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Tochigi, Japan

Akiyoshi T.,Cancer Institute Hospital | Watanabe T.,University of Tokyo | Miyata S.,Cancer Institute Hospital | Kotake K.,Tochigi Cancer Center | And 2 more authors.
Annals of Surgery | Year: 2012

Objective: 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. Background: 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. Methods: 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. Results: 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). Conclusions: 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. © 2012 by Lippincott Williams & Wilkins.

Kobayashi H.,Tokyo Medical and Dental University | Kotake K.,Tochigi Cancer Center | Sugihara K.,Tokyo Medical and Dental University
International Journal of Clinical Oncology | Year: 2014

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. © 2012 Japan Society of Clinical Oncology.

Watanabe T.,Teikyo University | Konishi T.,University of Tokyo | Kishimoto J.,Kyushu University | Kotake K.,Tochigi Cancer Center | And 2 more authors.
Inflammatory Bowel Diseases | Year: 2011

Background: 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. Methods: 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. Results: 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). Conclusions: 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. Inflamm Bowel Dis 2011 © 2010 Crohn's & Colitis Foundation of America, Inc.

Kobayashi H.,Tokyo Medical and Dental University | Kotake K.,Tochigi Cancer Center | Sugihara K.,Tokyo Medical and Dental University
International Journal of Clinical Oncology | Year: 2013

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. © 2012 Japan Society of Clinical Oncology.

Shimizu R.,Jichi Medical University | Kikuchi J.,Jichi Medical University | Wada T.,Jichi Medical University | Ozawa K.,Jichi Medical University | And 2 more authors.
Leukemia | Year: 2010

Anti-CD20 antibody rituximab is now essential for the treatment of CD20-positive B-cell lymphomas. Decreased expression of CD20 is one of the major mechanisms underlying both innate and acquired resistance to rituximab. In this study, we show that histone deacetylase (HDAC) inhibitors augment the cytotoxic activity of rituximab by enhancing the surface expression of CD20 antigen on lymphoma cells. HDAC inhibitors, valproic acid (VPA) and romidepsin, increased CD20 expression at protein and mRNA levels in B-cell lymphoma cell lines with relatively low CD20 expression levels. The VPA-mediated increase in CD20 expression occurred at 1 m, which is clinically achievable and safe, but insufficient for inducing cell death. Chromatin immunoprecipitation assays revealed that HDAC inhibitors transactivated the CD20 gene through promoter hyperacetylation and Sp1 recruitment. HDAC inhibitors potentiated the activity of rituximab in complement-dependent cytotoxic assays. In mouse lymphoma models, HDAC inhibitors enhanced CD20 expression along with histone hyperacetylation in transplanted cells, and acted synergistically with rituximab to retard their growth. The combination with HDAC inhibitors may serve as an effective strategy to overcome rituximab resistance in B-cell lymphomas. © 2010 Macmillan Publishers Limited All rights reserved.

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