Oncologic Status of Obturator Lymph Node Metastases in Locally Advanced Low Rectal Cancer: A Japanese Multi-Institutional Study of 3487 Patients.

BACKGROUND: The American Joint Committee on Cancer tumor-node-metastasis staging system for rectal cancer defines lateral pelvic lymph nodes (LPLNs) only in the internal iliac region as regional. However, the Japanese Society for Cancer of the Colon and Rectum (JSCCR) staging system, also considers obturator lymph nodes (LNs) as regional. This retrospective cohort study evaluated the oncologic status of obturator LNs in low rectal cancer. METHODS: The study identified 3487 patients with pT3-T4 low rectal cancer who had undergone curative resections without preoperative radiotherapy or chemotherapy between 2003 and 2011 in the JSCCR database and divided them into six groups. Overall survival (OS) and recurrence-free survival (RFS) were analyzed by groups. RESULTS: Histologic LPLN metastases were identified in 8% (279/3487) of all the patients and in 18.2% (279/1530) of the patients who underwent lateral pelvic node dissection. The 5-year OS and RFS rates of the obturator-LPLN group (P = 0.095) were worse than those of the internal-LPLN group (P = 0.075), but the difference was not significant. The OS of the obturator-LPLN group was similar to that of the resectable liver metastasis group (P = 0.731), and the RFS of the obturator-LPLN group was significantly better than that of the other-LPLN group (P = 0.016). CONCLUSION: The prognosis for obturator LN metastases in low rectal cancer was not significantly worse than for internal iliac LN metastases, defined as regional by the current American Joint Committee on Cancer staging system, and the oncologic status of obturator LNs warrants more studies.

Impact of Primary Tumor Location on Postoperative Recurrence and Subsequent Prognosis in Nonmetastatic Colon Cancers: A Multicenter Retrospective Study Using a Propensity Score Analysis.

OBJECTIVE: We aimed to clarify the prognostic impact of primary tumor location on recurrence after curative surgery and subsequent survival in patients with nonmetastatic colon cancer. SUMMARY OF BACKGROUND DATA: Right and left colon cancers are suggested to be oncologically different; however, their prognostic differences have been conflictingly reported. METHODS: A total of 5664 patients with curatively resected stage II-III colon cancer were reviewed, retrospectively. Relapse-free survival (RFS) after primary surgery and cancer-specific survival (CSS) after recurrence were compared between patients with right and left colon cancer. Patients' backgrounds were matched using propensity scores. RESULTS: Although patients with right colon cancer had more advanced disease, their 5-year RFS rate was significantly superior compared with that in those with left colon cancer (83.9% vs 81.1%, P = 0.019). However, the 5-year CSS after recurrence rate was significantly inferior in patients with right colon cancer compared with that in those with left colon cancer (30.6% vs 43.6%, P = 0.016). CONCLUSIONS: The primary tumor location of nonmetastatic colon cancer might have different prognostic implications for the rates of recurrence after curative resection and cancer-specific mortality after recurrence.

Polymeric micelles loaded with (1,2-diaminocyclohexane)platinum(II) against colorectal cancer.

BACKGROUND: We investigated the potential of nanomedicine in loading the oxaliplatin parent complex (1,2-diaminocyclohexane)platinum(II)-loaded polymeric micelles (DACHPt/m) against multiple liver metastases from colon cancer in a mouse model. MATERIALS AND METHODS: The efficacy of DACHPt/m or oxaliplatin (on days 14 and 21 after inoculation of tumor cells) was evaluated in a mouse model of liver metastasis for murine colon adenocarcinoma C26 cells. In vivo antitumor effects were evaluated by recording the number of liver metastases and weights of metastatic livers after treatment (day 28). The accumulation of drugs in tumors and liver parenchyma was analyzed using ion coupled plasma-mass spectrometry 24 h after administration of DACHPt/m or oxaliplatin (n = 5). We assessed renal and hepatic toxicities through changes in creatinine, aspartate transaminase, and alanine transaminase on the last day of the antitumor activity experiment. RESULTS: Mice receiving DACHPt/m had significantly fewer metastatic nodules (P = 0.038) and lower liver weights (P = 0.038) than those receiving oxaliplatin. The accumulation of DACHPt/m in the metastatic liver was significantly higher than that of oxaliplatin, whereas the distribution of micelles in healthy liver tissues was limited. Mice treated with DACHPt/m also showed significantly lower serum creatinine levels than those treated with oxaliplatin (P = 0.007), whereas serum aspartate transaminase and alanine transaminase levels for both drugs were not different. CONCLUSIONS: High levels of DACHPt/m accumulate in metastatic livers, producing a strong antitumor effect without severe adverse effects. DACHPt/m is a safe approach for managing liver metastasis from colorectal cancer.

Oncological Outcomes of Lateral Pelvic Lymph Node Metastasis in Rectal Cancer Treated With Preoperative Chemoradiotherapy.

BACKGROUND: Oncological outcomes of lateral pelvic lymph node metastasis in rectal cancer treated with preoperative chemoradiotherapy remain to be elucidated. OBJECTIVE: The purpose of this study was to clarify the therapeutic effect of chemoradiotherapy on lateral pelvic lymph node metastasis, the risk factors of lateral pelvic lymph node metastasis, and oncological outcomes of lateral pelvic lymph node dissection after chemoradiotherapy. DESIGN: This was a nonrandomized, retrospective study. SETTINGS: The study was conducted at a tertiary referral university hospital. PATIENTS: Patients with rectal cancer treated with chemoradiotherapy and radical surgery from 2003 to 2015 (N = 222) were included. INTERVENTIONS: Radiation (total, 50.4 Gy in 28 fractions) with concomitant fluorouracil-based chemotherapy was administered. Lateral pelvic lymph nodes with a diameter of ≥8 mm before chemoradiotherapy were selectively dissected. MAIN OUTCOME MEASURES: Frequency and risk factors of lateral pelvic lymph node metastasis were examined. RESULTS: Lateral pelvic lymph node dissection was performed in 31 patients (14.0%), and 16 (51.6%) of these patients were pathologically diagnosed as positive for metastasis. Among the patients treated with total mesorectal excision alone (n = 191), 2 (0.9%) had recurrence in the lateral pelvic lymph node area, which was pathologically confirmed after salvage R0 resection. T category downstaging (73.3% vs 12.5%; p < 0.01) and high histological regression of the primary lesion (73.3% vs 18.8%; p < 0.01) were more frequent in patients with pathologically negative lateral pelvic lymph nodes than in those with positive lateral pelvic lymph nodes. Young age, short distance from the anal verge, and enlarged lateral pelvic lymph node before chemoradiotherapy were associated with lateral pelvic lymph node metastasis. LIMITATIONS: The study was limited by its retrospective nature and small study population. CONCLUSIONS: The incidence of lateral pelvic lymph node metastasis after chemoradiotherapy was estimated to be 8.1% (18/222). Young age, short distance from the anal verge, and enlarged lateral pelvic lymph node before chemoradiotherapy were risk factors of lateral pelvic lymph node metastasis after chemoradiotherapy.

Oncological benefit of lateral pelvic lymph node dissection for rectal cancer treated without preoperative chemoradiotherapy: a multicenter retrospective study using propensity score analysis.

PURPOSE: We aimed to clarify the prognostic impact of lateral pelvic lymph node (LPN) dissection (LPND) for rectal cancer through a multicenter retrospective study using propensity score analysis. METHODS: A total of 1238 patients with pathological T2-4, M0 rectal cancer who had undergone curative operation between 2007 and 2008 were examined. Majority of the patients (96 %) were treated without preoperative chemoradiotherapy (CRT). Clinical background data of the patients treated with LPND and those treated without LPND were matched using propensity scores, and hazard ratios (HRs) for cancer-specific mortality were compared. RESULTS: LPND was performed more frequently for lower rectal cancers and in patients with more advanced disease, and 29 % of the patients were treated with LPND. After matching background features by propensity scores, LPND did not correlate with improved cancer-specific survival (CSS) among the entire study population [HR, 0.73; 95 % confidence interval (CI) 0.41-1.31; P = 0.28]; however, LPND was correlated with significantly improved CSS in female patients (HR, 0.23; 95 % CI, 0.06-0.89; P = 0.04) but not in male patients (HR, 0.95; 95 % CI, 0.48-1.89; P = 0.89). The results were similar when patients treated with LPND finally diagnosed as pathologically negative for LPN metastasis were compared with those curatively treated without LPND. CONCLUSIONS: It is suggested that the prognostic impact of LPND for rectal cancer treated without CRT might be different between sexes, and LPND should be considered for female rectal cancer patients although they are diagnosed as clinically negative for LPN metastasis.

Prognostic impact of lymph node dissection is different for male and female colon cancer patients: a propensity score analysis in a multicenter retrospective study.

PURPOSE: Colon cancers in male and female patients are suggested to be oncologically different. The aim of this study is to elucidate the prognostic impact of lymph node dissection (LND) in male and female colon cancer patients. METHODS: A total of 5941 stage I-III colon cancer patients who were curatively operated on during the period from 1997 to 2007 were retrospectively studied. Cancer-specific survival (CSS) was individually compared between for male and female patients treated with D3, D2, and D1 LND. Background differences of the patients were matched using propensity scores. RESULTS: D3, D2, and D1 LND were performed in 3756 (63 %), 1707 (29 %), and 478 (8 %), respectively, and more extensive LND was indicated for younger patients and more advanced disease. D2 LND was significantly associated with decreased cancer-specific mortality compared to D1 LND in male patients (HR 0.54, 95 % CI 0.32-0.89, p = 0.04), but not in female patients. D3 LND did not correlate to an improved prognosis compared to D2 LND both in male and female patients. CONCLUSIONS: D2 LND was associated with an improved CSS in male, but not female colon cancer patients, compared to D1 LND. This suggested that colon cancer in male and female patients might be oncologically different, and that the prognostic impact of the extent of surgical intervention for colon cancer might therefore be different between sexes.

Benefit of primary tumor resection in stage IV colorectal cancer with unresectable metastasis: a multicenter retrospective study using a propensity score analysis.

PURPOSE: Retrospective studies have shown that primary tumor resection improves the prognosis of patients with colorectal cancer (CRC) with unresectable metastasis (mCRC). The aim of this study was to investigate the prognostic impact of primary tumor resection in various subgroups of mCRC patients. METHODS: A total of 1982 patients with mCRC from January 1997 to December 2007 were retrospectively evaluated. The impact of primary tumor resection on cancer-specific survival (CSS) was analyzed using propensity score analysis to mitigate selection bias. Covariates in the models for propensity scores included treatment period, age, gender, tumor location, depth, lymph node metastasis, number of metastatic organs, and carcinoembryonic antigen (CEA) levels. RESULTS: Among the whole patient population, primary tumor resection significantly improved CSS [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.32-0.66, p < 0.01]. However, primary tumor resection did not significantly improve CSS in the following subgroups: patients treated in the first 5 years of the study (HR 0.56, 95% CI 0.28-1.13, p = 0.08), patients aged >65 years (HR 0.72, 95% CI 0.36-1.42, p = 0.31), female patients (HR 0.60, 95% CI 0.31-1.17, p = 0.13), patients with right-sided colon cancer (HR 0.68, 95% CI 0.39-1.20, p = 0.17), and patients without nodal involvement (HR 0.54, 95% CI 0.25-1.17, p = 0.09). CONCLUSIONS: Our study suggests that primary tumor resection improves the survival of patients with mCRC. However, the prognostic benefit is different among patient subpopulations.

Prognostic impact of tumor location in stage IV colon cancer: a propensity score analysis in a multicenter study.

BACKGROUND: Right-sided colon cancer is considered to be biologically different from left-sided colon cancer; however, conflicting results have been reported regarding differences in prognosis. We aimed to clarify the prognostic impact of tumor location in stage IV colon cancer. METHODS: Stage IV colon cancer treated from January 1997 to December 2007 (n = 2208) were retrospectively studied. Clinical and pathological features were compared between right-sided colon cancer (cecum, ascending, and transverse colon) and left-sided colon cancer (descending, sigmoid, and rectosigmoid colon). The impact of tumor location on cancer-specific survival (CSS) was analyzed in a multivariate analysis and propensity score analysis to mitigate the differences in background features. RESULTS: Right-sided colon cancer was associated with older age, female sex, larger tumor size, poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-ring cell carcinoma, a more advanced state within stage IV disease, and a worse CSS. In the cohort matched by propensity scores for background clinicopathological features, tumor location in the right-sided colon was associated with a significantly worse CSS (hazard ratio 1.2, 95% confidence interval 1.1-1.4, p = 0.008) in patients treated with palliative primary tumor resection, but not in those treated with R0 resection or no resection. CONCLUSION: Right-sided colon cancer were diagnosed at a more advanced state within stage IV disease and showed a significantly worse prognosis than left-sided colon cancer, suggesting that stage IV right-sided colon cancer is oncologically more aggressive than left-sided colon cancer.

Prognostic impact of primary tumor resection and lymph node dissection in stage IV colorectal cancer with unresectable metastasis: a propensity score analysis in a multicenter retrospective study.

BACKGROUND: Retrospective studies have shown that primary tumor resection improves the prognosis of patients with colorectal cancer with unresectable metastasis (mCRC). Prognostic significance of lymph node dissection (LND) in mCRC has not been examined previously. The aim of this study was to investigate the prognostic impact of primary tumor resection and LND in mCRC. METHODS: A total of 1,982 patients with mCRC from January 1997 to December 2007 were retrospectively studied. The impact of primary tumor resection and LND on overall survival (OS) was analyzed using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. Covariates in the models for propensity scores included treatment period, institution, age, sex, carcinoembryonic antigen, tumor location, histology, depth, lymph node metastasis, lymphovascular invasion, and number of metastatic organs. RESULTS: In a multivariate analysis, primary tumor resection and treatment in the latter period were associated with an improved OS, and age over 70 years, female sex, lymph node metastasis, and multiple organ metastasis were associated with a decreased OS. In the propensity-matched cohort, patients treated with primary tumor resection showed a significantly better OS than those without tumor resection (median OS 13.8 vs. 6.3 months; p = 0.0001). Furthermore, among patients treated with primary tumor resection, patients treated with D3 LND showed a significantly better OS than those with less extensive LND (median OS 17.2 vs. 13.7 months; p < 0.0001). CONCLUSIONS: It was suggested that primary tumor resection with D3 LND improves the survival of patients with mCRC.