-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND AND OBJECTIVES: We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with S-1 + cisplatin followed by gastrectomy in patients with linitis plastica (type 4) or large ulcero-invasive-type (type 3) gastric cancer. METHODS: Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3. Patients received two 28-day courses of preoperative chemotherapy of S-1 (80-120 mg/body, p.o., days 1-21) and cisplatin (CDDP; 60 mg/m(2) , i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment-related death (TRD). RESULTS: Among the 49 eligible patients with the median age of 61 years, 36 completed the protocol treatment comprising two courses of preoperative chemotherapy and R0/1 resection (73.5% completion, 80% CI, 63.7-81.7%). One TRD was observed during the first course of chemotherapy. Median survival and 3-year overall survival were 17.3 months and 24.5%, respectively. CONCLUSIONS: Preoperative chemotherapy with S-1 + CDDP followed by gastrectomy is a safe and promising treatment for type 4 and large type 3 gastric cancers. Based on the results of this study, we are now conducting a phase III study (JCOG0501) to confirm the superiority of this treatment. J. Surg. Oncol © 2013 Wiley Periodicals, Inc.
Journal of Surgical Oncology 02/2013; · 2.10 Impact Factor
-
Kenichi Nakamura, Hitoshi Katai,
Junki Mizusawa,
Takaki Yoshikawa,
Masahiko Ando,
Masanori Terashima,
Seiji Ito,
Masakazu Takagi,
Akinori Takagane,
Motoki Ninomiya,
Norimasa Fukushima,
Mitsuru Sasako
[show abstract]
[hide abstract]
ABSTRACT: A Phase III study was started in Japan to evaluate the non-inferiority of overall survival of laparoscopy-assisted distal gastrectomy with open distal gastrectomy in patients with clinical IA (T1N0) or IB [T1N1 or T2(MP)N0] gastric cancer. This study followed the previous Phase II study to confirm the safety of laparoscopy-assisted distal gastrectomy (JCOG0703) and began in March 2010. A total of 920 patients will be accrued from 33 institutions within 5 years. The primary endpoint is overall survival. The secondary endpoints are relapse-free survival, proportion of laparoscopy-assisted distal gastrectomy completion, proportion of conversion to open surgery, adverse events, short-term clinical outcomes, postoperative quality of life. Only a credentialed surgeon can be responsible for both open distal gastrectomy and laparoscopy-assisted distal gastrectomy.
Japanese Journal of Clinical Oncology 12/2012; · 1.78 Impact Factor
-
Jeong Goo Kim,
Hideyuki Takeshima,
Tohru Niwa,
Emil Rehnberg,
Yasuyuki Shigematsu,
Yukie Yoda,
Satoshi Yamashita,
Ryoji Kushima,
Takao Maekita,
Masao Ichinose, Hitoshi Katai,
Won Sang Park,
Young Seon Hong,
Cho Hyun Park,
Toshikazu Ushijima
[show abstract]
[hide abstract]
ABSTRACT: Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (CDH1, CTNNB1, ERBB2, KRAS, MLH1, PIK3CA, SMARCB1, and TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, CTNNB1, ERBB2, KRAS, and PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.
Cancer letters 11/2012; · 4.86 Impact Factor
-
Takeshi Fujita,
Kazuyoshi Yanagihara,
Fumitaka Takeshita,
Kazuhiko Aoyagi,
Takao Nishimura,
Misato Takigahira,
Fumiko Chiwaki,
Takeo Fukagawa, Hitoshi Katai,
Takahiro Ochiya,
Hiromi Sakamoto,
Hiroyuki Konno,
Teruhiko Yoshida,
Hiroki Sasaki
[show abstract]
[hide abstract]
ABSTRACT: The prognosis of patients with advanced diffuse-type gastric cancer (GC, especially scirrhous gastric cancer (SGC) remains extremely poor. Peritoneal carcinomatosis is a frequent form of metastasis of SGC. With survival rates of patients with peritoneal metastasis at 3 and 5 years being only 9.8% and 0%, respectively, development of a new treatment is urgently crucial. For such development, the establishment of a therapeutic mouse model is required. Among the 11 GC cell lines we examined, HSC-60 showed the most well-preserved expression profiles of the Hedgehog and epithelial-mesenchymal transition pathways found in primary SGCs. After 6 cycles of harvest of ascitic tumor cells and their orthotopic inoculation in scid mice, a highly metastatic subclone of HSC-60, 60As6 was obtained, by means of which we successfully developed peritoneal metastasis model mice. The mice treated with small interfering (si) RNA targeting NEDD1, which encodes a gamma-tubulin ring complex-binding protein, by the atelocollagen-mediated delivery system showed a significantly prolonged survival. Our mouse model could thus be useful for the development of a new therapeutic modality. Intraperitoneal administration of siRNAs of targeted genes such as NEDD1 could provide a new opportunity in the treatment of the peritoneal metastasis of SGC.
Cancer Science 10/2012; · 3.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: EGF receptor (EGFR) and HER2 positivity are considered to be negative prognostic factors in gastric cancer. Biomarker analysis was conducted to evaluate the impact of EGFR and HER2 expression on the outcome of patients enrolled in the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC), a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer.EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 patients (78.3%). The effects of EGFR and HER2 positivity on survival were analyzed on the basis of the 5-year survival data from the study. EGFR positivity was defined as an immunohistochemistry (IHC) score of 3+, and HER2 positivity as an IHC score of 3+ or an IHC score of 2+ with a positive dual-color in situ hybridization status.RESULTS: EGFR and HER2 were positive in 75 (9.0%) and 113 (13.6%) patients, respectively. The overall and relapse-free survival rates were significantly lower in EGFR-positive patients than in EGFR-negative patients, whereas they were similar in HER2-positive and HER2-negative patients. Multivariate analysis showed that EGFR positivity correlated with poor outcomes [HR = 1.504; 95% confidence interval (CI) = 1.020-2.149; P = 0.040]. Treatment with S-1 improved survival compared with surgery alone, irrespective of EGFR and HER2 status.CONCLUSIONS: EGFR positivity, but not HER2 positivity, was associated with poor patient outcomes after curative resection of stage II/III gastric cancer. There was no interaction between S-1 and EGFR or HER2 status with respect to survival outcome. Clin Cancer Res; 18(21); 1-9. ©2012 AACR.
Clinical Cancer Research 09/2012; · 7.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gastric perforation is one of the most serious complications that can occur during endoscopic submucosal dissection (ESD). In terms of the treatment of such perforations, we previously reported that perforations immediately observed and successfully closed with endoclips during endoscopic resection could be managed conservatively. We now report the first case in our medical facility of a gastric perforation during ESD that was ineffectively treated conservatively even after successful endoscopic closure. In December 2006, we performed ESD on a recurrent early gastric cancer in an 81-year-old man with a medical history of laparotomy for cholelithiasis. A perforation occurred during ESD that was immediately observed and successfully closed with endoclips so that ESD could be continued resulting in an en-bloc resection. Intensive conservative management was conducted following ESD, however, an endoscopic examination five days after ESD revealed dehiscence of the perforation requiring an emergency laparotomy.
World Journal of Gastroenterology 08/2012; 18(31):4224-7. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Amyloidosis most often manifests as a systemic involvement of multiple tissues and organs, and an amyloidal deposit confined to the stomach is extremely rare. It is sometimes difficult to provide a definitive diagnosis of localized gastric amyloidosis by biopsy specimen and diagnosis of amyloidosis in some cases has been finalized only after surgical resection of the stomach.
A 76-year-old Japanese woman with epigastric discomfort underwent an esophagogastroduodenoscopy procedure. The esophagogastroduodenoscopy revealed gastric wall thickening, suggesting scirrhous gastric carcinoma, at the greater curvature from the upper to the lower part of the gastric corpus. A biopsy specimen revealed amyloid deposits in the submucosal layer with no malignant findings. We resected a representative portion of the lesion by endoscopic mucosal resection using the strip biopsy method to obtain sufficient tissue specimens, and then conducted a detailed histological evaluation of the samples. The resected specimens revealed deposition of amyloidal materials in the gastric mucosa and submucosa without any malignant findings. Congo red staining results were positive for amyloidal protein and exhibited green birefringence under polarized light. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid protein type. Based on these results, gastric malignancy, systemic amyloidosis and amyloid deposits induced by inflammatory disease were excluded and this lesion was consequently diagnosed as localized gastric amyloidosis. Our patient was an older woman and there were no findings relative to an increase in gastrointestinal symptoms or anemia, so no further treatment was performed. She continued to be in good condition without any finding of disease progression six years after verification of our diagnosis.
We report an unusual case of primary amyloidosis of the stomach resembling scirrhous gastric carcinoma. This case of localized gastric amyloidosis was differentiated from scirrhous gastric cancer after performing endoscopic mucosal resection without an invasive surgical resection, as endoscopic mucosal resection provided sufficient tissue specimens from the lesion to make an accurate histological evaluation.
Journal of Medical Case Reports 08/2012; 6(1):231.
-
[show abstract]
[hide abstract]
ABSTRACT: The accurate detection of the presence of lymph node metastases (LNM) of gastric cancers (GCs) is useful for the implementation of necessary and sufficient treatment, but current methods of detection are unsatisfactory. In the present study, we focused on DNA methylation markers since they have several advantages, including biological and chemical stability and informativeness even in the presence of contaminating cells. Using three metastatic lymph nodes and three primary GCs without LNM, methylation bead array analyses were performed, which enabled the interrogation of 485,577 CpG sites. A total of 31 CpG sites that were hypermethylated in the metastatic lymph nodes, compared with the GCs without LNM, were isolated. Using primary GCs with and without LNM (28 GCs with LNM and 10 without), their methylation levels were measured using quantitative PCR following treatment with sodium bisulfite or a methylation-sensitive restriction enzyme. Of the genomic regions around the 31 CpG sites, 10 regions demonstrated higher methylation levels in the GCs with LNM compared with the GCs without LNM (P<0.05). Finally, the hypermethylation of the 10 regions was validated using another set of samples (129 GCs with LNM and 20 without). Hypermethylation of the region around the cg06436185 CpG site predicted the presence of LNM at a sensitivity of 43% and specificity of 85%. Additionally, the hypermethylation of the region was associated with a poor survival rate among GC patients with LNM. The results of the present study indicated that the methylation status of the region was a promising candidate marker to detect the presence of LNM of GCs and may reflect the malignant potential of GCs.
Oncology letters 08/2012; 4(2):268-274. · 0.11 Impact Factor
-
Atsushi Nashimoto,
Kohei Akazawa,
Yoh Isobe,
Isao Miyashiro, Hitoshi Katai,
Yasuhiro Kodera,
Shunichi Tsujitani,
Yasuyuki Seto,
Hiroshi Furukawa,
Ichiro Oda,
Hiroyuki Ono,
Satoshi Tanabe,
Michio Kaminishi
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008. METHODS: From 208 participating hospitals, 53 items including surgical procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed. RESULTS: The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed. CONCLUSIONS: Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.
Gastric Cancer 06/2012; · 2.42 Impact Factor
-
Daisuke Kubota,
Taketo Okubo,
Tsuyoshi Saito,
Yoshiyuki Suehara,
Akihiko Yoshida,
Kazutaka Kikuta,
Hitoshi Tsuda, Hitoshi Katai,
Yasuhiro Shimada,
Kazuo Kaneko,
Akira Kawai,
Tadashi Kondo
[show abstract]
[hide abstract]
ABSTRACT: This study aimed to validate two prognostic biomarkers, pfetin and adenosine triphosphate-dependent RNA helicase DDX39 (DDX39), in gastrointestinal stromal tumour. Prognostic biomarkers have long been required for the optimal use of kinase inhibitors in gastrointestinal stromal tumour.
The expression level of pfetin was immunohistochemically examined in 72 gastrointestinal stromal tumour cases, being correlated with the clinicopathological parameters. Meta-analysis of the prognostic value of pfetin was performed in a total of 371 cases. The prognostic utility of the combination of pfetin and DDX39 was examined in the 72 gastrointestinal stromal tumour cases.
Immunohistochemical study demonstrated the disease-free survival rate to be 94.7% for pfetin-positive patients and 20.0% for pfetin-negative patients among the 72 gastrointestinal stromal tumour cases (P < 0.0001). In the 371 cases, the disease-free survival rate was 93.8% for pfetin-positive patients and 40.6% for pfetin-negative patients (P < 0.0001). Both univariate and multivariate analyses revealed that pfetin expression was an independent prognostic factor (P< 0.0001). When evaluated in combination with pfetin and DDX39, the disease-free survival rates were 0.0% for the pfetin-negative and DDX39-strong patients.
These results established the clinical utility of pfetin as a novel prognostic biomarker for gastrointestinal stromal tumour. The combined use of pfetin and DDX39 appeared to have powerful prognostic value. These biomarkers will be useful in deciding whether to administer adjuvant therapy after surgery.
Japanese Journal of Clinical Oncology 06/2012; 42(8):730-41. · 1.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite the development of the surgical technique and improvements in perioperative management, anastomotic leakage still occurs at esophagojejunal anastomoses after total or proximal gastrectomy. Anastomotic leakage is one of the major complications of concern, chiefly because it can lead to death. The objective of the present study was to identify the risk factors for esophagojejunal anastomotic leakage.
The study was based on retrospective analysis of the data of a total of 1,640 consecutive patients who underwent total, proximal, or completion gastrectomy, including esophagojejunal anastomosis, between 1999 and 2008.
Thirty-five patients (2.1 %) developed anastomotic leakage. Univariate analysis revealed patient age, pulmonary insufficiency, lymph node dissection, combined resection of other organs, omental resection, operative time, blood loss, intraoperative blood transfusion, and postoperative creatinine level were the significant factors influencing anastomotic leakage. Multivariate analysis identified pulmonary insufficiency and the duration of the operation as the predictors of anastomotic leakage.
To avoid leakage, surgeons should take care in creating the anastomosis in gastrectomy patients, particularly in cases of poor pulmonary function or when the procedure requires a longer operation.
World Journal of Surgery 03/2012; 36(7):1617-22. · 2.36 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Early gastric cancer (EGC) has an excellent prognosis, but tumors recur in some patients even after apparently successful treatment. Among recurrent sites, the liver is one of the most common. In this study, we investigated clinicopathological features and factors predicting the development of liver metastasis from EGC.
We examined the medical records of 2,707 consecutive patients who underwent open gastrectomy for EGC (pT1; m, sm) between 1991 and 2005. We assessed clinicopathological features and predictive factors for EGC metastasis in the liver.
Fifteen (0.6%) of the 2,707 patients developed liver metastasis. All primary gastric tumors of patients with liver recurrence demonstrated invasion to the submucosal layer. Macroscopically, nine patients had elevated-type and six depressed-type. Nodal metastasis was documented in seven patients (47%). Lymphatic and vascular involvements were seen in 11 (73%) and 7 (47%) patients, respectively. Multivariate analysis of patients with submucosal invasion revealed macroscopic elevated type and vascular involvement to be independent risk factors for liver metastasis.
With submucosal cancer, the macroscopic elevated type and vascular involvement are significant predictive factors for EGC recurrence in the liver.
Journal of Gastrointestinal Surgery 12/2011; 16(4):837-41. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study.
Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety.
The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic.
On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.
Journal of Clinical Oncology 11/2011; 29(33):4387-93. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Currently in Japan, differentiated gastric submucosal invasive cancers <500 μm (SM1) with negative lymphovascular involvement are included in expanded pathological criteria for curative endoscopic treatment. This is based on a retrospective examination of surgical resection cases in which patients suitable for such expanded criteria were determined to have a negligible risk of lymph node metastasis. We performed endoscopic submucosal dissection on a 65-year-old male with early gastric cancer in April 2005, and pathology revealed a well-differentiated adenocarcinoma, 21 × 10 mm in size, SM1 invasion depth and negative lymphovascular invasion as well as tumor-free margins, so the case was diagnosed as a curative resection. This case, however, resulted in lymph node metastasis that was diagnosed by endoscopic ultrasonography with fine-needle aspiration biopsy in May 2009. Distal gastrectomy with D2 lymph node dissection was then performed, confirming lymph node metastasis from the original gastric cancer.
Gastric Cancer 11/2011; 15(2):221-5. · 2.42 Impact Factor
-
Kazutaka Kikuta,
Daisuke Kubota,
Tsuyoshi Saito,
Hajime Orita,
Akihiko Yoshida,
Hitoshi Tsuda,
Yoshiyuki Suehara, Hitoshi Katai,
Yasuhiro Shimada,
Yoshiaki Toyama,
Koichi Sato,
Takashi Yao,
Kazuo Kaneko,
Yasuo Beppu,
Yasufumi Murakami,
Akira Kawai,
Tadashi Kondo
[show abstract]
[hide abstract]
ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract, comprising a wide spectrum from a curable disorder to highly malignant disease. GIST is characterized by tyrosine kinase mutations, and molecular targeting therapies against these abnormal enzymes require prognostic biomarkers. To identify candidate prognostic biomarkers, we examined proteomic features corresponding to metastasis after surgery. Using two-dimensional difference gel electrophoresis with a large format gel, we compared the primary tumor tissues of GIST patients free of metastasis for two years after surgery (eight cases) with those of patients who developed metastasis within one year after surgery (nine cases). We found the intensities of 38 protein spots to differ significantly between the two groups. Mass spectrometric protein identification revealed that these corresponded to 25 unique genes. Immunohistochemical validation demonstrated ATP-dependent RNA helicase DDX39 to be significantly associated with metastasis and poor clinical outcomes in a group of 72 GIST patients. In conclusion, we have established a novel prognostic utility of ATP-dependent RNA helicase DDX39 in GIST.ATP-dependent RNA helicase DDX39, a novel biomarker for GIST likely to be associated with metastatic disease, can identify patients likely to benefit from new therapeutic strategies such as tyrosine kinase inhibitors.
Journal of proteomics 10/2011; 75(4):1089-98. · 5.07 Impact Factor
-
Daisuke Kubota,
Hajime Orita,
Akihiko Yoshida,
Masahiro Gotoh,
Tatsuo Kanda,
Hitoshi Tsuda,
Tadashi Hasegawa, Hitoshi Katai,
Yasuhiro Shimada,
Kazuo Kaneko,
Akira Kawai,
Tadashi Kondo
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study is to confirm the prognostic value of pfetin in gastrointestinal stromal tumor patients. We recently reported the utility of pfetin, a novel prognostic biomarker in gastrointestinal stromal tumor. Gastrointestinal stromal tumor spans a wide spectrum from cases with curable disease to those with fatal tumors due to metastasis and recurrence. There is no biomarker predicting metastasis and/or recurrence of gastrointestinal stromal tumor though imatinib mesylate can improve recurrence-free survival.
Pfetin expression was examined in 40 gastrointestinal stromal tumor patients from the Juntendo University Shizuoka Hospital using immunohistochemistry. Correlations between immunohistochemical findings and clinicopathologic parameters were examined. The pfetin expression results were integrated with the clinicopathologic data in a total of 299 cases including our 40 new gastrointestinal stromal tumor cases and 259 others with previously reported data.
Immunohistochemical study demonstrated the disease-free survival rate to be 93.75% for pfetin-positive and 25.0% for pfetin-negative patients among the 40 cases from the Juntendo University Shizuoka Hospital (P= 0.0006). When all 299 cases were included, the disease-free survival rate was 92.44% for pfetin-positive and 60.81% for pfetin-negative patients (P< 0.0001). Both uni- and multivariate analyses revealed that, among the clinicopathologic parameters examined, only pfetin expression was an independent prognostic factor (P< 0.05).
These results confirm the possible clinical utility of pfetin as a prognostic biomarker for gastrointestinal stromal tumor. Pfetin appears to be a novel clinically applicable prognostic factor, which may be useful for deciding whether to administer imatinib mesylate or not.
Japanese Journal of Clinical Oncology 09/2011; 41(10):1194-202. · 1.78 Impact Factor
-
Yoh Isobe,
Atsushi Nashimoto,
Kohei Akazawa,
Ichiro Oda,
Kenichi Hayashi,
Isao Miyashiro, Hitoshi Katai,
Shunichi Tsujitani,
Yasuhiro Kodera,
Yasuyuki Seto,
Michio Kaminishi
[show abstract]
[hide abstract]
ABSTRACT: The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registry in 2008. Approximately 50 data items, including surgical procedures, pathological diagnoses, and survival outcomes, for 12004 patients with primary gastric cancer treated in 2001 were collected retrospectively from 187 participating hospitals. Data were entered into the JGCA database according to the JGCA Classification of gastric carcinoma, 13th edition and the International Union Against Cancer (UICC) TNM Classification of malignant tumors, 5th edition by using an electronic data collecting system. Finally, data of 11261 patients with gastric resection were analyzed. The 5-year follow-up rate was 83.5%. The direct death rate was 0.6%. TNM 5-year survival rates (5YSRs)/JGCA 5YSRs were 91.8/91.9% for stage IA, 84.6/85.1% for stage IB, 70.5/73.1% for stage II, 46.6/51.0% for stage IIIA, 29.9/33.4% for stage IIIB, and 16.6/15.8% for stage IV. The proportion of patients more than 80 years old was 7.0%, and their 5YSR was 48.7%. Compared to the JGCA archived data, though the follow-up rate needs to be improved, these data suggest that the postoperative results of patients with primary gastric carcinoma have improved in those with advanced disease and in the aged population in Japan.
Gastric Cancer 09/2011; 14(4):301-16. · 2.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the optimal extent of lymph node dissection for carcinomas of the true cardia, otherwise called Siewert type II esophagogastric junction (EGJ) carcinomas.
In patients with cancer of the EGJ, comparable outcomes have been obtained with extended esophagectomy and total gastrectomy. The issue of the optimal surgical approach for EGJ tumors has been under debate. Nodal involvement is a strong predictor of survival, however, the optimal extent of prophylactic lymphadenectomy for Siewert type II tumors remains to be elucidated.
We retrospectively evaluated the distributions of the metastatic nodes, the recurrence pattern, and the oncological outcomes in a single-center large cohort of 225 patients with Siewert type II tumors. To assess the therapeutic outcomes of respective node dissection, we applied an index calculated by multiplication of the incidence of metastasis by the 5-year survival rate of patients with metastasis in the respective node stations.
The incidence of nodal metastasis was high in the right paracardial (38.2%), lesser curve (35.1%) and left paracardial (23.1%) nodes, and also the nodes along the left gastric artery (20.9%). Involvement of the suprapancreatic nodes along the celiac artery, splenic artery and common hepatic artery was found in 23, 25, and 14 patients, respectively. According to the index of estimated benefit from lymph node dissection, dissection of the paracardial and lesser curve nodes yielded the highest therapeutic benefit. The number of metastatic nodes in these areas was as predictive of the disease-free and overall survivals as the TNM pN category. The 5-year overall survival rates in patients with no or 1-2 metastatic nodes were 76.6% and 62.3%, respectively, whereas the 5-year survival rate in those with 3 or more positive nodes was only 22.4%, comparable with the rate of 17.4% in patients with TNM pN3 tumors.
Clear anatomic distinction of EGJ tumors is likely to provide insight into the appropriate extent of lymphadenectomy. Dissection of the paracardial and lesser curve nodes is essential for staging as well as for obtaining therapeutic benefit in surgery for in EGJ carcinomas (Siewert type II).
Annals of surgery 08/2011; 254(2):274-80. · 7.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Matrix metalloproteinases are responsible for proteolytic degradation of basement membrane and extracellular matrix. In tumor tissues, elevated expression of matrix metalloproteinase-1 (MMP-1) has been associated with tumor invasion and metastasis. However, little is known about the expression of MMP-1 in peripheral blood (PB) and bone marrow (BM) in gastric cancer patients. Thus, the aim of the present study is to determine MMP-1 messenger RNA (mRNA) expression levels in BM and PB of patients with gastric cancer.
The study group consisted of 857 patients with gastric cancer (577 males and 280 females) ranging in age from 27 to 87 years (average 61.6 years). MMP-1 mRNA expression levels in BM and PB were evaluated quantitatively by real-time reverse-transcription polymerase chain reaction (RT-PCR).
Expression of MMP-1 mRNA in BM and PB of patients with gastric cancer was significantly higher than in noncancer patients. High levels of MMP-1 mRNA expression were significantly associated with differentiated histology, tumor size, tumor invasiveness, lymph node metastasis, liver metastasis, and clinical stage. Particularly importantly, MMP-1 mRNA expression in PB was an independent factor of distant metastasis.
We disclosed that MMP-1 mRNA expression in peripheral blood and bone marrow of gastric cancer patients was very high, precisely reflecting staging of gastric cancer. MMP-1 mRNA expression in peripheral blood may be a useful marker for distant metastasis in gastric cancer.
Annals of Surgical Oncology 07/2011; 19 Suppl 3:S430-7. · 4.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endoscopic submucosal dissection (ESD) is a technique developed to enable the endoscopic resection (ER) of large and ulcerative neoplastic lesions that were previously unresectable using conventional endoscopic mucosal resection (EMR). We investigated the clinical outcomes of ER of early gastric cancer (EGC) before and after the introduction of ESD, with particular attention to surgery and its potential consequences.
We reviewed 2,785 consecutive surgical patients with EGC and 2,469 consecutive lesions treated by ER with curative intent between 1990 and 2005. The study was divided into an EMR period (1990-1999) and an ESD period (2000-2005). We analyzed the clinical outcomes of endoscopic and surgical resections and defined 'potentially avoidable surgery' as cases of surgery performed for lesions curable by ER.
The rate of potentially avoidable surgery was 3.8% (52/1,369) in the EMR period and 0.2% (3/1,416) in the ESD period (P < 0.001). For ER patients, the rate of overall non-curative ER was 36.9% (154/417) in the EMR group and 17.0% (348/2,052) in the ESD group (P < 0.001). The rate of non-curative ER for lesions defined as having 'positive or difficult to estimate horizontal margins only' decreased significantly, from 26.1% (109/417) in the EMR group to 1.4% (29/2,052) in the ESD group (P < 0.001). Conversely, the rate of non-curative ER for lesions defined as having 'possible lymph node metastasis' significantly increased in the ESD group (15.5%; 319/2,052) compared to that in the EMR group (10.8%; 45/417) (P < 0.01).
The application of a pathway involving ESD resulted in a significant decrease in the rate of potentially avoidable surgery, highlighting the advantages associated with performing ESD.
Gastric Cancer 02/2011; 14(1):56-62. · 2.42 Impact Factor
