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ABSTRACT: In vitro evaluations of chemosensitivity are important for experiments evaluating cancer therapies. The Scepter 2.0 cell counter, an automated handheld device based on the Coulter principle of impedance-based particle detection, enables the accurate discrimination of cell populations according to cell size and volume. In this study, the effects of SN-38, the active metabolite of irinotecan, on the colon cancer cell lines HCT116 and HT29 were evaluated using this device. The cell count data obtained with the Scepter counter were compared with those obtained with the (3)H-thymidine uptake assay, which has been used to measure cell proliferation in many previous studies. In addition, we examined whether the changes in the size distributions of these cells reflected alterations in the frequency of cell cycle arrest and/or apoptosis induced by SN-38 treatment. In our experiments using the Scepter 2.0 cell counter, the cell counts were demonstrated to be accurate and reproducible and alterations of cell diameter reflected G2/M cell cycle arrest and apoptosis. Our data show that easy-to-use cell counting tools can be utilized to evaluate the cell-killing effects of novel treatments on cancer cells in vitro.
Biochemical and Biophysical Research Communications 04/2013; · 2.48 Impact Factor
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Megumi Ishiguro, Kenjiro Kotake,
Genichi Nishimura,
Naohiro Tomita,
Wataru Ichikawa,
Keiichi Takahashi,
Toshiaki Watanabe,
Tomohisa Furuhata,
Ken Kondo,
Masaki Mori,
Yoshihiro Kakeji,
Akiyoshi Kanazawa,
Michiya Kobayashi,
Masazumi Okajima,
Ichinosuke Hyodo,
Keiko Miyakoda,
Kenichi Sugihara
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ABSTRACT: BACKGROUND: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied.Methods/design: The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients' clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. DISCUSSION: A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the "personalized therapy" in adjuvant chemotherapy for colon cancer.Trial registration: ClinicalTrials.gov: NCT00918827UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013.
BMC Cancer 03/2013; 13(1):149. · 3.01 Impact Factor
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ABSTRACT: BACKGROUND: Preoperative detection of small peritoneal metastases is difficult, and a convenient method is required to decide the nature of procedures subsequent to initial exploratory surgery. The aim of this study was to validate the Japanese classification of peritoneal metastasis from colorectal cancer. METHODS: This retrospective study analyzes data from a multi-center registry. Factors affecting the extent of peritoneal metastasis, macroscopic radical resection and prognosis were analyzed using data from patients with colorectal cancer and synchronous peritoneal metastasis. Peritoneal metastasis was classified depending on extent into three groups (P1-P3). RESULTS: Among 60,176 patients with colorectal surgery, 3,075 (5.1 %) had synchronous peritoneal metastasis. Tumor location on the right side (P < 0.0001), histological grade (P = 0.0014) and distant metastasis (P < 0.0001) were associated with the extent of peritoneal metastasis. Gender (P = 0.041), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis according to the present classification (P < 0.0001) and the period when the patient underwent the operation (operative period; P < 0.0001) were independently associated with macroscopic radical resection. Cox proportional hazards model disclosed that gender (P = 0.0046), tumor location (P = 0.032), age (P = 0.048), histological grade (P < 0.0001), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis (P < 0.0001), and macroscopic radical resection (P < 0.0001) were independent prognostic factors. CONCLUSIONS: Macroscopic radical resection was an independent prognostic factor even without hyperthermic intraperitoneal chemotherapy. The referral of patients without distant metastasis to centers with experienced peritoneal surgeons might be a potential option if the peritoneal metastasis is unresectable in general hospitals.
International Journal of Clinical Oncology 12/2012; · 1.41 Impact Factor
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ABSTRACT: We evaluated the predictive relevance of several biomarkers on the survival of patients with stage III colorectal cancer treated with adjuvant chemotherapy of oral fluoropyrimidines. This was a multicenter phase II trial on adult patients with histologically confirmed resected stage III (Dukes' C) colorectal cancer. Patients received oral doxifluridine (800 mg/m2/day) in 3 divided doses, or oral uracil/tegafur (UFT) (400 mg/m2/day) in 2 divided doses for 5 days, every 7 days for 12 months with a 5-year follow-up. Outcome measures were disease-free survival and tissue markers [thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) protein levels and TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT) mRNA levels in tumor samples and TS tandem-repeat type in blood samples]. There was a significant association between the intratumoral TP/DPD enzyme ratio and disease-free survival when the model included the drug, the parameter and the interactions between them [hazard ratio (HR)=2.76; P=0.00469]. The 5-year disease-free survival rate was statistically significantly higher in patients with high TP/DPD ratios [median ≥2.63: 71.9%; 95% confidence interval (CI) 61.4-80.0] compared to patients with low TP/DPD ratios (<2.63: 57.0%; 95% CI 46.3-66.3) (log-rank P=0.0277) following adjuvant therapy with oral fluoropyrimidines. No significant association was observed between the intratumoral TP/DPD enzyme ratio (cut-off value 2.0) and the disease-free survival rate in the doxifluridine group; primary endpoint (log-rank P=0.6850). The magnitude of the intratumoral TP/DPD enzyme ratio may be a potential indicator for the individualization of postoperative adjuvant chemotherapy with oral fluoropyrimidines for stage III colorectal cancer.
Oncology Reports 12/2012; · 1.84 Impact Factor
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Megumi Ishiguro,
Hidetaka Mochizuki,
Naohiro Tomita,
Yasuhiro Shimada,
Keiichi Takahashi, Kenjiro Kotake,
Masahiko Watanabe,
Yukihide Kanemitsu,
Hideki Ueno,
Toshiaki Ishikawa,
Hiroyuki Uetake,
Shigeyuki Matsui,
Satoshi Teramukai,
Kenichi Sugihara
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ABSTRACT: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy, but the usefulness of adjuvant chemotherapy for stage II colon cancer remains controversial. The major Western guidelines recommend adjuvant chemotherapy for "high-risk stage II" cancer, but this is not clearly defined and the efficacy has not been confirmed.
SACURA trial is a multicenter randomized phase III study which aims to evaluate the superiority of 1-year adjuvant treatment with UFT to observation without any adjuvant treatment after surgery for stage II colon cancer in a large population, and to identify "high-risk factors of recurrence/death" in stage II colon cancer and predictors of efficacy and adverse events of the chemotherapy. Patients aged between 20 and 80 years with curatively resected stage II colon cancer are randomly assigned to a observation group or UFT adjuvant therapy group (UFT at 500-600 mg/day as tegafur in 2 divided doses after meals for 5 days, followed by 2-day rest. This 1-week treatment cycle is repeated for 1 year). The patients are followed up for 5 years until recurrence or death. Treatment delivery and adverse events are entered into a web-based case report form system every 3 months. The target sample size is 2,000 patients. The primary endpoint is disease-free survival, and the secondary endpoints are overall survival, recurrence-free survival, and incidence and severity of adverse events. In an additional translational study, the mRNA expression of 5-FU-related enzymes, microsatellite instability and chromosomal instability, and histopathological factors including tumor budding are assessed to evaluate correlation with recurrences, survivals and adverse events.
A total of 2,024 patients were enrolled from October 2006 to July 2010. The results of this study will provide important information that help to improve the therapeutic strategy for stage II colon cancer.
ClinicalTrials.gov NCT00392899.
BMC Cancer 07/2012; 12:281. · 3.01 Impact Factor
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ABSTRACT: BACKGROUND: Stage IV colorectal cancer encompasses various clinical conditions. The aim of this study was to validate the utility of the recent AJCC stage IV colorectal cancer sub-classification, and to establish a prognostic scoring system using independent factors. METHODS: We conducted a retrospective analysis using data from the multicenter registry. Factors affecting the curative resection and prognosis were analyzed in patients with stage IV colorectal cancer. RESULTS: Of the 60,176 patients who received surgery for colorectal cancer, 9,624 (16.0 %) were classified as stage IV. The prognoses of patients with peritoneum-only metastasis were superior to those of patients with a stage IVB (P < 0.0001). Of the 11 independent prognostic factors identified, eight with a hazard ratio greater than 1.3 (depth of tumor invasion, regional lymph node metastasis, histologic grade, liver metastasis, lung metastasis, distant lymph node metastasis, peritoneal metastasis, and curative resection) were used in the prognostic scoring system. The scoring system gave one or two points for the presence of each prognosis risk factor, resulting in a total score ranging from 0 to 9. The 5-year overall survival rates of patients with a total score of 0-2, 3, 4, 5, and 6-9 were 50.4, 30.4, 17.7, 7.7, and 4.0 %, respectively (P < 0.0001). CONCLUSION: Although the AJCC staging for patients with stage IV colorectal cancer reflected the prognosis, patients with peritoneum-only metastases should be classified as stage IVA. The prognostic scoring system using eight independent factors is useful in predicting the survival of patients with stage IV colorectal cancer.
International Journal of Clinical Oncology 06/2012; · 1.41 Impact Factor
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ABSTRACT: To evaluate whether lateral pelvic lymph nodes (LNs) in low rectal cancer are metastatic disease or part of regional LNs that are amenable to curative resection.
It is highly controversial whether lateral pelvic LNs should be considered as regional or distant disease, although the American Joint Committee on Cancer (AJCC) defines internal iliac LNs as regional LNs of rectal cancer.
Data of patients with stage I to III low rectal cancer who underwent curative resection from 1978 to 1998 were extracted from the multi-institutional registry of large bowel cancer in Japan. Patients with only mesorectal LN metastasis were classified as the mesorectal-LN group. Patients with lateral pelvic LN metastasis localized to or extending beyond the internal iliac area were classified as the internal lateral pelvic lymph nodes (LPLN) group and external-LPLN group, respectively. Overall survival (OS) and cancer-specific survival (CSS) were compared between the groups.
Lateral pelvic LN dissection was performed in 5789 (50%) of 11,567 patients. Overall, 3905 (34%), 411 (3.6%), and 244 (2.1%) patients were classified as the mesorectal-LN, internal-LPLN, and external-LPLN groups, respectively. When the mesorectal LN group was subdivided as defined by the AJCC, both 5-year OS and CSS were not significantly different between the N2a and internal-LPLN groups (OS: 45% vs 45%, P = 0.9585; CSS: 51% vs 49%, P = 0.5742), and the N2b and external-LPLN groups (OS: 32% vs 29%, P = 0.3342; CSS: 37% vs 34%, P = 0.4347). OS and CSS were significantly better in the external-LPLN group than in stage IV patients who underwent curative resection (OS: 29% vs 24%, P = 0.0240; CSS: 34% vs 27%, P = 0.0117).
Lateral pelvic LNs can be considered as regional LNs in low rectal cancer, although metastasis extending beyond the internal iliac area is associated with poorer survival.
Annals of surgery 04/2012; 255(6):1129-34. · 7.90 Impact Factor
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ABSTRACT: BACKGROUND: The clinical significance of peritoneal lavage cytology for patients with gastric cancer is recognized, whereas that for patients with colorectal cancer remains controversial. The present study used a nationwide registry to clarify the prognostic significance of peritoneal lavage cytology in patients with colorectal cancer. METHODS: We retrospectively analyzed factors associated with recurrence and survival in patients with T3-T4 colorectal cancer without distant metastasis taken from the nationwide registry of the Japanese Society for Cancer of the Colon and Rectum between 1984 and 1999. RESULTS: Among 34,554 patients in this study, not all of whom received peritoneal lavage cytology, 35 had positive peritoneal lavage cytology. Gender (P = 0.0004), tumor location (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001), lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.015) were risk factors for peritoneal recurrence. Multivariate analysis revealed that tumor location (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001) and lymph node metastasis (P < 0.0001) were independent risk factors for peritoneal metastasis. Gender (P < 0.0001), tumor location (P < 0.0001), age (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001), lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.0004) were independent prognostic factors according to the Cox proportional hazards model. CONCLUSION: Positive peritoneal lavage cytology was associated with poorer survival in patients with stage II and III colorectal cancer. Positive cytology might be a good indicator of candidates for intensive adjuvant chemotherapy. The benefit of intensive adjuvant chemotherapy for such patients should be validated in prospective trials.
International Journal of Clinical Oncology 02/2012; · 1.41 Impact Factor
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Toshiaki Watanabe,
Michio Itabashi,
Yasuhiro Shimada,
Shinji Tanaka,
Yoshinori Ito,
Yoichi Ajioka,
Tetsuya Hamaguchi,
Ichinosuke Hyodo,
Masahiro Igarashi,
Hideyuki Ishida, [......],
Genichi Nishimura,
Yuh Sakata,
Keiichi Takahashi,
Hiroya Takiuchi,
Osamu Tsuruta,
Toshiharu Yamaguchi,
Masahiro Yoshida,
Naohiko Yamaguchi, Kenjiro Kotake,
Kenichi Sugihara
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ABSTRACT: Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms in women and the third largest number in men. Many new treatment methods have been developed over the last few decades. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer (JSCCR Guidelines 2010) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2010.
International Journal of Clinical Oncology 02/2012; 17(1):1-29. · 1.41 Impact Factor
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ABSTRACT: The new TNM classification is currently being implemented. We evaluated the TNM-7 staging system based on the two nationwide colon cancer registries in the United States and Japan to clarify whether this system better stratifies patients' prognoses than the TNM-6 did and to determine whether stratification can be effectively simplified.
The Surveillance, Epidemiology, and End Results population-based data from 1988 to 2001 for 50139 colon cancer patients and the multi-institutional registry data from the Japanese Society for Cancer of the Colon and Rectum from 1984 to 1994 for 10754 patients were analysed. We devised a modified version of the TNM-7 staging system to allow simpler classification of the TN categories and compared the TNM-6, TNM-7, modified TNM-7, and the Dukes staging system based on survival curves and objective statistical tests such as likelihood ratio χ(2) tests, Akaike's information criterion, and Harrell's c-index.
The TNM-7 was superior to the TNM-6 in all objective statistical tests in the United States (c-index; 0.700 vs 0.696, P<0.001) as well as in the Japan data sets (0.732 vs 0.729, P=0.035). The modified TNM-7 is much simpler, but it nevertheless showed similar values to those of the original TNM-7 (c-index; the United States 0.702, Japan 0.733).
The new TNM-7 is complicated but better at stratifying patients than the TNM-6 in the United States and Japan, and could be effectively simplified.
Colorectal Disease 12/2011; 14(9):1065-74. · 2.93 Impact Factor
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ABSTRACT: The number of lymph nodes retrieved is recognized to be a prognostic factor of Stage II colorectal cancer. However, the prognostic significance of the number of lymph nodes retrieved in Stage III colorectal cancer remains controversial.
The relationship between the number of lymph nodes retrieved and clinical and pathological factors, and significance of the number of lymph nodes retrieved for prognosis of Stage II and III colorectal cancer were investigated. A total of 16 865 patients with T3/T4 colorectal cancer who had R0 resection were analysed.
The arithmetic mean of the number of lymph nodes retrieved of all cases was 20.0. The number of lymph nodes retrieved were varied according to several clinical and pathological variables with significant difference, and the greater difference was observed in scope of nodal dissection. Survival of Stages II and III was significantly associated with the number of lymph nodes retrieved. Five-year overall survival of the patients with ≤ 9 of the number of lymph nodes retrieved and those with >27 differed by 6.4% for Stage II colon cancer, 8.8% for Stage III colon cancer, 12.5% for Stage II rectal cancer and 10.6% for Stage III rectal cancer. With one increase in the number of lymph nodes retrieved, the mortality risk was decreased by 2.1% for Stage II and by 0.8% for Stage III, respectively. The cut-off point of the number of lymph nodes retrieved was not obtained.
The number of lymph nodes retrieved was shown to be an important prognostic variable not only in Stage II but also in Stage III colorectal cancer, and it was most prominently determined by the scope of nodal dissection. A cut-off value for the number of lymph nodes retrieved was not found, and it is necessary to carry out appropriate nodal dissection and examine as many lymph nodes as possible.
Japanese Journal of Clinical Oncology 11/2011; 42(1):29-35. · 1.78 Impact Factor
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Yasuo Hamamoto,
Tomomi Komaki,
Junko Miyamoto,
Noriyuki Akutsu,
Etsuko Warita,
Yasuhiro Yamanaka,
Yoshinori Kuroki,
Hirofumi Shirakawa,
Heita Ozawa,
Morihiro Tomikawa,
Shoichi Hishinuma,
Sayuri Hoshi,
Seiji Igarashi,
Tomoe Ozasa,
Yasuyoshi Sugano, Kenjiro Kotake
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ABSTRACT: The introduction of monoclonal antibodies into the treatment protocols for metastatic colorectal cancer(mCRC)has significantly improved outcomes. There are some patients with mCRC, initially judged unresectable, who become resectable after chemotherapy. For patients with isolated liver metastases, surgical resection is recommended when feasible. We experienced a case in which an initially unresectable mCRC liver metastases converted into a resectable one after cetuximab monotherapy as third-line treatment. The sample from hepatectomy was a pathologically complete response; no remnants were detected. The management of liver metastases contributes to improvements in the clinical setting. For conducting a multimodal treatment of mCRC, the participation of various specialists such as medical oncologists, colorectal/hepaticsurgeons and diagnostic/therapeutic radiologists is indispensable. Furthermore, it is necessary to construct an evidence-based consensus on potentially resectable CRC liver metastases in each hospital.
Gan to kagaku ryoho. Cancer & chemotherapy 06/2011; 38(6):1017-9.
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ABSTRACT: In palliative chemotherapy, a focus on palliative treatment is recommended in cases that are unresponsive to multiple drugs. Careful judgment is needed, however, because when treatment is inadequate, cases that are considered to be unresponsive may include some in which chemotherapy would be effective. We treated a patient with metastatic colon cancer who was judged to be unresponsive to multiple drugs at another hospital, yet repetition of standard therapy proved effective. We report this case as an instructive example of the importance of maintaining dose intensity. The patient was a 60-year-old man. Lung metastasis appeared after he had undergone proctectomy and received adjuvant chemotherapy by his previous doctor. Low-dose intensity IFL therapy, FOLFOX4 therapy (once a month), and FOLFIRI therapy (once only) had been performed, but the patient's condition worsened and he was referred to our hospital. This case could not be considered unresponsive to multiple drugs because the treatment had been insufficient, and so we restarted FOLFIRI treatment with the international standard dose and obtained control of the disease. Treatment was then continued, and the patient died 2 years and 11 months after he was first examined at our hospital. Simple palliative treatment alone should not be given unthinkingly when patients are referred for outpatient palliative care. Full consideration of the dosing and schedule is needed.
Gan to kagaku ryoho. Cancer & chemotherapy 05/2011; 38(5):831-3.
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Kenjiro Kotake
Nippon rinsho. Japanese journal of clinical medicine 04/2011; 69 Suppl 3:242-6.
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ABSTRACT: The clinicopathological features of ulcerative colitis-associated colorectal cancer (UC-CRC) have not yet been fully clarified, especially in Asian populations. This study aimed to clarify the prognosis and clinicopathological features of UC-CRC in comparison with sporadic CRC in the Japanese population.
Histologically diagnosed UC-CRC patients between 1978 to 1998 were extracted from the Multi-Institutional Registry of Large-Bowel Cancer in Japan, a large nationwide CRC database, and the clinicopathological features and postoperative survival rates of UC-CRC patients and sporadic CRC patients were compared.
Among the 108,536 CRC patients registered between 1978 and 1998, a total of 169 UC-CRC patients were identified, including 121 patients who had been treated surgically. The proportion of UC-CRC patients increased in the period between 1995 and 1998 compared to that between 1978 and 1994. Comparisons with the sporadic CRC patients showed that the UC-CRC patients were younger, had a higher proportion of multiple cancer lesions, had higher proportions of superficial type lesions and invasive type lesions morphologically, and had higher proportions of mucinous or signet ring cell carcinomas. In stage III, UC-CRC patients had a poorer survival rate than the sporadic CRC patients (43.3% versus 57.4%, P = 0.0320).
UC-CRC increased over the investigated time periods and showed a poorer survival than sporadic CRC in the advanced stage, while no difference was observed in the early stage. By detecting UC-CRC at an early stage we can expect a similar postoperative outcomes to that of sporadic CRC. These results stress the importance of surveillance for the early detection of UC-CRC.
Inflammatory Bowel Diseases 03/2011; 17(3):802-8. · 4.86 Impact Factor
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Harunobu Sato,
Koutarou Maeda,
Kenichi Sugihara,
Hidetaka Mochizuki, Kenjiro Kotake,
Tetsuo Teramoto,
Shingo Kameoka,
Yukio Saito,
Keiichi Takahashi,
Takashi Hirai,
Masayuki Ohue,
Kazuo Shirouzu,
Yoshiharu Sakai,
Toshiaki Watanabe,
Koichi Hirata,
Katsuyoshi Hatakeyama
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ABSTRACT: This study was designed to clarify which attributes of stage II colon cancer are associated with tumor recurrence and survival after curative resection, and the effects of adjuvant chemotherapy (ACT).
We retrospectively reviewed outcomes and clinicopathological characteristics of 1476 patients with stage II colon cancer who underwent curative resection.
Of 1476 patients, 204 (13.8%) developed recurrence. Macroscopic type, serum CA19-9 levels, venous invasion, emergency operation, and postoperative ileus were independently associated with overall recurrence. Carbohydrate antigen (CA)19-9 levels, the number of dissected lymph nodes (LN), sex, age, ACT, emergency operation, venous invasion, and macroscopic type were independently associated with poor prognosis. Prognosis was significantly better in patients who received ACT than in those who did not. Among patients with extensive venous invasion, those with fewer than 13 dissected LNs, male patients, and patients >50 years old, the prognosis was significantly better in patients who received ACT than in those who did not.
ACT for stage II colon cancer is recommended to improve the prognosis of patients with extensive venous invasion, patients with fewer than 13 dissected LNs, patients >50 years old, and male patients, particularly patients with more than two of these risk factors.
Journal of Surgical Oncology 03/2011; 104(1):45-52. · 2.10 Impact Factor
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Hirotoshi Kobayashi,
Hidetaka Mochizuki,
Takayuki Morita, Kenjiro Kotake,
Tatsuo Teramoto,
Shingo Kameoka,
Yukio Saito,
Keiichi Takahashi,
Kazuo Hase,
Masatoshi Oya,
Koutarou Maeda,
Takashi Hirai,
Masao Kameyama,
Kazuo Shirouzu,
Kenichi Sugihara
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ABSTRACT: Because the rate of recurrence after curative resection for T1 colorectal cancer is low, the characteristics of recurrence remain obscure. This multicenter study attempted to clarify the characteristics of recurrence after curative resection for T1 colorectal cancer.
We analyzed the associations between recurrence and various clinicopathological features in 798 patients who had undergone curative resection alone for T1 colorectal cancer at 14 hospitals between 1991 and 1996.
The rate of lymph node metastasis (LNM) in patients with T1 colorectal cancer was 10.5% (84/798), and 18 (2.3%) of the 798 patients developed recurrence during the median follow-up of 7.8 years. The recurrence rates in patients with colon cancer with and without LNM were 3.6 and 1.3%, respectively (p = 0.19). These rates in patients with cancer of the rectum were 25.0 and 1.1% (p < 0.0001). Among various parameters, histological grade (p < 0.0001), location (p = 0.025), LNM (p < 0.0001), and venous invasion (p = 0.0013) were risk factors for recurrence. Among them, LNM (p = 0.0008) and histological grade (p = 0.041) were independent risk factors for recurrence after curative resection for T1 colorectal cancer. Time to recurrence was more likely to be shorter for patients with, than without nodal involvement. In patients with an unfavorable histological grade, all recurrences developed within 1 year.
The recurrence rate after curative resection for node-negative T1 colorectal cancer was very low. The effectiveness of surveillance to detect recurrence after curative resection for T1 colorectal cancer should be validated in further studies.
Journal of Gastroenterology 02/2011; 46(2):203-11. · 4.16 Impact Factor
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ABSTRACT: To examine the present state of dissemination and utilization of JSCCR Guidelines for the Treatment of Colorectal Cancer and to collect opinions about the contents and method of preparation in the guideline, we conducted a questionnaire survey with the purpose of using the data obtained as a basic resource for revision of the guidelines. The guidelines are widely used by physicians in their daily practice at institutions specializing in the treatment of colorectal cancer. Based on their opinions on the contents and the methods used in the preparation of the guidelines, we revised the guidelines using greater objectivity and transparency in the process of its preparation, and published the revised guideline in July 2009. The next issue that needs to be addressed is to establish a measurement system of the treatment outcome, in order to verify the effect of establishment of the guidelines.
Gan to kagaku ryoho. Cancer & chemotherapy 04/2010; 37(4):587-91.
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Hirotoshi Kobayashi,
Hidetaka Mochizuki,
Takayuki Morita, Kenjiro Kotake,
Tatsuo Teramoto,
Shingo Kameoka,
Yukio Saito,
Keiichi Takahashi,
Kazuo Hase,
Masatoshi Ohya,
Koutarou Maeda,
Takashi Hirai,
Masao Kameyama,
Kazuo Shirouzu,
Kenichi Sugihara
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ABSTRACT: The aim of this multicenter study was to clarify the influence of timing of relapse after curative resection for colorectal cancer on prognosis.
We enrolled 5,230 consecutive patients who underwent curative resection for colorectal cancer at 14 hospitals from 1991 to 1996. All patients were intensively followed up. Time to relapse (TR) was classified into three groups as follows: group A, TR < or =1 year; group B, TR >1 year and < or =3 years, and group C, TR >3 years. The prognoses after relapse were compared among the three groups.
Of the 5,230 patients, 906 experienced relapse (17.3%). The curative resection rates for recurrent tumors were 35.2% in group A, 46.6% in group B, and 45.1% in group C (p = 0.0045). There were significant differences in the prognoses after relapse among the three TR groups in patients with relapse to the liver (p = 0.0175) and in those with local relapses (p = 0.0021), but not in those with pulmonary or anastomotic recurrence. There were no differences in prognoses after relapse in any recurrence site among the three groups in patients who underwent curative resection for relapse.
If patients can undergo curative resection for relapse, they receive a survival benefit regardless of the timing of relapse.
Digestive surgery 08/2009; 26(3):249-55. · 1.37 Impact Factor
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ABSTRACT: BACKGROUND: This study aimed to classify colorectal carcinomas based on DNA ploidy and genetic alterations, and to establish whether there is a difference in the probability of survival for each type. METHODS: A total of 84 patients were included in this study based on the availability of high-quality DNA from paired normal and tumor tissues. DNA ploidy was analyzed using a flow cytometer, and genetic alterations were analyzed using the items of APC (mutation cluster region [MCR]), K-ras (codon 12, 13 and 61), p53 (exons 5 to 8), and microsatellite instability (MSI; eight loci). RESULTS: The 84 cases were divided into the following seven types: (1) A2-type, high genetic mutation in DNA aneuploid tumors; (2) A1-type, low genetic mutation in DNA aneuploid tumors; (3) A0-type, no detected mutation in DNA aneuploid tumors; (4) D1-type, genetic mutation in DNA diploid tumors; (5) MSI-H-type, microsatellite instability-high; (6) D0-type, no detected mutation in DNA diploid tumors; and (7) LM-type, cases unrelated to ploidy. Liver metastasis was confirmed before or after the operation. The survival analysis of three types, the A2 versus A1, A1 versus LM-type, and MSI-H versus D1-type, showed significant differences (respectively, P = 0.0410, P </= 0.001, and P = 0.0320). Also, although no significant difference was noted between wild-type p53 and mutated p53, the mutated p53 cases showed a strong tendency towards a poor prognosis as compared with wild-type p53 (P = 0.0624). CONCLUSION: This study suggests that not only known carcinogenesis mechanisms but also other factors related to survival exists in colorectal carcinomas. Our classification could be useful as a prognostic factor in colorectal carcinomas.
Journal of Gastroenterology 04/2009; · 4.16 Impact Factor
