNT) is a purified β-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer., Patients and Methods: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment., Results: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group., Conclusions: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer., Clinical Trial Registration Id Number: UMIN 000000574., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We report a curative resection of a case with advanced gastric cancer responding remarkably well to combination chemotherapy of docetaxel, cisplatin and S-1. The patient was a 71-year-old man with gastric cancer of Borrmann type 3 accompanied with N3. Staging laparoscopy revealed peritoneal dissemination. He was administered docetaxel intravenously at 40mg/ m2 on day 1, cisplatin intravenously at 60 mg/m2 on day 1, and S-1 orally at 80 mg/m2 on days 1 to 14. This treatment was repeated every 28 days as one course. According to gastroscope and CT findings, a significant tumor reduction was obtained after 4 courses. After 6 courses, a CT scan revealed partial response of the lymph node metastasis, and the serum CEA value was normalized. Curative total gastrectomy was performed. The histological effect of the primary lesion was judged to be grade 2. Combination chemotherapy of S-1, cisplatin and docetaxel can be effective and feasible for advanced gastric cancer.

A 63-year-old- female was admitted to our hospital complaining of cough. Based on CT, bone centigram and peripheral blood findings, a diagnosis of gastric carcinoma accompanied by bone marrow metastasis was made. As DIC developed following hospital admission, S-1 and docetaxel(DOC)therapy was initiated(daily oral administration of 80 mg/m(2) S-1 for 14 days and DOC at 40 mg/m(2) on day 1, q3w). Recovery from DIC was achieved. S-1 and DOC therapy is considered to be effective for DIC due to bone marrow metastasis of gastric carcinoma. S-1/DOC is thought to be an effective chemotherapy against progressive gastric carcinoma accompanied by disseminated carcinomatosis bone marrow with DIC.

Background/aims: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown., Methodology: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209)., Conclusions: WNT5A was more frequently methylated in early gastric carcinomas.

Aim: Detection of gastric cancer using serum assay of vimentin methylation., Methods: A quantitative methylation-specific polymerase chain reaction assay was used to detect vimentin gene (VIM) methylation in the serum of 71 patients with gastric cancer., Results: Mean VIM methylation in cancer patients (0.304 ± 0.558) was significantly higher than that in healthy donors (0.011 ± 0.015, p=0.018). The sensitivity of VIM methylation (33.8%) was similar to the one of carbohydrate antigen 19-9 (CA19-9) (25.4%), higher than the one of carcinoembryonic antigen (CEA) (12.7%), and significantly higher than the sensitivity of both markers for patients with stage I and IV disease (p=0.010 and 0.044, respectively). At all stages, the sensitivity of a combination of markers was higher than the sensitivity of any in isolation marker and was similar for stages I, II and III, reaching 76.9% for stage IV disease., Conclusion: VIM methylation may represent a useful marker for the detection of tumor DNA in the serum of patients with gastric cancer.

Background: Methylation of tissue factor pathway inhibitor-2 (TFPI2) has been detected in the stool of colorectal cancer patients. Using quantitative methylation-specific polymerase chain reaction (qMSP), 39 out of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that a significant number of methylated TFPI2 existed in colorectal cancer patients' sera., Materials and Methods: Methylation status of the TFPI2 gene was examined in sera derived from 73 patients with gastric cancer using qMSP and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Out of 73 serum samples, 7 (10%) exhibited TFPI2 methylation in their serum DNA by qMSP, suggesting that TFPI2 methylation existed in the serum of gastric cancer patients. After completion of qMSP analysis of all specimens, clinicopathological data were correlated with the molecular analysis. TFPI2 methylation was significantly more frequently found in serum of patients with lymph node metastasis (p=0.0040) and distant metastasis (p=0.0115)., Conclusion: In principle, knowledge of the methylation status of a primary tumor is not required in advance in order to be able to detect circulating tumor DNA. Therefore, qMSP could be used as a cancer screening method.

Background: Recently, we have reported an important role of epidermal growth factor-like domain 8 (EGFL8) in the progression of colorectal cancer (CRC) and documented EGFL8 to be a novel prognostic biomarker for this malignancy. However, the function of EGFL8 in the other human gastroenterological malignancies such as gastric cancer remains largely unknown., Patients and Methods: EGFL8 expression in 53 cases of gastric cancer and the corresponding normal tissues were determined by quantitative real-time PCR and the EGFL8 down-regulation score for each patient was calculated. Subsequently, the correlations between EGFL8 down-regulation score and the clinicopathological features of gastric cancer were evaluated., Results: EGFL8 expression was significantly lower in the gastric cancer tissues than the corresponding normal tissues (p=0.0001) and the down-regulation of EGFL8 was evident in 73.6% (39/53) of the gastric carcinomas. More importantly, EGFL8 down-regulation was correlated significantly with peritoneal dissemination (p=0.037) and high TNM stage (p=0.025) of gastric cancer., Conclusion: The down-regulation of EGFL8 might be a novel biomarker for advanced gastric cancer.

A 55-year-old woman was found to have a type-4 lesion centered on the greater curvature of the lower portion of her stomach during an upper gastrointestinal endoscopic examination.A diagnosis of inoperable advanced gastric carcinoma [type 4, tub 2/por, T3 (SE), N3, H0, P1, cStage IV], complicated by pyloric stenosis, liver dysfunction, and obstructive jaundice untreatable by bile drainage, was made.After obtaining the informed consent of the patient and her family and explain- ing that under the circumstances surgery was not indicated, chemotherapy [S-1 (granules) 80 mg/m2, CDDP 60 mg/m2] was selected. After starting treatment, an improvement in liver dysfunction and jaundice was observed, and at the start of the second course, the patient had become capable of oral feeding.The patient was discharged after completion of the second course. No choices associated with evidence exist for treatment of patients with inoperable advanced gastric cancer (complicated by obstructive jaundice), who are not elderly and have good performance status (PS).We report this case in which improvement of activity of daily living (ADL) was achieved relatively safely by treatment with S-1/CDDP, together with a brief discussion based on the literature.

Background: Recently, it has been shown that the loss of the human histone acetyl transferase, TIP60, led to an accumulation of double-strand DNA breaks and has been linked to a growing number of cancer types., Materials and Methods: TIP60 expression levels were examined in 46 gastric cancer samples using a quantitative real-time polymerase chain reaction (QRT-PCR). Subsequently, clinicopathological data were correlated with the TIP60 expression score., Results: A down-regulation of the TIP60 gene was observed in 28 out of 46 (61%) specimens of primary gastric cancer. TIP60 down-regulation showed significant correlation with patient age (p=0.0224), depth of tumor invasion (p=0.0401) and lymph node metastasis (p=0.0481)., Conclusion: The down-regulation of TIP60 is important for the malignant pathway of gastric carcinogenesis.

Background: The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor suppression. In the present study, the role of Mus81 in gastric cancer was explored., Materials and Methods: Mus81 expression in 53 cases of gastric cancer and the corresponding normal tissues was determined by quantitative real-time PCR. The correlations between Mus81 down-regulation and the clinicopathological data were also evaluated., Results: Mus81 expression was significantly lower in gastric cancer tissues than the corresponding normal tissues (p = 0.018) and the down-regulation of Mus81 occurred in 51% (27/53) of the gastric carcinomas. More importantly, Mus81 down-regulation correlated significantly to invasion depth (p = 0.015) and poorly-differentiated type (p = 0.016) of gastric cancer., Conclusion: Mus81 might be a potential marker for the malignancy of gastric cancer.

Background: Recently, Glockner et al. identified the methylation of TFPI2 as a frequent event in human colorectal cancer using a gene expression array-based strategy., Materials and Methods: Methylation status of the TFPI2 gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the TFPI2 gene was detected in 7 out of 38 (18%) primary gastric carcinomas, suggesting that the methylation of TFPI2 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the methylation results. A significant difference was observed in maximal tumour size (p=0.0084), extent of tumour (p=0.0068), and TNM stage (p=0.0392)., Conclusion: TFPI2 is frequently methylated in advanced gastric carcinomas.

Background: Recently, metastasis associated with the colon cancer 1 (MACC1) gene was identified by genome-wide search for differentially expressed genes in human colon cancer tissues and metastases. Previously, the MACC1 expression levels were examined in colorectal carcinomas and it was found that MACC1 expression showed significant correlation with peritoneal dissemination and higher stage of TNM classification., Materials and Methods: In this study, MACC1 expression levels were analysed in 41 gastric cancer samples using quantitative real-time polymerase chain reaction (QRT-PCR). Results. Distribution of MACC1 expression scores in primary gastric carcinomas was between 0.01 and 4.36 (average ± SD was 1.34 ± 1.31). Subsequently, clinicopathological data were correlated with the MACC1 expression. It was found that MACC1 expression showed significant correlation with peritoneal dissemination (p=0.038)., Conclusion: These results suggest that MACC1 is more frequently expressed in peritoneal-disseminated gastric carcinomas and may serve as a new parameter for the prognostic prediction of gastric cancer.

Background: A tumor suppressor gene, p16, was found to harbor promoter methylation associated with the loss of protein expression in cancer cells, suggesting that p16 inactivation due to promoter methylation may be important for gastric tumorigenesis., Patients and Methods: The methylation status of the p16 gene was examined in primary carcinomas and the corresponding normal tissues derived from 49 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the p16 gene was detected in 17 out of the 49 (34%) primary gastric carcinomas, suggesting that the aberrant methylation of p16 is frequently observed in gastric carcinomas. The clinicopathological data were then correlated with these results. Significant differences were observed with lymphatic invasion (p=0.046) and tumor site (p=0.010)., Conclusion: p16 might act as a tumor suppressor in gastric carcinomas and appears to be more frequently methylated in lymphatic-invasive gastric carcinomas.

Background: Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133(+) cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal and gastric carcinogenesis., Materials and Methods: The methylation status of the CD133 gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Demethylation of the CD133 gene was detected in 14 out of the 36 (39%) primary gastric carcinomas, suggesting that the demethylation of CD133 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the demethylation results. A significant decrease of CD133 methylation was observed in the extent of tumor (p=0.0421). Moreover, a trend was shown toward smaller maximal tumor size in tumors with demethylated CD133 (p=0.0556)., Conclusion: CD133 appears to be frequently demethylated in early gastric carcinomas.

Background: Deleted in colorectal carcinoma (DCC), one of the Netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, we examined the methylation status of the DCC gene in colorectal carcinomas and found that aberrant methylation of the DCC gene was detected in 28 out of the 50 (56%) primary colon carcinomas. This result prompted us to examine the methylation status of the DCC gene in gastric carcinoma., Materials and Methods: The methylation status of the DCC gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the DCC gene was detected in 16 out of the 36 (44%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0093)., Conclusion: DCC methylation was observed in the course of gastric carcinogenesis and disappeared in advanced gastric carcinoma.

Background: Recently, Herfarth et al. reported that a subset of colorectal tumors was characterized by a specific methylation pattern in the MGMT promoter associated with reduced MGMT expression., Materials and Methods: Methylation status of the MGMT gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the MGMT gene was detected in 4 out of the 38 (11%) primary gastric carcinomas, suggesting that the methylation of MGMT is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0470), lymph node metastasis (p=0.0470), and TNM stage (p=0.0377) (Table I). Moreover, a trend was shown toward large maximal tumor size in methylated tumors (p=0.134)., Conclusion: MGMT was more frequently methylated in advanced gastric carcinomas.

Background: UNC5C, one of the netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, aberrant methylation of the UNC5C gene was found in 34 out of 49 (69%) primary colon carcinomas., Materials and Methods: The methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction, and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the UNC5C gene was detected in 9 out of the 36 (25%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0455)., Conclusion: UNC5C methylation was observed in the course of gastric carcinogenesis and disappeared in highly advanced gastric carcinomas.

Background: We recently found that CDH3 was frequently demethylated in advanced colorectal carcinomas. This prompted us to examine the demethylation status of the CDH3 gene in gastric carcinomas., Materials and Methods: The demethylation status of the CDH3 gene was examined in primary tumors derived from 36 patients with gastric carcinoma using a quantitative methylation-specific PCR (qMSP) and was evaluated the correlation between the demethylation status and the clinicopathological findings., Results: Demethylation of the CDH3 gene was detected in 25 out of the 36 (69%) primary gastric carcinomas, suggesting that the aberrant demethylation of CDH3 is a frequent event in gastric carcinomas. Demethylation of CDH3 was significantly associated with increasing TNM stage (p=0.0261). Moreover, a trend was shown toward infiltration beyond the serosa being associated with demethylation of CDH3 (p=0.0733)., Conclusion: CDH3 was frequently demethylated in advanced gastric carcinomas.

Background/aims: Recently, it was examined the methylation status of the Protein Gene Product 9.5 (PGP9.5) gene in primary tumors derived from 49 patients with colorectal cancer and evaluated the correlation between the methylation status and the clinicopathological findings. A significant difference was observed in lymph node metastasis (p = 0.029), suggesting that PGP9.5 was less frequently methylated in metastatic colorectal cancer. This result prompted us to examine the methylation status of the PGP9.5 gene in gastric cancers., Methodology: It was examined the methylation status of the PGP9.5 gene in primary tumors derived from 30 patients with gastric cancer using qMSP and evaluated the correlation between the methylation status and the clinicopathological findings., Results: Aberrant methylation of the PGP9.5 gene was detected in 5 of 30 (17%) primary gastric cancers. The present results suggested that the aberrant methylation of the PGP9.5 gene was frequently observed in gastric cancers. Subsequently, clinicopathological data were correlated with the methylation results. A significant difference was observed in extent of tumor, lymph node metastasis, and TNM stage (p = 0.034, 0.015, and 0.028, respectively)., Conclusion: PGP9.5 was less frequently methylated in advanced gastric cancer compared to earlier one.

A tumor suppressor gene at 10q23.3, designated PTEN, encoding a dual-specificity phosphatase with lipid and protein phosphatase activity, has been shown to play an essential role in the pathogenesis of a variety of human cancers. Frequent mutations and deletions of PTEN genes are found in cancer. Little is known, however, about the role that PTEN plays in the pathogenesis of a primary choriocarcinoma derived from gastric adenocarcinoma, an extremely rare choriocarcinoma, or in extragonadal retroperitoneal choriocarcinoma. In this study, genetic alterations occurring in extragonadal choriocarcinoma in two Japanese male patients were examined. Loss of heterozygosity (LOH) analysis using a polymorphic marker of the PTEN gene, IVS4+109ins/delTCTTA, revealed a hemizygous deletion of PTEN not only in the primary gastric choriocarcinoma, but also in the gastric adenocarcinoma. Microsatellite marker D12S1051 likewise showed LOH in both the primary gastric choriocarcinoma and the gastric adenocarcinoma. Mutational analysis of the TP53 gene revealed a point mutation in exon 5 (A536G), which resulted in H179R in the gastric choriocarcinoma but not in the gastric adenocarcinoma. No LOH was found for PTEN in an extragonadal retroperitoneal choriocarcinoma. Microsatellite marker D9S162 showed LOH in the extragonadal retroperitoneal choriocarcinoma, but not in the primary gastric choriocarcinoma. These results indicate that LOH of the PTEN gene and of D12S1051 is the molecular pathogenesis of the gastric adenocarcinoma, and the mutation of the TP53 gene is an additional hit for the oncogenesis of choriocarcinoma arising from gastric adenocarcinoma. However, LOH of the PTEN gene is not a common molecular event for pathogenesis of extragonadal choriocarcinoma. In addition, it was found that expression of PTEN is significantly decreased in the nuclei of syncytiotrophoblast-like cancer cells, compared with those of cytotrophoblast-like cancer cells in choriocarcinoma.

Background: We recently examined the methylation status of the HACE1 gene in primary carcinomas derived from 32 patients with colorectal cancer. A significant increase was observed in the maximal tumor size of the tumors with methylated HACE1 (p=0.0304). Moreover, a trend was shown toward preferentially developing lymph node metastasis in the carcinomas with methylated HACE1 (p=0.0612), suggesting that HACE1 might present a malignant potential in colorectal cancer. These results prompted us to examine the methylation status of the HACE1 gene in gastric carcinomas., Materials and Methods: The methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 34 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: An aberrant methylation of the HACE1 gene was detected in 9 out of 34 (26%) primary gastric carcinomas. Subsequently, clinicopathological data were tested for correlation with the methylation score. A significant difference was observed in patient gender (p=0.0429)., Conclusion: HACE1 was frequently methylated in gastric carcinoma derived from male patients.

Background: Recently, it was shown that the vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma., Materials and Methods: The methylation status of the vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 37 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated., Results: Aberrant methylation of the vimentin gene was detected in 14 out of 37 (38%) primary gastric carcinomas. This result suggested that the aberrant methylation of the vimentin gene was frequent in gastric carcinomas. Subsequently, clinicopathological data were correlated with the methylation score. A significant difference was observed in histology (p=0.0429). In addition, a trend was shown toward advancement of gastric carcinomas with vimentin methylation (p=0.0588)., Conclusion: In gastric carcinomas, well-differentiated adenocarcinoma was significantly methylated compared to poorly differentiated.

A 69-year-old woman had been treated with insulin for diabetes over the last 8 years. Distal gastrectomy (D2) was undertaken for StageIV stomach cancer. CA19-9 showed marked increases after surgery, but returned to normal after administering S-1. After 12 cycles, the treatment was discontinued due to hepatic disorders, and the clinical course was monitored. Weekly paclitaxel therapy was initiated as second-line therapy when CA19-9 rose again to 467 U/mL. Marked efficacy was noted after completion of one cycle. A total of 23 cycles were conducted. CA19-9 returned to normal, and the patient remains recurrence-free. In the treatment with paclitaxel, pre-treatment with dexamethasone (20 mg each time) is made to prevent hypersensitivity reactions. Since the total dose becomes too large in weekly treatment, however, treatment was initiated at 12 mg in our patient, and the dose was reduced stepwise to 8 mg, 4 mg and 2 mg. At the same time, the dose of insulin at bedtime and before breakfast the following morning was increased in increments of 2 units. This made it possible to maintain good control of blood glucose levels and minimize changes in HbA1c. This experience suggests that the dosage regimen needs refinements in diabetic patients such as a reduction in the dose of steroids and increases in the dose of insulin in long-term treatment.

An 83-year-old male with Stage IV gastric cancer of performance status 1 (PS 1) was treated with fluoropyrimidine (TS-1) since January 2003 in our department. As the patient exhibited decreased renal function due to his age, we set the basic dose at 80% of the recommended dose of 80 mg/body/week. We administered 11 four-week cycles, each with a two-week drug-free washout period, and six two-week cycles, each with a two-week drug free washout period. The first cycle of chemotherapy ameliorated the subjective symptoms; the level of a tumor marker then returned to normal, and the ascites disappeared. The patient's condition was maintained at a favorable PS level without any subjective symptoms for approximately 20 months. In late September 2004, however, an exacerbation of the primary foci was confirmed by routine endoscopic examination. As second-line chemotherapy, we initiated weekly administration of paclitaxel (PTX). Due to the patient's age and high PS level (PS 2) at the time of intervention, we utilized a reduced dose of 70 mg/body/dose. After a short premedication period, the patient was administered PTX intravenously for one hour once a week for three weeks, then given a one-week drug-free washout period (one cycle). After the first cycle of PTX administration, all subjective symptoms disappeared, the PS level returned to zero,and the patient was discharged. In total, four cycles of the PTX regimen were given. Throughout the treatment period, we did not observe any significant adverse events (grade 2 or higher). Treatment achieved a favorable PS level. To design an effective chemotherapy regimen for elderly patients, it is important to establish an effective dose and dosing method based on the patient's chronologic age and a thorough evaluation of the patient's systemic conditions, including the PS level.

We report a rare case of subacute combined degeneration of the spinal cord concomitant with gastric cancer. A 67-year-old man was admitted because of posterior column symptoms, pyramidal tract sign and peripheral neuropathy with severe hyperchromic anemia. He was treated with mecobalamin 1 mg IM, after which his anemia and neurological signs recovered. He was diagnosed as having subacute combined degeneration with pernicious anemia. Subsequent stomach biopsy revealed gastric cancer, and the patient underwent gastrectomy. It is a well known association that chronic atrophic gastritis is associated with gastric cancer or subacute combined degeneration. Our findings suggest that in this case subacute combined degeneration and gastric cancer are independent of each other; rather, both resulted from chronic atrophic gastritis.

We report a case of myasthenia gravis (MG) associated with autoimmune thrombocytopenic purpura (AITP) and autoimmune hemolytic anemia (AIHA), and after that gastric cancer appeared. A 51-year-old man began to suffer from fluctuated muscle weakness in 1985. Muscle weaknesses became exacerbated, and he was admitted to our hospital in 1989. He was diagnosed as MG associated with AITP. After a thymectomy (hyperplasia), prednisolone therapy was started, subsequently his condition was satisfactory. In March 1995, he developed severe anemia and icterus. He was diagnosed as Evans' syndrome (AIHA and AITP) with MG. High-doses of immunoglobulin administration improved the anemia, but thrombocytopenia continued. In November 2002, he suffered marked petechia; the platelet count decreased to 1000/microl. Methylprednisolone pulse therapy and platelet transfusion were started. Gastrofiberscopy was performed and biopsy specimens revealed signet cell-type adenocarcinoma. On December 19, 2002, subtotal gastrectomy and splenectomy were performed. After that, his condition has remained satisfactory, without MG symptoms or thrombocytopenia. This is the first such case report in the literature.

Unlabelled: Gastric cancers that produce alpha feto protein (AFP) usually have a poor prognosis. We report an AFP-producing gastric cancer that showed a partial response to low-dose CPT-11 and low-dose cisplatin combination chemotherapy. AFP-producing gastric cancers successfully treated with chemotherapy have been reported, but to our knowledge this is the first report of successful treatment with low-dose CPT-11 and low-dose cisplatin combination chemotherapy., Case: A 49 year-old woman who had gastric cardiac cancer with esophageal invasion was admitted to our institution. Since AFP-positive cells were demonstrated immunohistochemically in biopsy specimens and levels of AFP in serum were high, AFP-producing cancer was diagnosed. Because of metastasis to Virchow's node and the paraaortic lymph nodes, the tumor was considered unresectable. The patient's poor general condition necessitated chemotherapy with low toxicity and high efficacy. She was treated with low-dose CPT-11 and low-dose cisplatin combination chemotherapy. After two cycles of this treatment, the tumor volume and the serum levels of AFP had decreased markedly. The only side effect of the treatment was leukopenia.

Background/aims: Lentinan is one of the host-mediated anti-cancer drugs which has been shown to affect host defense immune systems. Although the mechanisms involved in the antitumor effects of lentinan have been reported experimentally, the clinical outcome on prolongation of survival and improvement of quality of life in gastric cancer patients with unresectable or recurrent diseases has yet to be clarified. The aim of the present study was to investigate whether administration of lentinan prolonged survival or improved quality of life in these patients., Methodology: A multi-institutional randomized prospective protocol, consisting of patients administered tegafur and cisplatin (control group), and patients administered lentinan, tegafur and cisplatin (lentinan group), was performed. Quality of life was investigated using a questionnaire survey., Results: Median survival was significantly longer in the lentinan group than in the control group (297 days vs. 199 days, p = 0.028). One-year survival rate was greater in the lentinan group than in the control group (49.1% vs. 0%). Total QOL score, especially appetite and sleep quality, was significantly improved with the administration of lentinan., Conclusions: Lentinan is considered to prolong survival and improved quality of life when gastric cancer patients with unresectable or recurrent diseases are treated in combination with other chemotherapeutic agents.