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Sumiya Ishigami,
Shoji Natsugoe,
Shuichi Hokita,
Teruaki Aoki,
Hideyuki Kashiwagi,
Kosei Hirakawa,
Tetsuji Sawada, Yoshitaka Yamamura,
Seiji Itoh,
Koichi Hirata,
Keiichiro Ohta,
Kenichi Mafune,
Yasushi Nakane,
Tatsuo Kanda,
Hiroshi Furukawa,
Iwao Sasaki,
Tetsuro Kubota,
Masaki Kitajima,
Takashi Aikou
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ABSTRACT: The postoperative clinical superiority of the interposition of jejunum reconstruction (INT) to Roux-en-Y reconstruction (RY) after total gastrectomy has not been clarified. Postoperative quality of life (QOL) was evaluated between the 2 methods by a multi-institutional prospective randomized trial.
A total of 103 patients with gastric cancer were prospectively randomly divided into groups for RY (n = 51) or INT reconstruction (n = 52) after total gastrectomy. They were stratified by sex, age, institute, histology, and degree of lymph node dissection. Postoperatively, body mass index (BMI) and nutritional conditions were measured serially, and QOL and postoperative squalor scores were evaluated at 3, 12, and 60 months and compared between the 2 groups.
After removing patients who did not complete the follow-up survey or censured cases, 24 patients in the RY group and 18 patients in the INT group were clinically available and their postoperative status was assessed. QOL scores were increased and complication scores were improved in the postoperative periods (P < .01). Postoperative BMI significantly deteriorated compared with preoperative BMI in each group. The postoperative QOL and complication scores at 60 months after surgery were significantly better than those at 3 months after surgery in each group (P < .01). However, there was no significant difference of QOL scores and postoperative complication scores between the 2 reconstruction groups. The nutritional condition in the INT group was nearly the same as that in the RY group.
Although our patient sample was small and patients who did not complete the follow-up survey were present, we could not identify any clinical difference between INT and RY after total gastrectomy 60 months after surgery. The safer and simpler RY method may be a more suitable reconstruction method than INT after total gastrectomy.
American journal of surgery 09/2011; 202(3):247-53. · 2.36 Impact Factor
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ABSTRACT: We have previously reported the molecular detection of peritoneal micrometastases in patients with gastric cancer by quantifying carcinoembryonic antigen (CEA) mRNA in the peritoneal washes. Patients with CEA mRNA exceeding a cutoff value have a significant risk for developing peritoneal carcinomatosis, but optimal treatment for this population remains unknown.
CEA mRNA (+) patients with gastric cancer were treated postoperatively with S-1 monotherapy. Overall survival, the primary endpoint of this phase II trial, was compared with the historical control, which is comprised of CEA mRNA (+) patients who were not given postoperative chemotherapy.
A total of 32 patients with CEA mRNA (+) gastric cancer were enrolled. Twelve patients (37.5%) relapsed; ten showed peritoneal relapse. Three-year survival was similar between the study population and the historical control (67.3% vs. 67.1%, respectively).
S-1 monotherapy, which significantly reduced risk for recurrence in stage II/III gastric carcinoma in another phase III trial, seems not to be as effective in eradicating free cancer cells in the abdominal cavity.
World Journal of Surgery 04/2010; 34(9):2083-9. · 2.36 Impact Factor
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ABSTRACT: L1, a 200-220 kDa transmembrane glycoprotein of the immunoglobulin superfamily, has been shown to affect prognosis of various types of cancer and was shown to enhance peritoneal metastasis in ovarian cancer in vivo.
Immunostaining with anti-L1 antibody was performed with 72 surgically resected pT3-stage gastric cancer specimens. Correlation of immunoreactivity with clinicopathological variables was evaluated and survival curves were compared between L1-positive and negative cases.
L1 was detected in 15 specimens (21%), more often among the intestinal-type cancer. No correlation was observed between L1 expression and presence of free cancer cells in the peritoneal cavity or development of peritoneal carcinomatosis during the follow-up. Nevertheless, prognosis of patients with L1-positive cancer was significantly inferior (p=0.024), particularly among the diffuse-type cancer cases.
L1 was associated with poor outcome in gastric carcinoma. However, its association with the formation of peritoneal metastases or the presence of free cancer cells in the abdominal cavity was not observed. Further study to identify the role of L1 in gastric cancer progression and metastasis is warranted.
Anticancer research 10/2009; 29(10):4033-9. · 1.73 Impact Factor
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Keitaro Matsuo,
Kazuo Tajima,
Takeshi Suzuki,
Takakazu Kawase,
Miki Watanabe,
Kohei Shitara,
Kazunari Misawa,
Seiji Ito,
Akira Sawaki,
Kei Muro,
Tsuneya Nakamura,
Kenji Yamao, Yoshitaka Yamamura,
Nobuyuki Hamajima,
Akio Hiraki,
Hideo Tanaka
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ABSTRACT: A recent whole-genome association study identified a strong association between polymorphisms in the prostate stem cell antigen (PSCA) gene and stomach cancer risk. In this case-control study, we aimed to validate this association, and further to explore environmental factors possibly interacting with PSCA polymorphisms in 708 incident stomach cancer cases and 708 age-sex matched controls. The association between PSCA polymorphisms and Helicobacter pylori infection was also examined. We found that rs2294008 and rs2976392, which were strongly linked to each other (D' = 1.00), were significantly associated with stomach cancer risk. Per allele odds ratio for rs2994008 was 1.40 (95% confidence interval: 1.19-1.65; p = 3.7 x 10(-5)). We found significant interaction with a family history of stomach cancer in first-degree relatives (p-heterogeneity = 0.009). Similar to originally reported association, we found significant heterogeneity between diffuse and intestinal type (p-heterogeneity = 0.007). No association was seen between PSCA polymorphisms and H. pylori infection. In conclusion, PSCA polymorphisms are associated with stomach cancer risk in Japanese. A possible interaction with family history warrants further evaluation.
International Journal of Cancer 05/2009; 125(8):1961-4. · 5.44 Impact Factor
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ABSTRACT: CXCR4, a chemokine receptor, is considered to be involved in the metastastic formation of various types of cancer and could influence survival. More recently, CXCR4 was reported to be associated with peritoneal metastasis in gastric cancer, and CXCL12, its ligand, as a prognostic determinant among gastric cancer of various stages. In order to more specifically delineate the relevance of CXCR4 in peritoneal metastasis, 98 patients with pT3-stage gastric cancer who underwent gastrectomy and detection of intra-abdominal free cancer cells in the peritoneal washing samples were evaluated. Immunostaining with anti-CXCL12 and anti-CXCR4 antibodies were performed for the primary tumor specimens, and correlation of the immunoreactivities with various clinicopathologic factors was evaluated. CXCR4 was detected in 61 specimens and CXCL12 in 76 specimens. No significant correlation was observed between presence of free cancer cells in the peritoneal cavity or development of clinical peritoneal carcinomatosis and expression of either the chemokine or the receptor. On the other hand, there was a trend towards correlation of expression of these molecules with recurrences to the distant lymph nodes or to the liver, although the number of events in these categories were insufficient to reach a statistical significance. In gastric cancer, CXCL12/ CXCR4 axis seems to be more strongly associated with lymphatic or hematogenous metastasis than the establishment of peritoneal deposits.
Oncology Reports 12/2008; 20(5):1117-23. · 1.84 Impact Factor
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ABSTRACT: Diagnostic and treatment strategies for gastrointestinal stromal tumors (GISTs) have evolved greatly since the introduction of molecularly targeted therapies. Although several clinical practice guidelines are extant, such as those published by the National Comprehensive Cancer Network and the European Society of Medical Oncology, it is not clear as to whether these are appropriate for clinical practice in Japan. Therefore, clinical practice guidelines for the optimal diagnosis and treatment of GIST tailored for the Japanese situation have often been requested. For this reason, the Japanese Clinical Practice Guideline for GIST was proposed by the GIST Guideline Subcommittee, with the official approval of the Clinical Practice Guidelines Committee for Cancer of the Japan Society of Clinical Oncology (JSCO), and was published after assessment by the Guideline Evaluation Committee of JSCO. The GIST Guideline Subcommittee consists of members from JSCO, the Japanese Gastric Cancer Association (JGCA), and the Japanese Study Group on GIST, with the official approval of these organizations. The GIST Guideline Subcommittee is not influenced by any other organizations or third parties. Revision of the guideline may be done periodically, with the approval of the GIST Guideline Subcommittee, either every 3 years or when important new evidence that might alter the optimal diagnosis and treatment of GIST emerges. Here we present the English version of the Japanese Clinical Practice Guideline for GIST prepared by the GIST Guideline Subcommittee.
International Journal of Clinical Oncology 11/2008; 13(5):416-30. · 1.41 Impact Factor
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ABSTRACT: We retrospectively analyzed the efficacy of chemotherapy in patients whose gastric cancer recurred after adjuvant chemotherapy with S-1. A total of 51 patients were evaluated. Twenty-one patients received S-1-containing chemotherapy as first-line treatment after recurrence [cohort A: S-1 plus cisplatin (n = 10), S-1 monotherapy (n = 7), S-1 plus irinotecan (n = 3) and S-1 plus docetaxel (n = 1)]. The other 30 patients received a non-S-1-containing regimen [cohort B: paclitaxel or docetaxel (n = 22), irinotecan plus cisplatin (n = 6) and other drugs (n = 2)]. No objective responses occurred in cohort A, while five patients achieved a partial response in cohort B (response rate, 0 versus 16%; P = 0.04). Median progression-free survival was significantly longer in cohort B than in cohort A (4.3 versus 2.3 months, P = 0.02). S-1-containing chemotherapy does not appear to be effective in patients whose gastric cancer recurs after adjuvant S-1 chemotherapy. Other chemotherapeutic agents should be evaluated in this setting.
Japanese Journal of Clinical Oncology 10/2008; 38(11):786-9. · 1.78 Impact Factor
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Mitsuru Sasako,
Takeshi Sano,
Seiichiro Yamamoto,
Yukinori Kurokawa,
Atsushi Nashimoto,
Akira Kurita,
Masahiro Hiratsuka,
Toshimasa Tsujinaka,
Taira Kinoshita,
Kuniyoshi Arai, Yoshitaka Yamamura,
Kunio Okajima
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ABSTRACT: Gastrectomy with D2 lymphadenectomy is the standard treatment for curable gastric cancer in eastern Asia. Whether the addition of para-aortic nodal dissection (PAND) to D2 lymphadenectomy for stage T2, T3, or T4 tumors improves survival is controversial. We conducted a randomized, controlled trial at 24 hospitals in Japan to compare D2 lymphadenectomy alone with D2 lymphadenectomy plus PAND in patients undergoing gastrectomy for curable gastric cancer.
Between July 1995 and April 2001, 523 patients with curable stage T2b, T3, or T4 gastric cancer were randomly assigned during surgery to D2 lymphadenectomy alone (263 patients) or to D2 lymphadenectomy plus PAND (260 patients). We did not permit any adjuvant therapy before the recurrence of cancer. The primary end point was overall survival.
The rates of surgery-related complications among patients assigned to D2 lymphadenectomy alone and those assigned to D2 lymphadenectomy plus PAND were 20.9% and 28.1%, respectively (P=0.07). There were no significant differences between the two groups in the frequencies of anastomotic leakage, pancreatic fistula, abdominal abscess, pneumonia, or death from any cause within 30 days after surgery (the rate of death was 0.8% in each group). The median operation time was 63 minutes longer and the median blood loss was 230 ml greater in the group assigned to D2 lymphadenectomy plus PAND. The 5-year overall survival rate was 69.2% for the group assigned to D2 lymphadenectomy alone and 70.3% for the group assigned to D2 lymphadenectomy plus PAND; the hazard ratio for death was 1.03 (95% confidence interval [CI], 0.77 to 1.37; P=0.85). There were no significant differences in recurrence-free survival between the two groups; the hazard ratio for recurrence was 1.08 (95% CI, 0.83 to 1.42; P=0.56).
As compared with D2 lymphadenectomy alone, treatment with D2 lymphadenectomy plus PAND does not improve the survival rate in curable gastric cancer. (ClinicalTrials.gov number, NCT00149279.)
New England Journal of Medicine 08/2008; 359(5):453-62. · 53.30 Impact Factor
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ABSTRACT: Linitis plastica-type gastric carcinoma remains a disease with poor prognosis despite an aggressive surgical approach. Although a prominent pattern of disease failure is peritoneal carcinomatosis, some patients experience rapid disease progression without signs of the peritoneal disease.
Clinicopathologic data from 178 patients with linitis plastica-type gastric cancer operated on between 1991 and 2000 were analyzed. Survival stratified by curability of surgery, pN stage, and patterns of failure were evaluated by using the Kaplan-Meier method, and chi(2) test was used to evaluate correlation between the number of metastatic lymph nodes in terms of pN categories and the incidence of various patterns of metastasis and recurrence. Cox regression hazard model was used to identify independent prognostic factors.
R0 resection was performed only among 82 patients (46% of those who underwent laparotomy). Node metastasis was frequent with only 22 patients classified as pN0. Peritoneal carcinomatosis was observed in 131 patients and was the commonest pattern of recurrence. Bone metastasis, found in 13 patients, was associated with poor outcome, and its incidence was significantly correlated with the number of metastatic nodes. pT4 status and pN3 status were identified as significant independent prognostic determinants.
Treatment strategy for the linitis plastica should in general combine surgery with aggressive treatment directed toward peritoneal disease. However, patients with >16 metastatic nodes more often are associated with bone metastasis than those with modest nodal involvement and suffer from poor prognosis.
World Journal of Surgery 06/2008; 32(9):2015-20. · 2.36 Impact Factor
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Wasaburo Koizumi,
Hiroyuki Narahara,
Takuo Hara,
Akinori Takagane,
Toshikazu Akiya,
Masakazu Takagi,
Kosei Miyashita,
Takashi Nishizaki,
Osamu Kobayashi,
Wataru Takiyama,
Yasushi Toh,
Takashi Nagaie,
Seiichi Takagi, Yoshitaka Yamamura,
Kimihiko Yanaoka,
Hiroyuki Orita,
Masahiro Takeuchi
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ABSTRACT: Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone.
In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670.
305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13.0 months [IQR 7.6-21.9]) than in those assigned to S-1 alone (11.0 months [5.6-19.8]; hazard ratio for death, 0.77; 95% CI 0.61-0.98; p=0.04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6.0 months [3.3-12.9] vs 4.0 months [2.1-6.8]; p<0.0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43-65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23-41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group.
S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer.
The lancet oncology 04/2008; 9(3):215-21. · 14.47 Impact Factor
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Shinichi Sakuramoto,
Mitsuru Sasako,
Toshiharu Yamaguchi,
Taira Kinoshita,
Masashi Fujii,
Atsushi Nashimoto,
Hiroshi Furukawa,
Toshifusa Nakajima,
Yasuo Ohashi,
Hiroshi Imamura,
Masayuki Higashino, Yoshitaka Yamamura,
Akira Kurita,
Kuniyoshi Arai
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ABSTRACT: Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer.
Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended (D2) lymph-node dissection were randomly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only. In the S-1 group, administration of S-1 was started within 6 weeks after surgery and continued for 1 year. The treatment regimen consisted of 6-week cycles in which, in principle, 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks. The primary end point was overall survival.
We randomly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004. The trial was stopped on the recommendation of the independent data and safety monitoring committee, because the first interim analysis, performed 1 year after enrollment was completed, showed that the S-1 group had a higher rate of overall survival than the surgery-only group (P=0.002). Analysis of follow-up data showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The hazard ratio for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% confidence interval, 0.52 to 0.87; P=0.003). Adverse events of grade 3 or grade 4 (defined according to the Common Toxicity Criteria of the National Cancer Institute) that were relatively common in the S-1 group were anorexia (6.0%), nausea (3.7%), and diarrhea (3.1%).
S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer. (ClinicalTrials.gov number, NCT00152217 [ClinicalTrials.gov].).
New England Journal of Medicine 12/2007; 357(18):1810-20. · 53.30 Impact Factor
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ABSTRACT: Infection with Helicobacter pylori is linked to inflammation and is the main cause of peptic ulcer, gastritis, and gastric malignancies. To examine associations between gastric cancer risk and the erythrocyte composition of docosahexaenoic acid (DHA), a fatty acid with anti-inflammatory and apoptosis-inducing effects, here we conducted a case-control study of 179 incident gastric cancer cases and 357 noncancer controls (matched by age, sex, and season of sample collection). Dietary information and blood samples were collected from all subjects, and erythrocyte fatty acid levels were measured using accelerated solvent extraction and gas-liquid chromatography. Gastric cancer risk did not seem to be directly associated with dietary intake of fish and n-3 highly unsaturated fatty acids (HUFAs), such as DHA, derived from fish. However, risk was inversely associated with erythrocyte compositions of n-3 HUFAs [the highest to the lowest tertile, odds ratio (OR), 0.39; 95% confidence interval (95% CI), 0.23-0.68; P(trend)<0.005] and DHA (OR, 0.47; 95% CI, 0.28-0.79; P(trend)<0.01). Particularly strong associations were noted for well-differentiated type lesions and n-3 HUFAs (OR, 0.10; 95% CI, 0.03-0.35; P(trend)=0.0005) as well as DHA (OR, 0.20; 95% CI, 0.07-0.58; P(trend)<0.01) values. In conclusion, the erythrocyte composition of DHA was found to be negatively linked to risk of gastric cancer, especially of well-differentiated adenocarcinoma. Further studies are needed to investigate mechanisms of action of DHA relevant to antitumor effects in the stomach.
Cancer Epidemiology Biomarkers & Prevention 11/2007; 16(11):2406-15. · 4.12 Impact Factor
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ABSTRACT: Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT) have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy. mRNA expression of TS, DPD, TP, and OPRT were quantified by reverse-transcriptase polymerase chain reaction after harvesting cancer cells from 93 paraffin-embedded specimens of gastric cancer through laser capture microdissection. In vitro chemosensitivity testing by histoculture drug response assay was performed with surgically resected primary lesions of the same 93 patients. No significant correlation was observed between the mRNA expression and location of the tumor, histopathologic type, clinical stage, and other clinicopathologic variables, with the exception that OPRT mRNA had a weak correlation with drug sensitivity against 5FU (R=0.219, p=0.0343). OPRT was considered to have a major impact on drug sensitivity, although not sufficiently so to enable prediction of 5FU sensitivity solely based on the mRNA expression of this enzyme.
Cancer Letters 08/2007; 252(2):307-13. · 4.24 Impact Factor
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Toshimasa Tsujinaka,
Mitsuru Sasako,
Seiichiro Yamamoto,
Takeshi Sano,
Yukinori Kurokawa,
Atsushi Nashimoto,
Akira Kurita,
Hitoshi Katai,
Toshio Shimizu,
Hiroshi Furukawa,
Satoru Inoue,
Masahiro Hiratsuka,
Taira Kinoshita,
Kuniyoshi Arai, Yoshitaka Yamamura
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ABSTRACT: The impact of overweight on the outcome of gastrectomy with lymphadenectomy is controversial, and data from a well-controlled, randomized study are needed to identify a possible relationship.
We used data from 523 patients registered for a prospective randomized trial comparing D2 and extended para-aortic D3 lymphadenectomy to compare the effects of body mass index (BMI) and the extent of lymphadenectomy for the development of general or major surgical complications (anastomotic leakage, abdominal abscess, and pancreatic fistula).
Seventy-seven patients were classified as overweight with BMI >or= 25, and 38 and 39 of these patients underwent a D2 or D3 lymphadenectomy, respectively. Among the 446 patients classified as nonoverweight with BMI < 25, 225 received D2 and 221 received D3 lymphadenectomy. Surgical complications, operation time, and blood loss were statistically significantly associated with BMI, and logistic regression analysis revealed that overweight directly affected the occurrence of surgical complications even after considering operation time and blood loss as intermediate factors instead of outcome variables. Among patients undergoing D2 lymphadenectomy, being overweight increased the risk for surgical complications and blood loss, whereas overweight was associated with only blood loss and operation time among patients receiving D3 lymphadenectomy.
Overweight increased the risk of surgical complications in patients undergoing gastrectomy both directly and indirectly through operation time and blood loss. The impact of overweight on surgical complications was more evident in patients undergoing a D2 dissection.
Annals of Surgical Oncology 03/2007; 14(2):355-61. · 4.17 Impact Factor
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Masayasu Hara,
Hayao Nakanishi,
Qian Jun,
Yukihide Kanemitsu,
Seiji Ito,
Yoshinari Mochizuki, Yoshitaka Yamamura,
Yasuhiro Kodera,
Masae Tatematsu,
Takashi Hirai,
Tomoyuki Kato
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ABSTRACT: Peritoneal recurrence has a much lower incidence in colorectal cancer (CRC) patients than gastric cancer (GC) patients. The aim of this study is to clarify the reason for the rare peritoneal recurrence in CRC as compared with GC. The incidence and the abundance of free tumor cells in the peritoneal lavages from 102 CRC and 126 GC patients who underwent curative surgery were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) with carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) as genetic markers. Prognostic significance of CEA and CK20 mRNA was also compared between CRC and GC after 2 years of follow-up by Kaplan-Meyer method with overall and peritoneal recurrence-free survival as endpoints. Positivity rate and average values of CEA and CK20 mRNA in peritoneal lavages of CRC patients, which are correlated to the depth of tumor invasion (pT category), were essentially the same as those of GC cases. Overall survival was significantly (marginally) worse in CEA mRNA (CK20 mRNA)-positive CRC patients than negatives like GC. However, peritoneal recurrence-free survival was not different between CEA (CK20) mRNA-positive and -negative CRC patients, in quite contrast to GC cases. Multivariate analysis showed that CEA mRNA was an independent prognostic factor for overall survival in GC patients, but not in CRC patients. These results suggest that the rare peritoneal recurrence in CRC patients is not due to the low incidence or the small number of intraperitoneal free cancer cells, but more likely reflects due to the low-peritoneal metastatic potential of CRC cells.
Clinical and Experimental Metastasis 02/2007; 24(3):179-89. · 3.52 Impact Factor
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ABSTRACT: Bursectomy, which has been performed so as to resect peritoneal deposits disseminated within the omental bursa, is considered as an essential component of radical surgery for gastric carcinoma in Japan. Bursectomy has also been described in the Japanese Treatment Guidelines for Gastric Carcinoma as a mandatory procedure for the treatment of serosa-positive cancer. However, no evidence to support the prognostic significance of this procedure has been reported to date.
Cytologic examination and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of the peritoneal washes obtained from the Douglas pouch, left subphrenic cavity, and inside the omental bursa were performed for 136 patients who underwent potentially curative surgery for gastric carcinoma.
Carcinoembryonic antigen (CEA) or cytokeratin (CK) 20 mRNA was detected in one or more samples from the three different sites of peritoneal washes in 43 of the 136 patients. In 14 patients, the mRNAs were detected in samples obtained from the bursa omentalis (10.3% of all patients and 32.6% of patients with positive RT-PCR results). In 12 of these 14 patients, the mRNAs were also detected in samples taken from either or both of the remaining two sites. Only in the 2 other patients was the sample only from inside the omental bursa positive for CEA.
It is unlikely that viable cancer cells disseminated into the bursa remain restricted to this cavity without migrating into the free abdominal cavity. Routine bursectomy may not be an essential procedure for resecting gastric cancer, from the viewpoint of eliminating microscopic peritoneal deposits within the omental bursa.
Gastric Cancer 02/2007; 10(1):24-8. · 2.42 Impact Factor
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ABSTRACT: Therapy guided by chemotherapy sensitivity and resistance assays may lead to rational treatment decisions. Paclitaxel, one of several new drugs for gastric carcinoma, has not been extensively evaluated by in vitro chemosensitivity tests.
Chemosensitivity testing by histoculture drug response assay (HDRA) was performed with fresh specimens of primary tumor from 113 patients with gastric carcinoma. The test was performed in medium containing paclitaxel at three different concentrations for the initial 45 samples. Correlations between the results of chemosensitivity testing, determined at the optimal concentration, and the patients' clinicopathologic factors and outcome were then assessed for all patients.
By analyzing the initial 45 samples, 10 microg/ml was considered the optimal concentration of paclitaxel for this test. HDRA was successfully performed for 100 of 113 samples and chemosensitivity, calculated as the percentage of optical density of a tumor treated with anticancer drugs in relation to the optical density of the tumor cultured in the medium only, was distributed widely at this concentration. No significant correlation was observed between chemosensitivity and age, sex, clinical stage, histopathologic type, and outcome of patients with gastric carcinoma.
A histoculture drug response assay can now be performed to predict the chemosensitivity of paclitaxel at the concentration found in the current study. The accuracy of the assay to actually predict survival needs to be validated by a prospective clinical trial involving patients who have received paclitaxel in the postoperative adjuvant setting.
International Journal of Clinical Oncology 01/2007; 11(6):449-53. · 1.41 Impact Factor
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ABSTRACT: Our objective was to evaluate the efficacy and safety of capecitabine in chemotherapy-naive patients with unresectable advanced or metastatic gastric cancer. An open-label multicenter phase II study was conducted for previously untreated patients with advanced or metastatic gastric cancer. Oral capecitabine 828 mg/m2 twice daily was given on days 1-21 every 4 weeks. Baseline characteristics of 60 enrolled patients were: male/female 49/11, median age 64 years (range 28-74), good performance status (ECOG 0-1) in 98% of patients and 27 patients had prior gastrectomy (45%). A median of 4 treatment cycles were administered (range 1-37). Five patients were excluded from the efficacy analysis because they did not meet eligibility criteria. The overall response rate (RR) in the evaluable patient population (n=55) was 26% [95% confidence interval (95% CI) 15-39%] and a further 29% of patients had stable disease. The overall RR in the intent-to-treat population (n=60) was 23% (95% CI 13-36.0%). Median time to progression in the evaluable patient population was 3.4 months (95% CI 1.8-6.1) and overall survival time in the intent-to-treat population was 10.0 months (95% CI 6.4-13.6). The most frequent grade 3/4 drug-related adverse event was hand-foot syndrome (13%), but this was readily managed by treatment interruption and dose reduction. No patients developed grade 3/4 drug-related diarrhea, vomiting, leukopenia or thrombocytopenia. We conclude that this 4-week regimen of capecitabine showed promising activity and was well tolerated as first-line therapy for advanced/metastatic gastric cancer. Further investigation of this regimen is warranted.
Anti-Cancer Drugs 03/2006; 17(2):231-6. · 2.41 Impact Factor
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ABSTRACT: The presence of gastric cancer cells in the peritoneal cavity detected by cytologic examination is an important prognostic factor. A reverse transcriptase-polymerase chain reaction (RT-PCR) technique amplifying carcinoembryonic antigen mRNA was recently introduced to detect these cells more sensitively.
Five-year followup was completed for 284 gastric carcinoma patients who underwent CEA RT-PCR testing. Analyses to assess the accuracy and prognostic value of this procedure were performed, along with univariate and multivariable analyses to evaluate RT-PCR as a technique with peritoneal carcinomatosis and cancer death as the outcomes variables.
CEA mRNA levels exceeded the cutoff value defining a positive result in 9.5%, 29%, 66%, and 81% of patients with pT1, pT2, pT3, and pT4 stage disease, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for peritoneal carcinomatosis within 5 years of surgery were 88.5%, 81.6%, 64.5%, and 94.9%, respectively. Multivariable analysis revealed that a positive CEA mRNA result was an independent risk factor for cancer death (hazard ratio 2.82, 95% CI 1.17 -3.07) among 274 patients (10 patients with no record of nodal status were excluded from the analysis) and for peritoneal carcinomatosis (hazard ratio 1.57, 95% CI 1.07-2.29) among 242 patients who had no peritoneal deposits at operation.
CEA RT-PCR is useful as a prognostic marker for increased risk of cancer death and peritoneal carcinomatosis, and might be useful in the clinical setting for selecting patients for various adjuvant treatments.
Journal of the American College of Surgeons 03/2006; 202(2):231-6. · 4.55 Impact Factor
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Sanae Kabata Ikehara,
Yuzuru Ikehara,
Keitaro Matsuo,
Kaoru Hirose,
Toru Niwa,
Hidemi Ito,
Seiji Ito,
Yasuhiro Kodera, Yoshitaka Yamamura,
Hayao Nakanishi,
Masae Tatematsu,
Kazuo Tajima
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ABSTRACT: Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression.
Journal of Human Genetics 02/2006; 51(11):927-33. · 2.57 Impact Factor
