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Background: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin., Patients and Methods: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m 2 . The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity., Results: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death., Conclusions: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis., (© 2023. Society of Surgical Oncology.)

Background/aim: Surgery for elderly patients with gastric cancer is becoming more common. However, the risk factors of the laparoscopic surgery for these patients are unknown, and thus it is difficult to determine appropriate treatments for such patients. The aim of this retrospective study was to clarify the risk factors for the treatment outcomes after laparoscopic gastrectomy in elderly patients., Patients and Methods: Two hundred twenty-two patients who underwent laparoscopic gastrectomy for primary gastric cancer between January 2014 and December 2017 were enrolled. Clinical characteristics and short- and long-term prognoses were analyzed in 47 patients aged 75 years or older (elderly group) and in 175 patients who were under 75 years old (non-elderly group)., Results: The presence of comorbidities was more common in the elderly group than in the non-elderly group (91.5% vs. 61.7%, p<0.0001). The rate of postoperative complications in the elderly group was significantly higher than that in the non-elderly group (42.6% vs. 22.9%, p=0.01). The 5-year overall survival rate was significantly lower in the elderly group than in the non-elderly group (66.9% vs. 92.2%; p<0.0001). In the elderly group, 5-year overall survival in patients with a low preoperative prognostic nutritional index (PNI) was significantly worse than that in patients with a high preoperative PNI (25.0% vs. 80.9%; p<0.05). Multivariate analysis showed that the PNI value was independently associated with overall survival in elderly patients who underwent laparoscopic gastrectomy (p<0.05). In particular, the rate of non-cancer deaths after surgery in elderly patients was significantly higher than that in non-elderly patients (p<0.05)., Conclusion: PNI value is an independent prognostic factor for overall survival in elderly patients who have undergone laparoscopic gastrectomy for gastric cancer; therefore, in elderly patients with low preoperative PNI, attention should be paid not only to recurrence of cancer, but also to the deterioration of general condition caused by malnutrition., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Survivors of esophageal cancer post-esophagectomy may sometimes develop gastric tube cancer (GTC). However, its clinical characteristics have not been elucidated. We conducted a retrospective nationwide survey of GTCs to clarify them., Methods: A questionnaire on GTCs was sent by e-mail and mail to 116 institutions certified by the Japan Esophageal Society. A total of 608 GTC cases diagnosed and treated between 2001 and 2015 were registered from 62 institutions., Results: The median age at diagnosis was 71 years, with 88.9% being diagnosed with stage I. Sixty percent of GTC cases were in the anal third of the gastric tube and 79.7% were differentiated adenocarcinomas. The median interval between esophagectomy and GTC diagnosis was 6 years, with approximately 25% of patients being diagnosed more than 10 years later. The 5-year overall survivals (5-OSs) after endoscopic and surgical treatments for GTC were 75.9% and 52.7%, respectively. Patients whose GTC was diagnosed without symptoms or by regular follow-up examination showed better 5-OSs compared to others (69.7% vs. 41.2%, p < 0.0001; and 71.4% vs. 41.8%, p < 0.0001, respectively). The prognosis of GTC cases diagnosed within 2 years of the preceding upper gastrointestinal endoscopy (UGI) was better than that in cases diagnosed longer than 2 years (5-OS: 73.4% vs. 48.8%, p < 0.05)., Conclusion: This nationwide survey revealed the clinicopathological features of GTCs for the first time. Early detection is important in improving the prognosis of GTC, and it is recommended that UGI endoscopy be continued every 2 years for 10 or more years after esophagectomy., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Compared with open standard gastrectomy (OG), laparoscopic gastrectomy (LG) did not result in inferior disease-free survival for early-stage and locally advanced gastric cancer (AGC). However, whether LG for AGC in elderly patients is more beneficial than OG is unclear., Methods: This study examined 458 patients with AGC. The mortality, morbidity, and prognosis were compared by age, gender, T and N factors, and pathological stage in the LG and OG groups using propensity score matching analysis. For the final analysis, 151 pairs of patients were selected from at each group., Results: The results showed that no significant difference in mortality and morbidity existed between the two groups. The 5-year relapse-free survival (RFS) rates were 70% and 62% in the LG and OG groups, respectively (p = 0.104). The 5-year RFS rates in patients with pathological stages I, II, and III who had undergone LG were 84%, 80%, and 55%, respectively, and 78%, 70%, and 45%, respectively, in those who had undergone OG (p < 0.005). The 5-year RFS rates in nonelderly patients who underwent LG or OG were 75% and 68%, respectively, and 58% and 40%, respectively, in elderly patients who underwent LG or OG (p < 0.005)., Conclusion: The 5-year RFS rates in patients with AGC at each stage did not significantly differ between LG and OG. However, the benefits at 5-year RFS in patients who underwent LG compared with OG were larger in elderly patients than those in nonelderly patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aim: The safety and efficacy of laparoscopic total gastrectomy (LTG) for remnant gastric cancer (RGC) remains unclear. The purpose of this study was to compare the clinical outcomes of LTG with open total gastrectomy (OTG) for RGC., Patients and Methods: Twenty-two patients who underwent total gastrectomy for RGC were enrolled in this study., Results: LTG was carried out in seven patients, and OTG was performed in the remaining 15 patients. The mean operation time in the LTG group was longer than that in the OTG group. The estimated blood loss in the LTG group was less than that in the OTG group. No cases in the LTG group required open conversion. Postoperatively, the first meal and defecation were earlier in the LTG group than in the OTG group. The overall survival rates of the two groups were comparable., Conclusion: Laparoscopic total gastrectomy is a feasible surgical option for RGC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome that secretes incompletely processed high molecular weight insulin growth factor 2 (big-IGF2), which results in stimulation of the insulin receptor and subsequently induces hypoglycemia. Gastrointestinal stromal tumor (GIST) is a common intestinal mesenchymal neoplasm of the gastrointestinal tract. The most frequent site of GIST is the stomach; NICTH induced by IGF2-producing stomach GISTs is rare., Case Presentation: An 84-year-old man was admitted to the hospital due to impaired consciousness (JCS II-10) in the morning. At the time of admission, his serum glucose was 44 mg/dL; his consciousness was restored with 20 ml of 50% glucose. To avoid hypoglycemia, a continuous intravenous infusion of glucose as well as dietary intervention was required. At the time of hypoglycemia, the levels of insulin and C-peptide were suppressed. Additionally, IGF1 levels were below the normal range. Abdominal computed tomography revealed that he had a large lobulated mass (116 × 70 × 72 mm) around the gastric corpus. Pathological analysis of biopsy specimens identified disarray of spindle cells and positivity for c-kit as well as strong positivity for DOG-1. Further analysis revealed high levels of Ki-67 (Mib-1 index: 15.5%) and mitotic index (7/50HPF); the tumor was diagnosed as high-risk GIST, and complete surgical resection was performed. Hypoglycemia resolved immediately after tumor resection. The resected tumor specimen was positive for IGF2 staining, and big-IGF2 (11-18 kDa) was detected in preoperative serum and tumor samples; the patient was diagnosed with NICTH due to an IGF2-producing tumor., Conclusions: NICTH is rare in GIST of the stomach; however, the large GIST could produce big-IGF2 and subsequently cause severe hypoglycemia, requiring prompt evaluation and complete tumor resection.

Background: Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy., Methods: Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12)., Results: Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10 months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3 months for the 11 effective and 7 non-effective patients, respectively., Conclusions: A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.

Background: Laparoscopic surgery is frequently performed, and laparoscopic gastrectomy (LG) is also widely performed for gastric cancer. Elderly population with gastric cancer has increased in East Asia, including in Japan., Methods: We examined 1131 patients with gastric cancer who underwent laparoscopic and open standard surgeries (OG). A total of 921 patients of age < 75 years (non-E group) and 210 patients of age ≥ 75 years (E group) underwent surgery for gastric cancer. The mortality, morbidity, and prognosis of LG and OG were compared by propensity score-matched analysis., Results: Mortality and morbidity in the E group were significantly higher than those in the non-E group (p < 0.05). Propensity score-matching revealed that the incidence of postoperative complications of grade ≥ 2 in the OG subgroup was significantly higher than that in the LG subgroup in the E group (p < 0.05). The overall survival rate of the LG subgroup was significantly higher than that of the OG subgroup in both the non-E and E groups (p < 0.05). The depth of tumor invasion, lymph node metastasis, and the number of dissected lymph nodes were dependent factors for survival in the non-E group, whereas the depth of tumor invasion was the only dependent factor for survival in the E group in the multivariate analysis., Conclusion: The survival rate of patients who underwent LG showed significantly good prognosis in both the non-E and E groups, although the E group patients who underwent OG subgroup showed higher severe complication incidences than those who underwent LG subgroup.

Purpose: This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay., Methods: The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group., Results: No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size., Conclusion: Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

Purpose: To examine the short-term outcomes of intracorporeal anastomosis during totally laparoscopic total gastrectomy retrospectively at multiple institutions., Patients and Methods: We collected data of the patients who had undergone totally laparoscopic total gastrectomy at 4 institutions. All patients received an intracorporeal esophagojejunostomy., Results: Of the 215 patients evaluated, 147 underwent functional end-to-end anastomosis (FEEA) as the intracorporeal esophagojejunostomy (FEEA group), and 68 patients received a circular stapler anastomosis (Circular group). The rate of tumor invasion to the esophagus was significantly higher in the Circular group than in the FEEA group (33% vs. 6%, respectively; P<0.0001). Univariate and multivariate analyses revealed that the circular stapler anastomosis and high preoperative BMI were statistically significant risk factors for postoperative leakage. However, the rates of complications and mortality were not significantly different between groups., Consideration: Our results showed that each type of esophagojejunostomy is safe and feasible for patients with gastric cancer with acceptable morbidity and mortality.

Background: We performed esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) using functional end-to-end anastomosis (FEEA) as the first choice and laparoscopic-assisted total gastrectomy (LATG) using a circular stapler with a transorally inserted anvil as the second choice., Patients and Methods: We examined 109 patients with gastric cancer who underwent TLTG and LATG. Among these, 100 patients underwent TLTG and the rest underwent LATG., Results: The length of resected esophageal segment in LATG patients was significantly longer than that in TLTG patients (P<0.001). The length of the resected esophagus segment was inversely correlated with body mass index in cases of esophagojejunostomy by FEEA (P<0.05). Multivariate analysis revealed that T factor, N factor, and severe complications were the independent factors for survival., Conclusions: Esophagojejunostomy using FEEA or a circular stapler with a transorally inserted anvil should be selected according to the length of the resected esophageal segment and/or body mass index.

Background: Molecular profiling in gastric cancer (GC) is important for diagnosis and treatment. In this study, we investigated signal transduction pathways that might induce chromosomal instability in GC., Methods: Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and p-AKT expression were analyzed using immunohistochemistry, and chromosomal instability was assessed by DNA aneuploidy using laser scanning cytometry, in a total of 202 GC cases., Results: The rate of EGFR expression and p-AKT expression was 70.3 and 34.2 %, respectively, in GC patients. In total, 57.5 % of GC patients exhibited DNA aneuploidy, and p-AKT positively correlated with EGFR and HER2 (p = 0.0127 and p = 0.00031, respectively). Patients with EGFR overexpressing GC showed shorter disease-specific survival than the other cases (hazard ratio 2.00, 95 % confidence interval 1.19-3.53; p = 0.0104). Moreover, EGFR and p-AKT expression was significantly correlated with DNA aneuploidy (p = 0.0002 and p = 0.0302, respectively)., Conclusions: Our data showed that both EGFR and p-AKT overexpression were clearly associated with DNA aneuploidy. Aneuploidy could be a useful marker for therapies that target EGFR.

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.

Gastric cancer is the fourth most common cancer worldwide. Although it is important to identify patients at high risk for a poor outcome, factors correlating with prognosis in gastric cancer are largely unknown. Here, we focus on the correlations among expression of Polo-like kinase 1 (PLK1), DNA ploidy, and clinical outcome in gastric cancer patients. Gastric cancer specimens were analyzed from 207 consecutive patients. Patients were classified into two groups according to tumor PLK1 expression and DNA content, and an analysis of their clinical outcomes was carried out. Prognoses of patients with PLK1-high tumors were worse than those of patients with PLK1-low tumors, but the differences were not statistically significant. In cell lines, overexpression of PLK1 induced centrosome amplification and multipolar spindles, potentially leading to DNA aneuploidy. Indeed, high expression of PLK1 was also associated with DNA aneuploidy in clinical gastric cancer specimens. Patients with both high PLK1 expression and DNA aneuploidy had poor recurrence-free survival, whereas PLK1 expression and DNA ploidy status alone were not significantly associated with outcome. Here, we provide clinical evidence that high expression of PLK1 could have detrimental effects in tumors with DNA aneuploidy, which may increase the risk of recurrence in gastric cancer patients., (© 2016 S. Karger AG, Basel.)

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: 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.)

Results from the Trastuzumab for Gastric Cancer (ToGA) trial highlighted the clinical significance of trastuzumab in the treatment of HER2 (Human Epidermal Growth Factor Receptor type 2)-positive gastric cancer. However, whether expression of HER2 is related to prognosis of gastric cancer is still controversial. A total of 360 consecutive patients with gastric cancer who underwent surgical resection in our Department from 1994 to 2007 were analyzed. We performed immunohistochemical analysis of HER2 expression. HER2 expression level was classified into four scores (0, 1+, 2+ and 3+). There were 37 (10%) patients with a score of 3+. A score of 3+ was defined as being HER2-positive. Recurrence-free survival was worse in HER2-positive cases (p=0.045). When the analysis was conducted with intestinal types of cancer, RFS was considerably worse in the HER2-positive group (p=0.011). HER2 expression may have potential as a prognostic factor for intestinal cancer types. Further research is warranted., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Immunohistochemistry staining of p53 is a cheap and simple method to detect aberrant function of p53. However, there are some discrepancies between the result of immunohistochemistry staining and mutation analysis. This study attempted to find a new definition of p53 staining by its staining pattern. Immunohistochemistry staining of p53 and TP53 gene mutation analysis were performed in 148 gastric cancer patients. Also SNP-CGH array analysis was conducted to four cases. Positive staining of p53 was observed in 88 (59.5%) tumors. Tumors with positive p53 staining showed malignant features compared to negative tumors. Mutation of TP53 gene was observed in 29 (19.6%) tumors with higher age and differentiated type. In positive p53 tumors, two types could be distinguished; aberrant type and scattered type. With comparison to TP53 gene mutation analysis, all the scattered type had wild-type TP53 gene (P = 0.0003). SNP-CGH array showed that scattered-type tumors had no change in the structure of chromosome 17. P53-scattered-type staining tumors may reflect a functionally active nonmutated TP53 gene. In interpretation of p53 immunohistochemistry staining, distinguishing p53-positive tumors by their staining pattern may be important in gastric cancer., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: More effective treatment is necessary to improve the poor prognosis for patients with unresectable gastric cancer. We investigated the efficacy and feasibility of adjuvant surgery following chemotherapy., Patients and Methods: Records of 70 patients with unresectable stage IV gastric cancer who underwent induction chemotherapy were reviewed retrospectively. Patients who developed an absence of non-curative clinical factors during chemotherapy underwent gastrectomy [adjuvant surgery (AS) group]; the others continued chemotherapy [non-AS group]., Results: Non-AS and AS groups contained 56 (80%) and 14 (20%) patients, respectively. In the AS group, 92.9% of patients had one non-curative clinical factor, while 48.2% of patients in the non-AS group had two or more non-curative clinical factors (p=0.0386). In the AS group, operative outcomes, including the postoperative complication rate (21.4%), were acceptable. The 3-year overall survival rate in the AS group was 65.6% versus 7.7% in the non-AS group (p<0.0001). In patients with one non-curative clinical factor of peritoneal dissemination, the median survival of the AS group was 29.5 months versus 11.4 months in the non-AS group (p=0.0230)., Conclusion: Adjuvant surgery for initially unresectable stage IV gastric cancer was safe and feasible, and may improve the prognosis for patients with one non-curative clinical factor, such as peritoneal dissemination., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: PTEN (the encoding phosphate and tensin homolog) is a well-known cancer suppressor gene and its mutation and loss of heterozygosity (LOH) occurs in various types of carcinomas. This study aimed to examine the association between LOH of PTEN and prognosis in HER2-expressing and nonexpressing gastric cancer patients., Methods: Fresh-frozen tumor samples of 221 gastric cancer patients with a primary diagnosis of gastric carcinoma were examined for LOH of PTEN. The results were compared with pathological parameters and the HER2 status. To elucidate the role of LOH of PTEN, the activation of the PI3K/AKT pathway was examined immunohistochemically using a phosphorylation-specific antibody., Results: LOH of PTEN was observed in 20% of the patients (39 of 195 cases). LOH of PTEN was associated with vascular involvement (25 of 39 cases; p = 0.0083), equivocal to positive staining for HER2 (p = 0.0080), and phospho-Akt expression (p = 0.0067). Patients with HER2-expressing gastric cancer with LOH of PTEN had a significantly worse prognosis (p = 0.0050)., Conclusions: Although HER2 expression itself was not a prognostic factor, the combination of HER2 expression and LOH of PTEN exacerbates the malignant potential of gastric cancer through its proliferative function., (© 2014 S. Karger AG, Basel.)

Background: A gastrectomy for gastric cancer is sometimes required in patients older than 80 years due to the continuously increasing age of society. However, if a gastrectomy worsens the postoperative quality of life and daily activity in elderly patients because of poor nutrition, the procedure may not always be a useful treatment strategy., Patients and Methods: Clinicopathological data of patients with gastric cancer who underwent a gastrectomy at our Department between 1998 and 2008 (N=471) were collected and analyzed. The results of treatment for patients older than 80 years (N=41) were analyzed and compared against those of patients younger than 80 years (N=430)., Results: Patients older than 80 years had a higher frequency of preoperative co-morbidities than patients younger than 80 years. However, there was no statistical difference in postoperative complications regarding nutrition between the two groups., Conclusion: Older age is not a determinant of poor nutrition following gastrectomy. Gastrectomy for gastric cancer is, therefore, a useful treatment strategy, regardless of ageing., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The present study aimed to clarify the safety and feasibility of esophagojejunostomy during totally laparoscopic total gastrectomy (TLTG)., Patients and Methods: In 45 consecutive patients who underwent TLTG for gastric cancer, esophagojejunostomy was performed with a functional end-to-end anastomosis (FEEA) using a linear stapler in 24 patients or with a double stapling technique (DST) using a trans-orally inserted anvil (OrVil™) in 21 patients., Results: The DST was more likely to be chosen in patients with tumors located in the upper stomach. In the FEEA group, both the mean length of the operation and the mean postoperative hospital stay were significantly shorter compared to those in the DST group. Two patients in the FEEA group and four patients in the DST group developed postoperative complications but there were no postoperative deaths in either group., Conclusion: Both FEEA and DST in esophagojejunostomy during TLTG are safe and feasible., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The CXCL12/CXCR4 axis plays a pivotal role in cancer progression and metastases in various epithelial cancer cells. The aim of the present study was to evaluate the localization and correlation between CXCL12/CXCR4 expression and clinicopathological features in gastric cancers., Materials and Methods: This study included 111 Japanese patients with primary gastric cancers, which invade submucosa or more, all of whom underwent gastrectomy between 1992 and 1996. Immunohistochemical analysis was performed., Results: A significant correlation was found in the immunoreactivity of nuclear CXCR4 and poor differentiation (p=0.0026), infiltrated pattern (p<0.0001), larger size (p<0.0001), advanced stage (p=0.0342) and reduced 5-year survival rate (30% vs. 61%, p=0.0012). Multivariate analysis revealed that high nuclear CXCR4 immunoreactivity (RR: 3.077, p=0.0329) retained its strength as an independent prognostic factor for overall survival., Conclusion: High immunoreactivity of nuclear CXCR4 in gastric cancer suggests that CXCL12 binds to its unique receptor CXCR4 at the membrane, translocates to the nucleus and then becomes more invasive, and thus can be considered a prognostic factor., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: With the recent popularization of living donor liver transplantation (LDLT), providing treatment for comorbidities in LDLT recipients has become important. We report the first case of a patient who was successfully treated with LDLT followed by total gastrectomy for early gastric cancer concomitant with decompensated liver cirrhosis., Case Report: A 64-year-old female was admitted for the treatment of severe liver cirrhosis. The patient's preoperative liver function was evaluated as Child-Pugh classification grade C. Upper gastrointestinal endoscopy revealed early gastric cancer. We first performed LDLT to improve her liver function and coagulopathy. Nineteen days after the LDLT, we performed total gastrectomy., Results: The patient's postoperative course was uneventful and she left our hospital on the 18th day after gastrectomy. The final pathological diagnosis of gastric cancer was Stage IA., Conclusion: Aggressive and adequate surgical strategy including LDLT is effective as curative treatment in patients with controllable malignancy concomitant with severe liver dysfunction., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: Vascular endothelial growth factor C (VEGFC) is thought to promote lymphangiogenesis in various human cancer tissues., Materials and Methods: The present study analyzed data from 72 patients with gastric cancer. The lymphatic vessel density (LVD) was determined by immunohistochemical staining using a monoclonal antibody (mAb) against D2-40, and the expression of VEGFC was investigated using a mAb against VEGFC., Results: The intratumoral LVD was higher in cases with nodal metastasis. The VEGFC-positive cases had a higher intratumoral LVD and were more invasive to the lymphatic vessels or lymph nodes than negative cases. Patients with VEGFC-positive cancer had significantly lower survival than those with negative cancer (p<0.05)., Conclusion: The expression of VEGFC was related to intratumoral lymph angiogenesis and serves as a pertinent predictive factor for lymphatic invasion or metastasis, while also providing prognostic value., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: HER2 testing in gastric cancer differs from testing in breast cancer because of inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity and incomplete membrane staining. The aim of the present study was to evaluate the frequency and accuracy of detection of HER2 expression by application of standard criteria in Japanese patients with gastric cancer., Material and Methods: A total of 198 tumor specimens were assessed for HER2 expression by immunohistochemistry (IHC) using the antibodies HercepTest™ and 4B5. Both hand-operated and automated IHC were performed., Results: HER2 expression differed according to the IHC method and antibodies used. HER2 IHC3+ tumors were identified in 21 (10%) and 7 (3.5%) cases by hand-operated and automated IHC, respectively., Conclusion: Among patients with gastric cancer, FISH may be performed in cases of IHC1+ by automated IHC. Further research is required to clarify the relevance of HER2 staining and scoring for the clinical response to HER2-targeted therapy., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: We conducted a phase II trial to evaluate the efficacy and safety of preoperative chemotherapy with docetaxel (DTX) plus S-1 for resectable advanced gastric cancer., Patients and Methods: A total of 47 patients from 14 centers were centrally registered. Patients received DTX (35 mg/m(2)) on days 1 and 15, and daily oral administration of S-1 (80 mg/m(2)/day) for days 1-14 every 4 weeks for two courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR). This study was registered in the UMIN clinical trial registry (UMIN000000875)., Results: The primary endpoint pRR was 47 % (90 % confidence interval (CI), 34-60 %; p < 0.0001). The response rate to preoperative chemotherapy using Response Evaluation Criteria in Solid Tumors (RECIST) was 34 %. Forty-six patients (98 %) underwent surgery, and curative resection was performed in 44 patients. Thirty-seven patients completed the protocol treatment. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42 %), febrile neutropenia (4 %), grade 2 anorexia (21 %), and fatigue (15 %). Treatment-related death and operative mortality was not observed in this study., Conclusions: The combination of docetaxel and S-1 was well tolerated. This is promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer.

Background: Mortalin is a heat-non-inducible member of the heat shock protein 70 family. Mortalin binds to p53 and prevents p53 from entering the nucleus. To understand the significance of mortalin in gastric cancer, we investigated the expression of mortalin and p53., Methods: Expression of mortalin and p53 was examined by immunohistochemical staining of 182 clinical samples of gastric cancer., Results: Mortalin-positive and aberrant p53-positive tumors were found in 75.2 and 49.5 % of cases, respectively. Mortalin-positive tumors were deeper in invasion and had more lymph node and liver metastases compared with mortalin-negative tumors (P < 0.01, P < 0.05, respectively). Mortalin-positive tumors had worse prognosis compared with mortalin-negative tumors (P = 0.035). Moreover, in tumors with normal p53 function, mortalin-positive tumors had worse prognosis compared with mortalin-negative tumors (P = 0.017)., Conclusions: Mortalin has a great impact on gastric cancer with normal p53. Therefore, mortalin is a target molecule for treatment of gastric cancer, as well as a promising prognostic factor, especially in tumors with normal p53.

Aim/background: We previously reported that PSK-induced lymphocyte blastogenesis reaction (PSK-stimulation index; PSK-SI) may be a prognostic marker for immunochemotherapy using PSK in gastrointestinal cancer patients. In this study we evaluated the usefulness of PSK-SI as a prognostic marker for PSK therapy at higher and lower serum immunosuppressive acidic protein (IAP) levels., Patients and Methods: 98 gastric and 135 colorectal cancer patients were analyzed. PSK-SI and serum IAP levels were measured preoperatively. After operation, patients received UFT and PSK for two years., Results: There were no differences between patients with higher and those with lower PSK-SI with respect to the clinicopathological factors. In patients with higher serum IAP levels (> or = 500 microg/ml), recurrence-free survival (RFS) and overall survival (OS) were apparently more favorable in the higher PSK-SI group (gastric cancer; > or = 1.75, colorectal cancer; > or = 2.1) than in lower PSK-SI group, although the differences were not significant., Conclusion: Serum IAP levels and PSK-SI may be useful markers for prediction of response to immunochemotherapy using PSK, although further studies are necessary.

A 65-year-old man was admitted to our hospital with nausea, vomiting and appetite loss. First upper endoscopic examination and X-ray examination showed a peptic ulcer and a pyloric stenosis. Fiberscope could not go through the pyloric ring. Computed tomography examination and biopsy showed no evidence of malignancy. Though we considered surgical resection of the stenosis at first, he could eat a staple food with therapy of proton pump inhibitor. So we followed up with upper endoscopic examinations. Second, third and forth upper endoscopic examinations showed no evidence of malignancy. Fifth upper endoscopic examination showed an ulcer scar on the pyloric ring and a 0-IIc carcinoma in the antral greater curvature. Distal gastrectomy with D2 lymph node dissection and B-II reconstruction. Pathologically, a mucosal carcinoma with no lymph node metastasis and U1-III peptic ulcer were diagnosed.

Background: Leptomeningeal carcinomatosis (LMC) is a rare complication of gastric cancer. Case 1. A 57-year-old female was diagnosed with gastric cancer and underwent distal gastrectomy with D2 lymph node dissection. Two years later, the patient suffered from para-aortic lymph node metastases and provided chemotherapy. During the chemotherapy, the patient emergently visited our hospital with chief complaints of a severe headache and dizziness. The above symptoms promptly abated by meningeal drainage, with a high value of the cerebrospinal fluid (CSF) pressure. Despite the administration of subsequent chemotherapy, the patient's clinical state rapidly worsened, including gradual progression of both blindness and hearing loss. Case 2. A 42-year-old male was diagnosed with Stage IV gastric cancer due to both distant lymph node metastases and an ascites. Chemotherapy with S-1 plus docetaxel was initiated. Upon finishing the fifth course of treatment, the patient complained of a severe headache. The magnetic resonance imaging (MRI) findings were suggestive of LMC. Under suspicion of carcinomatous meningitis, the patient underwent both cerebrospinal drainage with a high pressure value of 180 mmH2O and a cytological examination with a diagnosis of Class V. Immediately following the cerebrospinal drainage, the patient's symptoms promptly diminished. Case 3. A 66-year-old female was diagnosed with gastric cancer and underwent total gastrectomy with D2 dissection. About a year later, the patient suffered from the peritoneal dissemination, and provided serial chemotherapy regimens for 13 months. Thereafter the patient suffered from mildly stiff shoulders followed by serial severe headaches, and meningeal drainage was performed. The CSF showed pleocytosis and the presence of neoplastic cells, leading a diagnosis of LMC. After the placement of an Ommaya reservoir, the intrathecal chemotherapy was performed. Within two weeks of treatment, the patient's condition improved significantly, and the cell counts in the CSF obtained from the Ommaya reservoir remained low for six months after the first diagnosis of LMC., Conclusions: Although gastric LMC-affected patients often exhibit a fatal clinical course, the administration of intrathecal chemotherapy may improve survival. Systemic chemotherapy may be also administered in a limited number of patients with a superior performance status. At present, each case requires the individual making treatment decisions. Further accumulation of clinical cases and improving the overall understanding of the pathogenesis of this disease is needed in order to advance in the treatment of gastric LMC.

Purpose: Although the use of laparoscopic gastrectomy for gastric cancer has been widespread, it has remained controversial whether it can be applied for the patients with advanced gastric cancer. The aim of this study was to clarify the safety and usefulness of totally laparoscopic gastrectomy for patients with advanced gastric cancer., Patients and Methods: Totally laparoscopic gastrectomy was applied for a total of 38 patients with pStage IB-III advanced gastric cancer at our institute. The surgical and long-term results were analyzed in those patients., Results: Twenty-seven patents underwent distal gastrectomy and 11 patients underwent total gastrectomy. The mean number of dissected lymph nodes was 41 (range, 16-87). The mean length of the operation and amount of blood loss was 324 min and 123 ml, respectively. Two cases of postoperative bleeding were noted, while neither anastomosis-related complications nor in-hospital death was observed. The follow-up period after surgery was 8-72 months. Postoperative recurrence was observed in 6 patients (peritoneal dissemination: 3 patients, pleural dissemination: 1 patient, liver metastasis: 1 patient, ovarian metastasis: 1 patient). The overall survival rates at 1, 3 and 5 years were 94.7%, 76.3% and 76.3%, respectively., Conclusion: Totally laparoscopic gastrectomy is safe and can lead to satisfactory long-term outcomes in cases of advanced gastric cancer. Prospective controlled studies are warranted to confirm our findings.

Background: The Myelin and lymphocyte-associated protein gene (MAL), which is located on the long arm of chromosome 2, assigned to the region cen-q13 in humans, has been reported as tumor suppressor in several cancers. The aim of this study was to clarify the clinical significance of MAL gene in gastric cancer., Patients and Methods: The expression levels of MAL mRNA was examined using 50 resected gastric cancer specimens used by laser microdissected to determine the clinicopathological significance. MAL expression was then examined by real-time quantitative PCR assay, and we analyzed the correlation between MAL expression and clinicopathological factors., Results: In clinicopathologic analysis, the low MAL expression group showed significantly higher incidence of lymph node metastasis than the high expression group (79% and 46%, respectively, p < 0.05). Furthermore, the low MAL expression group had a significantly poorer prognosis than the high expression group (p < 0.05)., Conclusions: The MAL gene repression related with lymph node metastasis and poor prognosis in gastric cancer, suggesting that the MAL may be a new candidate node metastasis-suppressor gene for gastric cancer.

Introduction: This study evaluated the feasibility of totally laparoscopic distal gastrectomy (TLDG) in elderly patients with gastric cancer., Methods: We retrospectively analyzed the data from 138 patients who underwent TLDG from April 2005 to March 2009. Of these 138 patients, 20 were older than 75 years of age, and 118 were 75 years of age or younger., Results: The preoperative respiratory function and American Society of Anesthesiologists (ASA) -physical status were significantly worse in the elderly patients than in the younger patients (P = 0.013). Hypertension and respiratory disease were more common in the elderly patients than in the younger patients (P = 0.032 / P = 0.005). The findings for the following parameters were similar in the two groups: intraoperative blood loss, operation time, severe postoperative complication rate, time required to start a solid diet, and duration of postoperative hospital stay. The rate of major complications was not different between the two groups, although minor complications were more commonly observed in the elderly patients., Conclusion: TLDG was found to be a safe procedure for elderly patients. This method can be used as one of the standard treatments for gastric cancer in elderly patients.

Adenosquamous carcinoma of the stomach is very rare; at present, there are only seven published reports. We report here an eighth case involving a 77-year-old Japanese man who was diagnosed with gastric cancer by upper endoscopy and computed tomography (CT). He underwent laparoscopic-assisted distal gastrectomy for early gastric cancer and the resected specimen was diagnosed as adenosquamous carcinoma limited to the submucosal layer. Only one lymph node metastasis was noted. Seven months later, liver metastasis (3 tumors, 15 mm maximum in diameter) was detected by abdominal CT. He was started on chemotherapy with S-1 and cisplatin (CDDP) and is alive 14 months after surgery. Almost all cases of adenosquamous carcinoma of the stomach are diagnosed in advanced stages and carry a very poor prognosis. Most patients with early adenosquamous carcinoma of the stomach survive for 2 or more years without recurrence, however our patient experienced recurrence 7 months after surgery. Therefore, future treatment for recurrent adenosquamous carcinoma of the stomach should be considered.

Simultaneous operations for synchronous cancers are thought to increase in the near future due to recent advancement of laparoscopic surgery. A 75-year-old male patient was admitted to our hospital and diagnosed as synchronous gastric and rectal cancer (gastric cancer: cT2N0M0 StageIB, rectal cancer: cSEN0M0 StagII). The simultaneous totally laparoscopic total gastrectomy and low anterior resection was scheduled. The low anterior resection was first performed with five ports on the lower abdomen, and followed by the total gastrectomy with addition of 3 ports on the upper abdomen. The postoperative course was uneventful. This case suggest that the simultaneous totally laparoscopic total gastrectomy and low anterior resection was useful operation for patients with synchronous gastric and rectal cancers. We herein report the case and discuss based on some literatures.

Background: The depressed type of early gastric cancer, in comparison to the elevated type, tends to invade the submucosal layer and metastasize to the lymph nodes. This study compared the differences in tumor cell proliferation and apoptosis between the elevated and depressed types of intramucosal differentiated gastric cancer., Methods: A total of 57 intramucosal differentiated gastric cancers were studied. Twenty samples were the elevated type and 37 were the depressed type. The tumor cells were analyzed by immunohistochemistry for Ki-67, Bcl-2, and Bax, and terminal deoxynucleotidyl transferase 2´-deoxyuridine, 5´-triphosphate (dUTP)-biotin nick end labeling was carried out to detect apoptotic cells., Results: (1) The Ki-67 labeling index (KI) was higher in the depressed type (median: 38.6) than in the elevated type (median: 21.2). (2) Immunopositivity for Bax and the apoptosis index (AI) were lower in the depressed type (median AI: 0.20) than the elevated type (median AI: 1.05). (3) The AI/KI was lower in the depressed type (median: 0.17) than in the elevated type (median: 5.57). (4) The AI in the tumors with a Bcl-2-negative and Bax-positive pattern (median: 2.0) was higher than that in the tumors with a Bcl-2-positive and Bax-negative pattern (median: 0.2)., Conclusion: These results show that, regarding cell proliferation and apoptosis, the depressed type of intramucosal differentiated-type gastric cancer has high malignant potential in comparison to the elevated type.

Purpose: The prognosis of gastric cancer patients undergoing curability B surgery was retrospectively examined to determine the effectiveness of the administration of oral anti-cancer drugs as postoperative adjuvant chemotherapy., Methods: This study was based on the outcomes of 86 potentially curative patients who had undergone curability B resection of gastric cancer with or without the subsequent administration of oral 5-fluorouracil analogue. There were 21 patients who underwent surgery alone with no oral anti-cancer agents (group A) and 65 patients who were treated postoperatively, mainly with UFT (Tegafur and uracil; group B). This study compared the ten-year survival times of these two groups using univariate and multivariate analyses., Results: The amount of UFT in group B was 354.2 +/- 122.0 mg and the administration period was 11.7 +/- 7.2 months. The backgrounds showed significantly more older patients in group A compared than group B (P = 0.0002). A univariate analysis showed the ten-year survival rate in group B to be higher than group A (P = 0.0079). A multivariate analysis showed that the postoperative administration of UFT was an independent factor associated with prolongation of survival times as well as the extent of lymph nodes metastasis and pathological stage (P = 0.0096)., Conclusion: This study provided conventional evidence that postoperative administration of oral 5-fluorouracil analogue is associated with better long-term prognoses in patients undergoing curability B resection for gastric carcinoma.

Purpose: Gastrointestinal stromal tumors (GISTs) should be surgically resected, even those smaller than 5 cm in size, which is the threshold of clinical malignancy for submucosal tumors (SMTs) in the gastrointestinal tract. This study reviewed the use of laparoscopic surgery for gastric partial resection of GISTs or SMTs that were suspected to be GISTs., Methods: Eighteen patients underwent laparoscopic partial resection of the stomach for GISTs or SMTs. The tumor location was confirmed by intraluminal endoscopy. One-half of the circumference around the tumor was dissected, and the tumor was turned toward the abdominal cavity. The nonresected part of the tumor and the edge of the incision line was lifted up using forceps, and the incision line was closed using laparoscopic stapling devices., Results: Two cases were diagnosed as GIST by endoscopic biopsy. Six patients underwent endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) examinations, which diagnosed five GISTs. There were 18 tumors smaller than 5 cm, including 10 GISTs, 4 leiomyomas, 3 schwannomas, and one heterotopic pancreas., Conclusions: Endoscopic ultrasound-guided FNAB is recommended for definite preoperative diagnosis of histopathologically unknown SMTs to determine the indications for surgery. The laparoscopic approach with the assistance of endoscopy is useful for improving the curability, with minimal invasiveness for the partial resection of GISTs.

Purpose: We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy., Methods: We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test., Results: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors., Conclusions: The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.

Cardiothoracic surgeons commonly use the internal thoracic artery (ITA) and the right gastroepiploic artery (RGEA) when performing a coronary artery bypass graft (CABG). Although the development of CABG surgery has enabled long-term survival in patients with coronary artery disease, malignant diseases are more common in older patients. We present the case of a 75-year-old man who had previously undergone CABG with the RGEA and had later developed advanced gastric cancer. We treated this patient with two courses of combination chemotherapy using S-1 and docetaxel as induction therapy, followed by successful tumor resection. Therefore, neoadjuvant chemotherapy was effective for preserving the CABG with the RGEA in a patient with advanced gastric cancer.

Purpose: Metachronous gastric carcinoma arising in a gastric tube used for esophageal reconstruction has been occasionally encountered in long-term survivors of esophageal cancer. This study investigated 10 cases of gastric tube cancer in order to clarify the characteristics and the outcome of these patients., Methods: Four hundred and seventy-one patients underwent a radical esophagectomy at Kyushu University Hospital between 1989 and 2003. There were 10 cases of gastric tube cancer after an esophagectomy., Results: The interval between the esophagectomy and the development of the gastric tube cancer ranged from 1.1 to 7 years. There was no peak for the incidence of gastric tube cancer. In 6 of 10 cases of gastric tube cancer, endoscopic or surgical resection were performed for the treatment; however, chemotherapy was administered to the other 4 cases for several reasons. The prognosis of patients who underwent resection was better than that of the other patients., Conclusions: Frequent endoscopic examinations are therefore important even several years after performing an esophagectomy, since the risk of gastric tube cancer is higher than the risk of a recurrence of esophageal cancer several years after an esophagectomy. Only an early diagnosis permits a less invasive and appropriate approach for the treatment of gastric tube cancer.

We herein present the case of a 66-year-old man with both gastric cancer and an infrarenal abdominal aneurysm. The patient's medical history included bladder cancer, chronic renal failure, and ischemic heart disease. We performed a simultaneous endovascular aneurysm repair (EVAR) and total gastrectomy. Following the procedure, the patient remained in the intensive care unit for 3 days. Oral feeding was resumed on postoperative day 7, and the patient was discharged from the hospital on postoperative day 13 with no complications. Despite the patient's medical problems and higher operative risk, he tolerated simultaneous EVAR and total gastrectomy, and had a good outcome after undergoing these simultaneous procedures.

Hepatic artery injury is one complication associated with surgery for gastric cancer. This complication does not occur frequently, but it can cause serious problems. Anatomical variations of the hepatic arteries are thought to be a factor in such injuries. Recognizing vascular variations before the operation is thus very important. This report presents a case with a rare variation of the hepatic arteries identified on three-dimensional computed tomography (3D-CT) angiography before gastric cancer surgery. Hepatic artery injury was avoided as a result of the recognition of this extremely rare variation. Preoperative 3D-CT angiography is useful for preventing the complications associated with hepatic artery injury during surgery for gastric cancer.

The prognosis of patients with liver metastasis from gastric cancer is dismal. This article reviews the characteristics of gastric cancer metastasizing to the liver, and multimodality of treatments. Differentiated adenocarcinoma, poorly differentiated adenocarcinoma with a medullary growth pattern, and special types, including endocrine carcinoma and hepatoid carcinoma, are likely to metastasize to the liver. The overexpression of growth factors or adhesion molecules is clinically significant for liver metastasis. Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if a complete resection seems feasible after careful preoperative staging. A hepatic resection should always be considered as an option for gastric cancer patients with hepatic metastases. Newer generation cytotoxic agents such as S-1, irinotecan, and taxanes show promising activity for patients with metastases. Adjuvant chemotherapy or molecular targeted therapy will provide significant benefits to patients in the future.

Gastric cancers show high frequency of DNA aneuploidy, a phenotype of chromosomal instability. It is suggested that the abnormal spindle assembly checkpoint is involved in DNA aneuploidy, but the underlying mechanism is still unclear. We studied the mechanism by assessing the expression of BUBR1 in gastric cancer. The DNA ploidy patterns of 116 gastric cancer samples obtained from the Department of Surgery and Science at Kyushu University Hospital were analyzed. Of those, DNA aneuploidy was seen in 70 (60.3%) cases of gastric cancer. The expression of BUBR1 was studied by immunohistochemistry in 181 gastric cancer samples and by real-time RT-PCR in several gastric cancer cell lines. Ninety-one (50.3%) cases had high expression of BUBR1 and those cases correlated significantly with DNA aneuploidy (P < 0.05). Also high expression of BUBR1 cases had significant correlation with deep invasion, lymph node metastasis, liver metastasis, and poor prognosis. In gastric cancer cell lines, high expression of BUBR1 had a significant relationship with DNA aneuploidy (P < 0.05). Then, gastric cancer cell lines MKN-28 and SNU-1 were transfected with full-length BUBR1 to observe the significance of the change in BUBR1 expression. Enforced expression of BUBR1 resulted in changes to the ploidy pattern and high Ki-67 expression. Collectively, our clinical and in vitro data indicate that high expression of BUBR1 may be one of causative factors for the induction of DNA aneuploidy and progression of gastric cancer.

Introduction: Conflicting data exist regarding the relevance of high-frequency microsatellite instability (MSI-H) for predicting the prognosis and benefits of 5-fluorouracil (5-FU)-based chemotherapy. This study investigated the usefulness of MSI as either a prognostic indicator or predictor of distinct clinical attributes regarding the use of adjuvant chemotherapy with 5-FU and its analogues in gastric cancer., Materials and Methods: Data and tumor specimens were collected from 240 gastric cancer patients from 1993 to 2002. Five microsatellite loci were analyzed using a high-intensity microsatellite analysis reported previously. A Cox proportional hazard model was used to compare the clinical data and survival as well as any associations between MSI and 5-FU treatment status of patients with MSI or microsatellite stability (MSS) gastric cancers. A 3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted in 168 cases to investigate chemosensitivity to 5-FU., Results: This analysis identified 22 MSI-H (9.4%), 25 MSI-L (10.7%), and 193 MSS (79.9%) tumors. Gastric cancer with MSI-H tended to have increased likelihood to show higher age, antral location of the tumor, and lymph vessel involvement (P < 0.05). Univariate analyses failed to show any difference between the MSI-H and MSS/MSI-L groups with respect to overall survival. Furthermore, survival after the administration of 5-FU did not correlate with MSI status, and MSI was not associated with 5-FU sensitivity by MTT assay., Conclusion: The results of this study indicate that MSI status has no clear influence on overall survival or response to 5-FU in gastric cancer.

Aim: To examine the methylation status of the promoter region of the checkpoint with forkhead-associated and ring finger (CHFR) and microsatellite mutator status in 59 primary gastric cancers., Methods: We investigated the promoter methylation of CHFR in 59 cases of gastric cancer using methylation-specific PCR. Five microsatellite loci were analyzed using high-intensity microsatellite analysis reported previously, and p53 gene mutations were investigated by direct sequencing., Results: Twenty cases (33.9%) showed promoter methylation and no relation was observed with the clinicopathological factors. We found that the promoter methylation of CHFR was frequently accompanied with microsatellite instability (MIN). Seven of 20 (35.0%) cases showed MIN in hypermethylation of the CHFR tumor, while three of 39 (7.7%) cases showed MIN in the non-methylated CHFR tumor (P < 0.01). However, we failed to find any relationship between CHFR methylation and p53 mutation status., Conclusion: The coordinated loss of both the mitotic check point function and mismatch repair system suggests the potential to overcome the cell cycle check point, which may lead to an accumulation of mutations. However, the p53 mutation was not related to hypermethylation of the CHFR promoter and MIN, which indicates that an abnormality in p53 occurs as an independent process from the mismatch repair deficiency in carcinogenesis.

Objective: This phase II study evaluated the toxicity and efficacy of a novel dosing schedule of docetaxel and S-1 as treatment for advanced gastric cancer., Methods: Patients with measurable advanced or recurrent gastric cancer and no prior exposure to the investigational drugs were treated with intravenous docetaxel 35 mg/m(2) on days 1 and 15, and oral S-1 80 mg/m(2)/day on days 1-14 every 4 weeks. The primary endpoint was objective response., Results: Thirty-five eligible patients were enrolled and received a total of 151 cycles of treatment (median 3, range 1-19). One complete response and 13 partial responses were observed, with an overall response rate of 40% (95% CI: 24-56%). Median progression-free survival and median overall survival times were 4.5 and 14.2 months, respectively. The most common grade 3-4 toxicities were neutropenia (23%) and leukocytopenia (15%)., Conclusion: Biweekly docetaxel combined with S-1 is active in advanced or recurrent gastric cancer, and can be administered with proper management of adverse events in an outpatient clinic., (Copyright 2009 S. Karger AG, Basel.)

Recently, standard therapies for either gastric cancer or colorectal cancer have been established through the development of multidrug systemic chemotherapy and the appearance of molecular targeting drugs. For example, either FOLFIRI or FOLFOX therapy is normally chosen for the treatment of unresectable liver metastasis from colorectal cancer. On the other hand, hepatic artery infusion (HAI) chemotherapy is generally used as only a second-line therapy. There are, however, some cases in which systemic chemotherapy is not indicated due to age and/or the risk of side effects. We herein report three cases that were treated by HAI after initially performing systemic chemotherapy in order to treat liver metastasis from either gastric cancer or colorectal cancer.