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Sample records for stage iii colon

  1. A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites.

    PubMed

    Zhang, Yan; Ma, Junli; Zhang, Sai; Deng, Ganlu; Wu, Xiaoling; He, Jingxuan; Pei, Haiping; Shen, Hong; Zeng, Shan

    2015-09-01

    Stage III colon cancer is currently treated as an entity with a unified therapeutic principle. The aim of the retrospective study is to explore the clinicopathological characteristics and outcomes of site-specific stage III colon cancers and the influences of tumor location on prognosis. Eight hundred ninety-five patients with stage III colon cancer treated with radical operation and subsequent adjuvant chemotherapy (5-fluorouracil/oxaliplatin) were divided into seven groups according to colon segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon). Expression of excision repair cross-complementing group 1 (ERCC1) and thymidylate synthase (TS) was examined by immunohistochemistry. We assessed if differences exist in patient characteristics and clinic outcomes between the seven groups. There were significant differences in tumor differentiation (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage (P < 0.001), metachronous liver metastasis (P < 0.001), metachronous lung metastasis (P < 0.001), and ERCCI expression (P < 0.001) between the seven groups. Both 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) exhibited significant differences (both P < 0.001) with survival gradually decreasing from cecum to sigmoid colon. Cox regression analyses identified that tumor location was an independent prognostic factor for RFS and OS. Stage III colon cancer located proximally carried a poorer survival than that located distally. Different efficacies of FOLFOX adjuvant chemotherapy may be an important factor affecting survival of site-specific stage III colon cancers.

  2. Fragmentation in specialist care and stage III colon cancer

    PubMed Central

    Hussain, Tanvir; Chang, Hsien-Yen; Veenstra, Christine M.; Pollack, Craig Evan

    2015-01-01

    Background Patients with cancer frequently transition between different types of specialists and across care settings. We explored how frequently the medical and surgical oncologic care of stage III colon cancer patients occurs across more than one hospital and whether this is associated with mortality and costs. Methods This is a retrospective SEER-Medicare cohort study of 9,075 stage III colon cancer patients diagnosed between 2000 and 2009 receiving both surgical and medical oncologic care within one year of diagnosis. Patients were assigned to the hospital where they had their cancer surgery and to their oncologist's primary hospital, and then characterized according to whether these hospitals were same or different. Outcomes included all-cause mortality, subhazards for colon cancer specific mortality, and cost of care at 12 months. Results 37% of patients received their surgical and medical oncologic care from different hospitals. Rural patients were less likely than urban patients to receive medical oncologic care from the same hospital (OR 0.62, 95%CI 0.43-0.90). Care from the same hospital was not associated with reduced all-cause or colon cancer specific mortality but resulted in lower costs at 12 months (dollars saved $5493, 95%CI $1799, $9525), 8% of median cost. Conclusions Delivery of surgical and medical oncology care at the same hospital was associated with lower costs; however, reforms which seek to improve outcomes and cost through integrating complex care will need to address the significant proportion of patients receiving care across more than one hospital. PMID:26043368

  3. Oncologic outcomes after adjuvant chemotherapy using FOLFOX in MSI-H sporadic stage III colon cancer.

    PubMed

    Oh, Seung Yeop; Kim, Do Yoon; Kim, Young Bae; Suh, Kwang Wook

    2013-10-01

    Little is known of the oncological outcomes after adjuvant FOLFOX chemotherapy in patients with stage III colon cancer showing microsatellite instability high (MSI-H). In the present study we investigated the prognostic impact of MSI-H in patients with stage III colon cancer receiving FOLFOX chemotherapy. We analyzed the MSI status in 127 patients with stage III colon cancer who underwent curative surgical resection followed by FOLFOX chemotherapy between January 2003 and December 2010. We assessed disease-free and overall survival (OS) in patients with MSI-H colon cancer compared with those showing microsatellite instability low or microsatellite stable (MSI-L/MSS) disease. Sixteen of the patients (12.6 %) were MSI-H, and 111 patients (87.4 %) were MSI-L/MSS. There was no significant difference between patients showing MSI-H and MSI-L/MSS except for age (P = 0.030), tumor location (P < 0.001), and differentiation (P = 0.031). Compared with MSI-L/MSS colon cancer, patients with MSI-H colon cancer had no significant difference in 5-year disease-free and OS (72.2 vs 68.5 %, P = 0.874; 68.1 vs 71.1 %, P = 0.437). Our study indicates that FOLFOX chemotherapy can be considered to treat stage III colon cancer patients with MSI-H after surgery, although the study was not randomized and included only a limited number of patients.

  4. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer

    PubMed Central

    Dalerba, Piero; Sahoo, Debashis; Paik, Soonmyung; Guo, Xiangqian; Yothers, Greg; Song, Nan; Wilcox-Fogel, Nate; Forgó, Erna; Rajendran, Pradeep S.; Miranda, Stephen P.; Hisamori, Shigeo; Hutchison, Jacqueline; Kalisky, Tomer; Qian, Dalong; Wolmark, Norman; Fisher, George A.; van de Rijn, Matt; Clarke, Michael F.

    2016-01-01

    Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P = 0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein–negative colon cancers than among the 276 (87.9%) with CDX2 protein–positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P = 0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P = 0.003) and in the validation data set (51% among 15 patients with CDX2

  5. Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients

    PubMed Central

    van den Broek, Evert; Krijgsman, Oscar; Sie, Daoud; Tijssen, Marianne; Mongera, Sandra; van de Wiel, Mark A.; Th. Belt, Eric J.; den Uil, Sjoerd H.; Bril, Herman; Stockmann, Hein B.A.C.; Ylstra, Bauke; Carvalho, Beatriz; Meijer, Gerrit A.; Fijneman, Remond J.A.

    2016-01-01

    Tumor profiling of DNA alterations, i.e. gene point mutations, somatic copy number aberrations (CNAs) and structural variants (SVs), improves insight into the molecular pathology of cancer and clinical outcome. Here, associations between genomic aberrations and disease recurrence in stage II and III colon cancers were investigated. A series of 114 stage II and III microsatellite stable colon cancer samples were analyzed by high-resolution array-comparative genomic hybridization (array-CGH) to detect CNAs and CNA-associated chromosomal breakpoints (SVs). For 60 of these samples mutation status of APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS was determined using targeted massive parallel sequencing. Loss of chromosome 18q12.1-18q12.2 occurred more frequently in tumors that relapsed than in relapse-free tumors (p < 0.001; FDR = 0.13). In total, 267 genes were recurrently affected by SVs (FDR < 0.1). CNAs and SVs were not associated with disease-free survival (DFS). Mutations in APC and TP53 were associated with increased CNAs. APC mutations were associated with poor prognosis in (5-fluorouracil treated) stage III colon cancers (p = 0.005; HR = 4.1), an effect that was further enhanced by mutations in MAPK pathway (KRAS, NRAS, BRAF) genes. We conclude that among multiple genomic alterations in CRC, strongest associations with clinical outcome were observed for common mutations in APC. PMID:27729614

  6. Patterns of adjuvant chemotherapy for stage II and III colon cancer in France and Italy.

    PubMed

    Bouvier, Anne-Marie; Minicozzi, Pamela; Grosclaude, Pascale; Bouvier, Véronique; Faivre, Jean; Sant, Milena

    2013-08-01

    European guidelines recommend adjuvant chemotherapy for stage III colon cancer but not for stage II. To determine the extent to which adjuvant chemotherapy was used in Italy and France. A common retrospective database of 2186 colon cancers diagnosed between 2003 and 2005 was analysed according to age, stage and presenting features. 38.9% of patients with stage II and 64.6% with stage III received chemotherapy in Italy, 21.7% and 65.1% in France. For stage II, the association between country and chemotherapy was only significant in patients diagnosed out of emergency (ORItaly/France: 3.05 [2.12-4.37], p<0.001) whereas patients diagnosed in emergency were as likely to receive chemotherapy in both countries. For stage III, there was a trend to a higher administration of chemotherapy for elderly patients in France compared to Italy. French patients were more likely than Italian to receive chemotherapy (OR: 1.91[1.32-2.78], p=0.001). Chemotherapy for stage III colon cancer was as extensively used in Italy as in France for young patients. Its administration could be increased in patients over 75. Stage II patients with a lower risk of relapse received chemotherapy more often in Italy than in France. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. Oral tegafur-uracil as metronomic therapy following intravenous FOLFOX for stage III colon cancer

    PubMed Central

    Huang, Wen-Yen; Ho, Ching-Liang; Lee, Chia-Cheng; Hsiao, Cheng-Wen; Wu, Chang-Chieh; Jao, Shu-Wen; Yang, Jen-Fu; Lo, Cheng-Hsiang; Chen, Jia-Hong

    2017-01-01

    The purpose of this study was to estimate the impact of metronomic therapy with oral tegafur-uracil (UFUR) following an intravenous FOLFOX regimen as surgical adjuvant chemotherapy on the overall survival (OS) and disease-free survival (DFS) of stage III colon cancer patients. From the retrospective database of patients who underwent a surgical resection for colorectal cancer at the Tri-Service General Hospital from October 2008 through December 2014, stage III colon carcinomas treated with radical R0 resection were reviewed. One hundred thirty two patients were treated with a FOLFOX regimen (comparison group), and 113 patients were treated with the same regimen followed by additional oral UFUR (UFUR group). The clinical characteristics and mean age of the comparison and UFUR groups were similar. Furthermore, for all study patients, DFS was not significantly different between the two groups. However, 5-year OS rates were 86.8% and 68.5% in the UFUR and comparison groups, respectively (p = 0.0107). Adding UFUR to a FOLFOX regimen was found to significantly improve the OS in patients with stage III colon cancer. UFUR as a maintenance therapy following FOLFOX regimen as an alternative therapeutic option for the treatment of stage III colon cancer patients. PMID:28328969

  8. Prognostic and predictive significance of MSI in stages II/III colon cancer.

    PubMed

    Saridaki, Zacharenia; Souglakos, John; Georgoulias, Vassilis

    2014-06-14

    In colon cancer, classic disease staging remains the key prognosis and treatment determinant. Although adjuvant chemotherapy has an established role in stage III colon cancer patients, in stage II it is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features. Patients with stage II tumors form a highly heterogeneous group, with five-year relative overall survival rates ranging from 87.5% (IIA) to 58.4% (IIC). Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging, and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed. The stronger candidate in this category seems to be microsatellite instability (MSI). The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stage II colorectal cancer patients in order to contribute in treatment decision-making regarding chemotherapy administration. The hypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address. Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature, and the matter is far from being settled. In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stage II and stage III colon cancer patients.

  9. Impact of Weight Changes After the Diagnosis of Stage III Colon Cancer on Survival Outcomes.

    PubMed

    Vergidis, Joanna; Gresham, Gillian; Lim, Howard J; Renouf, Daniel J; Kennecke, Hagen F; Ruan, Jenny Y; Chang, Jennifer T; Cheung, Winson Y

    2016-03-01

    Weight modification after a diagnosis of colon cancer and its impact on outcomes remain unclear. Thus we aimed to examine the association of obesity and weight changes from baseline oncology consultation with recurrence-free survival (RFS) and overall survival (OS) in patients with stage III colon cancer. Patients aged ≥ 18 years who were diagnosed with stage III colon cancer in British Columbia from 2008 to 2010 and who received adjuvant chemotherapy were included in the study. Cox proportional hazards regression models were fitted to evaluate the impact of different body compositions and degree of weight changes from baseline assessment with outcomes while controlling for potentially confounding covariates, such as age and sex. A total of 539 patients with stage III colon cancer were included: median age was 69 years (range, 26-94 years), 52% were men, and 53% had Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Those with weight gains of ≥ 10% had a median RFS of 37 months compared with 49 months in those with weight gains of < 10% (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.56-1.59; P = .82). However, this finding was not significant. In Cox models, patients who exhibited weight losses of ≥ 10% experienced significantly inferior RFS (HR, 3.45; 95% CI, 1.44-8.13; P = .0046) and OS (HR, 2.63; 95% CI, 1.04-6.67; P = .041) compared with those who experienced weight losses of < 10%. Weight gains, losses, or changes of equal or less magnitude did not show any significant associations with outcomes (all P > .05). Weight losses of ≥ 10% from baseline evaluation bodes a worse prognosis among patients with stage III colon cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Integrin genetic variants and stage-specific tumor recurrence in patients with stage II and III colon cancer.

    PubMed

    Bohanes, P; Yang, D; Loupakis, F; LaBonte, M J; Gerger, A; Ning, Y; Lenz, C; Lenz, F; Wakatsuki, T; Zhang, W; Benhaim, L; El-Khoueiry, A; El-Khoueiry, R; Lenz, H-J

    2015-06-01

    Integrins (ITGs) are key elements in cancer biology, regulating tumor growth, angiogenesis and lymphangiogenesis through interactions of the tumor cells with the microenvironment. Moving from the hypothesis that ITGs could have different effects in stage II and III colon cancer, we tested whether a comprehensive panel of germline single-nucleotide polymorphisms (SNPs) in ITG genes could predict stage-specific time to tumor recurrence (TTR). A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole-blood samples were analyzed for germline SNPs in ITG genes using PCR-restriction fragment length polymorphism or direct DNA sequencing. In the multivariable analysis, stage II colon cancer patients with at least one G allele for ITGB3 rs4642 had higher risk of recurrence (hazard ratio (HR)=4.027, 95% confidence interval (95% CI) 1.556-10.421, P=0.004). This association was also significant in the combined stage II-III cohort (HR=1.975, 95% CI 1.194-3.269, P=0.008). The predominant role of ITGB3 rs4642 in stage II diseases was confirmed using recursive partitioning, showing that ITGB3 rs4642 was the most important factor in stage II diseases. In contrast, in stage III diseases the combined analysis of ITGB1 rs2298141 and ITGA4 rs7562325 allowed to identify three distinct prognostic subgroups (P=0.009). The interaction between stage and the combined ITGB1 rs2298141 and ITGA4 rs7562325 on TTR was significant (P=0.025). This study identifies germline polymorphisms in ITG genes as independent stage-specific prognostic markers for stage II and III colon cancer. These data may help to select subgroups of patients who may benefit from ITG-targeted treatments.

  11. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial)

    PubMed Central

    Yoshida, M.; Ishiguro, M.; Ikejiri, K.; Mochizuki, I.; Nakamoto, Y.; Kinugasa, Y.; Takagane, A.; Endo, T.; Shinozaki, H.; Takii, Y.; Mochizuki, H.; Kotake, K.; Kameoka, S.; Takahashi, K.; Watanabe, T.; Watanabe, M.; Boku, N.; Tomita, N.; Nakatani, E.; Sugihara, K.

    2014-01-01

    Background S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur–uracil plus leucovorin (UFT/LV). Patients and methods Patients aged 20–80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80–120 mg/day on days 1–28 every 42 days; four courses) or UFT/LV (UFT: 300–600 mg/day and LV: 75 mg/day on days 1–28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. Results A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70–1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. Conclusion Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. ClinicalTrials.gov NCT00660894. PMID:24942277

  12. Collaboration Between Surgeons and Medical Oncologists and Outcomes for Patients With Stage III Colon Cancer

    PubMed Central

    Hussain, Tanvir; Chang, Hsien-Yen; Veenstra, Christine M.; Pollack, Craig E.

    2015-01-01

    Purpose: Collaboration between specialists is essential for achieving high-value care in patients with complex cancer needs. We explore how collaboration between oncologists and surgeons affects mortality and cost for patients requiring multispecialty cancer care. Patients and Methods: This was a retrospective cohort study of patients with stage III colon cancer from SEER-Medicare diagnosed between 2000 and 2009. Patients were assigned to a primary treating surgeon and oncologist. Collaboration between surgeon and oncologist was measured as the number of patients shared between them; this has been shown to reflect advice seeking and referral relationships between physicians. Outcomes included hazards for all-cause mortality, subhazards for colon cancer–specific mortality, and cost of care at 12 months. Results: A total of 9,329 patients received care from 3,623 different surgeons and 2,319 medical oncologists, representing 6,827 unique surgeon–medical oncologist pairs. As the number of patients shared between specialists increased from to one to five (25th to 75th percentile), patients experienced an approximately 20% improved survival benefit from all-cause and colon cancer–specific mortalities. Specifically, for each additional patient shared between oncologist and surgeon, all-cause mortality improved by 5% (hazard ratio, 0.95; 95%CI, 0.92 to 0.97), and colon cancer–specific mortality improved by 5% (subhazard ratio, 0.95; 95% CI, 0.91 to 0.97). There was no association with cost. Conclusion: Specialist collaboration is associated with lower mortality without increased cost among patients with stage III colon cancer. Facilitating formal and informal collaboration between specialists may be an important strategy for improving the care of patients with complex cancers. PMID:25873063

  13. Coffee Intake, Recurrence, and Mortality in Stage III Colon Cancer: Results From CALGB 89803 (Alliance)

    PubMed Central

    Guercio, Brendan J.; Sato, Kaori; Niedzwiecki, Donna; Ye, Xing; Saltz, Leonard B.; Mayer, Robert J.; Mowat, Rex B.; Whittom, Renaud; Hantel, Alexander; Benson, Al; Atienza, Daniel; Messino, Michael; Kindler, Hedy; Venook, Alan; Hu, Frank B.; Ogino, Shuji; Wu, Kana; Willett, Walter C.; Giovannucci, Edward L.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.

    2015-01-01

    Purpose Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown. Patients and Methods During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression. Results Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (Ptrend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; Ptrend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; Ptrend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality. Conclusion Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer. PMID:26282659

  14. Combination therapy in high-risk stage II or stage III colon cancer: current practice and future prospects

    PubMed Central

    Bastos, Diogo Assed; Ribeiro, Suilane Coelho; de Freitas, Daniela; Hoff, Paulo M.

    2010-01-01

    Colon cancer represents the second leading cause of cancer-related deaths. For patients who have undergone curative surgery, adjuvant therapy can reduce the risk of recurrence and death from relapsed or metastatic disease. Postoperative chemotherapy with a 5-fluorouracil-based regimen combined with oxaliplatin is the current standard of care for stage III patients. However, there is still controversy in stage II disease about the real impact of adjuvant monotherapy or combined therapy on survival. Better identification of a subgroup of patients with a higher risk of recurrence can select patients who might benefit from adjuvant therapy. For the elderly population, there is a well-established role for postoperative therapy, although the most appropriate regimen remains to be defined. Targeted agents for combined adjuvant therapy in stage II and III colon cancer is a promising area, but to date, there is no evidence supporting its use in this setting. Results from large prospective trials with targeted therapy have been disappointing and new drugs and strategies are needed to define the role of these types of agents in the adjuvant scenario of colon cancer. PMID:21789139

  15. Distribution of lymph node metastasis is a prognostic index in patients with stage III colon cancer.

    PubMed

    Kobayashi, Hirotoshi; Ueno, Hideki; Hashiguchi, Yojiro; Mochizuki, Hidetaka

    2006-04-01

    In the TNM classification of colorectal carcinoma, N-staging is dependent on the number of metastases; in the Japanese classification system, staging usually has been based on the distribution of metastases (N1, paracolic; N2, along the major vessels; N3, at the root of major vessels). The aim of our study was to examine whether the concept of the distribution of nodal metastasis could improve the TNM classification for colorectal cancer. We studied the survival rates of 485 and 136 patients with stage III colonic and rectal cancer, respectively, who underwent curative surgery between 1979 and 1998. The patients were categorized into 4 groups: group 1, TNM-N1 classified in J-N1; group 2, TNM-N2 in J-N1; group 3, TNM-N1 in J-N2-3; and group 4, TNM-N2 in J-N2-3. In the colon cancer arm, the 5-year survival rates of the patients in groups 1 to 4 were 74%, 51%, 52%, and 54%, respectively. There was a significant difference in survival rate between groups 1 and 3 (P = .0002). Thus, in colon cancer, nodal metastasis along the major vessels was a bad prognostic factor, even though the number of nodes that were involved was <4. In the rectum cancer arm, the 5-year survival rates of the patients in each group were 65%, 39%, 60%, and 32%, respectively. Only the number of nodal metastases was an independently significant prognostic variable. This study suggests that adding the concept of nodal distribution to the conventional TNM staging of colon cancer will improve the accuracy in the evaluation of the nodal status.

  16. Adjuvant Therapy for Stage II and III Colon Cancer: Consensus Report of the International Society of Gastrointestinal Oncology

    PubMed Central

    Marshall, John L.; Haller, Daniel G.; de Gramont, Aimery; Hochster, Howard S.; Lenz, Heinz-Josef; Ajani, Jaffer A.; Goldberg, Richard M.

    2007-01-01

    Chemotherapy agents available for the treatment of stage II and stage III colon cancer have changed substantially since the 1992 National Institutes of Health consensus report recommended that all stage III patients routinely receive adjuvant treatment with 5-fluorouracil/levamisole. Subsequent trials demonstrated superiority of 5-fluorouracil/leucovorin over 5-fluorouracil/levamisole in the adjuvant setting, and the recent addition of oxaliplatin to this regimen has further improved disease-free survival. While stage III colon cancer patients are routinely treated, the use of adjuvant chemotherapy in patients with stage II disease is still a subject of debate. Many trials that are assessing the potential role of biologics in the adjuvant setting will soon be completed. However, identifying molecular prognostic markers that accurately select patients with stage II or III cancers who are at risk of recurrence would be essential to select and individualize therapy. PMID:19262703

  17. Oncotype DX(®) colon cancer assay for prediction of recurrence risk in patients with stage II and III colon cancer: A review of the evidence.

    PubMed

    You, Y Nancy; Rustin, Rudolph B; Sullivan, James D

    2015-06-01

    Advances in molecular biology have enabled identification of tumor biomarkers that allow for individualized risk assessment for patients with cancer. Molecular predictors of clinical outcome can help inform discussion regarding the role of adjuvant chemotherapy in patients with resected colon cancer, such as those with stage II colon cancer in which the benefit of adjuvant therapy is controversial or those with stage III colon cancer who may have a lower risk of recurrence and less absolute benefit from oxaliplatin therapy. This article summarizes the data surrounding the development, validation, and clinical and economic utility of the Oncotype DX(®) colon cancer assay, a multigene expression assay validated to independently predict recurrence risk in patients with stage II and III colon cancer beyond traditional factors.

  18. Predictive and Prognostic Analysis of PIK3CA Mutation in Stage III Colon Cancer Intergroup Trial

    PubMed Central

    Liao, Xiaoyun; Imamura, Yu; Yamauchi, Mai; McCleary, Nadine J.; Ng, Kimmie; Niedzwiecki, Donna; Saltz, Leonard B.; Mayer, Robert J.; Whittom, Renaud; Hantel, Alexander; Benson, Al B.; Mowat, Rex B.; Spiegelman, Donna; Goldberg, Richard M.; Bertagnolli, Monica M.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.

    2013-01-01

    Background Somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. Methods We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. Results Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, disease-free, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (P interaction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (P interaction > .16). Conclusions Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy. PMID:24231454

  19. [Analysis of prognostic factors after radical resection in 628 patients with stage II or III colon cancer].

    PubMed

    Qin, Qiong; Yang, Lin; Zhou, Ai-ping; Sun, Yong-kun; Song, Yan; DU, Feng; Wang, Jin-wan

    2013-03-01

    To analyze the clinicopathologic factors related to recurrence and metastasis of stage II or III colon cancer after radical resection. The clinical and pathological data of 628 patients with stage II or III colon cancer after radical resection from Jan. 2005 to Dec. 2008 in our hospital were retrospectively reviewed and analyzed. The overall recurrence and metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis showed that age, smoking intensity, depth of tumor invasion, lymph node metastasis, TNM stage, gross classification, histological differentiation, blood vessel tumor embolus, tumor gross pathology, multiple primary tumors, preoperative and postoperative serum concentration of CEA and CA19-9, and the regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that regional lymph node metastasis, TNM stage, the regimen of postoperative adjuvant chemotherapy, and preoperative serum concentration of CEA and CA19-9 were independent factors affecting the prognosis of colon cancer patients. Regional lymph node metastasis, TNM stage, elevated preoperative serum concentration of CEA and CA19-9, the regimen of postoperative adjuvant chemotherapy with single fluorouracil type drug are independent risk factors of recurrence and metastasis in patients with stage II-III colon cancer after radical resection.

  20. Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

    PubMed Central

    Meyers, B.M.; Cosby, R.; Quereshy, F.; Jonker, D.

    2016-01-01

    Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer. PMID:28050138

  1. Real-world resource use and costs of adjuvant treatment for stage III colon cancer.

    PubMed

    van Gils, C W M; de Groot, S; Tan, S S; Redekop, W K; Koopman, M; Punt, C J A; Uyl-de Groot, C A

    2015-05-01

    Since the generalisability of trial-based economic evaluations may be limited, there is an increasing focus on real-world cost-effectiveness. Real-world studies involve evaluating the effects and costs of treatments in daily clinical practice. This study reports on the real-world resource use and costs of adjuvant treatments of stage III colon cancer in a population-based observational study. Analyses were based on a detailed retrospective medical chart review which was conducted for 206 patients with colon cancer treated in 2005 and 2006 in the Netherlands. Mean total costs per patient were €9681 for 5-FU/LV, €9736 for capecitabine, €32,793 for FOLFOX and €18,361 for CAPOX. Drug costs and the costs related to hospitalisations for chemotherapy administration were the main cost drivers. We identified a potential for substantial cost-savings when the 48 h administration of 5FU/LV in the FOLFOX regimen were to take place in an outpatient setting or be replaced by oral capecitabine as in the CAPOX regimen. This analysis based on detailed real-life data clearly indicates that clinical choices made in oncology based on efficacy of therapy have economic consequences. Considering today's reality of finite healthcare resources, these economic consequences deserve a formal role in clinical decision making, for instance in guideline development. © 2013 John Wiley & Sons Ltd.

  2. Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients.

    PubMed

    Taieb, J; Balogoun, R; Le Malicot, K; Tabernero, J; Mini, E; Folprecht, G; Van Laethem, J-L; Emile, J-F; Mulot, C; Fratté, S; Levaché, C-B; Saban-Roche, L; Thaler, J; Petersen, L N; Bridgewater, J; Perkins, G; Lepage, C; Van Cutsem, E; Zaanan, A; Laurent-Puig, P

    2017-04-01

    RAS mutations have been shown to confer resistance to anti- epidermal growth factor receptor (EGFR) treatment. We analysed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumours harbouring RAS and BRAF WT, and RAS mutations. The prognostic value of each individual mutation was also tested. Among the 2559 pts analysed, 745 pts (29%) were known to have KRAS exon 2 mutations and 163 pts (6.4%) the BRAF V600E mutation. Of the remaining 1651 pts, 1054 were assessed by NGS, showing that a further 227 pts (21%) had KRAS exon 2, 3, 4 or NRAS exon 2, 3, 4 mutations, and that 46 pts (4.4%) had a newly diagnosed BRAF mutation. Cetuximab added to FOLFOX did not significantly improve TTR, DFS or OS in pts with RAS WT or RAS and BRAF WT tumours (HR 0.77-1.03, all P > 0.05). Cetuximab addition was not either significantly deleterious in RAS mutant pts or in pts with rare RAS or BRAF mutations. In the overall trial population, NRAS and KRAS codon 61 mutations were the only rare mutations with the same pejorative prognostic value as KRAS exon 2 or BRAF V600E mutations. Though not significant, the clinically relevant 0.76 adjusted HR observed for DFS in favour of adding cetuximab to FOLFOX, in full RAS and BRAF WT stage III colon cancer pts, may justify a new randomized controlled trial testing EGFR inhibitors in this setting. This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

  3. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer.

    PubMed

    Bos, A C R K; van Erning, F N; van Gestel, Y R B M; Creemers, G J M; Punt, C J A; van Oijen, M G H; Lemmens, V E P P

    2015-11-01

    Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ⩽ 4, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus < 65 years 1.3 (95% confidence interval (CI): 1.14-1.58); OR ⩾ 75 versus < 65 years 1.6 (1.25-1.94)), emergency resection (OR 1.8 (1.41-2.32)), anastomotic leakage (OR 8.1 (6.14-10.62)), referral to another hospital for adjuvant chemotherapy (OR 1.9 (1.36-2.57)) and prolonged postoperative hospital admission (OR 4.7 (3.30-6.68)). Starting 5-8 weeks post-surgery showed no decrease in OS compared to initiation within 4 weeks (Hazard ratio (HR) 5-6 weeks 0.9 (0.79-1.11); HR 7-8 weeks 1.1 (0.91-1.30)). However, commencing beyond 8 weeks was associated with decreased OS compared to initiation within 8 weeks (HR 9-10 weeks 1.4 (1.21-1.68); HR 11-12 weeks 1.3 (1.06-1.59); HR 13-16 weeks 1.7 (1.23-2.23)). Our data support initiating adjuvant chemotherapy in stage III colon cancer patients within 8 weeks post-surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Clinical Outcome From Oxaliplatin Treatment in Stage II/III Colon Cancer According to Intrinsic Subtypes

    PubMed Central

    Song, Nan; Pogue-Geile, Katherine L.; Gavin, Patrick G.; Yothers, Greg; Kim, S. Rim; Johnson, Nicole L.; Lipchik, Corey; Allegra, Carmen J.; Petrelli, Nicholas J.; O’Connell, Michael J.; Wolmark, Norman; Paik, Soonmyung

    2016-01-01

    IMPORTANCE Oxaliplatin added to fluorouracil plus leucovorin therapy for patients with colon cancer has been shown to provide significant but modest absolute benefit for disease-free survival. However, acute and chronic neurotoxic effects from this regimen underscore the need for markers that predict oxaliplatin benefit. OBJECTIVE To test our hypothesis that molecular subtypes of colon cancer would be associated with differential prognosis and benefit from oxaliplatin added to fluorouracil plus leucovorin therapy. DESIGN, SETTING, AND PARTICIPANTS Participants in the NSABP C-07 trial were divided into discovery (n = 848) and validation (n = 881) cohorts based on the order of tissue block submission. A reestimated centroid using 72 genes was used to determine Colorectal Cancer Assigner subtypes and their association with oxaliplatin benefit in the discovery cohort. The validation cohort was examined with a locked-down algorithm for subtype classification and statistical analysis plan. Post hoc analysis included examination of the entire cohort with Colorectal Cancer Assigner, Colorectal Cancer Subtype (CCS), and Consensus Molecular Subtype (CMS) methods. INTERVENTIONS Fluorouracil plus leucovorin with or without oxaliplatin. MAIN OUTCOMES AND MEASURES Percent recurrence-free survival. RESULTS Among 1729 patients, 744 (43%) were female and mean (SD) age was 58 (11) years. Although C-07 participants with stage III disease with an enterocyte subtype showed a statistically significant benefit from oxaliplatin in the discovery cohort (hazard ratio, 0.22 [95% CI, 0.09–0.56]; P = .001 [N = 65]), no statistically significant benefit was observed in the validation cohort (hazard ratio, 0.53 [95% CI, 0.22–1.24]; P = .14 [N = 70]). The stemlike subtype was associated with poor prognosis and lack of benefit from oxaliplatin treatment (HR, 0.99 [95% CI, 0.73–1.34]; P = .96 [N = 367]). Examination of the different subtyping methods shows that all 3 methods robustly

  5. Preoperative serum markers for individual patient prognosis in stage I-III colon cancer.

    PubMed

    Giessen-Jung, Clemens; Nagel, Dorothea; Glas, Maria; Spelsberg, Fritz; Lau-Werner, Ulla; Modest, Dominik Paul; Schulz, Christoph; Heinemann, Volker; Di Gioia, Dorit; Stieber, Petra

    2015-09-01

    Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (βhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve

  6. Management of stage III colon cancer in the elderly: Practice patterns and outcomes in the general population.

    PubMed

    Merchant, Shaila J; Nanji, Sulaiman; Brennan, Kelly; Karim, Safiya; Patel, Sunil V; Biagi, James J; Booth, Christopher M

    2017-08-01

    Clinical trials have established surgical resection and adjuvant chemotherapy (ACT) as the standard management for stage III colon cancer; however, the extent to which these results apply to elderly patients in routine practice is unclear. This article describes the management and outcomes of elderly patients with stage III colon cancer. All cases of surgically resected colon cancer from 2002 to 2008 were identified with the population-based Ontario Cancer Registry. Pathology reports were obtained for a random sample (25% of all cases); those with stage III disease constituted the study population. The utilization of ACT, cancer-specific survival (CSS), and overall survival (OS) in elderly patients (≥70 years) and nonelderly patients (<70 years) were compared. The study population included 2920 patients, and 1521 (52%) were elderly. The 30- and 90-day mortality rates increased with advanced age: <70 years, 2% and 5%; 70 to 74 years, 3% and 7%; 75 to 79 years, 5% and 8%, and ≥80 years, 9% and 16% (P < .001). ACT was delivered to 48% of elderly patients and to 81% of younger patients (P < .001). Factors independently associated with ACT utilization among the elderly were a younger age (P < .001), male sex (P = .041), and no comorbidities (P = .001). Among elderly patients, ACT was associated with improved CSS (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.88) and OS (HR, 0.71; 95% CI, 0.60-0.83); however, the magnitude of the benefit was smaller for elderly patients than younger patients (HR for CSS, 0.53; 95% CI, 0.42-0.67; HR for OS 0.56; 95% CI, 0.45-0.69). Half of elderly patients with stage III colon cancer do not receive ACT. Although the effect size is smaller than that in younger patients, ACT is associated with improved long-term survival. Cancer 2017;123:2840-49. © 2017 American Cancer Society. © 2017 American Cancer Society.

  7. Referral to Medical Oncology: A Crucial Step in the Treatment of Older Patients with Stage III Colon Cancer

    PubMed Central

    Luo, RuiLi; Giordano, Sharon H.; Freeman, Jean L.; Zhang, Dong; Goodwin, James S.

    2007-01-01

    Purpose Adjuvant chemotherapy for stage III colon cancer produces a substantial survival benefit, but many older patients do not receive chemotherapy. This study examines factors associated with medical oncology consultation and evaluates the impact of such consultation on chemotherapy use. Patients and Methods We used the Surveillance Epidemiology and End Results–Medicare linked database and identified 7,569 patients, aged 66–99, with stage III colon cancer diagnosed from 1992–1999. Modified Poisson regression was used to assess the relative risk for seeing a medical oncologist and for receiving chemotherapy as a function of individual characteristics. Results 78.08% of patients saw a medical oncologist within 6 months of diagnosis. Patients who were female, white, married, had low comorbidity scores, were diagnosed in more recent years, or had four or more positive lymph nodes were more likely to see a medical oncologist. Patients seeing a medical oncologist were 10 times more likely to receive chemotherapy (odds ratio, 9.98; 95% confidence interval, 8.21–12.14), after controlling for demographic and tumor characteristics. Chemotherapy use increased over time, but was substantially lower among older, black, and unmarried patients. Conclusions Referral to medical oncology is one of the most important factors associated with receipt of chemotherapy among older patients with stage III colon cancer. Comorbidity decreases the likelihood of receiving chemotherapy, but its effect is the same for those who see a medical oncologist and all patients combined. Ensuring that high-risk patients are referred to medical oncology is a crucial step in quality care for patients with colon cancer. PMID:17030645

  8. Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803

    PubMed Central

    Ogino, Shuji; Shima, Kaori; Meyerhardt, Jeffrey A.; McCleary, Nadine J.; Ng, Kimmie; Hollis, Donna; Saltz, Leonard B.; Mayer, Robert J.; Schaefer, Paul; Whittom, Renaud; Hantel, Alexander; Benson, Al B.; Spiegelman, Donna; Goldberg, Richard M.; Bertagnolli, Monica M.; Fuchs, Charles S.

    2011-01-01

    Purpose Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colon and rectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer. Methods We assessed status of BRAF c.1799T>A (p.V600E) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess the prognostic role of BRAF mutation, adjusting for clinical features, adjuvant chemotherapy arm and MSI status. Results Compared to 431 BRAF-wild-type patients, 75 BRAF-mutated patients experienced significantly worse overall survival [OS; log-rank p=0.015; multivariate hazard ratio (HR)=1.66; 95% confidence interval (CI), 1.05-2.63]. By assessing combined status of BRAF and MSI, it appeared that BRAF-mutated MSS (microsatellite stable) tumor was an unfavorable subtype, while BRAF-wild-type MSI-high tumor was a favorable subtype, and BRAF-mutated MSI-high tumor and BRAF-wild-type MSS tumor were intermediate subtypes. Among patients with BRAF-mutated tumors, a non-significant trend toward improved OS was observed for IFL vs. FU/LV arm (multivariate HR=0.52; 95% CI, 0.25-1.10). Among patients with BRAF-wild-type cancer, IFL conferred no suggestion of benefit beyond FU/LV alone (multivariate HR=1.02; 95% CI, 0.72-1.46). Conclusions BRAF mutation is associated with inferior survival in stage III colon cancer. Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy. PMID:22147942

  9. Improved lymph node harvest from resected colon cancer specimens did not cause upstaging from TNM stage II to III.

    PubMed

    Storli, Kristian; Søndenaa, Karl; Furnes, Bjørg; Leh, Sabine; Nesvik, Idunn; Bru, Tore; Gudlaugsson, Einar; Bukholm, Ida; Norheim-Andersen, Solveig; Eide, Geir

    2011-12-01

    The number of lymph nodes retrieved and examined from a resected colon cancer specimen may be crucial for correct staging. We examined if efforts to increase the lymph node harvest to more than 12 lymph nodes per specimen would upstage some patients from TNM stage II to III. Three hospitals compared results from 2000 with those of 2007 in 421 resected patients with stage II and III colon cancer. Hospital A endeavored to improve the surgical procedure while the pathologists enhanced the quality of lymph node sampling. Hospital B did not make any marked changes, while hospital C introduced the GEWF lymph node solvent (glacial acetic acid, ethanol, distilled water, and formaldehyde) in their pathology method. In 2000, 12 or more lymph nodes were harvested in 39.6, 45.0, and 21.1% of the specimens from the three hospitals, while the figures for 2007 were 85.7, 42.0, and 90.3%, respectively. The significant increase in lymph node harvest in two of the hospitals in 2007 compared to 2000 (p < 0.001) did not affect the share of patients with stage III in 2007 (38.7%) compared to 2000 (44.1%) (p = 0.260). The number of positive lymph nodes and the lymph node ratio (LNR) decreased from 2000 to 2007. A lymph node yield of 12 or more was not associated with an increased probability of positive lymph nodes in a multivariable logistic regression analysis. More radical surgery and dedicated pathologists and the use of the GEWF solvent significantly increased the lymph node yield but did not upstage patients from TNM stage II to III.

  10. Validity of Adjuvant! Online in older patients with stage III colon cancer based on 2967 patients from the ACCENT database.

    PubMed

    Papamichael, Demetris; Renfro, Lindsay A; Matthaiou, Christiana; Yothers, Greg; Saltz, Leonard; Guthrie, Katherine A; Van Cutsem, Eric; Schmoll, Hans-Joachim; Labianca, Roberto; André, Thierry; O'Connell, Michael; Alberts, Steven R; Haller, Daniel G; Kountourakis, Panteleimon; Sargent, Daniel J

    2016-11-01

    Adjuvant! Online is a tool used for clinical decision making in patients with early stage colon cancer. As details of the tool's construction are not published, the ability of Adjuvant! Online to accurately predict outcomes for older patients (age 70+) with node positive colon cancer receiving adjuvant chemotherapy is unclear. Individual data from older patients with stage III colon cancer who enrolled into multiple trials within the ACCENT database were entered into the Adjuvant! Online program to obtain predicted probabilities of 5-year overall survival (OS) and recurrence-free survival (RFS). Median predictions were compared with known rates. As co-morbidities were not known for ACCENT patients, but required for calculator entry, patients were assumed to have either "minor" or "average for age" co-morbidities. 2967 older patients from 10 randomized studies were included. When "minor" co-morbidities were assumed, the median predicted 5-year OS rate of 64% nearly matched the actual rate of 65%; when "average for age" co-morbidities were assumed, the median prediction dropped to 58%, outside the CI for the actual rate. On the other hand, assuming "minor" co-morbidities gave a median 5-year RFS prediction of 62%, outside the 95% CI for the actual rate of 58%, while assuming "average for age" co-morbidities yielded a better median prediction of 57%. Adjuvant! Online is reasonably accurate overall for predicting outcomes in older trial patients with stage III colon cancer, though accuracy may differ between 5-year RFS and 5-year OS predictions when a fixed degree of co-morbidities is assumed. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. p27Kip1 in Stage III Colon Cancer: Implications for Outcome Following Adjuvant Chemotherapy in CALGB 89803

    PubMed Central

    Bertagnolli, Monica M.; Warren, Robert S.; Niedzwiecki, Donna; Mueller, Elke; Compton, Carolyn C.; Redston, Mark; Hall, Margaret; Hahn, Hejin P.; Jewell, Scott D.; Mayer, Robert J.; Goldberg, Richard M.; Saltz, Leonard B.; Loda, Massimo

    2010-01-01

    Background In retrospective studies, loss of p27Kip1 (p27), a cyclin dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for Stage III colon cancer. Methods Cancer and Leukemia Group B (CALGB) protocol 89803 randomized 1264 stage III colon cancer patients to receive weekly bolus fluorouracil/leucovorin (5FU/LV) or weekly bolus irinotecan, fluorouracil, and leucovorin (IFL). The primary endpoint was overall survival (OS); disease-free survival (DFS) was a secondary endpoint. Expression of p27 and DNA mismatch repair (MMR) proteins were determined by immunohistochemistry (IHC) in primary tumor and normal tissue from paraffin blocks. Data were analyzed using logrank test. Results Of 601 tumors analyzed, 207 (34.4%) demonstrated p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27 negative tumors showed reduced OS (5-year 66%; 95%CI 0.59-0.72 vs. 75%; 95%CI 0.70-0.79, logrank p=0.021). This relationship was not influenced by treatment arm. Combination of p27 status with MMR status, however, identified a small subset of patients that may benefit from IFL (n=36; 5-year DFS 81%; 95%CI 0.64-0.98 vs. 47%; 95%CI 0.21-0.72, logrank p=0.042; 5-year OS 81%; 95%CI 0.64-0.98 vs. 60%; 95%CI 0.35-0.85; logrank p=0.128). Conclusions Loss of p27 is associated with reduced survival in stage III colon cancer, but by itself does not indicate a significant difference in outcome between patients treated IFL or 5FU-LV. PMID:19276255

  12. [Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer--Drug Selection, Tolerability, and Safety in Clinical Practice].

    PubMed

    Okada, Kazutake; Sadahiro, Sotaro; Saito, Gota; Tanaka, Akira; Suzuki, Toshiyuki

    2016-05-01

    In the National Comprehensive Cancer Network (NCCN) guidelines, oxaliplatin (L-OHP)-based chemotherapeutic regimens, including 5-fluorouracil, Leucovorin (LV), and L-OHP (FOLFOX); capecitabine and L-OHP (CapeOX); and 5-fluorouracil, folinic acid, and L-OHP (FLOX) are designated as category 1 recommendations for postoperative adjuvant chemotherapy in Stage III colon cancer, followed by capecitabine and 5-fluorouracil plus LV as category 2A recommendations. We studied the selection of drugs for adjuvant chemotherapy and assessed the tolerability and safety of CapeOX and tegafur-uracil (UFT) plus LV (UFT/LV) in patients with Stage III colon cancer. The study group included 104 consecutive patients with Stage III colon cancer who underwent curative surgery. One patient changed hospitals immediately after surgery. Among the remaining 103 patients, 82 (80%) received adjuvant chemotherapy and 21 (20%) did not. CapeOX was administered to 32 patients (31%), UFT/LV to 49 patients (48%), and capecitabine to 1 patient (1%). In 59 patients, the treatment choice was determined according to the patient's preference; 32 patients (54%) selected CapeOX, 26 (44%) selected UFT/LV, and 1 (2%) selected no chemotherapy. The treatment completion rate was 80% for CapeOX and 84% for UFT/LV. Among patients who completed chemotherapy, dose reduction and drug withdrawal were not required in 22% of patients who received CapeOX and 80% of those who received UFT/LV. Neither CapeOX nor UFT/LV was associated with any serious adverse events. The tolerability and safety of CapeOX and UFT/LV were acceptable. However, CapeOX dose had to be carefully adjusted according to each patient's condition.

  13. Relative Effectiveness and Safety of Chemotherapy in Elderly and Nonelderly Patients With Stage III Colon Cancer: A Systematic Review

    PubMed Central

    Mullins, C. Daniel

    2013-01-01

    Background. Chemotherapy effectiveness in clinical practice may differ from the efficacy demonstrated in clinical trials, particularly among populations underrepresented in clinical trials, such as elderly patients with cancer. This review aims to examine the relative effectiveness of chemotherapy for stage III colon cancer in elderly versus nonelderly patients. Methods. A systematic literature review was conducted using the Agency for Healthcare Research and Quality approach. Literature searches were performed in Medline and Evidence-Based Medicine Reviews databases. Chemotherapy regimens approved for stage III colon cancer were reviewed. Four effectiveness and 15 safety outcomes were extracted. Results. From 708 identified articles, 25 articles provided data on the relative effectiveness and safety of chemotherapy among elderly versus nonelderly patients. Four of 14 studies showed lower overall survival treatment effects, whereas one of five and one of four studies indicated more favorable treatment effects for time to progression and overall response rate. Grade 3 or 4 adverse events were higher among elderly patients for cardiac disorder (2/5 studies), leukopenia (1/5), neutropenia (4/16), thrombocytopenia (2/13), febrile neutropenia (1/4), infection (2/10), dehydration (2/6), diarrhea (6/20), and fatigue (6/13). Grade 3 or 4 adverse events were lower for neutropenia (2/16 studies), nausea/vomiting (1/16), and neuropathy (1/9). Conclusion. The majority of the evidence suggests that chemotherapy has similar relative effectiveness and safety for patients >65 years of age versus younger patients with stage III colon cancer. When differences are reported, treatment effects are more often worse among the elderly. This review suggests that without other reasons for withholding treatment, elderly patients should receive chemotherapy as often as nonelderly patients. PMID:23299774

  14. Body mass index and body surface area and their associations with outcomes in stage II and III colon cancer.

    PubMed

    Alipour, Sina; Kennecke, Hagen F; Woods, Ryan; Lim, Howard J; Speers, Caroline; Brown, Carl J; Gill, Sharlene; Renouf, Daniel J; Cheung, Winson Y

    2013-06-01

    Our study aims were to measure the associations between body mass index (BMI) and body surface area (BSA) with outcomes for stage II and III colon cancer and to evaluate if the effect of obesity is modified by disease stage and receipt of adjuvant therapy. Using a prospective cohort of stage II and III colon cancer patients who were referred between 2001 and 2005, we compared 3-year relapse-free survival (3-year RFS), 5-year cancer-specific survival (5-year CSS), and 5-year overall survival (5-year OS) rates among different BMI and BSA categories. Cox proportional-hazards models were constructed to explore the relationships between different body compositions and outcomes while adjusting for confounders. Postoperative height and weight were used to classify 913 patients as normal weight (n = 424, BMI <25 kg/m(2)), overweight (n = 319, BMI 25-30 kg/m(2)), and obese (n = 170, BMI >30 kg/m(2)). Using Mosteller formula, 684 subjects had normal BSA (≤ 2.0 m(2)) and 229 had high BSA (>2.0 m(2)). Obese subjects experienced similar 3-year RFS (61.9 vs. 66.5 vs. 63.6 %, p = 0.51), 5-year CSS (65.6 vs. 72.4 vs. 68.0 %, p = 0.22), and 5-year OS (60.8 vs. 64.0 vs. 62.2 %, p = 0.69) when compared to overweight subjects and those with normal BMIs, respectively. Likewise, individuals with high BSA had similar outcomes as those with normal BSA (66.2 vs. 63.6 %, p = 0.64 for 3-year RFS, 70.3 vs. 68.6 %, p = 0.62 for 5-year CSS, and 64.5 vs. 61.9 %, p = 0.48 for 5-year OS). In Cox models, advanced age, male gender, stage III disease, and poor performance status correlated with inferior RFS, CSS, and OS, but BMI and BSA did not. Obesity as measured by either BMI or BSA was not associated with differences in outcomes in stage II and III colon cancer.

  15. Early stage colon cancer.

    PubMed

    Freeman, Hugh James

    2013-12-14

    Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent "curative" resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., "tumor budding") should lead to improved staging and clinical care.

  16. Effect of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Cetuximab on Survival Among Patients With Resected Stage III Colon Cancer

    PubMed Central

    Alberts, Steven R.; Sargent, Daniel J.; Nair, Suresh; Mahoney, Michelle R.; Mooney, Margaret; Thibodeau, Stephen N.; Smyrk, Thomas C.; Sinicrope, Frank A.; Chan, Emily; Gill, Sharlene; Kahlenberg, Morton S.; Shields, Anthony F.; Quesenberry, James T.; Webb, Thomas A.; Farr, Gist H.; Pockaj, Barbara A.; Grothey, Axel; Goldberg, Richard M.

    2012-01-01

    Context Leucovorin, fluorouracil, and oxaliplatin (FOLFOX) is the standard adjuvant therapy for resected stage III colon cancer. Adding cetuximab to FOLFOX benefits patients with metastatic wild-type KRAS but not mutated KRAS colon cancer. Objective To assess the potential benefit of cetuximab added to the modified sixth version of the FOLFOX regimen (mFOLFOX6) in patients with resected stage III wild-type KRAS colon cancer. Design, Setting, and Participants A randomized trial of 2686 patients aged 18 years or older at multiple institutions across North America enrolled following resection and informed consent between February 10, 2004, and November 25, 2009. The primary randomized comparison was 12 biweekly cycles of mFOLFOX6 with and without cetuximab. KRAS mutation status was centrally determined. The trial was halted after a planned interim analysis of 48% of predicted events (246/515) occurring in 1863 (of 2070 planned) patients with tumors having wild-type KRAS. A total of 717 patients with mutated KRAS and 106 with indeterminate KRAS were accrued. The 2070 patients with wild-type KRAS provided 90% power to detect a hazard ratio (HR) of 1.33 (2-sided α =.05), with planned interim efficacy analyses after 25%, 50%, and 75% of expected relapses. Main Outcome Measures Disease-free survival in patients with wild-type KRAS mutations. Secondary end points included overall survival and toxicity. Results Median (range) follow-up was 28 (0–68) months. The trial demonstrated no benefit when adding cetuximab. Three-year disease-free survival for mFOLFOX6 alone was 74.6% vs 71.5% with the addition of cetuximab (HR, 1.21; 95% CI, 0.98–1.49; P=.08) in patients with wild-type KRAS, and 67.1% vs 65.0% (HR, 1.12; 95% CI, 0.86–1.46; P=.38) in patients with mutated KRAS, with no significant benefit in any subgroups assessed. Among all patients, grade 3 or higher adverse events (72.5% vs 52.3%; odds ratio [OR], 2.4; 95% CI, 2.1–2.8; P < .001) and failure to complete 12

  17. The relation of presenting symptoms with staging, grading, and postoperative 3-year mortality in patients with stage I-III non-metastatic colon cancer.

    PubMed

    Bedir, Osman; Kızıltaş, Şafak; Köstek, Osman; Özkanlı, Şeyma

    2016-05-01

    To evaluate the association of presenting symptoms with staging, grading, and postoperative 3-year mortality in patients with colon cancer. A total of 132 patients-with a mean (standard deviation; SD) age of 63.0 (10.0) years and of whom 56.0% were males-with non-metastatic stage I-III colon cancer were included. Symptoms prior to diagnosis were evaluated with respect to tumor localization, tumor node metastasis (TNM) stage, histological grade, and postoperative 3-year mortality. Constipation and abdominal pain were the two most common symptoms appearing first (29.5% and 16.7%, respectively) and remained most predominant (25.0% and 20.0%, respectively) up to diagnosis. The frequency of admission symptoms significantly differed with respect to tumor location, TNM stage and histological grade. The postoperative 3-year survival rate was 61.4%. Multivariate logistic regression revealed that melena and rectal bleeding increased the likelihood of 3-year mortality by 13.6-fold (p=0.001) and 4.08-fold (p=0.011), respectively. Our findings revealed differences in presenting symptom profiles with respect to the time of manifestation and predominance as well as to the TNM stage, histological grade, and tumor location. Given that melena and rectal bleeding increased the 3-year mortality risk by 13.6-fold and 4.08-fold, respectively, our findings indicate the association of admission symptoms with outcome among patients with colon cancer.

  18. Laparoscopic versus open colectomy for TNM stage III colon cancer: results of a prospective multicenter study in Italy.

    PubMed

    Guerrieri, Mario; Campagnacci, Roberto; De Sanctis, Angelo; Lezoche, Giovanni; Massucco, Paolo; Summa, Massimo; Gesuita, Rosaria; Capussotti, Lorenzo; Spinoglio, Giuseppe; Lezoche, Emanuele

    2012-11-01

    There is still debate about the practicality of performing laparoscopic colectomy instead of open colectomy for patients with curable cancer, although laparoscopic surgery is now being performed even for patients with advanced colon cancer. We compared the long-term results of laparoscopic versus open colectomy for TNM stage III carcinoma of the colon in a large series of patients followed up for at least 3 years. The subjects of this prospective non-randomized multicentric study were 290 consecutive patients, who underwent open surgery (OS group; n = 164) or laparoscopic surgery (LS group; n = 126) between 1994 and 2005, at one of the four surgical centers. The same surgical techniques were used for the laparoscopic and open approaches to right and left colectomy. The distribution of TNM substages (III A, III B, IIIC) as well as the grading of carcinomas (G1, G2, G3) were similar in each arm of the study. The median follow-up periods were 76.9 and 58.0 months after OS and LS, respectively. There were 10 (6.1 %) versus 9 (7.1 %) deaths unrelated to cancer, 15 (9.1 %) versus 5 (4 %) cases of local recurrence, 7 (4.2 %) versus 5 (4 %) cases of peritoneal carcinosis, and 37 (22.5 %) versus 14 (11.1 %) cases of metastases in the OS and LS groups, respectively. There was also one case of port-site recurrence after LS (0.8 %). The OS group had a significantly higher probability of local recurrence and metastases (p < 0.001) with a significant higher probability of cancer-related death (p = 0.001) than the LS group. These findings support that LS is safe and effective for advanced carcinoma of the colon. Although the LS group in this study had a significantly better long-term outcome than the OS group, further investigations are needed to draw a definitive conclusion.

  19. TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients.

    PubMed

    Kandioler, Daniela; Mittlböck, Martina; Kappel, Sonja; Puhalla, Harald; Herbst, Friedrich; Langner, Cord; Wolf, Brigitte; Tschmelitsch, Jörg; Schippinger, Walter; Steger, Günther; Hofbauer, Friedrich; Samonigg, Hellmut; Gnant, Michael; Teleky, Bela; Kührer, Irene

    2015-08-01

    We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344-3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.

  20. Adjuvant sequential methotrexate → 5-fluorouracil vs 5-fluorouracil plus leucovorin in radically resected stage III and high-risk stage II colon cancer

    PubMed Central

    Sobrero, A; Frassineti, G; Falcone, A; Dogliotti, L; Rosso, R; Costanzo, F D; Bruzzi, P

    2004-01-01

    The aim of the study was to determine whether modulation of 5-fluorouracil (FU) by methotrexate (MTX) improves survival compared to FU+6-s-leucovorin (LV) following potentially curative resection of stage II and III colon cancer. Within 8 weeks from surgery, 1945 patients with stage III (44%) or high-risk stage II (55%) colon cancer were randomly assigned to receive either 6 monthly cycles of FU 370 mg m−2 i.v. bolus preceded by LV 100 mg m−2 i.v. bolus on days 1–5, or 6 monthly cycles of sequential MTX 200 mg m−2 i.v. days 1 and 15 and FU 600 mg m−2 i.v. on days 2 and 16 followed by LV rescue (15 mg given p.o. q 6 h × 6 doses). Levamisole 50 mg p.o. t.i.d. on days 1–3, every 14 days for 6 months, was planned to be given in both arms. After a median follow-up of 4.2 years, 568 patients have relapsed and 403 have died. Survival was similar with MTX → FU and FU+LV (77 vs 77% at 5 years; P=0.90), as were 5-year disease-free survivals (67 vs 63%; P=0.44). Efficacy results were similar for both stage III and II patients. There were two toxic deaths, two in the MTX → FU arm (0.2%) and zero in the control arm. We conclude that biochemical modulation of FU with LV or with MTX produces similar results in the adjuvant setting of colon cancer. PMID:15611795

  1. A Lymph Node Ratio of 10% Is Predictive of Survival in Stage III Colon Cancer: A French Regional Study

    PubMed Central

    Sabbagh, Charles; Mauvais, François; Cosse, Cyril; Rebibo, Lionel; Joly, Jean-Paul; Dromer, Didier; Aubert, Christine; Carton, Sophie; Dron, Bernard; Dadamessi, Innocenti; Maes, Bernard; Perrier, Guillaume; Manaouil, David; Fontaine, Jean-François; Gozy, Michel; Panis, Xavier; Foncelle, Pierre Henri; de Fresnoy, Hugues; Leroux, Fabien; Vaneslander, Pierre; Ghighi, Caroline; Regimbeau, Jean-Marc

    2014-01-01

    Lymph node ratio (LNR) (positive lymph nodes/sampled lymph nodes) is predictive of survival in colon cancer. The aim of the present study was to validate the LNR as a prognostic factor and to determine the optimum LNR cutoff for distinguishing between “good prognosis” and “poor prognosis” colon cancer patients. From January 2003 to December 2007, patients with TNM stage III colon cancer operated on with at least of 3 years of follow-up and not lost to follow-up were included in this retrospective study. The two primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) as a function of the LNR groups and the cutoff. One hundred seventy-eight patients were included. There was no correlation between the LNR group and 3-year OS (P = 0.06) and a significant correlation between the LNR group and 3-year DFS (P = 0.03). The optimal LNR cutoff of 10% was significantly correlated with 3-year OS (P = 0.02) and DFS (P = 0.02). The LNR was not an accurate prognostic factor when fewer than 12 lymph nodes were sampled. Clarification and simplification of the LNR classification are prerequisites for use of this system in randomized control trials. An LNR of 10% appears to be the optimal cutoff. PMID:25058763

  2. A lymph node ratio of 10% is predictive of survival in stage III colon cancer: a French regional study.

    PubMed

    Sabbagh, Charles; Mauvais, François; Cosse, Cyril; Rebibo, Lionel; Joly, Jean-Paul; Dromer, Didier; Aubert, Christine; Carton, Sophie; Dron, Bernard; Dadamessi, Innocenti; Maes, Bernard; Perrier, Guillaume; Manaouil, David; Fontaine, Jean-François; Gozy, Michel; Panis, Xavier; Foncelle, Pierre Henri; de Fresnoy, Hugues; Leroux, Fabien; Vaneslander, Pierre; Ghighi, Caroline; Regimbeau, Jean-Marc

    2014-01-01

    Lymph node ratio (LNR) (positive lymph nodes/sampled lymph nodes) is predictive of survival in colon cancer. The aim of the present study was to validate the LNR as a prognostic factor and to determine the optimum LNR cutoff for distinguishing between "good prognosis" and "poor prognosis" colon cancer patients. From January 2003 to December 2007, patients with TNM stage III colon cancer operated on with at least of 3 years of follow-up and not lost to follow-up were included in this retrospective study. The two primary endpoints were 3-year overall survival (OS) and disease-free survival (DFS) as a function of the LNR groups and the cutoff. One hundred seventy-eight patients were included. There was no correlation between the LNR group and 3-year OS (P=0.06) and a significant correlation between the LNR group and 3-year DFS (P=0.03). The optimal LNR cutoff of 10% was significantly correlated with 3-year OS (P=0.02) and DFS (P=0.02). The LNR was not an accurate prognostic factor when fewer than 12 lymph nodes were sampled. Clarification and simplification of the LNR classification are prerequisites for use of this system in randomized control trials. An LNR of 10% appears to be the optimal cutoff.

  3. Geographic variation and sociodemographic disparity in the use of oxaliplatin-containing chemotherapy in patients with stage III colon cancer.

    PubMed

    Panchal, Janki M; Lairson, David R; Chan, Wenyaw; Du, Xianglin L

    2013-06-01

    This study examined the geographic variation and sociodemographic disparities in the use of oxaliplatin chemotherapy, which has not been widely studied in the past. Our results suggest that chemotherapy use varies across geographic regions. Patterns of use that relate specifically to oxaliplatin-containing chemotherapy can inform providers and researchers how newer regimens are being used as standard chemotherapy in a real-world setting. According to the National Cancer Comprehensive Network (NCCN), oxaliplatin with 5-fluorouracil and leucovorin (5-FU/LV) is the recommended adjuvant chemotherapy for patients with resected stage III colon cancer. Age and race are considered strong predictors of chemotherapy receipt, whereas geographic disparity has received minimal attention. The purpose of this study was to examine geographic variation and sociodemographic disparity in the use of chemotherapy in patients with stage III colon cancer, focusing specifically on oxaliplatin. A retrospective cohort of 4106 Medicare patients was identified from the Surveillance, Epidemiology and End Results (SEER)/Medicare linked database. Descriptive statistics show how oxaliplatin-containing chemotherapy was used in various geographic regions among different age and racial groups. Multiple logistic regression analysis was performed to examine the relationship between receipt of oxaliplatin-containing chemotherapy and geographic region while adjusting for other sociodemographic and tumor characteristics. Only 49% of the patients with stage III disease received adjuvant chemotherapy within 3 to 6 months of colon cancer-specific surgery. Patients aged 66 to 70 years were 78% more likely to receive chemotherapy than were those aged 80 years and older (P<.001). Patients in less urban regions were approximately 42% less likely to receive oxaliplatin chemotherapy than those residing in a big metro region (odds ratio [OR], 0.58; P=.008). Chemotherapy use varies across geographic regions

  4. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3.

    PubMed

    Van Cutsem, Eric; Labianca, Roberto; Bodoky, György; Barone, Carlo; Aranda, Enrique; Nordlinger, Bernard; Topham, Claire; Tabernero, Josep; André, Thierry; Sobrero, Alberto F; Mini, Enrico; Greil, Richard; Di Costanzo, Francesco; Collette, Laurence; Cisar, Laura; Zhang, Xiaoxi; Khayat, David; Bokemeyer, Carsten; Roth, Arnaud D; Cunningham, David

    2009-07-01

    PURPOSE The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer. PATIENTS AND METHODS After curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m(2) as a 2-hour infusion, followed by FU; as a 400 mg/m(2) bolus and then a 600 mg/m(2) continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m(2) as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan. Results The principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia. CONCLUSION Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.

  5. MGL ligand expression is correlated to BRAF mutation and associated with poor survival of stage III colon cancer patients

    PubMed Central

    Lenos, Kristiaan; Goos, Jeroen A.C.M.; Vuist, Ilona M.; den Uil, Sjoerd H.; Delis-van Diemen, Pien M.; Belt, Eric J.Th.; Stockmann, Hein B.A.C.; Bril, Herman; de Wit, Meike; Carvalho, Beatriz; Giblett, Susan; Pritchard, Catrin A.; Meijer, Gerrit A.; van Kooyk, Yvette; Fijneman, Remond J.A.; van Vliet, Sandra J.

    2015-01-01

    Colorectal cancer (CRC) is the third most prevalent cancer type worldwide with a mortality rate of approximately 50%. Elevated cell-surface expression of truncated carbohydrate structures such as Tn antigen (GalNAcα-Ser/Thr) is frequently observed during tumor progression. We have previously demonstrated that the C-type lectin macrophage galactose-type lectin (MGL), expressed by human antigen presenting cells, can distinguish healthy tissue from CRC through its specific recognition of Tn antigen. Both MGL binding and oncogenic BRAF mutations have been implicated in establishing an immunosuppressive microenvironment. Here we aimed to evaluate whether MGL ligand expression has prognostic value and whether this was correlated to BRAFV600E mutation status. Using a cohort of 386 colon cancer patients we demonstrate that high MGL binding to stage III tumors is associated with poor disease-free survival, independent of microsatellite instability or adjuvant chemotherapy. In vitro studies using CRC cell lines showed an association between MGL ligand expression and the presence of BRAFV600E. Administration of specific BRAFV600E inhibitors resulted in decreased expression of MGL-binding glycans. Moreover, a positive correlation between induction of BRAFV600E and MGL binding to epithelial cells of the gastrointestinal tract was found in vivo using an inducible BRAFV600E mouse model. We conclude that the BRAFV600E mutation induces MGL ligand expression, thereby providing a direct link between oncogenic transformation and aberrant expression of immunosuppressive glycans. The strong prognostic value of MGL ligands in stage III colon cancer patients, i.e. when tumor cells disseminate to lymph nodes, further supports the putative immune evasive role of MGL ligands in metastatic disease. PMID:26172302

  6. MGL ligand expression is correlated to BRAF mutation and associated with poor survival of stage III colon cancer patients.

    PubMed

    Lenos, Kristiaan; Goos, Jeroen A C M; Vuist, Ilona M; den Uil, Sjoerd H; Delis-van Diemen, Pien M; Belt, Eric J Th; Stockmann, Hein B A C; Bril, Herman; de Wit, Meike; Carvalho, Beatriz; Giblett, Susan; Pritchard, Catrin A; Meijer, Gerrit A; van Kooyk, Yvette; Fijneman, Remond J A; van Vliet, Sandra J

    2015-09-22

    Colorectal cancer (CRC) is the third most prevalent cancer type worldwide with a mortality rate of approximately 50%. Elevated cell-surface expression of truncated carbohydrate structures such as Tn antigen (GalNAcα-Ser/Thr) is frequently observed during tumor progression. We have previously demonstrated that the C-type lectin macrophage galactose-type lectin (MGL), expressed by human antigen presenting cells, can distinguish healthy tissue from CRC through its specific recognition of Tn antigen. Both MGL binding and oncogenic BRAF mutations have been implicated in establishing an immunosuppressive microenvironment. Here we aimed to evaluate whether MGL ligand expression has prognostic value and whether this was correlated to BRAF(V600E) mutation status. Using a cohort of 386 colon cancer patients we demonstrate that high MGL binding to stage III tumors is associated with poor disease-free survival, independent of microsatellite instability or adjuvant chemotherapy. In vitro studies using CRC cell lines showed an association between MGL ligand expression and the presence of BRAF(V600E). Administration of specific BRAF(V600E) inhibitors resulted in decreased expression of MGL-binding glycans. Moreover, a positive correlation between induction of BRAF(V600E) and MGL binding to epithelial cells of the gastrointestinal tract was found in vivo using an inducible BRAF(V600E) mouse model. We conclude that the BRAF(V600E) mutation induces MGL ligand expression, thereby providing a direct link between oncogenic transformation and aberrant expression of immunosuppressive glycans. The strong prognostic value of MGL ligands in stage III colon cancer patients, i.e. when tumor cells disseminate to lymph nodes, further supports the putative immune evasive role of MGL ligands in metastatic disease.

  7. Image analysis-derived metrics of histomorphological complexity predicts prognosis and treatment response in stage II-III colon cancer

    PubMed Central

    Mezheyeuski, Artur; Hrynchyk, Ina; Karlberg, Mia; Portyanko, Anna; Egevad, Lars; Ragnhammar, Peter; Edler, David; Glimelius, Bengt; Östman, Arne

    2016-01-01

    The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study. Metrics obtained with the method acted as independent markers for natural course of the disease, and for benefit of adjuvant treatment. Comparative analyses demonstrated that MF metrics out-performed standard histomorphological features such as tumor grade, budding and configuration of invasive front. Notably, the MF analyses-derived “αmax” –metric constitutes the first response-predictive biomarker in stage II-III colon cancer showing significant interactions with treatment in analyses using a randomized trial-derived study population. Based on these results the method appears as an attractive and easy-to-implement tool for biomarker identification. PMID:27805003

  8. Prognostic Value of BRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer.

    PubMed

    Taieb, Julien; Le Malicot, Karine; Shi, Qian; Penault Lorca, Frédérique; Bouché, Olivier; Tabernero, Josep; Mini, Enrico; Goldberg, Richard M; Folprecht, Gunnar; Luc Van Laethem, Jean; Sargent, Daniel J; Alberts, Steven R; Emile, Jean Francois; Laurent Puig, Pierre; Sinicrope, Frank A

    2017-05-01

    The prognostic value of BRAF and KRAS mutations within microsatellite-unstable (MSI) and microsatellite-stable (MSS) subgroups of resected colon carcinoma patients remains controversial. We examined this question in prospectively collected biospecimens from stage III colon cancer with separate analysis of MSI and MSS tumors from patients receiving adjuvant FOLFOX +/- cetuximab in two adjuvant therapy trials. Three groups were defined: BRAF Mutant, KRAS Mutant, and double wild-type. The analytic strategy involved estimation of study-specific effects, assessment of homogeneity of results, and then analysis of pooled data as no differences in patient outcome were found between treatment arms in both trials. Associations of mutations with patient outcome were analyzed, and multivariable models were adjusted for treatment and relevant factors. Four thousand four hundred eleven tumors were evaluable for BRAF and KRAS mutations and mismatch repair status; 3934 were MSS and 477 were MSI. In MSS patients, all BRAF V600E mutations (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.23 to 1.92, P < .001), KRAS codon 12 alterations, and p.G13D mutations (HR = 1.60, 95% CI = 1.40 to 1.83, P < .001) were associated with shorter time to recurrence (TTR) and shorter survival after relapse (SAR; HR = 3.02 , 95% CI = 2.32 to 3.93, P < .001, and HR = 1.20, 95% CI = 1.01 to 1.44, P = .04, respectively). Overall survival (OS) in MSS patients was poorer for BRAF-mutant patients (HR = 2.01, 95% CI = 1.56 to 2.57, P < .001) and KRAS-mutant patients (HR = 1.62, 95% CI = 1.38 to 1.91, P < .001) vs wild-type. No prognostic role of KRAS or BRAF mutations was seen in MSI patients. Furthermore, no interaction was found between treatment arm (with or without cetuximab) and KRAS and BRAF mutations for TTR or OS in MSS patients. In a pooled analysis of resected stage III colon cancer patients receiving adjuvant FOLFOX, BRAF or KRAS mutations are

  9. Determining the Optimal Timing for Initiation of Adjuvant Chemotherapy After Resection for Stage II and III Colon Cancer.

    PubMed

    Sun, Zhifei; Adam, Mohamed A; Kim, Jina; Nussbaum, Daniel P; Benrashid, Ehsan; Mantyh, Christopher R; Migaly, John

    2016-02-01

    Several reports suggest that the efficacy of adjuvant chemotherapy on survival diminishes over time for colon cancer; however, precise timing of its loss of benefit has not been established. This study aimed to determine the relationship between time to adjuvant chemotherapy and survival and to identify a threshold for increased risk of mortality. This was a retrospective study. Multivariable Cox proportional hazard modeling with restricted cubic splines was used to evaluate the adjusted association between time to adjuvant chemotherapy and overall survival and to establish an optimal threshold for the initiation of therapy. Data were collected from the National Cancer Data Base. Adults who received adjuvant chemotherapy following resection of stage II to III colon cancers were selected. The primary outcome measured was overall survival. A total of 7794 patients were included. After adjusting for clinical, tumor, and treatment characteristics, our model determined a critical threshold of chemotherapy initiation at 44 days from surgery, after which there was an increase in the overall mortality. At a median follow-up of 61 months, the risk of mortality was increased in those who received adjuvant chemotherapy after 44 days from surgery (adjusted HR, 1.14; 95% CI, 1.05-1.24; p = 0.002), but not in those who received chemotherapy before 44 days from surgery (p = 0.11). Each additional week of delay was associated with a 7% decrease in survival (HR, 1.07; 95% CI, 1.04-1.10; p < 0.001). This study was limited by selection bias and the inability to compare specific chemotherapy regimens. This study objectively determines the optimal timing of adjuvant chemotherapy for patients with resected colon cancer. Delay beyond 6 weeks is associated with compromised survival. These findings emphasize the importance of the timely initiation of therapy, and suggest that efforts to enhance recovery following surgery have the potential to improve survival by decreasing delay to

  10. Association of Helicobacter pylori infection with chemotherapy-induced thrombocytopenia in patients with stage III colon cancer: a pilot study.

    PubMed

    Tanriverdi, Ozgur

    2014-01-01

    In this study, the effects of the pre-treatment presence of Helicobacter pylori (H. pylori) infection on chemotherapy-induced thrombocytopenia (CIT) were investigated in patients with stage III colon cancer (CC). A cohort of 74 patients with early stage CC was analysed through a review of clinical records and personal interviews. Helicobacter pylori infections were diagnosed in these patients prior to chemotherapy. The subjects were divided into two groups according to H. pylori infection status: Group 1, H. pylori-positive and Group 2, H. pylori-negative. In all patients, bone marrow toxicity and other study variables were compared. Helicobacter pylori infections were detected in 31 of the 74 CC patients. Helicobacter pylori-infected patients (Group 1) showed significantly higher incidences of CIT than did non-infected patients (Group 2; p = 0.029). Helicobacter pylori infection status correlated significantly with tumour location (r = 0.547; p = 0.043) and the most common location of CC in H. pylori-infected patients was the ascending colon (n = 13, 42%) in comparison to non-infected patients (n = 6, 14%; p= 0.042). The relationship between CIT and H. pylori infection status in CC was determined to be independent from the other study variables (p = 0.037; OR = 3.32, CI 95% = 1.16-9.70). In this study, the small number of patients resulted in an inadequate demonstration of the relationship between H. pylori infection and CIT. Therefore, clinical and molecular studies that include more patients are warranted.

  11. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

    PubMed

    Dienstmann, R; Mason, M J; Sinicrope, F A; Phipps, A I; Tejpar, S; Nesbakken, A; Danielsen, S A; Sveen, A; Buchanan, D D; Clendenning, M; Rosty, C; Bot, B; Alberts, S R; Milburn Jessup, J; Lothe, R A; Delorenzi, M; Newcomb, P A; Sargent, D; Guinney, J

    2017-05-01

    TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to 0.63-0.71 in models with added molecular markers, 0.65-0.73 with clinicopathological features and 0.66-0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include

  12. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.

    PubMed

    Emile, Jean-François; Julié, Catherine; Le Malicot, Karine; Lepage, Come; Tabernero, Josep; Mini, Enrico; Folprecht, Gunnar; Van Laethem, Jean-Luc; Dimet, Stéphanie; Boulagnon-Rombi, Camille; Allard, Marc-Antoine; Penault-Llorca, Frédérique; Bennouna, Jaafar; Laurent-Puig, Pierre; Taieb, Julien

    2017-09-01

    The prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use. According to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data. Among the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients. Although this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Race and Insurance Differences in the Receipt of Adjuvant Chemotherapy Among Patients With Stage III Colon Cancer

    PubMed Central

    Murphy, Caitlin C.; Harlan, Linda C.; Warren, Joan L.; Geiger, Ann M.

    2015-01-01

    Purpose Although the incidence and mortality of colon cancer in the United States has declined over the past two decades, blacks have worse outcomes than whites. Variations in treatment may contribute to mortality differentials. Methods Patients diagnosed with stage III colon cancer were randomly sampled from the SEER program from the years 1990, 1991, 1995, 2000, 2005, and 2010. Patients were categorized as non-Hispanic white (n = 835) or black (n = 384). Treatment data were obtained from a review of the medical records, and these data were verified through contact with the original treating physicians. Log-binomial regression models were used to estimate the association between race and receipt of adjuvant chemotherapy. Effect modification by insurance was assessed with use of single referent models. Results Receipt of adjuvant chemotherapy among both white and black patients increased from the period encompassing the years 1990 and 1991 (white, 58%; black, 45%) to the year 2005 (white, 72%; black, 71%) and then decreased in the year 2010 (white, 66%; black, 57%). There were marked racial disparities in the time period of 1990 to 1991 and again in 2010, with black patients less likely to receive adjuvant chemotherapy as compared with white patients (risk ratio [RR], .82; 95% CI, .72 to .93). For black patients, receipt of adjuvant chemotherapy did not differ across insurance categories (RR for private insurance, .80; 95% CI, .69 to .93; RR for Medicare, .84; 95% CI, .69 to 1.02; and RR for Medicaid, .84; 95% CI, .69 to 1.02), although a larger proportion had Medicaid in all years of the study as compared with white patients. Conclusion The chemotherapy differential narrowed after the time period of 1990 to 1991, but our findings suggest that the disparity reemerged in 2010. Recent decreases in chemotherapy use may be due, in part, to the economic downturn and an increase in Medicaid coverage. PMID:26150445

  14. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study

    PubMed Central

    Mason, M. J.; Sinicrope, F. A.; Phipps, A. I.; Tejpar, S.; Nesbakken, A.; Danielsen, S. A.; Sveen, A.; Buchanan, D. D.; Clendenning, M.; Rosty, C.; Bot, B.; Alberts, S. R.; Milburn Jessup, J.; Lothe, R. A.; Delorenzi, M.; Newcomb, P. A.; Sargent, D.; Guinney, J.

    2017-01-01

    Background TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)—N0147 (NCT00079274) and PETACC3 (NCT00026273)—was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). Results TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61–0.68 in the TNM alone model to 0.63–0.71 in models with added molecular markers, 0.65–0.73 with clinicopathological features and 0.66–0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Conclusions Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases

  15. PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy

    PubMed Central

    Yan, Dongwang; Cui, Feifei; Wang, Xiaoliang; Yu, Fudong; Xue, Yingming; Feng, Xiaodong; Wang, Jingtao; Wang, Xiao; Jiang, Tao; Zhang, Meng; Zhao, Senlin; Yu, Yang; Tang, Huamei; Peng, Zhihai

    2015-01-01

    p21-Activated kinase 6 (PAK6) has been implicated in radiotherapy and docetaxel resistance. We have further evaluated PAK6 as a predictor of 5-fluorouracil (5-FU) treatment response in colon cancer. Here we report that in colon cancer PAK6 promotes tumor progression and chemoresistance both in vitro and in vivo. In the clinical analysis, PAK6 was overexpressed in 104 of 147 (70.75%) stage II and III patients who received 5-FU based chemotherapy after surgery. Multivariate Cox regression analysis indicated that PAK6 was an independent prognostic factor for overall survival (P < 0.001) and disease-free survival (P < 0.001). Colon cancer cell lines showed increased PAK6 expression upon 5-FU treatment. In PAK6-knockdown cells treated with 5-FU, cell viability and phosphorylation of BAD decreased, and the number of apoptotic cells, levels of cleaved caspase 3 and PARP increased compared to control cells. The opposite was observed in PAK6 overexpressing cells. Short hairpin RNA knockdown of PAK6 blocked cells in G2-M phase. Furthermore, Animal experiments results in vivo are consistent with outcomes in vitro. This study demonstrates that PAK6 is an independent prognostic factor for adjuvant 5-FU-based chemotherapy in patients with stage II and stage III colon cancer. PMID:25426562

  16. Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.

    PubMed

    Viehl, Carsten T; Weixler, Benjamin; Guller, Ulrich; Dell-Kuster, Salome; Rosenthal, Rachel; Ramser, Michaela; Banz, Vanessa; Langer, Igor; Terracciano, Luigi; Sauter, Guido; Oertli, Daniel; Zuber, Markus

    2017-05-01

    The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5'fluoruracil-based adjuvant chemotherapy.

    PubMed

    Giráldez, María Dolores; Lozano, Juan José; Cuatrecasas, Míriam; Alonso-Espinaco, Virginia; Maurel, Joan; Mármol, Maribel; Hörndler, Carlos; Ortego, Javier; Alonso, Vicente; Escudero, Pilar; Ramírez, Gina; Petry, Christoph; Lasalvia, Luis; Bohmann, Kerstin; Wirtz, Ralph; Mira, Aurea; Castells, Antoni

    2013-03-01

    Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5'fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II-III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71-4.39; p = 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12-6.42; p = 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.

  18. Study protocol of the SACURA trial: a randomized phase III trial of efficacy and safety of UFT as adjuvant chemotherapy for stage II colon cancer

    PubMed Central

    2012-01-01

    Background 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. Methods/design 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. Discussion 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

  19. Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer

    PubMed Central

    Liu, Chang; Eng, Cathy; Shen, Jianjun; Lu, Yue; Takata, Yoko; Mehdizadeh, Amir; Chang, George J.; Rodriguez-Bigas, Miguel A.; Li, Yanan; Chang, Ping; Mao, Yixiang; Hassan, Manal M.; Wang, Fangyu; Li, Donghui

    2016-01-01

    Purpose The study was aimed to evaluate the prognostic or predictive value of serum exosomal microRNAs (miRNAs) for tumor recurrence and response to adjuvant therapy in stage II and stage III colon cancer. Results 145 differentially expressed mature miRNAs were identified (P<0.05) and 10 top hits were carried forward in validation test. MiR-4772-3p was significantly under-expressed in 27 patients with recurrence compared to in 57 patients without recurrence (P=0.002). The reduced expression was significantly related to increased risk of tumor recurrence and risk of death. As a predictor for tumor recurrence, ROC analysis revealed the AUC (95% CI) was 0.72 (0.59-0.85, P=0.001) for lower level of miR-4772-3p compared to 0.63 (0.51-0.75, P=0.062) for tumor site and 0.65 (0.51-0.78,P=0.034) for lymph node status. Among 66/84 patients who received FOLFOX adjuvant therapy, 9/10 (90%) patients with a lower level and 10/56 (18%) patients with a higher level of miR-4772-3p had tumor recurrence (P<0.001). Materials and Methods Blood samples were prospectively collected from84 patients with stage II/III colon cancer after tumor resection and before adjuvant therapy. Serum exosomal miRNA profiles were determined by RNA sequencing. Differentially expressed mature miRNAs were identified between patients with or without tumor recurrence. The top hits were validated in individual RNA samples using quantitative real-time reverse transcription PCR. Conclusions Reduced expression of serum exosomal miR-4772-3p is a prognostic biomarker for tumor recurrence in stage II and stage III colon cancer patients. The predictive value of this marker for response to FOLFOX adjuvant therapy needs further investigation. PMID:27788488

  20. Stages of Colon Cancer

    MedlinePlus

    ... for information about colorectal cancer in children. Health history affects the risk of developing colon cancer. Anything ... colorectal cancer include the following: Having a family history of colon or rectal cancer in a first- ...

  1. Pharmacogenetic predictors of outcome in patients with stage II and III colon cancer treated with oxaliplatin and fluoropyrimidine-based adjuvant chemotherapy.

    PubMed

    Custodio, Ana; Moreno-Rubio, Juan; Aparicio, Jorge; Gallego-Plazas, Javier; Yaya, Ricardo; Maurel, Joan; Rodríguez-Salas, Nuria; Burgos, Emilio; Ramos, David; Calatrava, Ana; Andrada, Encarna; Díaz-López, Esther; Sánchez, Antonio; Madero, Rosario; Cejas, Paloma; Feliu, Jaime

    2014-09-01

    Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G>A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training [RR = 4.103; 95% confidence interval (CI), 1.803-9.334; P = 0.001] and the validation cohorts (RR = 3.567; 95% CI, 1.253-10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988-11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144-13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes.

  2. Effect of CXCR4 and CD133 co-expression on the prognosis of patients with stage II~III colon cancer.

    PubMed

    Li, Xiao-Feng; Guo, Xiao-Guang; Yang, Yong-Yan; Liu, Ai-Yong

    2015-01-01

    To explore the relationship between CXCR4, CD133 co-expression and clinicopathological features as well as prognosis of patients with phase II~III colon cancer. Forty-nine paraffin-embedded samples of tumor tissue and epithelial tissue adjacent to cancer were collected from patients with colon cancer undergoing radical surgery in Baotou Cancer Hospital from January, 2010 to June, 2011. CXCR4 and CD133 expression was detected using immunohistochemistry and its relationship with clinicopathological features and the 3-year survival rate was analyzed. In the tumor tissue and colonic epithelial tissue adjacent to cancer, the positive expression rates of CXCR4 were respectively 61.2% (30/49) and 8.16% (4/49), while those of CD133 being 36.7% (18/49) and 6.12% (3/49). CXCR4 and CD133 expression in tumor tissue was not related to patient age, gender, primary focal sites, tumor size, TNM staging, histological type, tumor infiltration depth and presence or absence of lymphatic metastasis, but CXCR4 and CD133 co-expression was associated with TNM staging and lymphatic metastasis. The 3-year survival rate of patients with CXCR4 and CD133 co-expression was 27.3% (3/11), and that of the remainderwas 76.3% (29/38), the difference being significant (χ2=7.0206, p=0.0081). CXCR4 and CD133 co-expression may be a risk factor for poor prognosis of patients with stage II~III colon cancer.

  3. Proposal of new classification for stage III colon cancer based on the lymph node ratio: analysis of 4,172 patients from multi-institutional database in Japan.

    PubMed

    Sugimoto, Kiichi; Sakamoto, Kazuhiro; Tomiki, Yuichi; Goto, Michitoshi; Kotake, Kenjiro; Sugihara, Kenichi

    2015-02-01

    We retrospectively examined the optimal lymph node ratio (LNR) cutoff value and attempted to construct a new classification using the LNR in stage III colon cancer. The clinical and pathological data of 4,172 patients with histologically proven lymph node metastasis who underwent curative surgery for primary colon cancer at multiple institutions between 1995 and 2004 were derived from the multi-institutional database of the Japanese Society for Cancer of the Colon and Rectum (JSCCR). We determined independent prognostic factors and constructed a new classification using these factors. Finally, we compared the discriminatory ability between the new classification and the TNM seventh edition (TNM 7th) classification. The optimal LNR cutoff value was 0.18. Multivariate analysis revealed that year of surgery, age, gender, histological type, TNM 7th T category, lymphatic invasion, venous invasion, TNM 7th N category, and LNR were found to be significant independent prognostic factors. We attempted to construct a new classification based on the combination of TNM 7th T category and LNR. As a result, the cancer-specific survivals were well stratified (P < .0001). According to the Akaike's information criteria value, the new classification was judged to be superior to the TNM 7th classification with respect to both a better fit and lower complexity. The optimal LNR cutoff value that was found using the Japanese multi-institutional database and the new classification using LNR are considered to be extremely significant. Therefore, these findings strongly support the application of LNR in the stage classification in stage III colon cancer.

  4. Validity of Adjuvant! Online in Older Patients with Stage III Colon Cancer Based on 2,967 Patients from the ACCENT Database

    PubMed Central

    Papamichael, Demetris; Renfro, Lindsay A.; Matthaiou, Christiana; Yothers, Greg; Saltz, Leonard; Guthrie, Katherine; Van Cutsem, Eric; Schmoll, Hans-Joachim; Labianca, Roberto; André, Thierry; O’Connell, Michael; Alberts, Steven R.; Haller, Daniel G.; Kountourakis, Panteleimon; Sargent, Daniel J.

    2016-01-01

    Background Adjuvant! Online is a tool used for clinical decision making in patients with early stage colon cancer. As details of the tool’s construction are not published, the ability of Adjuvant! Online to accurately predict outcomes for older patients (age 70+) with node positive colon cancer receiving adjuvant chemotherapy is unclear. Methods Individual data from older patients with stage III colon cancer who enrolled into multiple trials within the ACCENT database were entered into the Adjuvant! Online program to obtain predicted probabilities of 5-year overall survival (OS) and recurrence-free survival (RFS). Median predictions were compared with known rates. As co-morbidities were not known for ACCENT patients, but required for calculator entry, patients were assumed to have either “minor” or “average for age” co-morbidities. Results 2,967 older patients from 10 randomized studies were included. When “minor” co-morbidities were assumed, the median predicted 5-year OS rate of 64% nearly matched the actual rate of 65%; when “average for age” co-morbidities were assumed, the median prediction dropped to 58%, outside the CI for the actual rate. On the other hand, assuming “minor” co-morbidities gave a median 5-year RFS prediction of 62%, outside the 95% CI for the actual rate of 58%, while assuming “average for age” co-morbidities yielded a better median prediction of 57%. Conclusion Adjuvant! Online is reasonably accurate overall for predicting outcomes in older trial patients with stage III colon cancer, though accuracy may differ between 5-year RFS and 5-year OS predictions when a fixed degree of co-morbidities is assumed. PMID:27468630

  5. Combined assays for serum carcinoembryonic antigen and microRNA-17-3p offer improved diagnostic potential for stage I/II colon cancer

    PubMed Central

    ZHU, JINHAI; DONG, HUIMING; ZHANG, QIONG; ZHANG, SHANGWU

    2015-01-01

    Colorectal cancer is among the leading causes of cancer-related mortality, one of the main reasons for which is the lack of an effective screening method for early-stage disease. The levels of carcinoembryonic antigen (CEA) and microRNA (miR)-17-3p in the serum of 70 patients with stage I/II colon cancer and 70 healthy volunteers were determined, and the diagnostic value of CEA plus miR-17-3p detection for colon cancer was assessed. The levels of CEA were measured by a radioimmunoassay method, and those of miR-17-3p using the reverse transcription-quantitative polymerase chain reaction method. miR-16 was used as the endogenous control, as it displayed high stability, high abundance and low variability in the analyzed serum samples. The receiver operating characteristic (ROC) curve analysis indicated the potential diagnostic value of the two markers and the area under the ROC curve (AUC) for CEA and miR-17-3p was 0.719 (95% CI: 0.658–0.843) and 0.807 (95% CI: 0.748–0.906), respectively. At a threshold of 9.6 ng/ml for CEA, the optimal sensitivity and specificity were 74.6 and 84.3%, respectively, in discriminating colon cancer patients from healthy controls. At a threshold of 2.98 for miR-17-3p, the sensitivity and the specificity were 83.6 and 72.9%, respectively. A combined ROC analysis using CEA and miR-17-3p revealed an AUC of 0.929 (95% CI: 0.834–0.978) with a sensitivity of 96.4% and a specificity of 95.7% in discriminating colon cancer patients from healthy controls. In conclusion, both CEA and miR-17-3p were highly expressed in the serum of our series of colon cancer patients. CEA plus miR-17-3p detection significantly increased the sensitivity and specificity in discriminating stage I/II colon cancer patients from healthy controls. Therefore, combined detection of serum CEA and miR-17-3p levels may have the potential to become a new laboratory method for the early clinical diagnosis of colon cancer. PMID:26807240

  6. Why adjuvant chemotherapy for stage III colon cancer was not given: Reasons for non-recommendation by clinicians or patient refusal.

    PubMed

    Gilbar, Peter; Lee, Andrew; Pokharel, Khageshwor

    2017-03-01

    Aim The aim of our study was to evaluate stage III colon cancer patients discussed at a multidisciplinary team meeting to identify reasons for clinicians not recommending adjuvant chemotherapy and reasons for patients declining recommended chemotherapy. Methods A retrospective, single institution Australian study was conducted on all surgically managed stage III colon cancer patients diagnosed at the regional cancer centre at Toowoomba Hospital between July 2010 and December 2014. Reasons why adjuvant chemotherapy was not recommended by the multidisciplinary team or following referral to a medical oncologist and patients' reasons for refusing chemotherapy despite medical oncology recommendation were determined. Results One hundred and nine patients were suitable for evaluation. Overall, 72 (66.1%) received adjuvant chemotherapy. Chemotherapy was not recommended in 25 (23.4%) of patients, with the majority (68%) having more than one cited reason. Multiple comorbidities and advanced age were the most common reasons for non-recommendation ( p < 0.01). Age alone was not a reason for not recommending chemotherapy. Twelve (11%) patients declined offered chemotherapy. The reasons for refusal were not detailed in the majority of patient charts (63.6%). Travel distance was not a factor in accepting or refusing chemotherapy. Conclusion Discussion at a multidisciplinary team meeting facilitates the identification of patients unsuitable for adjuvant treatment. The reasons for declining offered chemotherapy need to be assessed fully to ensure that patients' treatment preferences are balanced against the proven benefits of chemotherapy. Attendance at a regional cancer centre provides the opportunity for high standard care in the management of stage III colon cancer.

  7. Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study.

    PubMed

    Aldecoa, Iban; Atares, Begoña; Tarragona, Jordi; Bernet, Laia; Sardon, Jose Domingo; Pereda, Teresa; Villar, Carlos; Mendez, M Carmen; Gonzalez-Obeso, Elvira; Elorriaga, Kepa; Alonso, Guadalupe Lopez; Zamora, Javier; Planell, Nuria; Palacios, Jose; Castells, Antoni; Matias-Guiu, Xavier; Cuatrecasas, Miriam

    2016-10-01

    Stage I-II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I-II colon cancer patients. A total of 1940 LN from 149 pathologically assessed pN0 colon cancer patients were analysed for the amount of tumour cytokeratin 19 (CK19) messenger RNA (mRNA) with the quantitative reverse transcription loop-mediated isothermal amplification molecular assay One-Step Nucleic Acid Amplification. Patient's total tumour load (TTL) resulted from the sum of all CK19 mRNA tumour copies/μL of each positive LN from the colectomy specimen. A median of 15 LN were procured per case (IQR 12;20). Molecular positivity correlated with high-grade (p < 0.01), mucinous/signet ring type (p = 0.017), male gender (p = 0.02), number of collected LN (p = 0.012) and total LN weight per case (p < 0.01). The TTL was related to pT stage (p = 0.01) and tumour size (p < 0.01) in low-grade tumours. Multivariate logistic regression showed independent correlation of molecular positivity with gender, tumour grade and number of fresh LN [AUC = 0.71 (95 % CI = 0.62-0.79)]. Our results show that lymph node CK19 mRNA detection correlates with classical high-risk factors in stage I-II colon cancer patients. Total tumour load is a quantitative and objective measure that may help to better stage early colon cancer patients.

  8. Genome-wide DNA Copy-number Analysis in ACTS-CC Trial of Adjuvant Chemotherapy for Stage III Colonic Cancer.

    PubMed

    Ishikawa, Toshiaki; Uetake, Hiroyuki; Murotani, Kenta; Kobunai, Takashi; Ishiguro, Megumi; Matsui, Shigeyuki; Sugihara, Kenichi

    2016-03-01

    The adjuvant chemotherapy trial of TS-1 for colon cancer phase III trial was designed to validate the non-inferiority of the oral fluoropyrimidine S-1 to uracil and tegafur/leucovorin as adjuvant chemotherapy for stage III colonic cancer. As a prospective biomarker study of this trial, DNA copy number was studied using formalin-fixed, paraffin-embedded specimens. FFPE blocks were obtained from 795 patients of the 1,535 patients enrolled in the study. The quality of extracted DNA was assessed using arbitrarily primed polymerase chain reaction and microfluidic analysis. Genomic copy-number alterations in cancer were analyzed by high-density single-nucleotide polymorphism arrays. Copy-number changes in Japanese patients with colonic cancer were compared with those in Western countries using data from a previously reported meta-analysis. We then compared genome-wide segment copy number and clinicopathological features of colorectal cancer. Genome-wide copy number was analyzed in 161 samples and DNA copy-number alteration profiles showed frequent DNA copy-number gains at chromosome 7, 8q and 13, and losses at 4, 5q, 8p, 17p and 18q. The weighted kappa statistic from comparing copy-number alteration status with data from Western countries was 0.828 (95% confidence interval=0.786 -0.871). DNA copy-number alterations of 8,684 segments were compared with clinicopathological features in 161 patients. Location of the tumor correlated with genomic segments of chromosome 4, 5, 7, 8, 13, 14, 18 and 20. Differentiation of the tumor correlated with segments in chromosome 4, 6, 8, 11, 13, 14,15, 16, 17 and 20. Somatic copy-number alteration profiles of stage III colonic cancer in the Japanese ACTS-CC trial closely agreed with the results of previous Western studies. Location and differentiation of the tumor correlated with DNA copy-number alterations. Our findings will facilitate understanding the characteristics of colonic cancer. Further investigation may contribute to the

  9. LINE-1 Methylation Status Correlates Significantly to Post-Therapeutic Recurrence in Stage III Colon Cancer Patients Receiving FOLFOX-4 Adjuvant Chemotherapy

    PubMed Central

    Fan, Yun-Ching; Chang, Wei-Chiao; Lu, Chien-Yu; Wu, I-Chen; Hsu, Wen-Hung; Huang, Ching-Wen; Wang, Jaw-Yuan

    2015-01-01

    Background Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients. Materials and Methods 129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR) and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes. Results The LINE-1 methylation of all 129 patients was measured on a 0–100 scale (mean 63.3; median 63.7, standard deviation 7.1), LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019) and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041). Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012). Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01). In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (≦6 months) appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7

  10. LINE-1 Methylation Status Correlates Significantly to Post-Therapeutic Recurrence in Stage III Colon Cancer Patients Receiving FOLFOX-4 Adjuvant Chemotherapy.

    PubMed

    Lou, Yun-Ting; Chen, Chao-Wen; Fan, Yun-Ching; Chang, Wei-Chiao; Lu, Chien-Yu; Wu, I-Chen; Hsu, Wen-Hung; Huang, Ching-Wen; Wang, Jaw-Yuan

    2014-01-01

    Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients. 129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR) and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes. The LINE-1 methylation of all 129 patients was measured on a 0-100 scale (mean 63.3; median 63.7, standard deviation 7.1), LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019) and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041). Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012). Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01). In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (≦6 months) appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7.57, p=0.041). There was a significantly

  11. Family history of colorectal cancer and its impact on survival in patients with resected stage III colon cancer: results from NCCTG Trial N0147 (Alliance)

    PubMed Central

    Jansson-Knodell, Claire L.; Foster, Nathan R.; Sargent, Daniel J.; Limburg, Paul J.; Thibodeau, Stephen N.; Smyrk, Thomas C.; Sinicrope, Frank A.; Jahagirdar, Balkrishna; Goldberg, Richard M.

    2017-01-01

    Background Family history of colon cancer often portends increased risk of disease development; however, the prognostic significance of family history related to disease and survival outcomes is unclear. Methods To investigate the relationship between family history of colorectal cancer and survival outcomes in stage III colon cancer patients, a prospective cohort of 1,935 patients with resected stage III colon cancer enrolled in a randomized controlled trial (N0147), comparing the standard of care FOLFOX to FOLFOX with cetuximab, was studied. Patients completed a baseline questionnaire on family history and were followed every 6 months until death or 5 years after randomization. Results We examined the endpoints of disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS), comparing patients with a positive versus negative family history of colorectal cancer. The adjusted hazard ratios (HRs) for patients with a positive family history were 0.95 [95% confidence interval (CI), 0.78–1.16] for DFS, 0.94 (95% CI, 0.76–1.16) for TTR, and 0.92 (95% CI, 0.74–1.15) for OS (all adjusted P>0.47). A non-significant trend toward improved DFS (P=0.17; adjusted P=0.34) was observed when 2 or more relatives were affected as compared to 0 relatives (multivariate HR: 0.72; 95% CI, 0.45–1.15), whereas subjects with histories of 0 or 1 affected relatives had similar DFS (multivariate HR for 1 vs. 0: 1.00; 95% CI, 0.81–1.24). Interactions of the molecular factors KRAS, BRAF, and MMR with family history were also explored. The only significant interaction was for deficient MMR (dMMR) and first-degree relatives with a family history of colorectal cancer (0 vs. 1 vs. 2+ relatives) for a benefit on OS (univariate P=0.001), which remained significant after adjusting for other factors (P=0.029). Conclusions Among patients with stage III resected colon cancer treated with adjuvant FOLFOX, a family history of colorectal cancer did not significantly impact DFS

  12. Multivitamin Use Is Not Associated With Cancer Recurrence or Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803

    PubMed Central

    Ng, Kimmie; Meyerhardt, Jeffrey A.; Chan, Jennifer A.; Niedzwiecki, Donna; Hollis, Donna R.; Saltz, Leonard B.; Mayer, Robert J.; Benson, Al B.; Schaefer, Paul L.; Whittom, Renaud; Hantel, Alexander; Goldberg, Richard M.; Fuchs, Charles S.

    2010-01-01

    Purpose Multivitamin use is widespread in the United States, especially among patients with cancer. However, the influence of multivitamin supplementation on cancer recurrence and death after a curative resection of colon cancer is unknown. Patients and Methods We conducted a prospective, observational study of 1,038 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on multivitamin use during and 6 months after adjuvant chemotherapy. Patients were observed until March 2009 for disease recurrence and death. To minimize bias by occult recurrence, we excluded patients who recurred or died within 90 days of their multivitamin assessment. Results Among 1,038 patients, 518 (49.9%) reported multivitamin use during adjuvant chemotherapy. Compared with nonusers, the multivariate hazard ratio (HR) for disease-free survival was 0.94 (95% CI, 0.77 to 1.15) for patients who used multivitamins. Similarly, multivitamin use during adjuvant chemotherapy was not significantly associated with recurrence-free survival (multivariate HR, 0.93; 95% CI, 0.75 to 1.15) or overall survival (multivariate HR 0.92; 95% CI, 0.74 to 1.16). Multivitamin use reported 6 months after completion of adjuvant chemotherapy was also not associated with improved patient outcome, and consistent use both during and following adjuvant therapy conferred no benefit. Neither an increasing number of tablets nor increasing duration of use before cancer diagnosis was associated with cancer recurrence or mortality. Multivitamin use also did not improve the rates of grade 3 and higher GI toxicity. Conclusion Multivitamin use during and after adjuvant chemotherapy was not significantly associated with improved outcomes in patients with stage III colon cancer. PMID:20805450

  13. Genetic variants within obesity-related genes are associated with tumor recurrence in patients with stages II/III colon cancer.

    PubMed

    Sebio, Ana; Gerger, Armin; Matsusaka, Satoshi; Yang, Dongyun; Zhang, Wu; Stremitzer, Stefan; Stintzing, Sebastian; Sunakawa, Yu; Yamauchi, Shinichi; Ning, Yan; Fujimoto, Yoshiya; Ueno, Masashi; Lenz, Heinz-Josef

    2015-01-01

    Obesity is an established risk factor for colorectal cancer (CRC) incidence and it is also linked to CRC recurrence and survival. Polymorphisms located in obesity-related genes are associated with an increased risk of developing several cancer types including CRC. We evaluated whether single-nucleotide polymorphisms in obesity-related genes may predict tumor recurrence in colon cancer patients. Genotypes were obtained from germline DNA from 207 patients with stage II or III colon cancer at the Norris Comprehensive Cancer Center. Nine polymorphisms in eight obesity-related genes (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA, and DSCR1) were evaluated. The primary endpoint of the study was the 3-year recurrence rate. Positive associations were also tested in an independent Japanese cohort of 350 stage III CRC patients. In univariate analysis, for PPARrs1801282, patients with a CC genotype had significantly lower recurrence probability (29 ± 4% SE) compared with patients with a CG genotype (48 ± 8% SE) [hazard ratio (HR): 1.77; 95% confidence interval (CI), 1.01-3.10; P = 0.040]. For DSCR1rs6517239, patients with an AA genotype had higher recurrence probability than patients carrying at least one allele G (37 ± 4% SE vs. 15 ± 6% SE) (HR: 0.51; 95% CI, 0.27-0.94; P = 0.027). This association was stronger in the patients bearing a left-sided tumor (HR: 0.34; 95% CI, 0.13-0.88; P = 0.018). In the Japanese cohort, no associations were found. This hypothesis-generating study suggests a potential influence of polymorphisms within obesity-related genes in the recurrence probability of colon cancer. These interesting results should be evaluated further.

  14. The effects of inpatient exercise therapy on the length of hospital stay in stages I-III colon cancer patients: randomized controlled trial.

    PubMed

    Ahn, Ki-Yong; Hur, Hyuk; Kim, Dong-Hyun; Min, Jihee; Jeong, Duck Hyoun; Chu, Sang Hui; Lee, Ji Won; Ligibel, Jennifer A; Meyerhardt, Jeffrey A; Jones, Lee W; Jeon, Justin Y; Kim, Nam Kyu

    2013-05-01

    This study aimed to examine the effects of a postsurgical, inpatient exercise program on postoperative recovery in operable colon cancer patients We conducted the randomized controlled trial with two arms: postoperative exercise vs. usual care. Patients with stages I-III colon cancer who underwent colectomy between January and December 2011 from the Colorectal Cancer Clinic, were recruited for the study. Subjects in the intervention group participated in the postoperative inpatient exercise program consisted of twice daily exercise, including stretching, core, balance, and low-intensity resistance exercises. The usual care group was not prescribed a structured exercise program. The primary endpoint was the length of hospital stay. Secondary endpoints were time to flatus, time to first liquid diet, anthropometric measurements, and physical function measurements. A total of 31 (86.1 %) patients completed the trial, with adherence to exercise interventions at 84.5 %. The mean length of hospital stay was 7.82 ± 1.07 days in the exercise group compared with 9.86 ± 2.66 days in usual care (mean difference, 2.03 days; 95 % confidence interval (CI), -3.47 to -0.60 days; p = 0.005) in per-protocol analysis. The mean time to flatus was 52.18 ± 21.55 h in the exercise group compared with 71.86 ± 29.2 h in the usual care group (mean difference, 19.69 h; 95 % CI, -38.33 to -1.04 h; p = 0.036). Low-to-moderate-intensity postsurgical exercise reduces length of hospital stay and improves bowel motility after colectomy procedure in patients with stages I-III colon cancer.

  15. Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials.

    PubMed

    Sinicrope, Frank A; Foster, Nathan R; Yoon, Harry H; Smyrk, Thomas C; Kim, George P; Allegra, Carmen J; Yothers, Greg; Nikcevich, Daniel A; Sargent, Daniel J

    2012-02-01

    Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown. BMI (kg/m(2)) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively. Overall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m(2)). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients. Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.

  16. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial.

    PubMed

    Taieb, Julien; Tabernero, Josep; Mini, Enrico; Subtil, Fabien; Folprecht, Gunnar; Van Laethem, Jean-Luc; Thaler, Josef; Bridgewater, John; Petersen, Lone Nørgård; Blons, Hélène; Collette, Laurence; Van Cutsem, Eric; Rougier, Philippe; Salazar, Ramon; Bedenne, Laurent; Emile, Jean-François; Laurent-Puig, Pierre; Lepage, Come

    2014-07-01

    Since the 1990s, fluorouracil-based adjuvant chemotherapy has significantly reduced the risk of tumour recurrence in patients with stage III colon cancer. We aimed to assess whether the addition of cetuximab to standard adjuvant oxaliplatin, fluorouracil, and leucovorin chemotherapy (FOLFOX4) in patients with stage III colon cancer improved disease-free survival (DFS). For this open-label, randomised phase 3 study done in nine European countries, we enrolled patients through an interactive voice response system to the central randomisation centre, with a central stratified permuted block randomisation procedure. We randomly assigned patients with resected (R0) stage III disease (1:1) to receive 12 cycles of FOLFOX4 twice a week with or without cetuximab. Patients were stratified by N-status (N1 vs N2), T-status (T1-3 vs T4), and obstruction or perforation status (no obstruction and no perforation vs obstruction or perforation or both). A protocol amendment (applied in June, 2008, after 2096 patients had been randomly assigned to treatment-restricted enrolment to patients with tumours wild-type at codons 12 and 13 in exon 2 of the KRAS gene (KRAS exon 2 wild-type). The primary endpoint was DFS. Analysis was intention to treat in all patients with KRAS exon 2 wild-type tumours. The study is registered at EudraCT, number 2005-003463-23. Between Dec 22, 2005, and Nov 5, 2009, 2559 patients from 340 sites in Europe were randomly assigned. Of these patients, 1602 had KRAS exon 2 wild-type tumours (intention-to-treat population), 791 in the FOLFOX4 plus cetuximab group and 811 in the FOLFOX4 group. Median follow-up was 3·3 years (IQR 3·2-3·4). In the experimental and control groups, DFS was similar in the intention-to-treat population (hazard ratio [HR] 1·05; 95% CI 0·85-1·29; p=0·66), and in patients with KRAS exon 2/BRAF wild-type (n=984, HR 0·99; 95% CI 0·76-1·28) or KRAS exon 2-mutated tumours (n=742, HR 1·06; 95% CI 0·82-1·37). We noted heterogeneous

  17. The Course of Neuropathic Symptoms in Relation to Adjuvant Chemotherapy Among Elderly Patients With Stage III Colon Cancer: A Longitudinal Study.

    PubMed

    van Erning, Felice N; Janssen-Heijnen, Maryska L G; Wegdam, Johannes A; Slooter, Gerrit D; Wijsman, Jan H; Vreugenhil, Art; Beijers, Tonneke A J M; van de Poll-Franse, Lonneke V; Lemmens, Valery E P P

    2017-09-01

    Among the elderly, the impairment of functional capacities due to neuropathy can have a significant impact. The aim of the present study was to investigate the course of neuropathic symptoms among elderly patients with stage III colon cancer treated with CAPOX (capecitabine, oxaliplatin), capecitabine monotherapy, or no adjuvant chemotherapy. The Netherlands Cancer Registry was used to select patients with stage III colon cancer and aged ≥ 70 years. Questionnaires were sent after resection (T1) and 6 (T2) and 12 months (T3) later. Neuropathy was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20. Logistic generalized estimating equations analyses were used to evaluate the effect of chemotherapy on the course of neuropathic symptoms. Of 155 eligible patients, 117 (76%) completed the T1 questionnaire, and 69 and 59 completed the T2 and T3 questionnaires, respectively. The course of the sensory symptoms tingling fingers or hands, tingling toes or feet, numbness in fingers or hands, and numbness in toes or feet was significantly unfavorable for patients treated with adjuvant chemotherapy (CAPOX or capecitabine) compared with that for patients who had not received adjuvant chemotherapy. The course of numbness in toes or feet also differed significantly between patients treated with CAPOX (T1, 7%; T2, 50%; T3, 42%) and patients treated with capecitabine (T1, 17%; T2, 31%; T3, 8%). Additionally, patients treated with capecitabine reported significantly less tingling toes or feet (T1, 6%; T2, 25%; T3, 7%) compared with patients treated with CAPOX (T1, 0%; T2, 50%; T3, 58%). The course of several sensory symptoms over time was less favorable for elderly patients with colon cancer treated with chemotherapy. Moreover, CAPOX was associated with more symptoms in toes and feet compared with capecitabine. It is important to inform patients of these risks to enable

  18. Prognostic Impact of Deficient DNA Mismatch Repair in Patients With Stage III Colon Cancer From a Randomized Trial of FOLFOX-Based Adjuvant Chemotherapy

    PubMed Central

    Sinicrope, Frank A.; Mahoney, Michelle R.; Smyrk, Thomas C.; Thibodeau, Stephen N.; Warren, Robert S.; Bertagnolli, Monica M.; Nelson, Garth D.; Goldberg, Richard M.; Sargent, Daniel J.; Alberts, Steven R.

    2013-01-01

    Purpose The association of deficient DNA mismatch repair (dMMR) with prognosis in patients with colon cancer treated with adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy remains unknown. Patients and Methods Resected, stage III colon carcinomas from patients (N = 2,686) randomly assigned to FOLFOX ± cetuximab (North Central Cancer Treatment Group N0147 trial) were analyzed for mismatch repair (MMR) protein expression and mutations in BRAFV600E (exon 15) and KRAS (codons 12 and 13). Association of biomarkers with disease-free survival (DFS) was determined using Cox models. A validation cohort (Cancer and Leukemia Group B 88903 trial) was used. Results dMMR was detected in 314 (12%) of 2,580 tumors, of which 49.3% and 10.6% had BRAFV600E or KRAS mutations, respectively. MMR status was not prognostic overall (adjusted hazard ratio [HR], 0.82; 95% CI, 0.64 to 1.07; P = .14), yet significant interactions were found between MMR and primary tumor site (Pinteraction = .009) and lymph node category (N1 v N2; Pinteraction = .014). Favorable DFS was observed for dMMR versus proficient MMR proximal tumors (HR, 0.71; 95% CI, 0.53 to 0.94; P = .018) but not dMMR distal tumors (HR, 1.71; 95% CI, 0.99 to 2.95; P = .056), adjusting for mutations and covariates. Any survival benefit of dMMR was lost in N2 tumors. Mutations in BRAFV600E (HR, 1.37; 95% CI, 1.08 to 1.70; P = .009) or KRAS (HR, 1.44; 95% CI, 1.21 to 1.70; P < .001) were independently associated with worse DFS. The observed MMR by tumor site interaction was validated in an independent cohort of stage III colon cancers (Pinteraction = .037). Conclusion The prognostic impact of MMR depended on tumor site, and this interaction was validated in an independent cohort. Among dMMR cancers, proximal tumors had favorable outcome, whereas distal or N2 tumors had poor outcome. BRAF or KRAS mutations were independently associated with adverse outcome. PMID:24019539

  19. Comparison of Outcomes After Fluorouracil-Based Adjuvant Therapy for Stages II and III Colon Cancer Between 1978 to 1995 and 1996 to 2007: Evidence of Stage Migration From the ACCENT Database

    PubMed Central

    Shi, Qian; Andre, Thierry; Grothey, Axel; Yothers, Greg; Hamilton, Stanley R.; Bot, Brian M.; Haller, Daniel G.; Van Cutsem, Eric; Twelves, Chris; Benedetti, Jacqueline K.; O'Connell, Michael J.; Sargent, Daniel J.

    2013-01-01

    Purpose With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens. Methods Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage. Results Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages. Conclusion Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients. PMID:23980089

  20. Expression and prognostic significance of APAF-1, caspase-8 and caspase-9 in stage II/III colon carcinoma: caspase-8 and caspase-9 is associated with poor prognosis.

    PubMed

    Sträter, Jörn; Herter, Ines; Merkel, Gaby; Hinz, Ulf; Weitz, Jürgen; Möller, Peter

    2010-08-15

    Apoptosis protease activating factor-1 (APAF-1), caspase-8 and caspase-9 are important factors in the execution of death signals. To study their prognostic influence in colon carcinoma, expression of APAF-1, caspase-8 and caspase-9 was determined by immunohistochemistry in normal colon mucosa (n = 8) and R0-resected stage II/III colon carcinomas (n >or= 124) using a semiquantitative score. Staining results were correlated with disease-free survival by Kaplan-Meier estimates, and multivariate Cox analyses were performed. In normal colon, APAF-1 and caspase-8 are most strongly expressed in the luminal surface epithelium, whereas caspase-9 is expressed all along the crypt axis. In colon carcinomas, there is considerable variability in the expression of these proapoptotic factors, although complete loss of caspase-8 and caspase-9 is rare. APAF-1 expression did not correlate with disease-free survival. Instead, both expression of caspase-9 and high-level expression of caspase-8 in a majority of tumor cells were significantly associated with adverse prognosis (p = 0.004 and p = 0.029, respectively). The influence of caspase-8 expression was mainly seen in patients with stage III colon carcinoma (p = 0.011), whereas the prognostic influence of caspase-9 expression was significant in stage II cases (p = 0.037) and just failed to be significant in stage III tumors (p = 0.0581). After adjusting for confounding factors in a multivariate Cox analysis, the effect of caspase-9 in predicting disease-free survival was confirmed (p = 0.003). Our data suggest that, in colon carcinomas, expression of caspase-8 and caspase-9 is significantly associated with poor survival. Caspase-9 may be an independent prognosticator in colon carcinoma.

  1. Validation of the 12-Gene Colon Cancer Recurrence Score in NSABP C-07 As a Predictor of Recurrence in Patients With Stage II and III Colon Cancer Treated With Fluorouracil and Leucovorin (FU/LV) and FU/LV Plus Oxaliplatin

    PubMed Central

    Yothers, Greg; O'Connell, Michael J.; Lee, Mark; Lopatin, Margarita; Clark-Langone, Kim M.; Millward, Carl; Paik, Soonmyung; Sharif, Saima; Shak, Steven; Wolmark, Norman

    2013-01-01

    Purpose Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. Methods Recurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. Results Continuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P < .001), as well as disease-free and overall survival (both P < .001). Recurrence Score predicted recurrence risk (P = .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P = .90) or age (P = .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P = .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. Conclusion The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer. PMID:24220557

  2. Interim analysis of a phase II trial evaluating the safety and efficacy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer.

    PubMed

    Danno, Katsuki; Hata, Taishi; Tamai, Koki; Fujie, Yujiro; Ide, Yoshihito; Kim, Ho Min; Ohnishi, Tadashi; Morita, Shunji; Yoshioka, Shinichi; Kudo, Toshihiro; Nishimura, Junichi; Matsuda, Chu; Akamatsu, Hiroki; Mizushima, Tsunekazu; Nezu, Riichiro; Doki, Yuichiro; Mori, Masaki

    2017-08-19

    Adjuvant oxaliplatin plus oral capecitabine (XELOX) is recommended for patients with curatively resected colon cancer. However, its safety and tolerability in Asian patients is unclear; therefore, we evaluated the safety and efficacy of adjuvant XELOX in Japanese patients with curatively resected stage III colon cancer (MCSCO-1024) and present the interim safety data. This prospective, multi-center, open-label, single-arm phase II study recruited patients with curatively resected stage III colon cancer. The protocol was a 120-min intravenous infusion of oxaliplatin (130 mg/m(2)) on day 1 and oral capecitabine (2000 mg/m(2)/day) in two divided doses for 14 days of a 3-week cycle, for a total of eight cycles (24 weeks). The primary endpoint was the 3-year disease-free survival, and secondary endpoints were the treatment completion rate, safety profile (rate and severity of adverse events), and correlation of adverse events, such as peripheral sensory neuropathy (PSN), with the administration period of oxaliplatin, etc. From November 2011 to August 2014 (34 months), 196 patients were enrolled. Safety was analyzed in 190 patients. The median total doses of capecitabine and oxaliplatin were 215,586.9 and 777.2 mg/m(2), respectively, while the median relative dose intensities were 82.5 and 76.0%, respectively. The overall treatment completion rate was 73.7%. The most frequent treatment-related adverse event was PSN (88.4%), while the most frequent grade ≥3 treatment-related adverse events were neutropenia (12.6%), PSN (6.3%), diarrhea (4.2%), and thrombocytopenia (4.2%). There were no treatment-related deaths. Adjuvant XELOX is tolerable for Japanese patients with Stage III colon cancer.

  3. Population-Based Cost-Minimization Analysis of CAPOX Versus Modified FOLFOX6 in the Adjuvant Treatment of Stage III Colon Cancer.

    PubMed

    Ho, Maria Y; Chang, Albert Y; Ruan, Jenny Y; Cheung, Winson Y

    2016-06-01

    Evidence suggests that CAPOX (capecitabine and oxaliplatin) has efficacy similar to 5-fluorouracil and oxaliplatin (mFOLFOX6) in the adjuvant treatment of colon cancer. CAPOX is partly administered orally and associated with a 3-week rather than a 2-week treatment cycle. A population-based cost-minimization analysis was conducted from the health care payer and societal perspectives to evaluate the potential cost savings of replacing mFOLFOX6 with CAPOX. We applied treatment and toxicity data from phase III trials of CAPOX and FOLFOX-based regimens to the adjuvant colon cancer population in British Columbia, Canada. In this cost-minimization analysis we compared the total costs associated with chemotherapy medications, drug administration and delivery, hospital and clinic visits, treatment-related toxicities, and central venous access devices. Costs to patients in terms of lost time and travel were also considered. It was assumed that patients would receive either 8 cycles of CAPOX or 12 cycles of mFOLFOX6. From the payer perspective, the use of CAPOX resulted in cost savings of $5339 CAD per patient compared with the use of mFOLFOX6. From a societal perspective, CAPOX was also associated with savings of $6080 CAD per patient. The greatest cost savings with CAPOX were attributed to fewer visits for chemotherapy treatment and decreased central venous access device usage. CAPOX was also associated with reduced loss of time and decreased travel for patients because of the requirement of fewer clinic visits. Replacement of mFOLFOX6 with CAPOX in the adjuvant treatment of colon cancer might be associated with potential cost savings from the payer and societal perspectives. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Comparative effectiveness of different chemotherapeutic regimens on survival of people aged 66 and older with stage III colon cancer: a "real world" analysis using Surveillance, Epidemiology, and End Results-Medicare data.

    PubMed

    Hsiao, Fei-Yuan; Mullins, C Daniel; Onukwugha, Ebere; Pandya, Naimish; Hanna, Nader

    2011-09-01

    To compare the effectiveness and utilization trends of irinotecan (IRI)-based and oxaliplatin (OX)-based regimens with those of 5-fluorouracil and leucovorin (5FU/LV) alone in people aged 66 and older with Stage III colon cancer. Retrospective cohort study. Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. People with Stage III surgically resected colon cancer who received adjuvant chemotherapy were categorized into 5FU/LV-alone (n = 3,581), OX-based regimen (n = 814), and IRI-based regimen (n = 219) subgroups. Multivariable Cox proportional hazards models examined the effect of chemotherapies on overall survival, colon cancer-specific survival, and non-colon cancer-specific survival. Use of the OX-based regimen increased, and use of the 5FU/LV-alone and IRI-based regimens decreased over time. OX was statistically significantly associated with longer overall survival (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.62-0.86, P < .001) and colorectal cancer-specific survival (HR = 0.39, 95% CI, 0.28-0.55, P < .001) than 5FU/LV alone. There was a greater risk of overall mortality (HR = 1.38, 95% CI = 1.14-1.67, P<.001) and cancer-specific mortality (HR = 1.92, 95% CI=1.49-2.47, P < .001) associated with IRI than with 5FU/LV. The superiority of OX on survival was found in participants aged 66 to 79 but not in those aged 80 and older. This "real world" comparative effectiveness research extends randomized controlled trial results by documenting the relative survival benefit of OX in older adults with Stage III colon cancer. The associated shift in treatment away from 5FU/LV alone or IRI toward OX is consistent with evidence-based medicine from real-world outcomes research. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

  5. Microsatellite Instability and Loss of Heterozygosity at Chromosomal Location 18q: Prospective Evaluation of Biomarkers for Stages II and III Colon Cancer—A Study of CALGB 9581 and 89803

    PubMed Central

    Bertagnolli, Monica M.; Redston, Mark; Compton, Carolyn C.; Niedzwiecki, Donna; Mayer, Robert J.; Goldberg, Richard M.; Colacchio, Thomas A.; Saltz, Leonard B.; Warren, Robert S.

    2011-01-01

    Purpose Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors. Patients and Methods We studied two of these genomic defects—mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH)—in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH. Results Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS. Conclusion We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer. PMID:21747089

  6. Relationship Between Tumor Gene Expression and Recurrence in Four Independent Studies of Patients With Stage II/III Colon Cancer Treated With Surgery Alone or Surgery Plus Adjuvant Fluorouracil Plus Leucovorin

    PubMed Central

    O'Connell, Michael J.; Lavery, Ian; Yothers, Greg; Paik, Soonmyung; Clark-Langone, Kim M.; Lopatin, Margarita; Watson, Drew; Baehner, Frederick L.; Shak, Steven; Baker, Joffre; Cowens, J. Wayne; Wolmark, Norman

    2010-01-01

    Purpose These studies were conducted to determine the relationship between quantitative tumor gene expression and risk of cancer recurrence in patients with stage II or III colon cancer treated with surgery alone or surgery plus fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify the risk of recurrence as well as the likelihood of differential treatment benefit of FU/LV adjuvant chemotherapy for individual patients. Patients and Methods We performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor blocks from patients with stage II or III colon cancer who were treated with surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied in CC/C-06. Results A combined analysis of the four studies identified 48 genes significantly associated with risk of recurrence and 66 genes significantly associated with FU/LV benefit (with four genes in common). Seven recurrence-risk genes, six FU/LV-benefit genes, and five reference genes were selected, and algorithms were developed to identify groups of patients with low, intermediate, and high likelihood of recurrence and benefit from FU/LV. Conclusion RT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study. PMID:20679606

  7. Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma

    ClinicalTrials.gov

    2014-12-22

    Adenomatous Polyp; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  8. Short term results of complete (D3) vs. standard (D2) mesenteric excision in colon cancer shows improved outcome of complete mesenteric excision in patients with TNM stages I-II.

    PubMed

    Storli, K E; Søndenaa, K; Furnes, B; Nesvik, I; Gudlaugsson, E; Bukholm, I; Eide, G E

    2014-06-01

    The aim of the present study was to investigate whether the new method of complete mesocolic excision (CME) with a high (apical) vascular tie (D3 resection) had an immediate effect compared with a conventional (standard) approach even in those patients without lymph node metastases. A cohort of 189 consecutive patients with tumour-nodal-metastasis (TNM) stages I-II and a mean age of 73 years were operated on in the period from January 2007 to December 2008 in three community teaching hospitals. The CME approach (n = 89), used in hospital A, was compared to the standard technique used (n = 105) in two other hospitals, B and C. Lymph node yields from the specimens were used as a surrogate measure of radical resections. Outcome was analysed after a median follow-up of 50.2 months. In-hospital mortality rate was 2.8 % in the CME group and 8.6 % in the standard group. The 3-year overall survival (OS) in the CME group was 88.1 versus 79.0 % (p = 0.003) in the standard group, and the corresponding disease-free survival (DFS) was 82.1 versus 74.3 % (p = 0.026). Cancer-specific survival was 95.2 % in the CME group versus 90.5 % in the standard group (p = 0.067). Age, operative technique, and T category were significant in multiple Cox regressions of OS and DFS. Compared with the standard (D2) approach, introduction of CME surgical management of colon cancer resulted in a significant immediate improvement of 3-year survival for patients with TNM stage I-II tumours as assessed by OS and DFS.

  9. Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803.

    PubMed

    Sargent, D; Shi, Q; Yothers, G; Van Cutsem, E; Cassidy, J; Saltz, L; Wolmark, N; Bot, B; Grothey, A; Buyse, M; de Gramont, A

    2011-05-01

    The ACCENT group previously established disease-free survival (DFS) with 2 or 3 years median follow-up to predict 5 year overall survival (5 year OS) in stage II and III colon cancer. ACCENT further proposed (1) a stronger association between DFS and OS in stage III than II, and (2) 6 or 7 years necessary to demonstrate DFS/OS surrogacy in recent trials. The relationship between end-points in trials with oral fluoropyrimidines, oxaliplatin and irinotecan is unknown. Associations between the treatment effect hazard ratios (HRs) on 2 and 3 years DFS, and 5 and 6 years OS were examined in 6 phase III trials not included in prior analyses from 1997 to 2002. Individual data for 12,676 patients were analysed; two trials each tested oxaliplatin, irinotecan and oral treatment versus 5-FU/LV. Overall association between 2/3 year DFS and 5/6 year OS HRs was modest to poor (simple R² measures: 0.58-0.76, model-based R²: 0.17-0.49). In stage III patients, the association increased (model-based R² ≥ 0.79). Observed treatment effects on 2 year DFS accurately 5/6 year OS effects overall and in stage III patients. In recent trials of cytotoxic chemotherapy, 2 or 3 years DFS HRs are highly predictive of 5 and 6 years OS HRs in stage III but not stage II patients. In all patients the DFS/OS association is stronger for 6 year OS, thus at least 6 year follow-up is recommended to assess OS benefit. These data support DFS as the primary end-point for stage III colon cancer trials testing cytotoxic agents. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-04

    Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  11. Association between DPYD c.1129-5923 C>G/hapB3 and severe toxicity to 5-fluorouracil-based chemotherapy in stage III colon cancer patients: NCCTG N0147 (Alliance)

    PubMed Central

    Lee, Adam M.; Shi, Qian; Alberts, Steven R.; Sargent, Daniel J.; Sinicrope, Frank A.; Berenberg, Jeffrey L.; Grothey, Axel; Polite, Blase; Chan, Emily; Gill, Sharlene; Kahlenberg, Morton S.; Nair, Suresh G.; Shields, Anthony F.; Goldberg, Richard M.; Diasio, Robert B.

    2015-01-01

    Severe (grade≥3) adverse events (AEs) to 5-fluorouracil (5-FU)-based chemotherapy regimens can result in treatment delays or cessation, and, in extreme cases, life-threatening complications. Current genetic biomarkers for 5-FU toxicity prediction, however, account for only a small proportion of toxic cases. In the current study, we assessed DPYD variants suggested to correlate with 5-FU toxicity, a deep intronic variant (c.1129-5923 C>G) and four variants within a haplotype (hapB3), in 1953 stage III colon cancer patients who received adjuvant FOLFOX +/- cetuximab. Logistic regression was used to assess multivariable associations between DPYD variant status and AEs common to 5-FU (5FU-AEs). In our study cohort, 1228 patients (62.9%) reported any grade≥3 AE (overall AE), with 638 patients (32.7%) reporting any grade≥3 5FU-AE. Only 32 of 78 (41.0%) patients carrying DPYD c.1129-5923 C>G and the completely linked hapB3 variants c.1236 C>G and c.959-51 T>C displayed at least one grade≥3 5FU-AE, resulting in no statistically significant association (ORadj.=1.47, 95%CI=0.90-2.43, p=0.1267). No significant associations were identified between c.1129-5923 C>G/hapB3 and overall grade≥3 AE rate. Our results suggest that c.1129-5923 C>G/hapB3 have limited predictive value for severe toxicity to 5-FU-based combination chemotherapy. PMID:26658227

  12. Thymidine Phosphorylase Gene Expression in Stage III Colorectal Cancer

    PubMed Central

    Lindskog, Elinor B.; Wettergren, Yvonne; Odin, Elisabeth; Gustavsson, Bengt; Derwinger, Kristoffer

    2012-01-01

    Background The thymidine phosphorylase (TP) enzyme has several tumor-promoting functions. The aim of this study was to explore TP gene expression in relation to clinical and histopathological data obtained from patients with stage III colorectal cancer. Methods and results TP gene expression was analyzed by real-time quantitative PCR in tumor and mucosa samples from 254 patients. TP gene expression in tumors correlated with lymph node staging, with higher expression relating to a higher number of positive nodes and a worse N-stage. Higher TP expression was also associated with a worse histological tumor grade. Patients with rectal cancer had significantly higher TP expression in mucosa and tumors compared with patients having colon cancer. Conclusion Higher intratumoral TP expression appears to be related to a worse N stage, and thus, with a worse prognosis. TP gene expression measured in a preoperative biopsy could be of interest in preoperative staging. PMID:23115484

  13. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  14. Identification of Risk Factors for Recurrence in High-Risk Stage II Colon Cancer

    PubMed Central

    Hatano, Satoshi; Ishida, Hideyuki; Ishibashi, Keiichiro; Kumamoto, Kensuke; Haga, Norihiro; Miura, Ichiro

    2013-01-01

    To identify risk factors for recurrence in patients with stage II colon cancer, Cox proportional hazards regression analysis was performed in 194 patients with stage II colon cancer who underwent curative surgery between April 1997 and December 2008. Thirteen clinical and pathologic factors, including use of fluoropyrimidine-based adjuvant chemotherapy in 113 of the patients (58.2%), were assessed. By multivariate analysis, only obstruction, perforation, and T4-level invasion were identified as independent risk factors affecting disease-free survival (DFS) (P < 0.01). The 5-year DFS rate was 70.6% in patients with one or more risk factors (n = 68) and 96.0% in patients with no risk factors (n = 126) (P < 0.01). These results suggest that obstruction, perforation, and T4-level invasion are suitable candidates for prediction of tumor recurrence in patients with stage II colon cancer. The oxaliplatin-based adjuvant chemotherapy, which has been reported to be effective in stage III colon cancer patients, may improve the prognosis in high-risk stage II colon cancer patients. PMID:23701145

  15. [Exclusive radiotherapy in stage III esophageal cancer].

    PubMed

    Tombolini, V; Banelli, E; Cavaceppi, P; Donato, V; Montagna, A; Raffetto, N; Santarelli, M; Vitturini, A

    2000-01-01

    The purpose of the report is to evaluate the role of radiotherapy in the treatment of stage III esophageal carcinoma and to analyze the influence of site, extension, grade of dysphagia and histology on local control and survival. Twenty males and 6 females were submitted to external beam therapy with 4-6 MV X-rays and received 60-70 Gy in fractions of 180 cGY to 200 cGy per day, 5 days a week. Radiation therapy technique was two posterior oblique portals and a single anterior field at 100 cm SAD. After 4500 cGy portals were coned down, holding the spinal cord dose below 4500 cGy. Global response to therapy was 73.1%. Median survival was 11 months. The 2-year survival rate was 12.5% in patients with lesions smaller than 5 cm and 5.5% for those with lesions greater than 5 cm. Patients with grade 2 dysphagia had a median survival of 16 months, those with grade 1, 11 months and 2 patients with grade 0, 4 and 9 months. In all patients mild to moderate esophagitis was observed. Two patients developed esophagotracheal fistula. Exclusively radiotherapy cannot be considered the treatment of choice in III stage patients. Primary chemoradiotherapy may emerge as the treatment of choice for cancer of the esophagus.

  16. C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management.

    PubMed

    Thirunavukarasu, Pragatheeshwar; Sukumar, Shyamsunder; Sathaiah, Magesh; Mahan, Meredith; Pragatheeshwar, Kothai Divya; Pingpank, James F; Zeh, Herbert; Bartels, Christopher J; Lee, Kenneth K W; Bartlett, David L

    2011-04-20

    The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion. Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided. C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001). C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.

  17. Telomere Length in Predicting Toxicity in Older Patients With Stage III-IV Colorectal Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-09-08

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  18. Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

    ClinicalTrials.gov

    2014-04-21

    Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

  19. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-05-03

    Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  20. Adjuvant Chemotherapy for Stage II Right- and Left-Sided Colon Cancer: Analysis of SEER-Medicare Data

    PubMed Central

    Weiss, Jennifer M.; Schumacher, Jessica; Allen, Glenn O.; Neuman, Heather; Lange, Erin O’Connor; LoConte, Noelle K.; Greenberg, Caprice C.; Smith, Maureen A.

    2014-01-01

    Purpose Survival benefit from adjuvant chemotherapy is established for stage III colon cancer; however, uncertainty exists for stage II patients. Tumor heterogeneity, specifically microsatellite instability (MSI) which is more common in right-sided cancers, may be the reason for this observation. We examined the relationship between adjuvant chemotherapy and overall 5-year mortality for stage II colon cancer by location (right- versus left-side) as a surrogate for MSI. Methods Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified Medicare beneficiaries from 1992 to 2005 with AJCC stage II (n=23,578) and III (n=17,148) primary adenocarcinoma of the colon who underwent surgery for curative intent. Overall 5-year mortality was examined with Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. Results Eighteen percent (n=2,941) of stage II patients with right-sided cancer and 22% (n=1,693) with left-sided cancer received adjuvant chemotherapy. After adjustment, overall 5-year survival benefit from chemotherapy was observed only for stage III patients (right-sided: HR 0.64; 95% CI, 0.59–0.68, p<0.001 and left-sided: HR 0.61; 95% CI, 0.56–0.68, p<0.001). No survival benefit was observed for stage II patients with either right-sided (HR 0.97; 95% CI, 0.87–1.09, p=0.64) or left-sided cancer (HR 0.97; 95% CI, 0.84–1.12, p=0.68). Conclusions Among Medicare patients with stage II colon cancer, a substantial number receive adjuvant chemotherapy. Adjuvant chemotherapy did not improve overall 5-year survival for either right- or left-sided colon cancers. Our results reinforce existing guidelines and should be considered in treatment algorithms for older adults with stage II colon cancer. PMID:24643898

  1. VAC protocol for treatment of dogs with stage III hemangiosarcoma.

    PubMed

    Alvarez, Francisco J; Hosoya, Kenji; Lara-Garcia, Ana; Kisseberth, William; Couto, Guillermo

    2013-01-01

    Hemangiosarcomas (HSAs) are aggressive tumors with a high rate of metastasis. Clinical stage has been considered a negative prognostic factor for survival. The study authors hypothesized that the median survival time (MST) of dogs with metastatic (stage III) HSA treated with a vincristine, doxorubicin, and cyclophosphamide (VAC) chemotherapy protocol would not be different than those with stage I/II HSA. Sixty-seven dogs with HSA in different anatomic locations were evaluated retrospectively. All dogs received the VAC protocol as an adjuvant to surgery (n = 50), neoadjuvant (n = 3), or as the sole treatment modality (n = 14). There was no significant difference (P = 0.97) between the MST of dogs with stage III and stage I/II HSA. For dogs presenting with splenic HSA alone, there was no significant difference between the MST of dogs with stage III and stage I/II disease (P = 0.12). The overall response rate (complete response [CR] and partial response [PR]) was 86%). No unacceptable toxicities were observed. Dogs with stage III HSA treated with the VAC protocol have a similar prognosis to dogs with stage I/II HSA. Dogs with HSA and evidence of metastases at the time of diagnosis should not be denied treatment.

  2. Stage 0 to stage III breast cancer in young women.

    PubMed

    Gajdos, C; Tartter, P I; Bleiweiss, I J; Bodian, C; Brower, S T

    2000-05-01

    Breast cancer survival is improving because mammography is leading to diagnosis at earlier stages of the disease. Because young women with breast cancer rarely undergo mammography before diagnosis, outcomes for breast cancer in young women may not be improving. In addition to advanced stage, young age at diagnosis is associated with biologically more aggressive cancers with higher rates of local and distant recurrence. Risk factors, clinical presentations, pathologic findings, tumor characteristics, extent of disease, treatment, and outcomes for 101 women under age 36 treated for breast cancer between 1989 and 1997 were compared with 631 patients 36 years and older treated by us during the same interval. Stage IV patients were excluded. Patients younger than 36 years were more likely to present with a palpable mass (87% versus 55%, p < 0.001) and were less likely to undergo spot localization breast biopsy for mammographic findings (40% versus 6%, p < 0.001). Patients younger than 36 years had larger tumors (median 2.0 cm versus 1.5 cm, p < 0.001), more nodal involvement (50% versus 37%, p = 0.022), more nodes involved (median 1.0 versus 0, p = 0.010), and were more likely to be diagnosed with stage II or III cancer (60% versus 43%, overall p < 0.001). Young patients' cancers were more poorly differentiated (80% versus 44%, overall p < 0.001), estrogen receptor-negative (52% versus 31%, p < 0.001), aneuploid (70% versus 49%, p = 0.013), and had higher S-phase fractions (59% versus 29%, p = 0.001). Patients less than 36 years were treated more often with mastectomy (59% versus 22%, p < 0.001) and adjuvant chemotherapy (80% versus 54%, p < 0.001) and less often with tamoxifen (36% versus 58%, p = 0.001). Cumulative 5-year local and distant disease-free survival were significantly worse for patients younger than 36 years (p = 0.011 and p = 0.044, respectively). The higher rate of local recurrence in patients less than 36 years was from an excess number of local

  3. [One staged laparoscopic surgery of colon cancer with liver metastasis in the Guillermo Almenara Hospital, Lima, Peru].

    PubMed

    Núñez Ju, Juan José; Coronado3, Cesar Carlos; Anchante Castillo, Eduardo; Sandoval Jauregui, Javier; Arenas Gamio, José

    2016-01-01

    We report a patient who was diagnosed sigmoid colon cancer associated with liver metastases in segment III. The patient underwent laparoscopic surgery where the sigmoid colon resection and hepatic metastasectomy were performed in a “one staged” surgical procedure. The pathological results showed moderately differentiated tubular adenocarcinoma in sigmoid colon, tubular adenocarcinoma metastases also in liver. Oncological surgical results were obtained with free edges of neoplasia, R0 Surgery, T3N0M1. After the optimal surgical results, the patient is handled by oncology for adjuvant treatment. We report here the sequence of events and a review of the literature.

  4. Pretreatment staging of colon cancer in the Swedish population.

    PubMed

    Sjövall, A; Blomqvist, L; Martling, A

    2013-11-01

    Preoperative staging of colon cancer according to Swedish national guidelines implies imaging evaluation of the primary tumour, liver and lungs. Failure to adhere to these guidelines results in negative scorings in the national registration system. In the present study we report the extent of compliance with these guidelines. Since 2007 clinical data on all patients diagnosed with colon cancer in Sweden have been collected in a national database. This includes information on pretherapeutic diagnostic imaging performed, pretherapeutic TNM stage and data on treatment and follow-up. All patients diagnosed with colon cancer in Sweden between 2007 and 2010 were included. Nine thousand and eight-three patients (i.e. 60.5% of all patients) had a complete pretherapeutic radiological evaluation; 65.2% had a CT or MRI of the primary tumour, whereas over 80% had examinations of the liver and lungs. There were no difference related to sex, but more patients under 75 years had a complete evaluation. There were large differences between different regions; one region performed a complete evaluation of 78.3% of all patients. The proportion of patients examined increased from 53.9 to 65.0% during the study period. Elective cases were more frequently evaluated before treatment than those with an emergency presentation. Most patients in Sweden had a complete pretreatment imaging evaluation of the colon cancer with geographical and time-dependent variations. Knowledge of the importance of these variations and correlation of pre- and postoperative TNM stage is warranted, and such studies are ongoing. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  5. Postoperative surveillance recommendations for early stage colon cancer based on results from the clinical outcomes of surgical therapy trial.

    PubMed

    Tsikitis, Vassiliki L; Malireddy, Kishore; Green, Erin A; Christensen, Brent; Whelan, Richard; Hyder, Jace; Marcello, Peter; Larach, Sergio; Lauter, David; Sargent, Daniel J; Nelson, Heidi

    2009-08-01

    Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB and III) colon cancer. We hypothesized that stage I and IIA colon cancer patients would experience similar benefits. Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I and IIA, 537 patients) and late (stage IIB and III, 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by chi(2) test. Salvage rates for early- and late-stage disease patients with recurrence were the same (35.9% v 37%; P = .9, respectively). Median survival after second surgery after recurrence was 51.2 and 35.8 months for early- and late-stage patients, respectively. Single sites of first recurrence did not significantly differ between early and late stage, but multiple sites of recurrence occurred less often in early-stage patients (3.6% v 28.6%, for early v late, respectively; P < .001). METHODS of first detection of recurrence were not significantly different: carcinoembryonic antigen (29.1% v 37.4%), computed tomography scan (23.6% v 26.4%), chest x-ray (7.3% v 12.1%), and colonoscopy (12.7% v 8.8%), for early versus late stage disease, respectively. Patients with early-stage colon cancer have similar sites of recurrence, and receive similar benefit from postrecurrence therapy as late-stage patients; implementation of surveillance guidelines for early-stage patients is appropriate.

  6. Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2012-10-11

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  7. The Impact of Delayed Chemotherapy on Its Completion and Survival Outcomes in Stage II Colon Cancer Patients

    PubMed Central

    Xu, Fang; Rimm, Alfred A.; Fu, Pingfu; Krishnamurthi, Smitha S.; Cooper, Gregory S.

    2014-01-01

    Background Delayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients. Patients and Methods Patients (age ≥66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER–Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples. Results 4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2–3 months), and 12.3% had delayed chemotherapy (≥3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival). Conclusion Although the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation. PMID:25238395

  8. Carcinoma obstruction of the proximal colon cancer and long-term prognosis--obstruction is a predictor of worse outcome in TNM stage II tumor.

    PubMed

    Chin, Chih-Chien; Wang, Jeng-Yi; Changchien, Chung-Rong; Huang, Wen-Shih; Tang, Reiping

    2010-07-01

    Colon obstruction is suggested to be a predictor of poor outcome in colon cancer. However, the effect of obstruction on outcome in patients with different tumor-nodes-metastases (TNM) stage cancer has not been fully addressed. The aim of this study is to determine whether colon obstruction predicts surgical and long-term oncologic outcomes in patients with proximal colon cancer. A total of 1,492 consecutive patients underwent open resection of primary adenocarcinoma of right colon in a single institution between January 1995 and December 2005. Clinical and follow-up data were extracted from a prospective colorectal cancer database. Univariate and multivariate analyses were performed to identify colon obstruction and other predictors of surgical and oncologic outcomes. Among 1,492 patients, 306 (20.5%) patients presented with colon obstruction. The rates of surgical morbidity and mortality were greater in patients with an obstruction as compared to patients without an obstruction (22.2% and 3.9% vs. 14.1% and 1.9%; p = 0.0005 and 0.041, respectively). Obstruction predicted a worse long-term disease-free survival (DFS) among patients with stage II-III disease (log-rank test, p = 0.0003). The data were stratified by TNM stage. Obstruction predicted a worse DFS among patients with TNM stage II cancer (598 patients; log-rank test, p = 0.001; Cox regression, p = 0.012), but it was not a predictor in TNM stage III cancer patients (424 patients; p = 0.116; p = 0.108). Colon obstruction was an independent predictor of long-term outcome only in TNM stage II but not in stage III proximal colon cancer. Patients with TNM stage II obstructive colon cancer could be included in future trials of adjuvant therapies.

  9. Comparison of dietary and lifestyle habits among stage III and metastatic colorectal cancer patients: findings from CALGB 89803 and CALGB 80405.

    PubMed

    Van Loon, Katherine; Wigler, Devin; Niedzwiecki, Donna; Venook, Alan P; Fuchs, Charles; Blanke, Charles; Saltz, Leonard; Goldberg, Richard M; Meyerhardt, Jeffrey A

    2013-06-01

    Self-administered questionnaires were completed by patients undergoing chemotherapy for stage III colon cancer (n=1095) and metastatic colorectal cancer (n=875). We describe the prevalence of a wide-range of health-related dietary patterns and lifestyle behaviors among colorectal cancer patients with stage III and metastatic disease and report notable similarities in these 2 cohorts. Cancer patients often pursue lifestyle and dietary changes with the aim to improve outcomes. Using data from 2 large National Cancer Institute-sponsored clinical trials, we report on the dietary and lifestyle practices of patients receiving therapy for stage III colon or metastatic colorectal cancer. Self-administered questionnaires were completed by patients undergoing chemotherapy for stage III colon cancer (n=1095) and metastatic colorectal cancer (n=875). Descriptive statistical analyses were performed to evaluate anthropometrics, diet, and lifestyle in each cohort. Median body mass index was comparable for stage III and metastatic patients (27.3 vs. 26.5 kg/m2). Stage III patients reported a modestly higher median level of physical activity than metastatic patients (4.6 vs. 3.4 metabolic equivalent task-hours per week). Ten percent of stage III and 9% of metastatic patients reported ongoing cigarette use. Avoidance of alcohol was reported by 47% of stage III and 43% of metastatic patients. Dietary patterns for both groups were comparable with more than 80% of stage III and metastatic patients failing to meet the recommended daily intake of vegetables, fruits, and milk products. Usage of at least 2 multivitamins per week was reported by 49% of stage III and 40% of metastatic patients. Two percent of stage III and 5% of metastatic patients reported vitamin D supplement use. We observed notable similarities in dietary and lifestyle behaviors between stage III colon and metastatic colorectal cancer patients actively receiving chemotherapy. Future research should aim to elucidate the

  10. Production and characterization of monoclonal antibodies to a pilus colonization factor (colonization factor antigen III) of human enterotoxigenic Escherichia coli.

    PubMed Central

    Honda, T; Wetprasit, N; Arita, M; Miwatani, T

    1989-01-01

    Three monoclonal antibodies (MAbs) to a pilus colonization factor (colonization factor antigen III [CFA/III]) of human enterotoxigenic Escherichia coli (ETEC) were developed and characterized. All of the MAbs isolated belonged to the immunoglobulin G2a subclass. The specificity of these MAbs for CFA/III pili was demonstrated by the immunogold-labeling technique. The presence of more than one epitope in CFA/III pili was suggested. One of the three MAbs appears to recognize a polymeric conformational epitope(s) of CFA/III. CFA/III antigenicity distinct from that of other pilus colonization factors of ETEC was demonstrated by both a bacterial agglutination test and a sandwich enzyme-linked immunosorbent assay using the MAbs. Of the 100 strains of ETEC isolated from persons with traveler's diarrhea, 8% were found to carry CFA/III pili. Two enzyme-linked immunosorbent assay systems which could detect as little as several or 50 ng of CFA/III per ml were developed. Images PMID:2572553

  11. MM2 LRSLA Testing Stage III Propellant.

    DTIC Science & Technology

    1983-04-01

    tested Grain 70 data. This is the oldest CYR third stage pro- pellant in the OOALC inventory having been cast in June 1960. Motor serial numbers, lot ... numbers , cast dates and plot symbols are shown below. Motor S/N Lot Number Cast Date Symbol Grain 70 SR-47-60 Jun 60 0 0031064 SR-56-62 21 Oct 62

  12. Analysis of stage and clinical/prognostic factors for colon and rectal cancer from SEER registries: AJCC and collaborative stage data collection system.

    PubMed

    Chen, Vivien W; Hsieh, Mei-Chin; Charlton, Mary E; Ruiz, Bernardo A; Karlitz, Jordan; Altekruse, Sean F; Ries, Lynn A G; Jessup, J Milburn

    2014-12-01

    The Collaborative Stage (CS) Data Collection System enables multiple cancer registration programs to document anatomic and molecular pathology features that contribute to the Tumor (T), Node (N), Metastasis (M) - TNM - system of the American Joint Committee on Cancer (AJCC). This article highlights changes in CS for colon and rectal carcinomas as TNM moved from the AJCC 6th to the 7th editions. Data from 18 Surveillance, Epidemiology, and End Results (SEER) population-based registries were analyzed for the years 2004-2010, which included 191,361colon and 73,341 rectal carcinomas. Overall, the incidence of colon and rectal cancers declined, with the greatest decrease in stage 0. The AJCC's 7th edition introduction of changes in the subcategorization of T4, N1, and N2 caused shifting within stage groups in 25,577 colon and 10,150 rectal cancers diagnosed in 2010. Several site-specific factors (SSFs) introduced in the 7th edition had interesting findings: 1) approximately 10% of colon and rectal cancers had tumor deposits - about 30%-40% occurred without lymph node metastases, which resulted in 2.5% of colon and 3.3% of rectal cases becoming N1c (stage III A/B) in the AJCC 7th edition; 2) 10% of colon and 12% of rectal cases had circumferential radial margins <1 mm; 3) about 46% of colorectal cases did not have a carcinoembryonic antigen (CEA) testing or documented CEA information; and 4) about 10% of colorectal cases had perineural invasion. Adoption of the AJCC 7th edition by the SEER program provides an assessment tool for staging and SSFs on clinical outcomes. This evidence can be used for education and improved treatment for colorectal carcinomas. © 2014 American Cancer Society.

  13. Analysis of Stage and Clinical/Prognostic Factors for Colon and Rectal Cancer from SEER Registries: AJCC and Collaborative Stage Data Collection System

    PubMed Central

    Chen, Vivien W.; Hsieh, Mei-Chin; Charlton, Mary E.; Ruiz, Bernardo A.; Karlitz, Jordan; Altekruse, Sean; Ries, Lynn A.; Jessup, J. Milburn

    2014-01-01

    Background The Collaborative Stage (CS) Data Collection System enables multiple cancer registration programs to document anatomic and molecular pathology features that contribute to the Tumor (T), Node (N), Metastasis (M) (TNM) system of the American Joint Committee on Cancer (AJCC). This chapter highlights changes in CS for colon and rectal carcinomas as TNM moved from the AJCC 6th to the 7th edition. Methods Data from 18 Surveillance, Epidemiology, and End Results (SEER) population-based registries were analyzed for the years 2004-2010, which included 191 361colon and 73 341 rectal carcinomas. Results Overall, the incidence of colon and rectal cancer declined, with the greatest decrease in stage 0. The AJCC's 7th edition introduction of changes in the subcategorization of T4, N1, and N2 caused shifting within stage groups in 25 577 colon and 10 150 rectal cancers diagnosed in 2010. Several site-specific factors (SSFs) introduced in the 7th edition had interesting findings: 1) approximately 10% of colon and rectal cancers had tumor deposits - about 30-40% occurred without lymph node metastases which resulted in 2.5% of colon and 3.3% of rectal cases becoming N1c (stage III A/B) in AJCC 7th edition ; 2) 10% of colon and 12% of rectal cases had circumferential radial margins <1 mm; 3) about 46% of colorectal cases did not have a CEA testing or documented CEA information; and 4) about 10% of colorectal cases had perineural invasion. Conclusion Adoption of AJCC 7th edition by the SEER Program provides an assessment tool for staging and SSFs on clinical outcomes. This evidence can be used for education and improved treatment for colorectal carcinomas. PMID:25412391

  14. Endoscopic mucosal resection of early stage colon neuroendocrine carcinoma

    PubMed Central

    Yamasaki, Yasushi; Uedo, Noriya; Ishihara, Ryu; Tomita, Yasuhiko

    2015-01-01

    Early stage colorectal neuroendocrine carcinoma is rare. A small colon tumour was found in a 56-year-old man during diagnostic colonoscopy performed after a positive faecal occult blood test, and he was referred for treatment. A slightly reddish superficial elevated lesion with a shallow depression 10 mm in size was found in the transverse colon. Magnifying narrow-band imaging revealed disrupted irregular microvessels and the absence of a surface pattern in the depressed area. En bloc endoscopic mucosal resection (EMR) of the tumour was undertaken. The tumour was positive for chromogranin A and synaptophysin, and had a mitotic rate of >20/10 high-power fields and a Ki-67 proliferative index of >50%; it was diagnosed as a neuroendocrine carcinoma. The tumour minimally invaded the submucosa (300 μm) without lymphovascular involvement. The patient was followed up carefully, and at 1 year after EMR, no recurrence was found using colonoscopy and CT scans. PMID:25737221

  15. High copy number of mitochondrial DNA predicts poor prognosis in patients with advanced stage colon cancer.

    PubMed

    Wang, Yun; He, Shuixiang; Zhu, Xingmei; Qiao, Wei; Zhang, Juan

    2016-12-23

    The aim of this investigation was to determine whether alterations in mitochondrial DNA (mtDNA) copy number in colon cancer were associated with clinicopathological parameters and postsurgical outcome. By quantitative real-time PCR assay, the mtDNA copy number was detected in a cohort of colon cancer and matched adjacent colon tissues (n = 162). The majority of patients had higher mtDNA content in colon cancer tissues than matched adjacent colon tissues. Moreover, high mtDNA content in tumor tissues was associated with larger tumor size, higher serum CEA level, advanced TNM stage, vascular emboli, and liver metastases. Further survival curve analysis showed that high mtDNA content was related to the worst survival in patients with colon cancer at advanced TNM stage. High mtDNA content is a potential effective factor of poor prognosis in patients with advanced stage colon cancer.

  16. New approaches to assessing and treating early-stage colon and rectal cancers: cooperative group strategies for assessing optimal approaches in early-stage disease.

    PubMed

    Benson, Al B

    2007-11-15

    The U.S. Gastrointestinal Intergroup (GI Intergroup), including the National Cancer Institute of Canada, has created a portfolio of clinical trials for patients with stage II and III colon and rectal cancer, integrating therapeutic strategies from recent advanced disease trials. Fluoropyrimidine-based combination therapy for metastatic disease, with either irinotecan or oxaliplatin plus bevacizumab, has resulted in significant improvement in response and disease-free and overall survival. Cetuximab and irinotecan have produced intriguing response and progression-free survival data from randomized phase II trials. Although patients with stage II and III rectal cancer are uniformly included in individual clinical trials, the GI Intergroup conducts separate trials in patients with stage II and III colon cancer, with the exception of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which continues to merge both stages in their statistical designs. The U.S. chemotherapy platform for adjuvant therapy clinical trials is based on the positive adjuvant data from NSABP C-07 [FLOX with bolus 5-fluorouracil (5-FU)] and the MOSAIC trial (FOLFOX with infusional 5-FU). Three irinotecan-based adjuvant trials (one U.S. and two European) did not reach designated statistical end points. In addition, the GI Intergroup has consistently integrated molecular biological and other laboratory projects as important components of past and current trials. NSABP has recently completed accrual of patients to C-08, which is evaluating FOLFOX with or without bevacizumab in stage II/III colon cancer. E5202, the largest U.S. stage II colon cancer trial, determines patient risk by the initial evaluation of tumor 18q loss of heterozygosity and microsatellite instability status. Low-risk patients are observed, whereas high-risk patients are randomized to FOLFOX with or without bevacizumab. N0147 evaluates FOLFOX with or without cetuximab in patients with stage III disease. Two large

  17. Estimation of Life-Year Loss and Lifetime Costs for Different Stages of Colon Adenocarcinoma in Taiwan

    PubMed Central

    Chen, Po-Chuan; Lee, Jenq-Chang; Wang, Jung-Der

    2015-01-01

    Backgrounds and aims Life-expectancy of colon cancer patients cannot be accurately answered due to the lack of both large datasets and long-term follow-ups, which impedes accurate estimation of lifetime cost to treat colon cancer patients. In this study, we applied a method to estimate life-expectancy of colon cancer patients in Taiwan and calculate the lifetime costs by different stages and age groups. Methods A total of 17,526 cases with pathologically verified colon adenocarcinoma between 2002 and 2009 were extracted from Taiwan Cancer Registry database for analysis. All patients were followed-up until the end of 2011. Life-expectancy, expected-years-of-life-lost and lifetime costs were estimated, using a semi-parametric survival extrapolation method and borrowing information from life tables of vital statistics. Results Patients with more advanced stages of colon cancer were generally younger and less co-morbid with major chronic diseases than those with stages I and II. The LE of stage I was not significantly different from that of the age- and sex-matched general population, whereas those of stages II, III, and IV colon cancer patients after diagnosis were 16.57±0.07, 13.35±0.07, and 4.05±0.05 years, respectively; the corresponding expected-years-of-life-lost were 1.28±0.07, 5.93±0.07 and 16.42±0.06 years, significantly shorter than the general population after accounting for lead time bias. Besides, the lifetime cost of managing stage II colon cancer patients would be US $8,416±1939, 14,334±1,755, and 21,837±1,698, respectively, indicating a big saving for early diagnosis and treatment after stratification for age and sex. Conclusions Treating colon cancer at younger age and earlier stage saves more life-years and healthcare costs. Future studies are indicated to apply these quantitative results into the cost-effectiveness evaluation of screening program for colon cancers. PMID:26207912

  18. Effect of Incorporation of Pretreatment Serum Carcinoembryonic Antigen Levels Into AJCC Staging for Colon Cancer on 5-Year Survival.

    PubMed

    Thirunavukarasu, Pragatheeshwar; Talati, Chetasi; Munjal, Sumeet; Attwood, Kris; Edge, Stephen B; Francescutti, Valerie

    2015-08-01

    The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) levels (C stage) into the conventional TNM staging system of colon cancer. The latter proposal has yet to be widely adopted because of the lack of long-term survival estimates of after C-stage incorporation into AJCC staging. To evaluate whether long-term overall and cancer-specific survival is affected by inclusion of C stage into the standard AJCC TNM staging and to study the implications on survival estimates. We performed a retrospective study of all patients diagnosed as having histologically proven colonic adenocarcinoma from January 1, 2004, through December 31, 2005, from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. We stratified each AJCC stage as C0 (normal) or C1 (elevated) based on the pretreatment serum CEA level. Median follow-up was 71 months. Five-year estimates of overall and disease-specific survival and hazard ratios (HRs) for estimates of risk of overall and disease-specific mortality. A total of 16 619 patients were evaluated, and of these, 8878 patients had C0 disease and 7741 had C1 disease. C1 stage was independently associated with a 51% and 59% increased risk of overall (HR, 1.51; 95% CI, 1.44-1.59; P < .001) and disease-specific mortality (HR, 1.59; 95% CI, 1.49-1.69; P < . 001) at a median follow-up of 71 months. Analysis of survival of the AJCC stages subdivided as C0 or C1 revealed a significant worse prognosis of C1 AJCC stages compared with the respective C0 AJCC stages. The magnitude of change in survival was large enough to cause clustering of survival estimates of C1 vs C0 cancers across various AJCC stages. Analysis of patients with stage I, II, and III cancer revealed that node-negative C1 disease was associated with prognosis similar or worse than node-positive C0 disease. Inclusion of C stage into the AJCC TNM staging of colon cancer revealed significant

  19. Acceptance and Commitment Therapy in Improving Well-Being in Patients With Stage III-IV Cancer and Their Partners

    ClinicalTrials.gov

    2017-09-21

    Malignant Female Reproductive System Neoplasm; Malignant Hepatobiliary Neoplasm; Partner; Stage III Breast Cancer; Stage III Cervical Cancer; Stage III Colorectal Cancer; Stage III Lung Cancer; Stage III Prostate Cancer; Stage III Skin Melanoma; Stage III Uterine Corpus Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Lung Carcinoma; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Breast Cancer; Stage IV Cervical Cancer; Stage IV Colorectal Cancer; Stage IV Lung Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVA Colorectal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Cervical Cancer; Stage IVB Colorectal Cancer; Stage IVB Uterine Corpus Cancer

  20. Stage III xanthogranulomatous pyelonephritis treated with antibiotherapy and percutaneous drainage.

    PubMed

    Ergun, T; Akin, A; Lakadamyali, H

    2011-01-01

    Xanthogranulomatous pyelonephritis (XPN) is a rare inflammatory condition usually secondary to chronic obstruction caused by nephrolithiasis and resulting in infection and irreversible destruction of the renal parenchyma. Its standard therapy consists of total or partial nephrectomy. A case of stage III xanthogranulomatous pyelonephritis treated with antibiotherapy and percutaneous drainage is presented in this paper.

  1. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    ClinicalTrials.gov

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  2. Estrogen in obesity-associated colon cancer: friend or foe? Protecting postmenopausal women but promoting late-stage colon cancer.

    PubMed

    Chen, Jiezhong; Iverson, Don

    2012-11-01

    Obesity is associated with the increased incidence of colon cancer. Many cancer risk factors have been identified including increased blood levels of insulin, leptin, interleukin-6, interleukin-17, tumor necrosis factor-alpha, and decreased blood levels of adiponectin. However, the role of blood levels of estrogen in obesity-associated colon cancer is controversial. Evidence showed that obesity affected men more strongly than women in the carcinogenesis of colon cancer, indicating protective effect of estrogen which is increased in obesity. However, an epidemiological study has also shown that endogenous estradiol level is an independent risk factor for colon cancer, positively associated with colon cancer after normalizing insulin, IGF-1. The controversial opinions may be caused by different effects of ER-alpha and ER-beta. ER-alpha can increase colon cancer cell proliferation and increase cancer incidence. ER-beta has the opposite effect to ER-alpha, and it causes apoptosis of colon cancer cells. The normal colonocytes mainly express ER-beta. Therefore, increased estrogen in obesity may have protective effect via ER-beta in obesity-associated colon cancer. However, with the development of colon cancer, ER-alpha is increased and ER-beta is decreased. In the late stage of colon cancer, estrogen may promote cancer development via ER-alpha. The different effects and expression of ER-alpha and ER-beta may explain the different results observed in several epidemiological studies as well as several animal experiments. Therefore, manipulation of estrogen-caused signal pathways to inhibit ER-alpha and stimulate ER-beta may have preventive and therapeutic effect for obesity-associated colon cancer.

  3. Value of routine staging imaging studies for patients with stage III breast cancer.

    PubMed

    Piatek, Caroline I; Ji, Lingyun; Kaur, Chandan; Russell, Christy A; Tripathy, Debu; Church, Terry; Sposto, Richard; Sener, Stephen F; Garcia, Agustin A

    2016-12-01

    Routine staging imaging studies (RSIS) are optional in stage III breast cancer (BC). The impact of RSIS on treatment decisions and patient outcomes has not been extensively studied. The goal of this study was to determine whether RSIS in stage III BC affected treatment or patient outcomes. Stage III BC patients from 2000 to 2010 were retrospectively identified. RSIS results and treatment plan in response to RSIS results were recorded. Univariate and multivariate Cox proportional hazards regression models with time-dependent covariates were used to assess associations between RSIS use and recurrence-free survival (RFS). Of 420 patients, 362 (86.2%) received RSIS. RSIS were negative in 264 (72.9%), indeterminate in 77 (18.3%), and positive in 21 patients (5.0%) for metastatic disease. Treatment was altered in 21 (5.8%) patients based on RSIS results (20 with metastatic disease, 1 with indeterminate disease). There was no difference in RFS with RSIS use on multivariate analysis (hazard ratio 1.3; 95% confidence interval 0.73-2.5, P = 0.32). Most stage III BC patients underwent RSIS, but RSIS results infrequently affected treatment decisions. There was no significant difference in RFS with RSIS use. RSIS to identify metastatic disease for stage III BC has limited value. J. Surg. Oncol. 2016;114:917-921. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-02-02

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

  5. DETERMINANTS OF ADJUVANT OXALIPLATIN RECEIPT AMONG OLDER STAGE II AND III COLORECTAL CANCER PATIENTS

    PubMed Central

    Lund, Jennifer L; Stürmer, Til; Sanoff, Hanna K; Brookhart, Alan; Sandler, Robert S; Warren, Joan L

    2013-01-01

    Purpose Controversy exists regarding adjuvant oxaliplatin treatment among older stage II and III colorectal cancer (CRC) patients. We sought to identify patient/tumor, physician, hospital, and geographic factors associated with oxaliplatin use among older patients. Methods Individuals diagnosed at age>65 with stage II/III CRC from 2004–2007 undergoing surgical resection and receiving adjuvant chemotherapy were identified using the Surveillance, Epidemiology and End Results program (SEER)-Medicare, a database including patient/tumor and hospital characteristics. Physician information was obtained from the American Medical Association. We used Poisson regression to identify independent predictors of oxaliplatin receipt. The discriminatory ability of each category of characteristics to predict oxaliplatin receipt was assessed by comparing the area under the receiver operating curve (AUC) from logistic regression models. Results We identified 4,388 individuals who underwent surgical resection at 773 hospitals and received chemotherapy from 1,517 physicians. Adjuvant oxaliplatin use was higher among stage III (colon=56%, rectum=51%) compared to stage II patients (colon=37%, rectum=35%). Overall, patients who were older, diagnosed before 2006, separated, divorced or widowed, living in a higher poverty census tract or in the East or Midwest, or with higher levels of comorbidity were less likely to receive oxaliplatin. Patient factors and calendar year accounted for most of the variation in oxaliplatin receipt (AUC=75.8%). Conclusion Adjuvant oxaliplatin use increased rapidly from 2004–2007 despite uncertainties regarding its effectiveness in older patients. Physician and hospital characteristics had little influence on adjuvant oxaliplatin receipt among older patients. PMID:23512326

  6. Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Stage III or Stage IV Low-Grade Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-02-26

    Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Small Lymphocytic Lymphoma

  7. Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

    ClinicalTrials.gov

    2017-04-12

    Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

  8. Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer

    ClinicalTrials.gov

    2017-09-21

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Tongue Cancer

  9. Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

    ClinicalTrials.gov

    2017-09-12

    Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  10. Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-02-17

    Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  11. Diagnostic accuracy of computed tomography for colon cancer staging: a systematic review.

    PubMed

    Leufkens, Anke M; van den Bosch, Maurice A A J; van Leeuwen, Maarten S; Siersema, Peter D

    2011-07-01

    Computed Tomography (CT) is a frequently used staging modality for colon cancer patients in clinical practice. Our aim was to systemically review the available literature on diagnostic accuracy of CT for TNM staging of colon cancer. A systematic review of literature was performed. PubMed was searched using MeSH terms with the following search terms: "Tomography, X-Ray Computed" or "Tomography, Spiral Computed" and Colonic Neoplasms. Studies on rectal cancer and studies without separate analyses for the colon were excluded. We identified 779 publications, of which 11 were included for review. Overall and sample-size-weight sensitivity, specificity, accuracy, true-positive, true-negative, false-positive, false-negative, positive and negative predictive values were calculated for T, N and M stages. In the 11 studies, a total of 753 patients with 759 colon cancers underwent CT for staging. Sample-size-weighted sensitivity, specificity and accuracy for T-staging was 77%, 3% and 67%, respectively; for N-staging 76%, 55% and 69%, respectively; and for M-staging 85%, 98% and 95%, respectively. Additional clinical findings were reported in 59/372 (16%) patients, with 12 having a malignant and 47 a benign origin. While accuracy of CT for TN-staging of colon cancer is only reasonable, the real value of CT is its high accuracy to detect distant metastases.

  12. Two-stage minimally invasive surgical management of colonic gallstone ileus.

    PubMed

    Lujan, Henry J; Bisland, William B

    2010-08-01

    Colonic gallstone ileus is an unusual cause of colonic obstruction. Management of these patients is not standardized and can be challenging. As these patients are often ill and frail at presentation, surgical management needs to be individualized to decrease morbidity and mortality. We report a case that was managed by staged minimally invasive techniques with an excellent outcome.

  13. Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

    ClinicalTrials.gov

    2013-01-15

    Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

  14. Plastin polymorphisms predict gender- and stage-specific colon cancer recurrence after adjuvant chemotherapy.

    PubMed

    Ning, Yan; Gerger, Armin; Zhang, Wu; Hanna, Diana L; Yang, Dongyun; Winder, Thomas; Wakatsuki, Takeru; Labonte, Melissa J; Stintzing, Sebastian; Volz, Nico; Sunakawa, Yu; Stremitzer, Stefan; El-Khoueiry, Rita; Lenz, Heinz-Josef

    2014-02-01

    Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer treated with adjuvant chemotherapy. Genetic single-nucleotide polymorphisms (SNP) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future drug development. Recent in vitro and in vivo studies have demonstrated that the plastin genes PLS3 and LCP1 are overexpressed in colon cancer cells and play an important role in tumor cell invasion, adhesion, and migration. Hence, we hypothesized that functional genetic variations of plastin may have direct effects on the progression and prognosis of locally advanced colorectal cancer. We tested whether functional tagging polymorphisms of PLS3 and LCP1 predict time to tumor recurrence (TTR) in 732 patients (training set, 234; validation set, 498) with stage II/III colorectal cancer. The PLS3 rs11342 and LCP1 rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. PLS3 rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and tumor location. Female patients with the PLS3 rs6643869 AA genotype had the shortest median TTR compared with those with any G allele in the training set [1.7 vs. 9.4 years; HR, 2.84; 95% confidence interval (CI), 1.32-6.1; P = 0.005] and validation set (3.3 vs. 13.7 years; HR, 2.07; 95% CI, 1.09-3.91; P = 0.021). Our findings suggest that several SNPs of the PLS3 and LCP1 genes could serve as gender- and/or stage-specific molecular predictors of tumor recurrence in stage II/III patients with colorectal cancer as well as potential therapeutic targets.

  15. Type I/type III collagen ratio associated with diverticulitis of the colon in young patients.

    PubMed

    Brown, Shaun R; Cleveland, Elane M; Deeken, Corey R; Huitron, Sonni S; Aluka, Kanayochukwu J; Davis, Kurt G

    2017-01-01

    The incidence of diverticulitis in young patients is rising, whereas the type I:III collagen ratio of the colon decreases with age. Perhaps a lower type I:III collagen ratio in younger patients may predispose these patients to the development of the disease. The purpose of this study was to evaluate the collagen content and type I:III collagen ratio in patients with diverticulitis versus a control group. Patients who underwent a colon resection were identified. Three groups of patients were created for analysis: those with diverticulitis aged <50 y, >50 y, and a control group. Tissue samples were stained with Sirius red/fast green and photographed. Photos analysis was performed to quantify the amount of type I collagen and type III collagen. The type I:III collagen ratio was calculated for each patient and compared. The quantity of type I collagen and type III collagen was higher in patients with diverticulitis aged >50 y (P = 0.04 and P < 0.0001, respectively); however, the collagen ratio was greatest in those patients with diverticulitis aged <50 y (P = 0.01). Further analysis demonstrated a significant higher type I:III ratio in all patients aged less than 50 y compared with all patients aged over 50 y (P = 0.04). Our study demonstrated that diverticulitis in the younger patient was not associated with a lower type I:III collagen ratio. It appears that the decrease in collagen ratio of the colon with age is associated with an increase in type III collagen deposition. Published by Elsevier Inc.

  16. Prospective multicenter trial of staging adequacy in colon cancer: preliminary results.

    PubMed

    Bilchik, Anton J; DiNome, Maggie; Saha, Sukamal; Turner, Roderick R; Wiese, David; McCarter, Martin; Hoon, Dave S B; Morton, Donald L

    2006-06-01

    Lymph node evaluation is an important prognostic factor in colorectal cancer (CRC). A 25% recurrence rate in patients with node-negative CRC suggests that current staging practices are inadequate. Focused analysis of the sentinel node (SN) by multiple sectioning and immunohistochemistry improves staging accuracy. Prospective phase 2 multicenter trial. Tertiary referral cancer centers. Between March 2001 and June 2005, 132 patients were enrolled with clinical stage I and II CRC in a prospective multicenter trial (R01-CA90484). During a standard oncologic resection, lymphatic mapping was performed and the SN identified either by the surgeon or the pathologist. Hematoxylin-eosin staining was performed on all lymph nodes and immunohistochemistry, on lymph nodes negative by hematoxylin-eosin staining. Micrometastases greater than 0.2 mm but less than 2 mm and isolated tumor cells less than 0.2 mm were defined according to the sixth edition of the American Joint Committee on Cancer Cancer Staging Manual. The 63 men and 69 women had a median age of 74 years. Sixty-eight patients (52%) underwent a right hemicolectomy; 3 (2.3%), a transverse colectomy; 9 (7%), a left colectomy; 15 (11%), a sigmoid colectomy; 34 (26%), a low anterior resection; 1 (1%), an abdominal perineal resection; and 2 (2%), a total colectomy. Of the 111 evaluable primary tumors, 19 (17%) were T1 lesions; 17 (15%), T2; 72 (65%), T3; and 3 (2.7%), T4 tumors. Thirty-three patients (30%) were classified as stage I; 46 (41%), stage II, and 32 (29%), stage III. The SN was identified by the surgeon in 127 patients (96%) and by the pathologist in 5 patients (4%). The median number of SNs and total lymph nodes examined were 3 and 14.5, respectively. The sensitivity of lymphatic mapping and SN analysis was 88.2% and the false-negative rate, 7.4% (6/81). Of the 6 false-negative results, 4 were attributed to lymphatic channels obliterated by tumor. Upstaging occurred in 28 patients (23.6%). In a multicenter trial

  17. Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-09-08

    Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  18. Forward-viewing radial-array echoendoscope for staging of colon cancer beyond the rectum

    PubMed Central

    Kongkam, Pradermchai; Linlawan, Sittikorn; Aniwan, Satimai; Lakananurak, Narisorn; Khemnark, Suparat; Sahakitrungruang, Chucheep; Pattanaarun, Jirawat; Khomvilai, Supakij; Wisedopas, Naruemon; Ridtitid, Wiriyaporn; Bhutani, Manoop S; Kullavanijaya, Pinit; Rerknimitr, Rungsun

    2014-01-01

    AIM: To evaluate feasibility of the novel forward-viewing radial-array echoendoscope for staging of colon cancer beyond rectum as the first series. METHODS: A retrospective study with prospectively entered database. From March 2012 to February 2013, a total of 21 patients (11 men) (mean age 64.2 years) with colon cancer beyond the rectum were recruited. The novel forward-viewing radial-array echoendoscope was used for ultrasonographic staging of colon cancer beyond rectum. Ultrasonographic T and N staging were recorded when surgical pathology was used as a gold standard. RESULTS: The mean time to reach the lesion and the mean time to complete the procedure were 3.5 and 7.1 min, respectively. The echoendoscope passed through the lesions in 13 patients (61.9%) and reached the cecum in 10 of 13 patients (76.9%). No adverse events were found. The lesions were located in the cecum (n = 2), ascending colon (n = 1), transverse colon (n = 2), descending colon (n = 2), and sigmoid colon (n = 14). The accuracy rate for T1 (n = 3), T2 (n = 4), T3 (n = 13) and T4 (n = 1) were 100%, 60.0%, 84.6% and 100%, respectively. The overall accuracy rates for the T and N staging of colon cancer were 81.0% and 52.4%, respectively. The accuracy rates among traversable lesions (n = 13) and obstructive lesions (n = 8) were 61.5% and 100%, respectively. Endoscopic ultrasound and computed tomography had overall accuracy rates of 81.0% and 68.4%, respectively. CONCLUSION: The echoendoscope is a feasible staging tool for colon cancer beyond rectum. However, accuracy of the echoendoscope needs to be verified by larger systematic studies. PMID:24627604

  19. Forward-viewing radial-array echoendoscope for staging of colon cancer beyond the rectum.

    PubMed

    Kongkam, Pradermchai; Linlawan, Sittikorn; Aniwan, Satimai; Lakananurak, Narisorn; Khemnark, Suparat; Sahakitrungruang, Chucheep; Pattanaarun, Jirawat; Khomvilai, Supakij; Wisedopas, Naruemon; Ridtitid, Wiriyaporn; Bhutani, Manoop S; Kullavanijaya, Pinit; Rerknimitr, Rungsun

    2014-03-14

    To evaluate feasibility of the novel forward-viewing radial-array echoendoscope for staging of colon cancer beyond rectum as the first series. A retrospective study with prospectively entered database. From March 2012 to February 2013, a total of 21 patients (11 men) (mean age 64.2 years) with colon cancer beyond the rectum were recruited. The novel forward-viewing radial-array echoendoscope was used for ultrasonographic staging of colon cancer beyond rectum. Ultrasonographic T and N staging were recorded when surgical pathology was used as a gold standard. The mean time to reach the lesion and the mean time to complete the procedure were 3.5 and 7.1 min, respectively. The echoendoscope passed through the lesions in 13 patients (61.9%) and reached the cecum in 10 of 13 patients (76.9%). No adverse events were found. The lesions were located in the cecum (n = 2), ascending colon (n = 1), transverse colon (n = 2), descending colon (n = 2), and sigmoid colon (n = 14). The accuracy rate for T1 (n = 3), T2 (n = 4), T3 (n = 13) and T4 (n = 1) were 100%, 60.0%, 84.6% and 100%, respectively. The overall accuracy rates for the T and N staging of colon cancer were 81.0% and 52.4%, respectively. The accuracy rates among traversable lesions (n = 13) and obstructive lesions (n = 8) were 61.5% and 100%, respectively. Endoscopic ultrasound and computed tomography had overall accuracy rates of 81.0% and 68.4%, respectively. The echoendoscope is a feasible staging tool for colon cancer beyond rectum. However, accuracy of the echoendoscope needs to be verified by larger systematic studies.

  20. Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2017-04-05

    Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  1. Community assembly in epiphytic lichens in early stages of colonization.

    PubMed

    Gjerde, Ivar; Blom, Hans H; Lindblom, Louise; Saetersdal, Magne; Schei, Fride Høstad

    2012-04-01

    Colonization studies may function as natural experiments and have the potential of addressing important questions about community assembly. We studied colonization for a guild of epiphytic lichens in a former treeless heathland area of 170 km2 in southwest Norway. We investigated if epiphytic lichen species richness and composition on aspen (Populus tremula) trees corresponded to a random draw of lichen individuals from the regional species pool. We compared lichen communities of isolated young (55-120 yr) and old (140-200 yr) forest patches in the heathland area to those of aspen forest in an adjacent reference area that has been forested for a long time. All thalli (lichen bodies) of 32 selected lichen species on trunks of aspen were recorded in 35 aspen sites. When data for each site category (young, old, and reference) were pooled, we found the species richness by rarefaction to be similar for reference sites and old sites, but significantly lower for young sites. The depauperated species richness of young sites was accompanied by a skew in species composition and absence of several species that were common in the reference sites. In contrast, genetic variation screened with neutral microsatellite markers in the lichen species Lobaria pulmonaria showed no significant differences between site categories. Our null hypothesis of a neutral species assembly in young sites corresponding to a random draw from the regional species pool was rejected, whereas an alternative hypothesis based on differences in colonization capacity among species was supported. The results indicate that for the habitat configuration in the heathland area (isolated patches constituting < 0.4% of the area) lichen communities may need a colonization time of 100-150 yr for species richness to level off, but given enough time, isolation will not affect species richness. We suggest that this contradiction to expectations from classical island equilibrium theory results from low extinction rates.

  2. Cisplatin and Paclitaxel in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-29

    Chemotherapeutic Agent Toxicity; Endometrial Adenocarcinoma; Fallopian Tube Carcinoma; Gastrointestinal Complication; Malignant Ovarian Mixed Epithelial Tumor; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage II Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  3. Extended surgical staging for uterine papillary serous carcinoma: survival outcome of locoregional (Stage I-III) disease.

    PubMed

    Bristow, R E; Asrari, F; Trimble, E L; Montz, F J

    2001-05-01

    The aim of this study was to evaluate survival outcome in patients with locoregional uterine papillary serous carcinoma (UPSC) after extended surgical staging (ESS). All patients diagnosed with FIGO Stage I-III UPSC undergoing ESS (vertical incision, peritoneal cytology, TAH/BSO, omental biopsy, lymph node sampling, peritoneal biopsy) between 1/1/89 and 12/31/98 were identified retrospectively from the tumor registry database. Pathologic features predictive of regional extrauterine spread were evaluated using the log-rank test. The Kaplan-Meier method was used to generate survival curves, and median survival determinations were compared using the log-rank test or the proportional hazards regression model. Twenty-six patients with locoregional UPSC were identified: FIGO Stage I (n = 11), Stage II (n = 7), and Stage III (n = 8). The median age at diagnosis was 66 years. Preoperative endometrial pathology correctly identified the presence of UPSC in 76.9% of cases. The only pathologic feature found to be predictive of regional extrauterine spread (Stage III) was myometrial invasion > or =50% (P = 0.028). Adjuvant radiation therapy (RT) was administered to 6/18 patients with Stage I/II disease and 5/8 patients with Stage III disease. Platinum-based chemotherapy was administered to 5 patients with Stage III disease. All recurrences of Stage I/II disease were located within the pelvis (16.7%). For Stage III disease, all recurrences occurred at distant sites (42.9%). The median follow-up time for surviving patients was 39.0 months (mean = 45.0 months). For all patients, the overall 5-year survival rate was 61.2%. According to FIGO stage, the overall 5-year survival rates were Stage I, 81.8%; Stage II, 64.3%; and Stage III, 31.3%. No significant differences were detected in the risk of death by stage, although there was a trend toward worse survival with Stage III disease: Stage I hazard ratio [HR] = 1.00, Stage II HR = 1.68, 95% confidence interval [CI] = 0

  4. Comparison of Two Combination Chemotherapy Regimens Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

    ClinicalTrials.gov

    2015-04-30

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Stage III Uterine Corpus Cancer

  5. Incorporation of CEA Improves Risk Stratification in Stage II Colon Cancer.

    PubMed

    Spindler, Blake A; Bergquist, John R; Thiels, Cornelius A; Habermann, Elizabeth B; Kelley, Scott R; Larson, David W; Mathis, Kellie L

    2017-03-13

    High-risk features are used to direct adjuvant therapy for stage II colon cancer. Currently, high-risk features are identified postoperatively, limiting preoperative risk stratification. We hypothesized carcinoembryonic antigen (CEA) can improve preoperative risk stratification for stage II colon cancer. The National Cancer Database (NCDB 2004-2009) was reviewed for stage II colon adenocarcinoma patients undergoing curative intent resection. A novel risk stratification including both traditional high-risk features (T4 lesion, <12 lymph nodes sampled, and poor differentiation) and elevated CEA was developed. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. Concordance Probability Estimates (CPE) assessed discrimination. Seventy-four thousand nine hundred forty-five patients were identified; 40,844 (54.5%) had CEA levels reported and were included. Chemotherapy administration was similar between normal and elevated CEA groups (23.8 vs. 25.1%, p = 0.003). Compared to patients with CEA elevation, 5-year overall survival in patients with normal CEA was improved (74.5 vs. 63.4%, p < 0.001). Restratification incorporating CEA resulted in reclassification of 6912 patients (16.9%) from average to high risk. CPE increased for novel risk stratification (0.634 vs. 0.612, SE = 0.005). The routinely available CEA test improved risk stratification for stage II colon cancer. CEA not only may improve staging of colon cancer but may also help guide additional therapy.

  6. A comparative analysis and guidance for individualized chemotherapy of stage II and III colorectal cancer patients based on pathological markers

    PubMed Central

    Han, Yang; Lu, Su; Yu, Fudong; Liu, Xisheng; Sun, Huimin; Wang, Jingtao; Zhu, Xingwu; Lu, Huijun; Yue, Hao; Wang, Jing; Lin, Jun; Zhou, Chongzhi; Tang, Huamei; Peng, Zhihai

    2016-01-01

    Adjuvant chemotherapy is considered the standard of care for patients with colorectal cancer after curative resection. Although current guidelines provide clear instructions for chemotherapy for stage II high-risk and stage III colorectal cancer, it is insufficient to individualize therapy. We analyzed the outcomes of 902 patients with colorectal cancer treated with or without chemotherapy in our hospital. We found Chinese survival benefit for chemotherapy was consistent with current guidelines. Moreover, our data added to the evidence that chemotherapy might be used for elderly patients with stage II high-risk colorectal cancer. Pathological markers could predict response to individualize therapy in a convenient, fast and inexpensive way. We compared survivals of patients with stage II high-risk and stage III colorectal cancer with chemotherapy in different pathological markers expression, and furthermore used 458 colon adenocarcinoma samples from The Cancer Genome Atlas to verify our preliminary results. We confirmed TOPIIα, EGFR and P170 may be sufficiently predictive markers to individualize chemotherapy. FOLFOX was the optimal adjuvant chemotherapy for patients with stage II high-risk and stage III colorectal cancer when TOPIIα was positive or EGFR or P170 was negative. PMID:27845412

  7. The development and validation of a CT-based radiomics signature for the preoperative discrimination of stage I-II and stage III-IV colorectal cancer

    PubMed Central

    He, Lan; Chen, Xin; Ma, Zelan; Dong, Di; Tian, Jie; Liang, Changhong; Liu, Zaiyi

    2016-01-01

    Objectives To investigative the predictive ability of radiomics signature for preoperative staging (I-IIvs.III-IV) of primary colorectal cancer (CRC). Methods This study consisted of 494 consecutive patients (training dataset: n=286; validation cohort, n=208) with stage I–IV CRC. A radiomics signature was generated using LASSO logistic regression model. Association between radiomics signature and CRC staging was explored. The classification performance of the radiomics signature was explored with respect to the receiver operating characteristics(ROC) curve. Results The 16-feature-based radiomics signature was an independent predictor for staging of CRC, which could successfully categorize CRC into stage I-II and III-IV (p <0.0001) in training and validation dataset. The median of radiomics signature of stage III-IV was higher than stage I-II in the training and validation dataset. As for the classification performance of the radiomics signature in CRC staging, the AUC was 0.792(95%CI:0.741-0.853) with sensitivity of 0.629 and specificity of 0.874. The signature in the validation dataset obtained an AUC of 0.708(95%CI:0.698-0.718) with sensitivity of 0.611 and specificity of 0.680. Conclusions A radiomics signature was developed and validated to be a significant predictor for discrimination of stage I-II from III-IV CRC, which may serve as a complementary tool for the preoperative tumor staging in CRC. PMID:27120787

  8. Stage dependent expression and tumor suppressive function of FAM134B (JK1) in colon cancer.

    PubMed

    Islam, Farhadul; Gopalan, Vinod; Wahab, Riajul; Smith, Robert A; Qiao, Bin; Lam, Alfred King-Yin

    2017-01-01

    The aims of the present study are to investigate sub-cellular location, differential expression in different cancer stages and functional role of FAM134B in colon cancer development. FAM134B expression was studied and quantified at protein and mRNA levels in cell lines using immunocytochemistry, Western blot and real-time PCR. In vitro functional assays and an in vivo xenotransplantation mouse models were used to investigate the molecular role of FAM134B in cancer cell biology in response to FAM134B silencing with shRNA lentiviral particles. FAM134B protein was noted in both cytoplasm and nuclei of cancer cells. In cancer cells derived from stage IV colon cancer, FAM134B expression was remarkably reduced when compared to non-cancer colon cells and cancer cells derived from stage II colon cancer. FAM134B knockdown significantly (P < 0.05) increased the proliferation of colon cancer cells following lentiviral transfection. Furthermore, FAM134B suppression significantly increased (34-52%; P < 0.05) the clonogenic capacity, wound healing potential of and increases the proportion of cells performing DNA synthesis (P < 0.01). Xenotransplantation model showed that larger and higher-grade tumors were formed in mice receiving FAM134B knockdown cells. To conclude, expression analysis, in vitro and in vivo indicated that FAM134B acts as a cancer suppressor gene in colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

    ClinicalTrials.gov

    2012-10-30

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

  10. Gefitinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III or Stage IV Head and Neck Cancer

    ClinicalTrials.gov

    2013-01-24

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

  11. Desmoplasia influenced recurrence of disease and mortality in stage III colorectal cancer within five years after surgery and adjuvant therapy.

    PubMed

    Zippi, Maddalena; De Toma, Giorgio; Minervini, Giovanni; Cassieri, Claudio; Pica, Roberta; Colarusso, Diodoro; Stock, Simon; Crispino, Pietro

    2017-01-01

    In patients with colon cancer who undergo resection for potential cure, 40-60% have advanced locoregional disease (stage III). Those who are suitable for adjuvant treatment had a definite disease-free-survival benefit. The aim of the present study was to demonstrate whether the presence of desmoplasia influenced the mortality rate of stage III colorectal cancer (CRC) within 5 years from the surgery and adjuvant therapy. Sixty-five patients with stage III CRC underwent resection and adjuvant therapy. Qualitative categorization of desmoplasia was obtained using Ueno's stromal CRC classification. Desmoplasia was related to mortality using Spearman correlation and stratified with other histological variables (inflammation, grading) that concurred to the major determinant of malignancy (venous invasion and lymph nodes) using the Chi-square test. The 5-year survival rate was 65% and the relapse rate was 37%. The mortality rate in patients with immature desmoplasia was 86%, 27% in intermediate desmoplasia, and 0% in mature desmoplasia (Spearman correlation coefficient: -0.572,P= 0.05). Immature desmoplasia appears to be associated with disease recurrence and mortality in stage III CRC patients.

  12. Desmoplasia Influenced Recurrence of Disease and Mortality in Stage III Colorectal Cancer within Five Years after Surgery and Adjuvant Therapy

    PubMed Central

    Zippi, Maddalena; De Toma, Giorgio; Minervini, Giovanni; Cassieri, Claudio; Pica, Roberta; Colarusso, Diodoro; Stock, Simon; Crispino, Pietro

    2017-01-01

    Background/Aims: In patients with colon cancer who undergo resection for potential cure, 40–60% have advanced locoregional disease (stage III). Those who are suitable for adjuvant treatment had a definite disease-free-survival benefit. The aim of the present study was to demonstrate whether the presence of desmoplasia influenced the mortality rate of stage III colorectal cancer (CRC) within 5 years from the surgery and adjuvant therapy. Patients and Methods: Sixty-five patients with stage III CRC underwent resection and adjuvant therapy. Qualitative categorization of desmoplasia was obtained using Ueno's stromal CRC classification. Desmoplasia was related to mortality using Spearman correlation and stratified with other histological variables (inflammation, grading) that concurred to the major determinant of malignancy (venous invasion and lymph nodes) using the Chi-square test. Result: The 5-year survival rate was 65% and the relapse rate was 37%. The mortality rate in patients with immature desmoplasia was 86%, 27% in intermediate desmoplasia, and 0% in mature desmoplasia (Spearman correlation coefficient: −0.572, P = 0.05). Conclusion: Immature desmoplasia appears to be associated with disease recurrence and mortality in stage III CRC patients. PMID:28139499

  13. Duration of symptoms, stage at diagnosis and relative survival in colon and rectal cancer.

    PubMed

    Jullumstrø, Eivind; Lydersen, Stian; Møller, Bjørn; Dahl, Olav; Edna, Tom-H

    2009-09-01

    In colorectal cancer, the relation between duration of symptoms and stage at presentation and prognosis is not yet settled. All 1263 patients treated for colorectal cancer at Levanger Hospital, 1980-2004, and 2892 patients treated in Norway during 2004 were included. The association between symptom duration as an explanatory variable and tumour stage as a dependent variable was analysed using a proportional odds logistic regression model. Known duration of symptoms was divided into four categories: <1 week, 1-8 weeks, 2-6 months and >6 months. There was an inverse relationship between symptom duration and colon cancer TNM-stage, OR=0.73 (95% CI 0.63-0.84), p<0.001 (Levanger Hospital) and 0.84 (0.75-0.95), p=0.004 (Norway 2004), where the OR is per category of symptom duration. Duration of symptoms were also inversely associated with T-stage, N-stage and M-stage in colon cancer. These relationships were not found for rectal cancer. In colon cancer the relative five-year survival for the four intervals of symptom duration was 44%, 39%, 54% and 66%, p<0.001, in Levanger, 1980-2004, and four-year survival was 46%, 62%, 75% and 74%, p<0.001, in Norway 2004, respectively. For rectal cancer survival was not dependent on symptom duration. In a multivariate analysis of relative survival of patients with colon cancer, duration of symptoms was associated with survival independent of tumour differentiation and TNM-stage. Increasing duration of symptoms was positively associated with less advanced disease and better survival in colon cancer, but not in rectal cancer.

  14. Qualification of Minuteman stage III motor for spin stabilized perigee stages

    NASA Astrophysics Data System (ADS)

    Day, E. E.

    1980-06-01

    The third stage of the Minuteman III ICBM was recently qualified for Space Transportation System launch as a tailored upper stage in order to use its unique combination of performance (2.1 million lbf-sec), reliability (100% on 140 tests), and maturity (900 built). The motor was static fired while spinning at 70 rpm and 100 F, and the propellant was also tested for spin effects up to 27 g in small motors. The ignition system, propellant, and case materials were also subjected to long vacuum exposure. Analyses of carry and launch from the Shuttle showed higher margins than previous qualification on the expendable missile vehicle. Early space flights are expected by the McDonnell Douglas Astronautics PAM-A (SSUS-A) version, and for the Hughes LEASAT.

  15. Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

    ClinicalTrials.gov

    2017-04-04

    Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

  16. Different effects of ERβ and TROP2 expression in Chinese patients with early-stage colon cancer.

    PubMed

    Fang, Yu-Jing; Wang, Guo-Qiang; Lu, Zhen-Hai; Zhang, Lin; Li, Ji-Bin; Wu, Xiao-Jun; Ding, Pei-Rong; Ou, Qing-Jian; Zhang, Mei-Fang; Jiang, Wu; Pan, Zhi-Zhong; Wan, De-Sen

    2012-12-01

    Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T(3)N(0)M(0) (stage IIa) and T(4)N(0)M(0) (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan-Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

  17. Tumour budding is a reproducible index for risk stratification of patients with stage II colon cancer.

    PubMed

    Lai, Y-H; Wu, L-C; Li, P-S; Wu, W-H; Yang, S-B; Xia, P; He, X-X; Xiao, L-B

    2014-04-01

    High-risk patients with Stage II colon cancer may benefit from adjuvant chemotherapy, but it is difficult to identify such a patient group. A robust and reproducible index would be helpful to select the subset of Stage II colon cancer patients at high risk. This study investigated the potential prognostic significance of tumour budding in Stage II colon cancer. In all, 135 Stage II colon cancer patients with known outcome were identified. The degree of tumour budding was assessed by two individual observers and was classified, according to the number of tumour buds in the area with the greatest budding intensity on haematoxylin and eosin slides, as high-grade budding (10 or more tumour buds) and low-grade budding (0-9 buds). Inter-observer agreement for two observers was assessed by using the kappa test. Progression-free and cancer-specific survivals were analysed using the Kaplan-Meier method and Cox regression. The 5-year progression-free survival rates for patients with high-grade tumour budding (n = 36) and those with low-grade budding (n = 99) were 57.6% and 89.0% (P < 0.001). The 5-year cancer-specific survival rates were 66.7% vs 92.0% (P < 0.001). Cox regression analyses demonstrated tumour budding as an independent predictor of disease progression (hazard ratio 4.982, P < 0.001) and cancer-related death (hazard ratio 4.142, P = 0.003). The two observers agreed on the classification of tumour budding in 118 cases (87.4%) and the inter-observer agreement was good (κ = 0.692). Tumour budding is a strong and reproducible prognostic factor for adverse outcome in Stage II colon cancer, which may serve as a prognostic marker to identify patients with a high risk of recurrence who may benefit from adjuvant therapy. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  18. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia

    PubMed Central

    Pearson, John; Aitchison, Alan; Dixon, Liane; Frizelle, Frank A.; Keenan, Jacqueline I.

    2017-01-01

    Background Enterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Here, we aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum. Methods Mucosal tissue from up to four different colonic sites was obtained from a consecutive series of 150 patients referred for colonoscopy. The presence and relative abundance of the B. fragilis toxin gene (bft) in each tissue sample was determined using quantitative PCR, and associations with clinicopathological characteristics were analysed. Findings We found a high concordance of ETBF between different colonic sites (86%). Univariate analysis showed statistically significant associations between ETBF positivity and the presence of low-grade dysplasia (LGD), tubular adenomas (TA), and serrated polyps (P-values of 0.007, 0.027, and 0.007, respectively). A higher relative abundance of ETBF was significantly associated with LGD and TA (P-values of < 0.0001 and 0.025, respectively). Increased ETBF positivity and abundance was also associated with left-sided biopsies, compared to those from the right side of the colon. Conclusion Our results showing association of ETBF positivity and increased abundance with early-stage carcinogenic lesions underlines its importance in the development of colorectal cancer, and we suggest that detection of ETBF may be a potential marker of early colorectal carcinogenesis. PMID:28151975

  19. Colon Cancer Staging in Vulnerable Older Adults: Adherence to National Guidelines and Impact on Survival

    PubMed Central

    Leal, TB; Holden, T; Cavalcante, L; Allen, GO; Schumacher, JR; Smith, MA; Weiss, JM; Neuman, HB; LoConte, NK

    2015-01-01

    Background There is concern that elders are not adequately evaluated prior to colon cancer surgery. We sought to determine adherence with ACOVE-3 (Assessing Care of Vulnerable Elders) quality indicators for pre-operative staging prior to colectomy for colon cancer utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (1992–2005). Methods We determined the proportion of patients aged 75 and older who had preoperative staging prior to colectomy for colon adenocarcinoma. Preoperative staging was defined as abdominopelvic computed tomography or magnetic resonance imaging scan (SCAN) and colonoscopy or flexible sigmoidoscopy (SCOPE). Multivariate logistic regression identified predictors of adherence. Odds ratios were adjusted for comorbidity, socioeconomic status, and disease severity. The association of adherence to ACOVE-3 and survival was quantified. Results Of the 37,862 patients, the majority were 75–84 years, 28% of the patients were ≥85 years. Regarding preoperative staging in the 6-month interval prior to surgical resection, 8% had neither SCAN nor SCOPE, 6% had only SCAN, 43% had only SCOPE, and 43% had both SCAN and SCOPE. Compared to patients who were not staged, those evaluated with either SCOPE alone or SCAN plus SCOPE had lower odds of 3-year mortality. Patients who were staged with SCAN alone had an increased odds of death compared to those who had neither SCAN or SCOPE. Conclusions These data demonstrate that the majority of vulnerable elders with colon cancer did not receive appropriate preoperative staging prior to resection. The findings also confirm that adherence to ACOVE-3 guidelines is associated with improved long-term survival. PMID:25914900

  20. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    ClinicalTrials.gov

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  1. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer.

    PubMed

    Cheruvu, Praveena; Metcalfe, Su K; Metcalfe, Justin; Chen, Yuhchyau; Okunieff, Paul; Milano, Michael T

    2011-06-30

    Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed.

  2. Early-stage primary signet ring cell carcinoma of the colon.

    PubMed

    Kim, Jae Hyun; Park, Seun Ja; Park, Moo In; Moon, Won; Kim, Sung Eun

    2013-06-28

    Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.

  3. Predicting survival after curative colectomy for cancer: individualizing colon cancer staging.

    PubMed

    Weiser, Martin R; Gönen, Mithat; Chou, Joanne F; Kattan, Michael W; Schrag, Deborah

    2011-12-20

    Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy. Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves. Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line. Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer.

  4. Relation between Medicare screening reimbursement and stage at diagnosis for older patients with colon cancer.

    PubMed

    Gross, Cary P; Andersen, Martin S; Krumholz, Harlan M; McAvay, Gail J; Proctor, Deborah; Tinetti, Mary E

    2006-12-20

    Medicare's reimbursement policy was changed in 1998 to provide coverage for screening colonoscopies for patients with increased colon cancer risk, and expanded further in 2001 to cover screening colonoscopies for all individuals. To determine whether the Medicare reimbursement policy changes were associated with an increase in either colonoscopy use or early stage colon cancer diagnosis. Patients in the Surveillance, Epidemiology, and End Results Medicare linked database who were 67 years of age and older and had a primary diagnosis of colon cancer during 1992-2002, as well as a group of Medicare beneficiaries who resided in Surveillance, Epidemiology, and End Results areas but who were not diagnosed with cancer. Trends in colonoscopy and sigmoidoscopy use among Medicare beneficiaries without cancer were assessed using multivariate Poisson regression. Among the patients with cancer, stage was classified as early (stage I) vs all other (stages II-IV). Time was categorized as period 1 (no screening coverage, 1992-1997), period 2 (limited coverage, January 1998-June 2001), and period 3 (universal coverage, July 2001-December 2002). A multivariate logistic regression (outcome = early stage) was used to assess temporal trends in stage at diagnosis; an interaction term between tumor site and time was included. Colonoscopy use increased from an average rate of 285/100,000 per quarter in period 1 to 889 and 1919/100,000 per quarter in periods 2 (P<.001) and 3 (P vs 2<.001), respectively. During the study period, 44,924 eligible patients were diagnosed with colorectal cancer. The proportion of patients diagnosed at an early stage increased from 22.5% in period 1 to 25.5% in period 2 and 26.3% in period 3 (P<.001 for each pairwise comparison). The changes in Medicare coverage were strongly associated with early stage at diagnosis for patients with proximal colon lesions (adjusted relative risk period 2 vs 1, 1.19; 95% confidence interval, 1.13-1.26; adjusted relative risk

  5. Incidence and Predictors of Bowel Obstruction in Elderly Patients With Stage IV Colon Cancer

    PubMed Central

    Winner, Megan; Mooney, Stephen J.; Hershman, Dawn L.; Feingold, Daniel L.; Allendorf, John D.; Wright, Jason D.; Neugut, Alfred I.

    2015-01-01

    IMPORTANCE Research has been limited on the incidence, mechanisms, etiology, and treatment of symptoms that require palliation in patients with terminal cancer. Bowel obstruction (BO) is a common complication of advanced abdominal cancer, including colon cancer, for which small, single-institution studies have suggested an incidence rate of 15% to 29%. Large population-based studies examining the incidence or risk factors associated with BO in cancer are lacking. OBJECTIVE To investigate the incidence and risk factors associated with BO in patients with stage IV colon cancer. DESIGN AND SETTING Retrospective cohort, population-based study of patients in the Surveillance, Epidemiology, and End Results and Medicare claims linked databases who were diagnosed as having stage IV colon cancer from January 1, 1991, through December 31, 2005. PATIENTS Patients 65 years or older with stage IV colon cancer (n = 12 553). MAIN OUTCOMES AND MEASURES Time to BO, defined by inpatient hospitalization for BO. We used Cox proportional hazards regression models to determine associations between BO and patient, prior treatment, and tumor features. RESULTS We identified 1004 patients with stage IV colon cancer subsequently hospitalized with BO (8.0%). In multivariable analysis, proximal tumor site (hazard ratio, 1.22 [95% CI, 1.07–1.40]), high tumor grade (1.34 [1.16–1.55]), mucinous histological type (1.27 [1.08–1.50]), and nodal stage N2 (1.52 [1.26–1.84]) were associated with increased risk of BO, as was the presence of obstruction at cancer diagnosis (1.75 [1.47–2.04]). A more recent diagnosis was associated with decreased risk of subsequent obstruction (hazard ratio, 0.84 [95% CI, 0.72–0.98]). CONCLUSIONS AND RELEVANCE In this large population of patients with stage IV colon cancer, BO after diagnosis was less common (8.0%) than previously reported. Risk was associated with site and histological type of the primary tumor. Future studies will explore management and

  6. DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.

    PubMed

    Toiyama, Yuji; Inoue, Yasuhiro; Yasuda, Hiromi; Saigusa, Susumu; Yokoe, Takeshi; Okugawa, Yoshinaga; Tanaka, Koji; Miki, Chikao; Kusunoki, Masato

    2011-02-01

    We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease. The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer. DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients. DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

  7. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer

    PubMed Central

    Swets, Marloes; Zaalberg, Anniek; Boot, Arnoud; van Wezel, Tom; Frouws, Martine A.; Bastiaannet, Esther; Gelderblom, Hans; van de Velde, Cornelis J. H.; Kuppen, Peter J. K.

    2016-01-01

    Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated. PMID:28035987

  8. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer.

    PubMed

    Swets, Marloes; Zaalberg, Anniek; Boot, Arnoud; van Wezel, Tom; Frouws, Martine A; Bastiaannet, Esther; Gelderblom, Hans; van de Velde, Cornelis J H; Kuppen, Peter J K

    2016-12-27

    Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03-2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13-3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated.

  9. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

    PubMed

    Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age <65 years, male sex, nonwhite race, use of a community treatment facility, non-Medicare insurance, and diagnosis before 2004. Improved and clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, <12 lymph nodes evaluated, positive resection margins, or T4 histology), age, or chemotherapy regimen, even after adjustment for covariates and propensity score weighting (hazard ratio, 0.76; P<.001). There was no difference in survival noted between single and multiagent adjuvant chemotherapy regimens. In what to the authors' knowledge is the largest group of patients with stage II colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy

  10. Overall survival after resection for colon cancer in a national cohort study was adversely affected by TNM stage, lymph node ratio, gender, and old age.

    PubMed

    Storli, Kristian E; Søndenaa, Karl; Bukholm, Ida R K; Nesvik, Idunn; Bru, Tore; Furnes, Bjørg; Hjelmeland, Bjarte; Iversen, Knut B; Eide, Geir E

    2011-10-01

    A national surveillance program of colon cancer treatment was introduced in 2007. We examined prognostic factors for colon cancer operated in 2000 with an aim of improving survival in the new program and a special focus on the merit of lymph node yield. A cohort of 269 patients, 152 women (56.5%), with a mean age of 71 years, was operated for colon cancer in 2000 at three teaching hospitals and followed up for 7 years. Overall 5-year survival was 58.0%, and overall hospital mortality was 5.2%, with 4.5% in elective cases and 12.5% after urgent surgery. In only 41.1% of the specimens were 12 or more lymph nodes retrieved, but this did not affect survival in the combined cohort, although one of the hospitals achieved a significantly better result with a harvest of 12 or more lymph nodes. In a multivariate analysis, old age, gender, a high lymph node ratio (LNR) at stage III, and tumor-node-metastasis stage were adverse factors for survival. The operative mortality was high and should be reassessed. The lymph node count did not have a significant impact on outcome overall, whereas the LNR proved significant for stage III. A prospective protocol using overall lymph node yield as a surrogate measure for more radical surgery, nevertheless, seems warranted to improve the lymph node harvest according to international recommendations.

  11. Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope

    PubMed Central

    Saldua, Meagan A.; Olsovsky, Cory A.; Callaway, Evelyn S.; Chapkin, Robert S.

    2012-01-01

    Abstract. Large area confocal microscopy may provide fast, high-resolution image acquisition for evaluation of tissue in pre-clinical studies with reduced tissue processing in comparison to histology. We present a rapid beam and stage-scanning confocal fluorescence microscope to image cellular and tissue features along the length of the entire excised mouse colon. The beam is scanned at 8,333  lines/sec by a polygon scanning mirror while the specimen is scanned in the orthogonal axis by a motorized translation stage with a maximum speed of 7  mm/sec. A single 1×60 mm2 field of view image spanning the length of the mouse colon is acquired in 10 s. Z-projection images generated from axial image stacks allow high resolution imaging of the surface of non-flat specimens. In contrast to the uniform size, shape, and distribution of colon crypts in confocal images of normal colon, confocal images of chronic bowel inflammation exhibit heterogeneous tissue structure with localized severe crypt distortion. PMID:22352656

  12. Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope

    NASA Astrophysics Data System (ADS)

    Saldua, Meagan A.; Olsovsky, Cory A.; Callaway, Evelyn S.; Chapkin, Robert S.; Maitland, Kristen C.

    2012-01-01

    Large area confocal microscopy may provide fast, high-resolution image acquisition for evaluation of tissue in pre-clinical studies with reduced tissue processing in comparison to histology. We present a rapid beam and stage-scanning confocal fluorescence microscope to image cellular and tissue features along the length of the entire excised mouse colon. The beam is scanned at 8,333 lines/sec by a polygon scanning mirror while the specimen is scanned in the orthogonal axis by a motorized translation stage with a maximum speed of 7 mm/sec. A single 1×60 mm2 field of view image spanning the length of the mouse colon is acquired in 10 s. Z-projection images generated from axial image stacks allow high resolution imaging of the surface of non-flat specimens. In contrast to the uniform size, shape, and distribution of colon crypts in confocal images of normal colon, confocal images of chronic bowel inflammation exhibit heterogeneous tissue structure with localized severe crypt distortion.

  13. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    ClinicalTrials.gov

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  14. Soluble interleukin-2 receptor in stage I-III melanoma.

    PubMed

    Ottaiano, Alessandro; Leonardi, Enrico; Simeone, Ester; Ascierto, Paolo Antonio; Scala, Stefania; Calemma, Rosa; Bryce, Jane; Caracò, Corrado; Satriano, Rocco A; Gianfranco, Nicoletti; Franco, Renato; Botti, Gerardo; Castello, Giuseppe

    2006-02-07

    The aim of the present study was to assess the prognostic value of soluble interleukin-2 receptor (sIL-2R) serum levels in stage I-III melanoma patients. The levels of sIL-2R were determined using an enzyme immunometric test kit in 329 patients affected by malignant melanoma (MM) from 1995 to 2004. Correlations between sIL-2R values, baseline patients and tumour features were studied by contingency tables and the chi-square test. The Kaplan-Meier product limit method was applied to plot disease-free survival (DFS) curves. Univariate analysis was performed with the Log-rank test. Cox proportional-hazards regression was used to analyse the effect of several risk factors on DFS. In total, 2330 blood samples were collected during follow-up of 329 MM patients. Forty-five (13.7%) patients had Breslow tumour thickness1.00 and 2.00 and 4.00 mm. Ulceration was present in 64 cases (19.4%). Thirty-nine sentinel lymph nodes (SLNs) (11.8%) were infiltrated by MM. Soluble IL-2R values ranged from 130 to 1420 U/ml; median value was 500 U/ml. One hundred twenty-one (36.8%) patients presented with sIL-2R>600 U/ml at first measure (FM), 194 patients (58.9%) with values increasing up to or more than 600 U/ml [increasing values (IV) pattern]. A correlation was found between Breslow's tumour values and the IV sIL-2R pattern group (P=0.0304 with chi2 test). Gender, presence of ulceration, Breslow tumour thickness, FM and IV sIL-2R pattern groups had a significant prognostic value for DFS. At multivariate analysis, presence of ulceration, gender, FM and IV sIL-2R pattern groups emerged as independent prognostic factors for DFS. The 5-year DFS rate was 88% for patients with FM<600 U/ml and 76.9% for patients with FM>600 U/ml. In IV pattern, the 5-year DFS rate was 69.5% compared to 87% for patients with no sIL-2R values>600 U/ml during follow-up. sIL-2R values are associated with

  15. Multimodal Therapy for Stage III Retinoblastoma (International Retinoblastoma Staging System): A Prospective Comparative Study.

    PubMed

    Chawla, Bhavna; Hasan, Fahmi; Seth, Rachna; Pathy, Sushmita; Pattebahadur, Rajesh; Sharma, Sanjay; Upadhyaya, Ashish; Azad, Rajvardhan

    2016-09-01

    To compare the efficacy of 2 chemotherapeutic drug combinations as part of multimodal therapy for orbital retinoblastoma. Prospective, comparative, study. Patients with stage III retinoblastoma (International Retinoblastoma Staging System). Demographic and clinical features were recorded at presentation. Treatment consisted of a multimodal protocol with neoadjuvant chemotherapy, enucleation, orbital external-beam radiotherapy, and adjuvant chemotherapy. For chemotherapy, patients were randomized into 2 groups: group A patients were treated with vincristine, etoposide, and carboplatin (VEC) and group B patients were treated with carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Treatment outcomes and adverse effects were recorded. Efficacy parameters were compared between the groups. Survival probability, cause of death, and chemotherapy-related toxicity. A total of 54 children were recruited (27 in each group). The mean ± SD follow-up was 21.3±11.34 months. The overall Kaplan-Meier survival probability was 80% (95% confidence interval [CI], 0.67-0.89) and 42% (95% CI, 0.24-0.59) at 1 year and 4 years, respectively. There were 9 deaths in group A and 15 deaths in group B. The Kaplan-Meier survival probability at 1 year was similar between the groups: 81% (95% CI, 0.60-0.91) and 79% (95% CI, 0.58-0.9) for groups A and B, respectively. At 4 years, the survival probability for group A was higher (63% [95% CI, 0.41-0.79] vs. 25% [95% CI, 0.08-0.46] for groups A and B, respectively), with a strong trend of better survival in group A over time (P = 0.05). The major cause of death was central nervous system relapse (8 patients in group A and 7 patients in group B). Two patients in group B died of sepsis after febrile neutropenia. Grade 3 and grade 4 hematologic toxicities were more common in group B, with a significant difference in grade 4 neutropenia (P = 0.002). This study compared the outcomes of VEC chemotherapy with a 5

  16. Prognostic value of stem cell quantification in stage II colon cancer.

    PubMed

    Vaz, Maria Angeles; Martinez, Juan Carlos; Devesa, José Manuel; Trill, Javier Die; Abraira, Victor; Riquelme, Alejandro; Carrato, Alfredo

    2014-01-01

    Cancer stem cells (CSCs) are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer. One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: <10%, 11-25%, 26-50% and >50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival. The average patient age was 68 years (patients were between 45-92 years of age) and median follow up was 5.8 years. There was recurrent disease in 17 (17%); CD133 expression (defined by >10% positivity) was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS) or overall survival (OS). However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS. Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.

  17. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    ClinicalTrials.gov

    2017-08-22

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  18. Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

    ClinicalTrials.gov

    2017-08-01

    Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

  19. Association of symptoms of colon cancer patients with tumor location and TNM tumor stage.

    PubMed

    Alexiusdottir, Kristin K; Möller, Pall Helgi; Snaebjornsson, Petur; Jonasson, Larus; Olafsdottir, Elinborg J; Björnsson, Einar Stefan; Tryggvadottir, Laufey; Jonasson, Jon G

    2012-07-01

    Colon cancer is the second most common cause of cancer death in Iceland and accounts for 8% of malignancies. We related information on symptoms of colon cancer patients with information on tumor location and pTNM-stage. The study is retrospective and population-based. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 was obtained. Information on symptoms of patients and blood hemoglobin was collected from patients' files. The pathological parameters were derived from a previously performed study. A total of 768 patients (422 males, 346 females) participated in this study. Median age was 73 years. Nearly 60% had anemia at the time of diagnosis, 53% had visible blood in stools, and 65% had changes in bowel habits. Around 84% had visible blood in stools and/or anemia. Of those with right-sided tumors, 75% had anemia and were more likely to be diagnosed incidentally (40%) than those with left-sided tumors (20%). Left-sided tumors were associated with blood in stools (68% compared to 41%, p < 0.05) and changes in bowel habits (74% compared to 57%, p < 0.05). Multivariate analysis indicated that blood in stools was strongly associated with a lower TNM-stage (OR = 0.75, p < 0.05). Anemia was strongly associated with a higher TNM-stage (OR = 1.84, p < 0.05). Right-sided tumors were associated with anemia and incidental diagnosis; left-sided tumors were associated with visible blood in stools and changes in bowel habits. Visible blood in stools was significantly associated with lower TNM-stage, whereas abdominal pain, general and acute symptoms were associated with higher TNM-stage.

  20. Comparison of the feasibility of laparoscopic resection of the primary tumor in patients with stage IV colon cancer with early and advanced disease: the short- and long-term outcomes at a single institution.

    PubMed

    Wang, Jui-Ho; King, Tai-Ming; Chang, Min-Chi; Hsu, Chao-Wen

    2013-10-01

    The role of resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Laparoscopic resection has become an accepted therapeutic option for treating early stage I-III CRC; however, it has not been evaluated for use in patients with advanced stage disease. We conducted a retrospective observational study to evaluate the feasibility of laparoscopic resection of the primary tumor exclusively in patients with stage IV colon cancer compared to open resection in patients with stage IV colon cancer and laparoscopic resection in patients with stage I-III colon cancer in terms of operative results and short- and long-term outcomes. Laparoscopic resection was performed in 35 stage IV patients and open resection was performed in 40 stage IV patients. One hundred and eighteen stage I-III patients who underwent laparoscopic resection were evaluated. In the comparison between the laparoscopic group and the open group among patients with stage IV colon cancer, postoperative recovery appeared to be better in the laparoscopic group than in the open group, as reflected by shorter times to resumption of a regular diet (p = 0.049), shorter lengths of hospitalization (p = 0.083), increased feasibility of postoperative chemotherapy (p < 0.001), shorter time intervals from surgery to chemotherapy (p = 0.031) and longer median survival (p = 0.078) at the expense of longer operative times (p = 0.025). In the comparison between the laparoscopic resection in stage IV and stage I-III disease groups, no significant differences were observed in operative results and short- and long-term outcomes, except for the rate of ostomy creation (48.5 vs. 8.5%, p = 0.02). Laparoscopic resection of the primary tumor in patients with stage IV colon cancer achieves equivalent results to that performed in patients with stage I-III disease and that performed in patients with stage IV disease using open resection. The use of a minimally invasive approach in the

  1. Single stage management of a unique variant of congenital pouch colon with triplet fistula and normal anus.

    PubMed

    Pandey, Vaibhav; Gangopadhyay, Ajay Narayan; Gupta, Dinesh Kumar; Sharma, Shiv Prasad

    2015-01-01

    Congenital pouch colon (CPC) in the female patient presents with highly variable and anomalous anatomy. We herein report the first case of CPC with uterus didelphys having normal anal opening, H-type vestibular fistula, two other fistulous communications between pouch colon and two vagina managed in a single stage with excellent postoperative outcome.

  2. IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery

    ClinicalTrials.gov

    2017-03-29

    Stage III Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  3. Epacadostat Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2017-01-31

    Stage III Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  4. Colon trauma--clinical staging for surgical decision making. Analysis of 119 cases.

    PubMed

    Morgado, P J; Alfaro, R; Morgado, P J; León, P

    1992-10-01

    A retrospective study is presented of 119 patients admitted to the Central Hospital of the Venezuelan Institute of Social Security, in Caracas, between 1982 and 1990, with the diagnosis of colon trauma. Several parameters including age, etiology, time elapsed between the accident or assault and hospital admission, preoperative and postoperative hemoglobin and diastolic blood pressure, associated lesions, procedure practiced, complication rate, and hospital mortality are reviewed. The second and third decades of life appear most often involved. Most patients reached the hospital within the first four hours of the accident or assault. Anemia, sustained diastolic hypotension, and number of organs involved in addition to the colon were important prognostic factors for complications. Apparently the surgical procedure, with simple suture or resection, mostly without "protective" colostomy, was not very relevant. Hospital mortality was 2.4 percent. A staging system based on clinical conditions for decision making in the operating room was used in an attempt to inject some objectivity into the surgical approach.

  5. Distinct Transcriptional Changes and Epithelial-stromal Interactions are Altered in Early Stage Colon Cancer Development

    PubMed Central

    Mo, Allen; Jackson, Stephen; Varma, Kamini; Carpino, Alan; Giardina, Charles; Devers, Thomas J.; Rosenberg, Daniel W.

    2016-01-01

    While the progression of mutated colonic cells is dependent upon interactions between the initiated epithelium and surrounding stroma, the nature of these interactions is poorly understood. Here the development of an ultra-sensitive laser-capture microdissection (LCM)/RNA-seq approach for studying the epithelial and stromal compartments of aberrant crypt foci (ACF) is described. ACF are the earliest identifiable pre-neoplastic lesion found within the human colon and are detected using high-definition endoscopy with contrast dye-spray. The current analysis focused on the epithelium of ACF with somatic mutations to either KRAS, BRAF, or APC, with expression patterns compared to normal mucosa from each patient. By comparing gene expression patterns between groups, an increase in a number of pro-inflammatory NF-κB target genes were identified that were specific to ACF epithelium, including TIMP1, RELA and RELB. Distinct transcriptional changes associated with each somatic mutation were observed and a subset display a BRAFV600E-mediated senescence-associated transcriptome characterized by increased expression of CDKN2A. Finally, LCM-captured ACF-associated stroma was found to be transcriptionally distinct from normal stroma, with an up-regulation of genes related to immune cell infiltration and fibroblast activation. Immunofluorescence confirmed increased CD3+ T cells within the stromal microenvironment of ACF and an abundance of activated fibroblasts. Collectively, these results provide new insight into the cellular interplay that occurs at the earliest stages of colonic neoplasia, highlighting the important role of NF-kB, activated stromal fibroblasts and lymphocyte infiltration. Implications Fibroblasts and immune cells in the stromal microenvironment play an important role during the earliest stages of colon carcinogenesis. PMID:27353028

  6. The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

    PubMed Central

    Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Muscarella, Aaron M.; Tian, Lin; Zhao, Hong; Zhao, Zhen; Du, Shiyu; Tao, Jianning; Lee, Brendan; Westbrook, Thomas F.; Wong, Stephen T. C.; Jin, Xin; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H.-F.

    2014-01-01

    Summary Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We further elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human datasets analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases. Significance In advanced stages, breast cancer bone metastases are driven by paracrine crosstalk among cancer cells, osteoblasts, and osteoclasts, which constitute a vicious osteolytic cycle. Current therapies targeting this process limit tumor progression, but do not improve patient survival. On the other hand, bone micrometastases may remain indolent for years before activating the vicious cycle, providing a therapeutic opportunity to prevent macrometastases. Here, we show that bone colonization is initiated in a microenvironment niche exhibiting active osteogenesis. Cancer and osteogenic cells form heterotypic adherens junctions, which enhance mTOR activity and drive early-stage bone colonization prior to osteolysis. These results reveal a strong connection between osteogenesis and micrometastasis and suggest potential therapeutic targets to prevent bone macrometastases. PMID:25600338

  7. Is obesity associated with advanced stage or grade of colon cancer?

    PubMed

    Neumann, Katerina; Mahmud, Salaheddin M; McKay, Andrew; Park, Jason; Metcalfe, Jennifer; Hochman, David J

    2015-04-01

    Population-based studies from Europe have suggested that obesity is associated with more advanced stage colorectal cancer on presentation. Obesity is an even more prevalent issue in North America, but comparable data on associations with cancer are lacking. We reviewed the cases of 672 patients with colon cancer diagnosed between 2004 and 2008 in the province of Manitoba who underwent surgical resection at a Winnipeg Regional Health Authority–affiliated hospital. We tested if obesity was associated with more advanced cancer stage or grade. On multivariate analysis, after adjusting for age, sex,tumour location and socioeconomic status, we were unable to show any significant associations between body mass index of 30 or more and advanced stage or grade cancer on presentation. The reasons for the lack of association are likely multifactorial, including the pathophysiology of the disease and process factors, such as screening habits and colonoscopic diagnostic success rates in obese patients.

  8. Radiotherapy Improves Survival in Unresected Stage I-III Bronchoalveolar Carcinoma

    SciTech Connect

    Urban, Damien; Mishra, Mark; Onn, Amir; Dicker, Adam P.; Symon, Zvi; Pfeffer, M. Raphael; Lawrence, Yaacov Richard

    2012-11-01

    Purpose: To test the hypothesis that radiotherapy (RT) improves the outcome of patients with unresected, nonmetastatic bronchoalveolar carcinoma (BAC) by performing a population-based analysis within the Surveillance, Epidemiology, and End Results (SEER) registry. Methods and Materials: Inclusion criteria were as follows: patients diagnosed with BAC, Stage I-III, between 2001 and 2007. Exclusion criteria included unknown stage, unknown primary treatment modality, Stage IV disease, and those diagnosed at autopsy. Demographic data, treatment details, and overall survival were retrieved from the SEER database. Survival was analyzed using the Kaplan-Meier method and log-rank test. Results: A total of 6933 patients with Stage I-III BAC were included in the analysis. The median age at diagnosis was 70 years (range, 10-101 years). The majority of patients were diagnosed with Stage I (74.4%); 968 patients (14%) did not undergo surgical resection. Unresected patients were more likely to be older (p < 0.0001), male (p = 0.001), black (p < 0.0001), and Stage III (p < 0.0001). Within the cohort of unresected patients, 300 (31%) were treated with RT. The estimated 2-year overall survival for patients with unresected, nonmetastatic BAC was 58%, 44%, and 27% in Stage I, II, and III, respectively. Factors associated with improved survival included female sex, earlier stage at diagnosis, and use of RT. Median survival in those not receiving RT vs. receiving RT was as follows: Stage I, 28 months vs. 33 months (n = 364, p = 0.06); Stage II, 18 months vs. not reached (n = 31, nonsignificant); Stage III, 10 months vs. 17 months (n = 517, p < 0.003). Conclusions: The use of RT is associated with improved prognosis in unresected Stage I-III BAC. Less than a third of patients who could have potentially benefited from RT received it, suggesting that the medical specialists involved in the care of these patients underappreciate the importance of RT.

  9. Ipilimumab, Cetuximab, and Intensity-Modulated Radiation Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck Cancer

    ClinicalTrials.gov

    2016-10-12

    Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  10. Prospective multicenter study of the impact of oncotype DX colon cancer assay results on treatment recommendations in stage II colon cancer patients.

    PubMed

    Srivastava, Geetika; Renfro, Lindsay A; Behrens, Robert J; Lopatin, Margarita; Chao, Calvin; Soori, Gamini S; Dakhil, Shaker R; Mowat, Rex B; Kuebler, J Philip; Kim, George; Mazurczak, Miroslaw; Lee, Mark; Alberts, Steven R

    2014-05-01

    The Oncotype DX colon cancer assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. This prospective study evaluated the impact of recurrence score (RS) results on physician recommendations regarding adjuvant chemotherapy in T3, mismatch repair-proficient (MMR-P) stage II colon cancer patients. Patients and Methods. Stage IIA colon cancer patients were enrolled in 17 centers. Patient tumor specimens were assessed by the RS test (quantitative reverse transcription-polymerase chain reaction) and mismatch repair (immunohistochemistry). For each patient, the physician's recommended postoperative treatment plan of observation, fluoropyrimidine monotherapy, or combination therapy with oxaliplatin was recorded before and after the RS and mismatch repair results were provided. Results. Of 221 enrolled patients, 141 patients had T3 MMR-P tumors and were eligible for the primary analysis. Treatment recommendations changed for 63 (45%; 95% confidence interval: 36%-53%) of these 141 T3 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy decreased from 73 patients (52%) to 42 (30%), following review of RS results by physician and patient. Increased treatment intensity was more often observed at higher RS values, and decreased intensity was observed at lower values (p = .011). Conclusion. Compared with traditional clinicopathological assessment, incorporation of the RS result into clinical decision making was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients in this prospective multicenter study. Use of the RS assay may lead to overall reduction in adjuvant chemotherapy use in this subgroup of stage II colon cancer patients.

  11. Prospective Multicenter Study of the Impact of Oncotype DX Colon Cancer Assay Results on Treatment Recommendations in Stage II Colon Cancer Patients

    PubMed Central

    Srivastava, Geetika; Renfro, Lindsay A.; Behrens, Robert J.; Lopatin, Margarita; Chao, Calvin; Soori, Gamini S.; Dakhil, Shaker R.; Mowat, Rex B.; Kuebler, J. Philip; Kim, George; Mazurczak, Miroslaw; Lee, Mark

    2014-01-01

    Purpose. The Oncotype DX colon cancer assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. This prospective study evaluated the impact of recurrence score (RS) results on physician recommendations regarding adjuvant chemotherapy in T3, mismatch repair-proficient (MMR-P) stage II colon cancer patients. Patients and Methods. Stage IIA colon cancer patients were enrolled in 17 centers. Patient tumor specimens were assessed by the RS test (quantitative reverse transcription-polymerase chain reaction) and mismatch repair (immunohistochemistry). For each patient, the physician’s recommended postoperative treatment plan of observation, fluoropyrimidine monotherapy, or combination therapy with oxaliplatin was recorded before and after the RS and mismatch repair results were provided. Results. Of 221 enrolled patients, 141 patients had T3 MMR-P tumors and were eligible for the primary analysis. Treatment recommendations changed for 63 (45%; 95% confidence interval: 36%–53%) of these 141 T3 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy decreased from 73 patients (52%) to 42 (30%), following review of RS results by physician and patient. Increased treatment intensity was more often observed at higher RS values, and decreased intensity was observed at lower values (p = .011). Conclusion. Compared with traditional clinicopathological assessment, incorporation of the RS result into clinical decision making was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients in this prospective multicenter study. Use of the RS assay may lead to overall reduction in adjuvant chemotherapy use in this subgroup of stage II colon cancer patients. PMID:24710310

  12. Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy.

    PubMed

    Khan, Akbar; Andrews, Douglas; Blackburn, Anneke C

    2016-10-16

    Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death). A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer.

  13. Early-stage primary signet ring cell carcinoma of the colon

    PubMed Central

    Kim, Jae Hyun; Park, Seun Ja; Park, Moo In; Moon, Won; Kim, Sung Eun

    2013-01-01

    Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature. PMID:23840131

  14. Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy

    PubMed Central

    Khan, Akbar; Andrews, Douglas; Blackburn, Anneke C

    2016-01-01

    Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define “response” by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death). A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer. PMID:27803917

  15. [Clinical significance of tumor budding detection in stage II colon cancer].

    PubMed

    Liu, Shao-jie; Yang, Xiao-hong; Ren, Jing-qing; Zhu, Xuan-jin

    2013-08-01

    To investigate the association of tumor budding with recurrence and survival of patients with stage II colon cancer, in order to identify patients with high-risk recurrence who may benefit from adjuvant therapy. Clinical data of 112 stage II colon cancer patients in Guangzhou Red Cross Hospital between 1998 and 2007 were analyzed retrospectively. The degree of tumor budding was assessed by two observers and classified according to the number of tumor buds in the area with the greatest budding intensity on HE stain slides, as high-grade budding (≥10, n=30) and low-grade budding (≤9, n=82). Progression-free and cancer-specific survival were analyzed using the Kaplan-Meier method and Cox regression. All the patients were followed up and the median follow-up was 78 months. The 5-year progression-free survival rates for patients with high-grade and low-grade budding were 65.3% and 90.7% respectively (P=0.008). The 5-year cancer-specific survival rates were 72.1% and 93.8% respectively (P=0.001). Cox regression analysis demonstrated tumor budding was an independent predictor of disease progression (RR=4.572, 95%CI:2.218-11.746, P=0.002) and cancer-related death (RR=4.116, 95%CI:1.657-10.384, P=0.012). Tumor budding is a strong prognostic index for adverse outcome in stage II colon cancer patients,which may serve as a prognostic marker to identify patients with high risk of recurrence who may benefit from adjuvant therapy.

  16. STAGE 64: SIMULATOR PROGRAMMING SPECIFICATIONS MANUAL. VOLUME III. DAMAGE.

    DTIC Science & Technology

    The Damage package of the STAGE Simulator is a group of six complexes which under normal running conditions assess damage to the following five types...preliminary control routine. Under nonoptimal running conditions, the damage assessment is made by the five complexes at the end of each time period during which ground zero has occurred.

  17. Staged resection or primary anastomosis for obstructing lesions to the left colon.

    PubMed

    Maher, M; Caldwell, M P; Waldron, R; Murchan, P; Beesley, W; Feeley, T M; Tanner, W A; Keane, F B

    1996-01-01

    The management of obstructing left-sided colonic and rectal lesions has traditionally been by a staged procedure. The introduction of 'on-table lavage', has made primary resection and anastomosis of the large bowel feasible for patients presenting as emergencies. We have studied the perioperative course of 28 patients who presented with left colonic obstruction to determine whether primary anastomosis conferred additional morbidity. The patients ranged in age from 29 to 89 years (mean 66 years) at presentation. The ASA status of patients was comparable in both groups (Table 1). Fourteen patients underwent resection, on-table lavage, and primary anastomosis (PA) and 14 a Hartmann's procedure (HP). The mean operative time for the PA procedure was 200 minutes compared to 110 minutes for the HP group. There was no significant difference in the postoperative complication rate nor mean hospital stay rate for the primary procedures between the two groups. There was no clinical anastomotic leak in patients undergoing primary anastomosis. However secondary surgery for patients undergoing colorectal reconnection conferred added morbidity for patients who had a HP. We conclude that resection, on-table lavage, and primary anastomosis is safe in the management of left-sided colonic obstruction and in most cases is the treatment of choice.

  18. Theory of work-hardening applied to stages III and IV

    NASA Astrophysics Data System (ADS)

    Kuhlmann-Wilsdorf, D.; Hansen, N.

    1989-11-01

    Stage IV has become the accepted name for that work-hardening stage within which large plastic strains can occur at a very low, virtually constant work-hardening rate, as exemplified by cold rolling and wire drawing. By contrast, in the preceding stage III, the work-hardening rate decreases sharply with strain, whereas in the still earlier stage II, the work-hardening rate is also almost constant but has a high value. The classical paper by Langford and Cohen on drawn iron wire is now recognized as one of the earliest studies of stage IV. Already in 1970, a detailed theoretical analysis of that work based on the mesh length theory was presented[2] which has stood the test of time, although in it the Langford and Cohen experiments were considered to represent stage II on account of the operation of similitude and the almost constant work-hardening rate. The present paper re-examines the 1970 theoretical interpretation in terms of stage IV behavior, which necessitates reinterpretation of stage III. Included in the present interpretation are more recent insights regarding dislocation behavior in so-called LEDS, low-energy dislocation structures. It is concluded that stages II and IV differ, because in stage II, cross slip is insignificant, while in stage IV, it is unlimited. Accordingly, cross slip is gradually established in the course of stage III. However, similitude appears to operate in all three stages. By extension of the argument regarding stages III and IV, it is seen that stages V and VI could follow, including similitude, through the establishment of climb.

  19. [Morphology of III stage larvae of Angiostrongylus cantonensis in Pomacea canaliculata].

    PubMed

    Zhang, Chao-Wei; Zhou, Xiao-Nong; Lv, Shan; Zhang, Yi; Liu, He-Xiang

    2008-06-30

    To observe the morphologic characteristics of III stage larvae of Angiostrongylus cantonensis from Pomacea canaliculata. P. canaliculata, the intermediate host snail of A. cantonensis, was infected with I stage larvae of A. cantonensis in laboratory. After 61 days, III stage larvae of A. cantonensis were harvested from snail's lungs and muscle of head-foot, followed by HE stain to observe morphological characteristics. The whole body of III stage larva was curling with obtuse head. Its pharyngeal canal extends from the buccal hole on the top of the head to the intestines at the pharyngeal intestine joint place, with apex cauda and clear anal tube. The tegument of the III stage larva was eosin-stained, with a transparent sheath outside of tegument. Some of the larvae cauda showed in circular cylinder, and some larvae presented ventral gland with two very short uterine which used to be the feature only showed in early IV stage larva. Morphologically characteristics of the III stage larvae is helpful to better understand the life-cycle and the control of A. cantonensis.

  20. Effect of enrofloxacin in the carrier stage of Haemophilus parasuis in naturally colonized pigs.

    PubMed

    Macedo, Nubia; Rovira, Albert; Oliveira, Simone; Holtcamp, Andrew; Torremorell, Montserrat

    2014-01-01

    The purpose of this study was to determine the effect of enrofloxacin in the carrier stage of Haemophilus parasuis in naturally colonized weaned pigs. Twenty-three pigs colonized by H. parasuis received either 7.5 mg/kg body weight (BW) of enrofloxacin or a saline solution intramuscularly at weaning. Nasal and tonsillar swab samples were collected daily throughout the study and at necropsy and tested by quantitative polymerase chain reaction (qPCR). The H. parasuis isolates obtained from samples collected at necropsy were subjected to genotyping by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) and a multiplex PCR for the detection of the virulence-associated trimeric autotransporter (vtaA) genes. Haemophilus parasuis was detected in the nasal cavity and tonsils of pigs in the control group throughout the study. Antibiotic-treated pigs tested negative for H. parasuis at 1 d post-treatment and the proportion of nasal samples that tested positive was higher for control pigs than for treated pigs at 1, 2, 3, 4, 5, 6, and 7 d post-treatment and at 2, 4, and 5 d post-treatment for tonsil samples (P < 0.003). Genotyping by ERIC-PCR demonstrated that pigs were colonized with a common H. parasuis strain at the end of the study. Isolates were negative for the vtaA gene, which indicates the absence of vtaA virulence factor. In conclusion, enrofloxacin significantly reduced the H. parasuis load in naturally colonized pigs, but was unable to completely eliminate the organism.

  1. Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer.

    PubMed

    Alawadi, Zeinab; Phatak, Uma R; Hu, Chung-Yuan; Bailey, Christina E; You, Y Nancy; Kao, Lillian S; Massarweh, Nader N; Feig, Barry W; Rodriguez-Bigas, Miguel A; Skibber, John M; Chang, George J

    2017-04-01

    Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society. © 2016 American Cancer Society.

  2. Previously unrecognized stages of species-specific colonization in the mutualism between Xenorhabdus bacteria and Steinernema nematodes.

    PubMed

    Chaston, John M; Murfin, Kristen E; Heath-Heckman, Elizabeth A; Goodrich-Blair, Heidi

    2013-09-01

    The specificity of a horizontally transmitted microbial symbiosis is often defined by molecular communication between host and microbe during initial engagement, which can occur in discrete stages. In the symbiosis between Steinernema nematodes and Xenorhabdus bacteria, previous investigations focused on bacterial colonization of the intestinal lumen (receptacle) of the nematode infective juvenile (IJ), as this was the only known persistent, intimate and species-specific contact between the two. Here we show that bacteria colonize the anterior intestinal cells of other nematode developmental stages in a species-specific manner. Also, we describe three processes that only occur in juveniles that are destined to become IJs. First, a few bacterial cells colonize the nematode pharyngeal-intestinal valve (PIV) anterior to the intestinal epithelium. Second, the nematode intestine constricts while bacteria initially remain in the PIV. Third, anterior intestinal constriction relaxes and colonizing bacteria occupy the receptacle. At each stage, colonization requires X. nematophila symbiosis region 1 (SR1) genes and is species-specific: X. szentirmaii, which naturally lacks SR1, does not colonize unless SR1 is ectopically expressed. These findings reveal new aspects of Xenorhabdus bacteria interactions with and transmission by theirSteinernema nematode hosts, and demonstrate that bacterial SR1 genes aid in colonizing nematode epithelial surfaces.

  3. Previously unrecognized stages of species-specific colonization in the mutualism between Xenorhabdus bacteria and Steinernema nematodes

    PubMed Central

    Chaston, John M.; Murfin, Kristen E.; Heath-Heckman, Elizabeth A.; Goodrich-Blair, Heidi

    2013-01-01

    Summary The specificity of a horizontally transmitted microbial symbiosis is often defined by molecular communication between host and microbe during initial engagement, which can occur in discrete stages. In the symbiosis between Steinernema nematodes and Xenorhabdus bacteria, previous investigations focused on bacterial colonization of the intestinal lumen (receptacle) of the nematode infective juvenile (IJ), as this was the only known persistent, intimate, and species-specific contact between the two. Here we show that bacteria colonize the anterior intestinal cells of other nematode developmental stages in a species-specific manner. Also, we describe three processes that only occur in juveniles that are destined to become IJs. First, a few bacterial cells colonize the nematode pharyngeal-intestinal valve (PIV) anterior to the intestinal epithelium. Second, the nematode intestine constricts while bacteria initially remain in the PIV. Third, anterior intestinal constriction relaxes and colonizing bacteria occupy the receptacle. At each stage, colonization requires X. nematophila symbiosis region 1 (SR1) genes and is species-specific: X. szentirmaii, which naturally lacks SR1, does not colonize unless SR1 is ectopically expressed. These findings reveal new aspects of Xenorhabdus bacteria interactions with and transmission by their Steinernema nematode hosts, and demonstrate that bacterial SR1 genes aid in colonizing nematode epithelial surfaces. PMID:23480552

  4. Bioimpedance Spectroscopy in Detecting Lower-Extremity Lymphedema in Patients With Stage I, Stage II, Stage III, or Stage IV Vulvar Cancer Undergoing Surgery and Lymphadenectomy

    ClinicalTrials.gov

    2016-02-09

    Lymphedema; Perioperative/Postoperative Complications; Stage IA Vulvar Cancer; Stage IB Vulvar Cancer; Stage II Vulvar Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Vulvar Cancer; Stage IVB Vulvar Cancer

  5. Entolimod in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Receiving Cisplatin and Radiation Therapy

    ClinicalTrials.gov

    2013-12-10

    Mucositis; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral

  6. Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

    PubMed Central

    Puppa, G; Maisonneuve, P; Sonzogni, A; Masullo, M; Chiappa, A; Valerio, M; Zampino, M G; Franceschetti, I; Capelli, P; Chilosi, M; Menestrina, F; Viale, G; Pelosi, G

    2007-01-01

    Fascin, an actin-bundling protein involved in cell motility, has been shown to be upregulated in several types of carcinomas. In this study, we investigated the expression of fascin in 228 advanced colonic adenocarcinoma patients with a long follow-up. Fascin expression was compared with several clinicopathologic parameters and survival. Overall, fascin immunoreactivity was detected in 162 (71%) tumours with a prevalence for right-sided tumours (P<0.001). Fascin correlated significantly with sex, tumour grade and stage, mucinous differentiation, number of metastatic lymph nodes, extranodal tumour extension, and the occurrence of distant metastases. Patients with fascin-expressing tumours experienced a shorter disease-free and overall survival in comparison with those with negative tumours, and fascin immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Moreover, patients with the same tumour stages could be stratified in different risk categories for relapse and progression according to fascin expression. Our findings suggest that fascin is a useful prognostic marker for colonic adenocarcinomas. PMID:17375048

  7. Use of Mueller polarimetric imaging for the staging of human colon cancer

    NASA Astrophysics Data System (ADS)

    Pierangelo, Angelo; Manhas, Sandeep; Benali, Abdelali; Antonelli, Maria Rosaria; Novikova, Tatiana; Validire, Pierre; Gayet, Brice; De Martino, Antonello

    2011-03-01

    In this paper we show the results of multi-spectral Mueller Imaging applied to the analysis of human colon cancer in a backscattering configuration with diffuse light illumination. The analyzed sample behaves as a pure depolarizer. The depolarization power, for both healthy and cancerous zones, is lower for linearly than for circularly polarized incident light for all used wavelengths and increases with increasing wavelength. Based on their visual staging and polarimetric responses, we chose specific zones which we correlated to the histology of the corresponding cuts. The histological examination shows that we see a multilayer interaction in both healthy and abnormal zones, if the light penetration depth is sufficient. The measured depolarization depends on several factors: the presence or absence of tumor, the microscopic structure of cancer (ratio between cellular density and stroma), its exophytic (budding) or endophytic (penetrating) nature, its thickness, the degree of cancer penetration in deeper layers and the nature of healthy tissue left under abnormal layers. These results demonstrate that multi-spectral Mueller imaging can provide useful contrasts for the quick staging of human colon cancer ex-vivo, with additional information about cancerous zones with different microscopic structures.

  8. Comparative study of one-stage colectomy of the descending colon in emergency and elective surgery without mechanical preparation.

    PubMed

    Ciga, Miguel A; Oteiza, Fabiola; Fernández, Lorantz; de Miguel, Mario; Ortiz, Héctor

    2010-11-01

    The aim of this study was to compare one-stage colectomy of the descending colon without mechanical preparation in emergency and elective surgery. From January 2004 to September 2009, 327 consecutive patients underwent surgery in a coloproctology unit for several conditions of the descending colon, 122 on an emergency basis and 205 as elective surgery. In the emergency surgery group, patients with septic shock, multiorgan failure, immunodeficiency or corticoid treatment, ASA IV stage, generalized fecal peritonitis (Hinchey IV stage), nonviable cecum or unresectable tumors were excluded (n = 54). In the elective surgery group, patients who underwent intraoperative colonoscopy, total abdominal colectomy, or an ostomy were excluded (n = 59). In the remaining 214 patients, a colectomy of the descending colon with primary colorectal anastomosis was performed without mechanical bowel preparation, 68 in emergency surgery and 146 in elective surgery. The end points of the study were mortality, anastomotic dehiscence, and surgical site infection. No differences were found in mortality (0 in the emergency group vs 3 (2%) in the elective group; P = .571), symptomatic anastomotic dehiscence (1 in the emergency group (1.4%) vs 4 in the elective group (2.7%); P = 1.000), or surgical site infection (7 (10.2%) in the emergency group vs 8 (5.4%) in the elective group; P = .250). In emergencies involving the descending colon one-stage surgery may be performed without colonic preparation as safely as elective surgery in selected patients considered suitable for segmental resection of the descending colon and primary anastomosis.

  9. Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

    2011-11-15

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  10. Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients

    PubMed Central

    Álvarez-Fernández, Sheila María; Barbariga, Marco; Cannizzaro, Luca; Cannistraci, Carlo Vittorio; Hurley, Laura; Zanardi, Alan; Conti, Antonio; Sanvito, Francesca; Innocenzi, Anna; Pecorelli, Nicolò; Braga, Marco; Alessio, Massimo

    2016-01-01

    A humoral immune response against aberrant tumor proteins can be elicited in cancer patients, resulting in the production of auto-antibodies (Abs). By serological proteome analysis we identified the surface membrane protein ADAM10, a metalloproteinase that has a role in epithelial-tumor progression and invasion, as a target of the immune response in colorectal cancer (Crc). A screening carried out on the purified protein using testing cohorts of sera (Crc patients n = 57; control subjects n = 39) and validation cohorts of sera (Crc patients n = 49; control subjects n = 52) indicated that anti-ADAM10 auto-Abs were significantly induced in a large group (74%) of colon cancer patients, in particular in patients at stage II and III of the disease. Interestingly, in Crc patients classified as stage III disease, the presence of anti-ADAM10 auto-Abs in the sera was associated with a favourable follow-up with a significant shifting of the recurrence-free survival median time from 23 to 55 months. Even though the ADAM10 protein was expressed in Crc regardless the presence of auto-Abs, the immature/non-functional isoform of ADAM10 was highly expressed in the tumor of anti-ADAM10-positive patients and was the isoform targeted by the auto-Abs. In conclusion, the presence of anti-ADAM10 auto-Abs seems to reflect the increased tumor expression of the immunogenic immature-ADAM10 in a group of Crc patients, and is associated with a favourable prognosis in patients at stage III of the disease. PMID:27517630

  11. Modified cervicopexy: a novel, less-invasive technique for Stages III and IV uterine prolapse.

    PubMed

    Elsaman, Ali M; Salem, Hosam T; Amin, Magdy; Fetih, Ahmed N; Othman, Essam-Edin R; Zahran, Kamal M

    2014-12-01

    To evaluate modified anterior abdominal wall cervicopexy (AWC) as a less invasive (via 3-cm minilaparotomy) and more augmented (via securing posterior vaginal wall to uterosacral ligaments) technique. Case series of 30 women with Stages III and IV apical uterine prolapse assessed by the pelvic organ prolapse quantification system. The modified AWC procedure was performed successfully for 17 cases with Stage III uterovaginal prolapse and 13 cases with Stage IV uterovaginal prolapse. The procedure was conducted safely with no operative or postoperative complications, apart from two cases with postoperative urinary retention. Operative time ranged from 45 to 70min. Follow-up was available for 1-3 years. Overall, 27 cases were satisfied with the procedure, and three cases developed recurrence after caesarean section due to cutting the supporting sutures. The modified AWC procedure is less invasive, simple and effective for Stages III and IV uterine prolapse. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

    ClinicalTrials.gov

    2017-07-07

    Head and Neck Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

  13. Redefining Adjuvant Therapy for Colon Cancer

    Cancer.gov

    In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

  14. Perspectives on current tumor-node-metastasis (TNM) staging of cancers of the colon and rectum.

    PubMed

    Hu, Huankai; Krasinskas, Alyssa; Willis, Joseph

    2011-08-01

    Improvements in classifications of cancers based on discovery and validation of important histopathological parameters and new molecular markers continue unabated. Though still not perfect, recent updates of classification schemes in gastrointestinal oncology by the American Joint Commission on Cancer (tumor-node-metastasis [TNM] staging) and the World Health Organization further stratify patients and guide optimization of treatment strategies and better predict patient outcomes. These updates recognize the heterogeneity of patient populations with significant subgrouping of each tumor stage and use of tumor deposits to significantly "up-stage" some cancers; change staging parameters for subsets of IIIB and IIIC cancers; and introduce of several new subtypes of colon carcinomas. By the nature of the process, recent discoveries that are important to improving even routine standards of patient care, especially new advances in molecular medicine, are not incorporated into these systems. Nonetheless, these classifications significantly advance clinical standards and are welcome enhancements to our current methods of cancer reporting. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Targeting Lymph Node Retrieval and Assessment in Stage II Colon Cancer: A Quality Outcome Community-Based Cancer Center Study

    PubMed Central

    Grote, Thomas; Hughes, Amy H.; Rimmer, Cathy C.; Less, Dale A.; Abernethy, Amy P.

    2008-01-01

    Purpose Adequate lymph node evaluation is required for the proper staging of colon cancer. The current recommended number of lymph nodes that should be retrieved and assessed is 12. Methods The multidisciplinary Gastrointestinal Tumor Board at the Derrick L. Davis Forsyth Regional Cancer Center reviewed and recommended that a minimum of 12 lymph nodes be examined in all cases of colon cancer to ensure proper staging. This recommendation occurred at the end of the first quarter of 2005. To ensure this new standard was being followed, an outcomes study looking at the number of lymph nodes evaluated in stage II colon cancer was initiated. All patients with stage II colon cancer diagnosed between 2004 and 2006 were reviewed. Results There was a statistically significant improvement in the number of stage II colon cancer patients with 12 or more lymph nodes evaluated. Before the Gastrointestinal Tumor Board's recommendation, 49% (40 out of 82 patients) had 12 or more lymph nodes sampled. The median number of lymph nodes evaluated was 11. After the Gastrointestinal Tumor Board's recommendation, 79% (70 out of 88 patients) had 12 or more lymph nodes sampled. The median number of lymph nodes was 16. Conclusion Multidisciplinary tumor boards can impact the quality of care of patients as demonstrated in this study. Although we do not yet have survival data on these patients, based on the previous literature referenced in this article, we would expect to see an improvement in survival rates in patients with 12 or more nodes retrieved and assessed. PMID:20856779

  16. The impact of tumor deposits on colonic adenocarcinoma AJCC TNM staging and outcome.

    PubMed

    Jin, Ming; Roth, Rachel; Rock, Jonathan B; Washington, Mary Kay; Lehman, Amy; Frankel, Wendy L

    2015-01-01

    The definition of tumor deposits (TDs) in colonic adenocarcinoma has been modified in different editions of the AJCC/TNM staging system. Studies have shown that the presence of TD is associated with advanced tumor growth and poor prognosis. Most of these data were obtained in patients with simultaneous lymph node (LN) metastases. Reports focusing on the impact of TD in patients without LN metastasis are limited. We retrospectively restaged all right-sided colonic adenocarcinomas over a 10-year period using criteria from the fifth, sixth, and seventh AJCC edition. We compared the number of tumor nodule interpreted as LN and TD in each edition and evaluated the stage migration caused by TD definition change. We then assessed clinical significance of TD in the AJCC seventh edition by comparing 5-year overall survival of N1c patients versus other N category (N0, N1, N2) patients with similar T and M status. We showed that the average number of tumor nodules interpreted as LNs per case and the number of cases with positive LNs were significantly decreased with the seventh edition compared with fifth/sixth; however, numbers of cases with TDs and <12 LNs were significantly increased with the seventh edition compared with fifth/sixth. These changes, however, resulted in minimal effects on the final stage grouping. Our survival analysis showed that N1c patients had significantly worse survival compared with N0 patients. Although not statistically significant, the hazard ratios indicated that the N1c group might have worse survival than the N1 group and better survival than the N2 group. Therefore, we conclude that TDs predict patient outcome at least similarly to positive LNs.

  17. A varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong

    2014-04-15

    Currently, adaptive phase II/III clinical trials are typically carried out with a strict two-stage design. The first stage is a learning stage called phase II, and the second stage is a confirmatory stage called phase III. Following phase II analysis, inefficacious or harmful dose arms are dropped, then one or two promising dose arms are selected for the second stage. However, there are often situations in which researchers are in dilemma to make 'go or no-go' decision and/or to select 'best' dose arm(s), as data from the first stage may not provide sufficient information for their decision making. In this case, it is challenging to follow a strict two-stage plan. Therefore, we propose a varying-stage adaptive phase II/III clinical trial design, in which we consider whether there is a need to have an intermediate stage to obtain more data, so that a more informative decision could be made. Hence, the number of further investigational stages in our design is determined on the basis of data accumulated to the interim analysis. With respect to adaptations, we consider dropping dose arm(s), switching another plausible endpoint as the primary study endpoint, re-estimating sample size, and early stopping for futility. We use an adaptive combination test to perform final analyses. By applying closed testing procedure, we control family-wise type I error rate at the nominal level of α in the strong sense. We delineate other essential design considerations including the threshold parameters and the proportion of alpha allocated in the two-stage versus three-stage setting.

  18. Use of a combination of CEA and tumor budding to identify high-risk patients with stage II colon cancer.

    PubMed

    Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin

    2017-07-24

    High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

  19. Effect of Spirogyra neglecta on the early stages of 1, 2-dimethylhydrazine-induced colon carcinogenesis in rats.

    PubMed

    Taya, Sirinya; Thumvijit, Tarika; Chewonarin, Teera; Punvittayagul, Charatda; Wongpoomchai, Rawiwan

    2016-12-06

    This study focused on the chemopreventive effects of Spirogyra neglecta extract (SNE) and dried S. neglecta mixed diet on the early stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. Male Wistar rats were injected with DMH to initiate aberrant crypt foci (ACF) formation. In the initiation stage, SNE significantly decreased the number of ACF in the colon of DMH-treated rats. Rats that received a low dose of SNE showed enhanced activity of several detoxifying and antioxidant enzymes. In the postinitiation stage, a low dose of SNE significantly decreased the number of ACF in the colon of DMH-treated rats. It significantly reduced the number of proliferating cell nuclear antigen-positive cells and increased the number of apoptotic cells in colonic crypts. S. neglecta thus inhibited the development of the early stages of DMH-induced colon carcinogenesis in rats by modulation of xenobiotic metabolizing enzymes and inhibition of cell proliferation as well as induction of apoptosis.

  20. Radiation Dose Escalation in Stage III Non-Small-Cell Lung Cancer

    PubMed Central

    Terakedis, Breanne; Sause, William

    2011-01-01

    For patients with stage III non-small-cell lung cancer with unresectable or inoperable tumors, definitive chemoradiotherapy is often utilized. Historically, local control and overall survival rates have been poor. In an effort to improve local control, new chemotherapeutic agents in combination with higher doses of radiotherapy have been investigated. Early dose escalation trials date back to the 1980s, and the feasibility and efficacy of dose escalation for patients with inoperable stage III lung cancer continue to be topics of investigation. Herein, we review the evolution of chemotherapy as it relates to treatment of unresectable stage III lung cancer, and we outline the early and the more recent dose escalation studies. While dose escalation appears to provide a modest benefit in terms of preventing local failure and improving overall survival, advances in diagnostic imaging and radiotherapy treatment have possibly resulted in selection of a more favorable patient population. These variables make statements regarding the benefit of dose escalation challenging. PMID:22645713

  1. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  2. A modified varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. A Three-Stage Colonization Model for the Peopling of the Americas

    PubMed Central

    Kitchen, Andrew; Miyamoto, Michael M.; Mulligan, Connie J.

    2008-01-01

    Background We evaluate the process by which the Americas were originally colonized and propose a three-stage model that integrates current genetic, archaeological, geological, and paleoecological data. Specifically, we analyze mitochondrial and nuclear genetic data by using complementary coalescent models of demographic history and incorporating non-genetic data to enhance the anthropological relevance of the analysis. Methodology/Findings Bayesian skyline plots, which provide dynamic representations of population size changes over time, indicate that Amerinds went through two stages of growth ≈40,000 and ≈15,000 years ago separated by a long period of population stability. Isolation-with-migration coalescent analyses, which utilize data from sister populations to estimate a divergence date and founder population sizes, suggest an Amerind population expansion starting ≈15,000 years ago. Conclusions/Significance These results support a model for the peopling of the New World in which Amerind ancestors diverged from the Asian gene pool prior to 40,000 years ago and experienced a gradual population expansion as they moved into Beringia. After a long period of little change in population size in greater Beringia, Amerinds rapidly expanded into the Americas ≈15,000 years ago either through an interior ice-free corridor or along the coast. This rapid colonization of the New World was achieved by a founder group with an effective population size of ≈1,000–5,400 individuals. Our model presents a detailed scenario for the timing and scale of the initial migration to the Americas, substantially refines the estimate of New World founders, and provides a unified theory for testing with future datasets and analytic methods. PMID:18270583

  4. Tumor Heterogeneity of FIGO Stage III Carcinoma of the Uterine Cervix

    SciTech Connect

    Kim, Yong Bae; Lee, Ik Jae; Kim, Song Yih; Kim, Jun Won; Yoon, Hong In; Kim, Sang Wun; Kim, Sunghoon; Kim, Young Tae; Suh, Chang Ok; Kim, Gwi Eon

    2009-12-01

    Purpose: The purpose of this study was to analyze tumor heterogeneity based on tumor extent and suggest reappraisal of the system of the International Federation of Gynecology and Obstetrics (FIGO) for Stage III carcinoma of the uterine cervix from a radiotherapeutic viewpoint. Methods and Materials: Between 1986 and 2004, 407 patients with FIGO Stage III (FIGO Stage IIIa in 19 and IIIb in 388) were treated with external beam radiotherapy (RT) and high-dose rate brachytherapy. All patients were reviewed with respect to tumor extent. Patterns of failure and survival parameters were analyzed by use of the chi{sup 2} test and Kaplan-Meier method. Results: The complete response rate was 79.6%, and the 5-year overall survival rates for Stage IIIa and Stage IIIb carcinoma of the cervix were 82.1% and 54.8%, respectively. To determine which parameters of tumor extent had an influence on prognosis for Stage IIIb patients, pelvic wall (PW) extension and hydronephrosis (HD) retained significance on multivariate analysis. Stage IIIb patients were divided into three subgroups according to PW extension and HD: low risk (unilateral PW extension without HD), intermediate risk (HD without PW extension or bilateral PW extension without HD), and high risk (unilateral or bilateral PW extension with HD). The high-risk group had a remarkably low complete response rate, high locoregional failure rate, and low 5-year survival rate compared with the intermediate- and low-risk groups. Conclusions: FIGO Stage III carcinoma of the cervix covers considerably heterogeneous subgroups according to tumor extent. Before initiation of treatment, we suggest that physicians determine a tailored treatment policy based on tumor heterogeneity for each Stage III patient.

  5. Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing.

    PubMed

    Liu, Jixi; Liu, Fang; Li, Xiaoou; Song, Xin; Zhou, Lei; Jie, Jianzheng

    2017-07-01

    Colon adenocarcinoma is the third leading cause of cancer-related deaths across the world, developing novel and non-invasive diagnostic and prognostic biomarkers for the early-stage colon adenocarcinoma at molecular level is essential. In our study, RNA-sequencing was performed to identify the differentially expressed genes and miRNAs (DEmiRNAs) in early-stage colon adenocarcinoma compared to tissues of precancerous lesions, colonic intraepithelial neoplasia. The DEmiRNA-target interaction network was constructed and functional annotation of targets of DEmiRNAs was performed. The Cancer Genome Atlas was used to verify the expression of selected differentially expressed genes. The receiver operating characteristic analyses of selected differentially expressed genes was performed. In total, 865 differentially expressed genes, 26 DEmiRNAs, and 329 DEmiRNA-target pairs were obtained. Based on the early-stage colon adenocarcinoma network, miR-548c-5p, miR-548i, and miR-548am-5p were the top three DEmiRNAs that covered most differentially expressed genes. NTRK2, DTNA, and BTG2 were the top three differentially expressed genes regulated by most DEmiRNAs. Cancer and colorectal cancer pathways were two significantly enriched pathways in early-stage colon adenocarcinoma. The common differentially expressed genes in both the pathways were AXIN2, Smad2, Smad4, PIK3R1, and BCL2. The expression levels of eight differentially expressed genes (NTRK2, DTNA, BTG2, COL11A1, Smad2, Smad4, PIK3R1, and BCL2) in The Cancer Genome Atlas database were compatible with our RNA-sequencing. All these eight differentially expressed genes and AXIN2 had the potential diagnosis value for Colon adenocarcinoma. In conclusion, a total of ten differentially expressed genes (NTRK2, DTNA, BTG2, COLCA1, COL11A1, AXIN2, Smad2, Smad4, PIK3R1, and BCL2) and four DEmiRNAs (miR-548c-5p, miR-548i, mir-424-5p, and miR-548am-5p) may be involved in the pathogenesis of early-stage colon adenocarcinoma which may

  6. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

    Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  7. Management of stage II colon cancer - the use of molecular biomarkers for adjuvant therapy decision

    PubMed Central

    2013-01-01

    Background There is uncertainty on the benefit of adjuvant chemotherapy in patients with stage II colorectal cancers. The aim of this study is to investigate the combined role of clinical, pathological and molecular parameters to identify those stage II patients who better benefit from adjuvant therapy. Methods We examined 120 stage II colon cancer patients. Of these, 60 patients received adjuvant 5-FU chemotherapy after surgery and the other 60 did not receive therapy. Immunohistochemical (IHC) analyses were performed to evaluate the expressions of Thymidylate synthetase (TYMS), TP53 (p53), β-catenin (CTNNB1) and CD8. For TYMS, its mRNA expression levels were also investigated by real time qRT-PCR. The entire case study was characterized by the presence of a defect in the MMR (mismatch repair) system, the presence of the CpG island methylator phenotype (CIMP or CIMP-High) and for the V600E mutation in the BRAF gene. At the histo-pathological level, the depth of tumour invasion, lymphovascular invasion, invasion of large veins, host lymphocytic response and tumour border configuration were recorded. Results The presence of the V600E mutation in the BRAF gene was a poor prognostic factor for disease free and overall survival (DFS; hazard ratio [HR], 2.57; 95% CI: 1.03 -6.37; p = 0.04 and OS; HR, 3.68; 95% CI: 1.43-9.47; p < 0.01 respectively), independently of 5-FU treatment. Adjuvant therapy significantly improved survival in patients with high TYMS levels (p = 0.04), while patients with low TYMS had a better outcome if treated by surgery alone (DFS; HR, 6.07; 95% CI, 0.82 to 44.89; p = 0.04). In patients with a defect in the MMR system (dMMR), 5-FU therapy was associated to reduced survival (DFS; HR, 37.98; 95% CI, 1.04 to 1381.31; p = 0.04), while it was beneficial for CIMP-High associated tumours (DFS; HR, 0.17; 95% CI, 0.02 to 1.13; p = 0.05). Conclusions Patients’ characterization according to MMR status, CIMP phenotype and TYMS m

  8. Associations Between Cigarette Smoking Status and Colon Cancer Prognosis Among Participants in North Central Cancer Treatment Group Phase III Trial N0147

    PubMed Central

    Phipps, Amanda I.; Shi, Qian; Newcomb, Polly A.; Nelson, Garth D.; Sargent, Daniel J.; Alberts, Steven R.; Limburg, Paul J.

    2013-01-01

    Purpose By using data from North Central Cancer Treatment Group Phase III Trial N0147, a randomized adjuvant trial of patients with stage III colon cancer, we assessed the relationship between smoking and cancer outcomes, disease-free survival (DFS), and time to recurrence (TTR), accounting for heterogeneity by patient and tumor characteristics. Patients and Methods Before random assignment to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or FOLFOX plus cetuximab, 1,968 participants completed a questionnaire on smoking history and other risk factors. Cox models assessed the association between smoking history and the primary trial outcome of DFS (ie, time to recurrence or death), as well as TTR, adjusting for other clinical and patient factors. The median follow-up was 3.5 years among patients who did not experience events. Results Compared with never-smokers, ever smokers experienced significantly shorter DFS (3-year DFS proportion: 70% v 74%; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.42). This association persisted after multivariate adjustment (HR, 1.23; 95% CI, 1.02 to 1.49). There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer. Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer (HR, 1.50 [95% CI, 1.12 to 2.00] v HR, 1.09 [95% CI, 0.85 to 1.39]), although interaction by KRAS mutation status was not statistically significant (P = .07). Associations were comparable in analyses of TTR. Conclusion Overall, smoking was significantly associated with shorter DFS and TTR in patients with colon cancer. These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer. PMID:23547084

  9. Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAF Mutant Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-10-11

    BRAF V600E Mutation Present; BRAF V600K Mutation Present; Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  10. Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

    ClinicalTrials.gov

    2017-08-23

    Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

  11. Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

    2009-07-01

    Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived {>=} 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

  12. Minuteman Stage III Operational Surveillance Program Seven-Year Testing Bondline Aging Study,

    DTIC Science & Technology

    1985-12-01

    Liner Gel Fraction at Various Motor Locations ......... . . 25 14 Liner Moisture at Various Motor Locations ............. ... 26 6 15 Motor TC 30005 ...PageI ,,. 18 Shore A Hardness Gradient of ANB-3066 Propellant at the Forward Equator ........ ...................... .. 30 19 Motor TC 30005 ...75 I 2 Matrix for Minuteman Stage III Bondline Aging Program ........ 76 3 Motor TC 30005 Material Properties Data, Forward

  13. Efficacy of computed tomography features in predicting stage III thymic tumors

    PubMed Central

    Shen, Yan; Ye, Jianding; Fang, Wentao; Zhang, Yu; Ye, Xiaodan; Ma, Yonghong; Chen, Libo; Li, Minghua

    2017-01-01

    Accurate assessment of the invasion of intrathoracic structures by stage III thymic tumors assists their appropriate management. The present study aimed to evaluate the efficacy of computed tomography (CT) features for the prediction of stage III thymoma invasion. The pre-operative CT images of 66 patients with confirmed stage III thymic tumors were reviewed retrospectively. The CT features of invasion into the mediastinal pleura, lungs, pericardium and great vessels were analyzed, and their sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy were calculated. For mediastinal pleural and pericardial invasion, an absence of space between the tumor and the mediastinal pleura/pericardium with mediastinal pleural/pericardial thickening and pleural/pericardial effusion exhibited a specificity and PPV of 100%, respectively. For lung invasion, a multi-lobular tumor convex to the lung with adjacent lung abnormalities exhibited a specificity and PPV of 91.2 and 81.3%, respectively. For vessel invasion, the specificity and PPV were each 100% for tumors abutting ≥50% of the vessel circumference, and for tumor oppression, deformation and occlusion of the vessel. In conclusion, recognition of the appropriate CT features can serve as a guide to invasion by stage III thymic tumors, and can facilitate the selection of appropriate pre-operative treatment. PMID:28123518

  14. Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

    ClinicalTrials.gov

    2016-05-02

    HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  15. Management and Outcomes of Bowel Obstruction in Patients with Stage IV Colon Cancer: A Population-Based Cohort Study

    PubMed Central

    Winner, Megan; Mooney, Stephen J.; Hershman, Dawn L.; Feingold, Daniel L.; Allendorf, John D.; Wright, Jason D.; Neugut, Alfred I.

    2015-01-01

    BACKGROUND Bowel obstruction is a common complication of late-stage abdominal cancer, especially colon cancer, which has been investigated predominantly in small, single-institution studies. OBJECTIVE We used a large, population-based data set to explore the surgical treatment of bowel obstruction and its outcomes after hospitalization for obstruction among patients with stage IV colon cancer. DESIGN This was a retrospective cohort study. SETTING AND PATIENTS We identified 1004 patients aged 65 years or older in the Surveillance, Epidemiology and End Results-Medicare database diagnosed with stage IV colon cancer January 1, 1991 to December 31, 2005, who were later hospitalized for bowel obstruction. MAIN OUTCOME MEASURES We describe outcomes after hospitalization and analyzed the associations between surgical treatment of obstruction and outcomes. RESULTS Hospitalization for bowel obstruction occurred a median of 7.4 months after colon cancer diagnosis, and median survival after obstruction was approximately 2.5 months. Median hospitalization for obstruction was about 1 week and in-hospital mortality was 12.7%. Between discharge and death, 25% of patients were readmitted to the hospital at least once for obstruction, and, on average, patients lived 5 days out of the hospital for every day in the hospital between obstruction diagnosis and death. Survival was 3 times longer in those whose obstruction claims suggested an adhesive obstruction origin. In multivariable models, surgical compared with nonsurgical management was not associated with prolonged survival (p = 0.134). LIMITATIONS Use of an administrative database did not allow determination of quality of life or relief of obstruction as an outcome, nor could nonsurgical interventions, eg, endoscopic stenting or octreotide, be assessed. CONCLUSIONS In this population-based study of patients with stage IV colon cancer who had bowel obstruction, overall survival following obstruction was poor irrespective of

  16. Accuracy of water-enema multidetector computed tomography (WE-MDCT) in colon cancer staging: a prospective study.

    PubMed

    Sibileau, E; Ridereau-Zins, Catherine; Vanel, D; Pavageau, A H; Bertrais, S; Metivier-Cesbron, E; Venara, A; Aubé, C

    2014-10-01

    To assess the accuracy of water-enema multidetector computed tomography (WE-MDCT) in extra-rectal colon cancer staging. Fifty-three patients (mean age 70 years) with extra-rectal colon cancer proven by colonoscopy and biopsy were prospectively evaluated by preoperative WE-MDCT. CT scans were both intraluminal (water enema or WE) and intravenous (iodinated) contrast enhanced (CE). All patients underwent surgery. Tumors were classified with the TNM staging system. Noted CT features were: tumor size and location; tumor form and edges; spread to the pericolic fat or neighboring organs; thickening of retroperitoneal fascia; number, size, and enhancement of the peritumoral lymph nodes. Tumors were classified on CT into 3 T-stage groups: T1/T2, T3, and T4. Lymph nodes were classified by their density after injection [positive over 100 Hounsfield units (HU)]. Tumor localization to the specific colon segment was correct in all the cases. The agreement between WE-MDCT staging and histopathology staging was good (k = 0.64). An irregular and bowl-shaped aspect of the external edges of tumor provided excellent sensitivity for T3/T4 inclusion (Se 97.7%, NPV 85.7%). Thickening of a fascia or the abdominal wall provided good specificity for T4 stage (Sp 88.1%, NPV 94.9%). Enhancement over 100 HU of at least one peritumoral lymph node was the best criterion of N+ staging (Sp 67.7%, NPV 87.5%). WE-MDCT permits good staging of colon cancer based on objective features.

  17. Titan III Mars Explorer Transfer Orbital Stage Delivery to the PHSF

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This NASA Kennedy Space Center video presents live footage of the delivery of the Titan III Mars Explorer Transfer Orbital Stage (TOS) to the Payload Hazardous Servicing Facility (PHSF). The TOS is a single-stage, solid propellant upper stage vehicle used to propel a spacecraft from low Earth orbit toward it's ultimate destination. The TOS is delivered to the PHSF where it is designed to accommodate a variety of NASA and NASA customer payloads and can be used as a payload processing facility (PPF) or a hazardous processing facility (HPF).

  18. Titan III Mars Explorer Transfer Orbital Stage Delivery to the PHSF

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This NASA Kennedy Space Center video presents live footage of the delivery of the Titan III Mars Explorer Transfer Orbital Stage (TOS) to the Payload Hazardous Servicing Facility (PHSF). The TOS is a single-stage, solid propellant upper stage vehicle used to propel a spacecraft from low Earth orbit toward it's ultimate destination. The TOS is delivered to the PHSF where it is designed to accommodate a variety of NASA and NASA customer payloads and can be used as a payload processing facility (PPF) or a hazardous processing facility (HPF).

  19. Pegylated Liposomal Doxorubicin as Adjuvant Therapy for Stage I-III Operable Breast Cancer.

    PubMed

    Lu, Yin-Che; Ou-Yang, F U; Hsieh, Chia-Ming; Chang, King-Jen; Chen, Dar-Ren; Tu, Chi-Wen; Wang, Hwei-Chung; Hou, Ming-Feng

    2016-01-01

    Conventional anthracyclines play an essential role for the treatment of breast cancer and have potent cytotoxic activity, but are associated with severe toxicity. In metastatic breast cancer, pegylated liposomal doxorubicin (PLD) is a formulation with efficacy similar to conventional doxorubicin but with reduced toxicity. This multicenter study evaluated the efficacy and safety of PLD-based adjuvant chemotherapy for women with stage I-III operable breast cancer. One hundred and eighty women with stage I-III breast cancer who received PLD-based adjuvant chemotherapy at six different Institutions in Taiwan from February 2002 to March 2008 were included and followed-up until April 2015. Treatment efficacy was determined by disease-free survival (DFS) rate and safety was evaluated by adverse events. The 5- and 10-year DFS rates were 76.3 and 72.6%, respectively. Univariate analysis revealed that tumor size >5 cm (p=0.045; hazard ratio=3.31) and stage III (hazard ratio=3.54; p=0.019) were each associated with shorter DFS. Only stage III (hazard ratio=5.60; p=0.018) retained statistical significance with regard to DFS in the multivariate analysis. Grade 3/4 hematological toxicity was neutropenia (n=13; 7.2%). The women receiving PLD had low-grade 3 or 4 nausea/vomiting, mucositis, and alopecia. Grade 3 hand-foot syndrome occurred in three patients (1.7%). PLD could be considered an effective and safe alternative to conventional anthracyclines in the treatment of stage I-III operable breast cancer. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients

    PubMed Central

    Mactier, Swetlana; Kaufman, Kimberley L; Wang, Penghao; Crossett, Ben; Pupo, Gulietta M; Kohnke, Philippa L; Thompson, John F; Scolyer, Richard A; Yang, Jean Y; Mann, Graham J; Christopherson, Richard I

    2014-01-01

    Summary Outcomes for melanoma patients with stage III disease differ widely even within the same subcategory. Molecular signatures that more accurately predict prognosis are needed to stratify patients according to risk. Proteomic analyses were used to identify differentially abundant proteins in extracts of surgically excised samples from patients with stage IIIc melanoma lymph node metastases. Analysis of samples from patients with poor (n = 14, <1 yr) and good (n = 19, >4 yr) survival outcomes identified 84 proteins that were differentially abundant between prognostic groups. Subsequent selected reaction monitoring analysis verified 21 proteins as potential biomarkers for survival. Poor prognosis patients are characterized by increased levels of proteins involved in protein metabolism, nucleic acid metabolism, angiogenesis, deregulation of cellular energetics and methylation processes, and decreased levels of proteins involved in apoptosis and immune response. These proteins are able to classify stage IIIc patients into prognostic subgroups (P < 0.02). This is the first report of potential prognostic markers from stage III melanoma using proteomic analyses. Validation of these protein markers in larger patient cohorts should define protein signatures that enable better stratification of stage III melanoma patients. PMID:24995518

  1. Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients.

    PubMed

    Mactier, Swetlana; Kaufman, Kimberley L; Wang, Penghao; Crossett, Ben; Pupo, Gulietta M; Kohnke, Philippa L; Thompson, John F; Scolyer, Richard A; Yang, Jean Y; Mann, Graham J; Christopherson, Richard I

    2014-11-01

    Outcomes for melanoma patients with stage III disease differ widely even within the same subcategory. Molecular signatures that more accurately predict prognosis are needed to stratify patients according to risk. Proteomic analyses were used to identify differentially abundant proteins in extracts of surgically excised samples from patients with stage IIIc melanoma lymph node metastases. Analysis of samples from patients with poor (n = 14, <1 yr) and good (n = 19, >4 yr) survival outcomes identified 84 proteins that were differentially abundant between prognostic groups. Subsequent selected reaction monitoring analysis verified 21 proteins as potential biomarkers for survival. Poor prognosis patients are characterized by increased levels of proteins involved in protein metabolism, nucleic acid metabolism, angiogenesis, deregulation of cellular energetics and methylation processes, and decreased levels of proteins involved in apoptosis and immune response. These proteins are able to classify stage IIIc patients into prognostic subgroups (P < 0.02). This is the first report of potential prognostic markers from stage III melanoma using proteomic analyses. Validation of these protein markers in larger patient cohorts should define protein signatures that enable better stratification of stage III melanoma patients.

  2. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial.

    PubMed

    Lu, Charles; Lee, J Jack; Komaki, Ritsuko; Herbst, Roy S; Feng, Lei; Evans, William K; Choy, Hak; Desjardins, Pierre; Esparaz, Benjamin T; Truong, Mylene T; Saxman, Scott; Kelaghan, Joseph; Bleyer, Archie; Fisch, Michael J

    2010-06-16

    BACKGROUND AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P = .73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to

  3. Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2017-01-20

    Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage III Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  4. Prognostic and Predictive Markers in Stage II Colon Cancer: Is There a Role for Gene Expression Profiling?

    PubMed Central

    Kelley, Robin K.; Venook, Alan P.

    2011-01-01

    Conventional clinical and pathologic risk factors in stage II colon cancer provide limited prognostic information and do not predict response to adjuvant 5-fluorouracil-based chemotherapy. New prognostic and predictive biomarkers are needed to identify patients with highest recurrence risk who will receive the greatest absolute risk reduction from adjuvant chemotherapy. We review below the evidence for conventional risk factors in node-negative colon cancer patients, followed by a discussion of promising new molecular and genetic markers in this malignancy. Gene expression profiling is an emerging tool with both prognostic and predictive potential in oncology. For stage II colon cancer patients, the Oncotype DX Colon Cancer test is now commercially available as a prognostic marker, and the ColoPrint assay is expected to be released later this year. Current evidence for both of these assays is described below, concluding with a discussion of potential future directions for gene expression profiling in colon cancer risk stratification and treatment decision-making. PMID:21859557

  5. Extended surgical resections of advanced thymoma Masaoka stages III and IVa facilitate outcome.

    PubMed

    Ried, Michael; Potzger, Tobias; Sziklavari, Zsolt; Diez, Claudius; Neu, Reiner; Schalke, Berthold; Hofmann, Hans-Stefan

    2014-03-01

    Extended thymoma resections including adjacent structures and pleurectomy/decortication (P/D) with hyperthermic intrathoracic chemotherapy (HITHOC) perfusion were performed in a multidisciplinary treatment regime. Between July 2000 and February 2012, 22 patients with Masaoka stage III (n = 9; 41%) and Masaoka stage IVa (n = 13; 59%) thymic tumors were included. Mean age was 55 years (25-84 years) and 50% (11 out of 22) of patients were female. World Health Organization histological classification was as follows: B2 (n = 15), A (n = 1), B1 (n = 1), B3 (n = 2), and thymic carcinoma (C; n = 3). Radical thymectomy and partial resection of the mediastinal pleura and pericardium were performed. Of the 13, 9 patients with pleural involvement (stage IVa) received radical P/D followed by HITHOC (cisplatin). Macroscopic complete resection (R0/R1) was achieved in 19 (86%) patients. All patients received multimodality treatment depending on tumor stage, histology, and completeness of resection. Thirty-day mortality was 0% and three (13.6%) patients needed operative revision. Recurrence of thymoma was documented in five (22.7%) patients (stage III, n = 1; stage IVa, n = 4). Mean disease-free interval of patients with complete resection (n = 14 out of 22) was 30.2 months. After a mean follow-up of 29 months, 18 out of the 22 (82%) patients are alive. After P/D and HITHOC, 89% (8 out of 9 patients) are alive (current median survival is 25 months) without recurrence. Extended surgical resection of advanced thymic tumors infiltrating adjacent structures (stage III) or with pleural metastases (stage IVa) is safe and feasible. It provides a low recurrence rate and an acceptable survival. Additional HITHOC in patients with pleural thymoma spread seems to offer a better local tumor control. Georg Thieme Verlag KG Stuttgart · New York.

  6. Radiation Therapy With Cisplatin, Docetaxel, or Cetuximab After Surgery in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-03-14

    Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  7. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Koshy, Matthew; Goloubeva, Olga; Suntharalingam, Mohan

    2011-04-01

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

  8. GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy.

    PubMed

    Lin, Wey-Ran; Chiang, Jy-Ming; Liang, Kung-Hao; Lim, Siew-Na; Lai, Ming-Wei; Tsou, Yung-Kuan; Hsieh, Tzu-Yun; Hsu, Chih-Kai; Yeh, Chau-Ting

    2016-04-01

    Adjuvant oxaliplatin-based chemotherapy is widely used for stage III colorectal cancer (CRC) after curative surgery. CRC is a molecularly heterogeneous disease, and our current knowledge of therapeutic response-related genetic factors remains limited. N-acetylgalactosaminyltransferase 14 (GALNT14)-rs9679162 genotype is a prognostic predictor for chemotherapy response in advanced hepatocellular carcinoma. Here, we investigated whether this genotype was related to the therapeutic outcome of stage III CRC.A cohort of 300 stage III CRC patients receiving curative resection followed by oxaliplatin-based chemotherapy was retrospectively recruited. GALNT14 genotypes and the clinicopathological factors were correlated with posttherapeutic prognosis.Of these patients, 18% patients had GALNT14-rs9679162 "TT" and 82% had the "GT" + "GG" genotypes. The analysis showed that the "TT" genotype was associated with unfavorable overall survival (OS, P = 0.009) but not with recurrence-free survival (RFS, P = 0.700). The subgroup analysis showed that the "TT" genotype was associated with unfavorable OS in the following subgroups: age ≤65 years, men, left side CRC, N2 stage, carcinoembryonic antigen >5 ng/mL, and mucinous histology (P = 0.012, 0.011, 0.009, 0.025, 0.013, and 0.007, respectively). Within the latter 2 subgroups, the "TT" genotype was the only independent predictor for OS. Finally, the "TT" genotype was associated with the T4 tumor stage (P = 0.017) and in patients with T4 tumors, the "TT" genotype was the only independent predictor for unfavorable RFS (P = 0.007).GALNT14 "TT" genotype was associated with unfavorable OS in stage III CRC patients receiving curative surgery and adjuvant oxaliplatin-based chemotherapy.

  9. Plasma of argon accelerates murine fibroblast adhesion in early stages of titanium disk colonization.

    PubMed

    Canullo, Luigi; Cassinelli, Clara; Götz, Werner; Tarnow, Dennis

    2013-01-01

    This study was conducted to analyze how a cleaning treatment using plasma of argon would affect fibroblast growth on titanium disks at different time points to determine whether this treatment could enhance soft tissue healing around titanium dental implant abutments. Sixty sterile disks made of machined grade 5 titanium were divided into two groups; 30 disks were left untreated (control) and 30 were cleaned using plasma of argon (test). To simulate clinical conditions during soft tissue healing around titanium abutments, both groups were immersed in a culture of murine fibroblasts (L929) for 2, 8, or 48 hours. After preparation, they were stained using 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) to label the cellular nuclei and fluorescent phalloidin to label the cellular bodies. The nuclei were counted, and cellular bodies were analyzed with fluorescent microscopy and imaging analysis software. Analysis was performed at the three different time points. Fibroblast adhesion for the test group was statistically significantly greater versus the control group at 2 and 8 hours but not at 48 hours. At 2 and 8 hours, the cellular bodies in the test group appeared flatter and more spread out, revealing more advanced cellular adhesion, compared to the cells observed in the control group. At 48 hours, the test and control specimens were nearly indistinguishable. The removal of organic and inorganic contaminants from the surfaces of titanium disks using plasma of argon accelerated fibroblast adhesion in the early stages of colonization (2 to 8 hours). This effect disappeared after 48 hours as a result of saturation. Clinically, abutment cleaning using plasma of argon might positively affect soft tissue healing in early stages.

  10. Aberrant drainage of sentinel lymph nodes in colon cancer and its impact on staging and extent of operation.

    PubMed

    Saha, Sukamal; Johnston, Gregory; Korant, Alpesh; Shaik, Mohammed; Kanaan, Mohammed; Johnston, Rebecca; Ganatra, Balvant; Kaushal, Sunil; Desai, Dilip; Mannam, Sreenivas

    2013-03-01

    The role of aberrant lymphatic drainage in changing operations for patients undergoing sentinel lymph node mapping in colon cancer has not been described on a large scale. Patients with colon cancer underwent sentinel lymph node mapping and standard oncologic resection. Aberrant lymphatic drainage was identified outside the standard resection margin, requiring change of the extent of operation. Objectives were to identify the frequency of aberrant lymphatic drainage leading to changes of operation and staging. Among 192 patients undergoing standard oncologic resection, 42 (22%) had extended surgery because of aberrant lymphatic drainage. Nodal positivity was higher in patients undergoing change of operation, at 62% compared with 43% of those undergoing only standard oncologic resection. In 19 of 192 patients (10%), positive sentinel nodes were found in aberrant locations. Sentinel node mapping in patients with colon cancer detects aberrant drainage in 22% of patients, changing the extent of operation. Copyright © 2013. Published by Elsevier Inc.

  11. Clinicopathologic Significance of Survivin Expression in Relation to CD133 Expression in Surgically Resected Stage II or III Colorectal Cancer

    PubMed Central

    Li, Wanlu; Lee, Mi-Ra; Choi, EunHee; Cho, Mee-Yon

    2017-01-01

    Background Cancer stem cells have been investigated as new targets for colorectal cancer (CRC) treatment. We recently reported that CD133+ colon cancer cells showed chemoresistance to 5-fluorouracil through increased survivin expression and proposed the survivin inhibitor YM155 as an effective therapy for colon cancer in an in vitro study. Here, we investigate the relationship between survivin and CD133 expression in surgically resected CRC to identify whether the results obtained in our in vitro study are applicable to clinical samples. Methods We performed immunohistochemical staining for survivin and CD133 in surgically resected tissue from 187 stage II or III CRC patients. We also comparatively analyzed apoptosis according to survivin and CD133 expression using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Results The results of the Mantel-Haenszel test established a linear association between nuclear survivin and CD133 expression (p = .018), although neither had prognostic significance, according to immunohistochemical expression level. No correlation was found between survivin expression and the following pathological parameters: invasion depth, lymph node metastasis, or histologic differentiation (p > .05). The mean apoptotic index in survivin+ and CD133+ tumors was higher than that in negative tumors: 5.116 ± 4.894 in survivin+ versus 4.103 ± 3.691 in survivin– (p = .044); 5.165 ± 4.961 in CD133+ versus 4.231 ± 3.812 in CD133– (p = .034). Conclusions As observed in our in vitro study, survivin expression is significantly related to CD133 expression. Survivin may be considered as a new therapeutic target for chemoresistant CRC. PMID:27989099

  12. Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma

    ClinicalTrials.gov

    2017-09-04

    Stage I Pleural Malignant Mesothelioma AJCC v7; Stage IA Pleural Malignant Mesothelioma AJCC v7; Stage IB Pleural Malignant Mesothelioma AJCC v7; Stage II Pleural Malignant Mesothelioma AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7

  13. Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomised controlled phase III trial.

    PubMed

    Nordlinger, Bernard; Rougier, Philippe; Arnaud, Jean-Pierre; Debois, Muriel; Wils, Jaques; Ollier, Jean-Claude; Grobost, Olivier; Lasser, Philippe; Wals, Jacob; Lacourt, Jerome; Seitz, Jean-François; Guimares dos Santos, Jose; Bleiberg, Harry; Mackiewickz, Rémy; Conroy, Thierry; Bouché, Olivier; Morin, Thierry; Baila, Liliana; van Cutsem, Eric; Bedenne, Laurent

    2005-07-01

    Systemic adjuvant chemotherapy can improve overall survival and reduce the incidence of distant metastases for patients with advanced colon cancer. This study aimed to investigate whether regional chemotherapy (given by intraperitoneal or intraportal methods) combined with systemic chemotherapy was more effective than was systemic chemotherapy alone in terms of survival and recurrence for patients with stage II-III colorectal cancer. The study also compared systemic chemotherapy with fluorouracil and folinic acid with that of fluorouracil and levamisole. During surgery, 753 patients with stage II-III colorectal cancer were randomly assigned to systemic chemotherapy alone (379 with fluorouracil and folinic acid, and 374 with fluorouracil and levamisole), and 748 to postoperative regional chemotherapy with fluorouracil followed by systemic chemotherapy with fluorouracil and folinic acid (n=368) or with fluorouracil and levamisole (n=380). Regional chemotherapy was given intraperitoneally (n=415) or intraportally (n=235) according to institution. The primary endpoint was 5-year overall survival. Secondary endpoints were 5-year disease-free survival and toxic effects. Analyses were by intention to treat. Median follow-up was 6.8 years (range 0.0-10.1). 5-year overall survival was 72.3% (95% CI 69.0-75.6) for patients assigned regional and systemic chemotherapy, compared with 72.0% (68.7-75.3) for those assigned systemic chemotherapy alone (hazard ratio [HR] 0.97 [0.81-1.15], p=0.69). 5-year overall survival for all patients assigned fluorouracil and levamisole was 72.0% (68.7-75.2) compared with 72.3% (69.0-75.6) for all those assigned fluorouracil and folinic acid (HR 0.98 [0.82-1.17], p=0.81). The hazard ratios for 5-year disease-free survival were 0.94 (0.80-1.10) for regional versus non-regional treatment, and 0.92 (0.79-1.08) for all fluorouracil and levamisole versus fluorouracil and folinic acid. Grade 3-4 toxic effects were low in all groups. Fluorouracil

  14. Intraovarian transplantation of stage I-II follicles results in viable zebrafish embryos.

    PubMed

    Csenki, Zsolt; Zaucker, Andreas; Kovács, Balázs; Hadzhiev, Yavor; Hegyi, Arpád; Lefler, Katalin-Kinga; Müller, Tamás; Kovács, Robert; Urbányi, Béla; Váradi, László; Müller, Ferenc

    2010-01-01

    Maternal gene products drive early embryogenesis almost exclusively until the mid blastula transition (MBT) in many animal models including fish. However, the maternal contribution to embryogenesis does not stop at MBT, but continues to be an essential regulator of key developmental processes. The extent to which maternal effects contribute to embryonic and larval development is hard to estimate due to the technical difficulty of interfering with maternal gene products by conventional forward and reverse genetic tools. Therefore, novel methods to manipulate maternal factors in oocytes need to be developed. Here, we provide a proof of principle protocol for transplanting stage I-II zebrafish follicles into recipient mothers where donor stage I oocytes can develop to stage IV in 2 weeks and in 3 weeks they develop into mature eggs and produce viable offspring. Moreover, we show that simple microinjection of stage I-II follicles with RNA results in reporter gene expression in oocytes and paves the way for developing tools for interfering with maternal gene activity. This early stage oocyte transplantation protocol provides a means to study cellular and molecular aspects of oocyte development in the zebrafish.

  15. Colonization of Mucin by Human Intestinal Bacteria and Establishment of Biofilm Communities in a Two-Stage Continuous Culture System

    PubMed Central

    Macfarlane, Sandra; Woodmansey, Emma J.; Macfarlane, George T.

    2005-01-01

    The human large intestine is covered with a protective mucus coating, which is heavily colonized by complex bacterial populations that are distinct from those in the gut lumen. Little is known of the composition and metabolic activities of these biofilms, although they are likely to play an important role in mucus breakdown. The aims of this study were to determine how intestinal bacteria colonize mucus and to study physiologic and enzymatic factors involved in the destruction of this glycoprotein. Colonization of mucin gels by fecal bacteria was studied in vitro, using a two-stage continuous culture system, simulating conditions of nutrient availability and limitation characteristic of the proximal (vessel 1) and distal (vessel 2) colon. The establishment of bacterial communities in mucin gels was investigated by selective culture methods, scanning electron microscopy, and confocal laser scanning microscopy, in association with fluorescently labeled 16S rRNA oligonucleotide probes. Gel samples were also taken for analysis of mucin-degrading enzymes and measurements of residual mucin sugars. Mucin gels were rapidly colonized by heterogeneous bacterial populations, especially members of the Bacteroides fragilis group, enterobacteria, and clostridia. Intestinal bacterial populations growing on mucin surfaces were shown to be phylogenetically and metabolically distinct from their planktonic counterparts. PMID:16269790

  16. Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement.

    PubMed

    Bingham, Brian; Orton, Andrew; Boothe, Dustin; Stoddard, Greg; Huang, Y Jessica; Gaffney, David K; Poppe, Matthew M

    2017-04-01

    To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log-rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score-matched analysis was also conducted among women with cervical involvement. We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log-rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score-matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma

    PubMed Central

    Sharmab, Anup; Xie, Fei; Liu, Yanliang; Li, Kai; Wan, Weiwei; Baylin, Stephen B.; Wolfgang, Christopher L.; Ahuja, Nita

    2016-01-01

    Background O6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA. Methods Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations. Results MGMT methylation was detected in 17 of 64 (26.6%) patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS) and disease-free survival (DFS) on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups. Conclusions Our results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs. PMID:27643594

  18. A novel technique for the treatment of stages III to IV hemorrhoids

    PubMed Central

    Lin, Guoqiang; Ge, Qiongxiang; He, Xiaokang; Qi, Haixin; Xu, Li

    2017-01-01

    Abstract To compare the efficacy of homemade anal cushion suspension clamp combined with harmonic scalpel (ACS) and Milligan–Morgan hemorrhoidectomy combined with electric knife (MMH) in the treatment of stages III to IV hemorrhoids. We conducted a retrospective study of 99 patients with stages III to IV hemorrhoids hospitalized from January to December in 2013. Among them, 51 patients were treated with ACS, while 48 patients received MMH. Data from clinical recording and follow-up included operative time, intraoperative blood loss, hospitalization information, postoperative pain, and postoperative complications. Operative time, intraoperative blood loss and hospitalization time in ACS group were significantly less than those in MMH group (P < .05). Compared with MMH group, ACS group had a lower postoperative static pain score from days 1 to 14 (P < .01). The patients in ACS group exhibited less postoperative defecation pain scores from days 3 to 20 than those of MMH group (P < .05). The incidence of postoperative anal edema and delayed wound healing in ACS group was lower than that in MMH group (P < .05). Compared with MMH, our novel technique ACS was more effective and had fewer postoperative complications in the treatment of stages III to IV hemorrhoids. PMID:28658138

  19. Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

    SciTech Connect

    Patel, Samir; Portelance, Lorraine . E-mail: lorraine.portelance@muhc.mcgill.ca; Gilbert, Lucy; Tan, Leonard; Stanimir, Gerald; Duclos, Marie; Souhami, Luis

    2007-08-01

    Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.

  20. Efficacy of docetaxel combined with oxaliplatin and fluorouracil against stage III/IV gastric cancer

    PubMed Central

    Yu, Yao-Jun; Sun, Wei-Jian; Lu, Ming-Dong; Wang, Fei-Hai; Qi, Dan-Si; Zhang, Yi; Li, Pi-Hong; Huang, He; You, Tao; Zheng, Zhi-Qiang

    2014-01-01

    AIM: To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stage III/IV gastric cancer. METHODS: A total of 53 stage III/IV gastric cancer patients were enrolled into the study and treated with neoadjuvant chemotherapy. Two of the cases were excluded. The program was as follows: 75 mg/m2 docetaxel and 85 mg/m2 oxaliplatin on day 1 and 1500 mg/m2 fluorouracil on days 1 to 3 for three weeks. RESULTS: The tumour changes, postoperative remission rate, changes in the symptoms and adverse reactions were observed. The overall clinical efficacy (complete remission + partial remission) of the neoadjuvant chemotherapy was 62.7%. R0 radical resection was performed on 60.8% of the patients, with a remission rate (pathological complete response + pathological subtotal response + pathological partial response) of 74.2%. The Karnofksy score improved in 42 cases. The toxicity reactions mostly included myelosuppression, followed by gastrointestinal mucosal lesions, nausea, vomiting and diarrhoea. CONCLUSION: Neoadjuvant chemotherapy consisting of docetaxel combined with oxaliplatin and fluorouracil is effective for stage III/IV gastric cancer. However, the treatment is associated with a high incidence of bone marrow suppression, which should be managed clinically. PMID:25561810

  1. Standard treatment option in stage III non-small-cell lung cancer: case against trimodal therapy and consolidation drug therapy.

    PubMed

    Jeremić, Branislav

    2015-03-01

    Prospective randomized trials and meta-analyses established concurrent radiochemotherapy (RT-CHT) as standard treatment approach in patients with inoperable, locally advanced (stage IIIA and B) non-small-cell lung cancer (NSCLC). In patients with either clinically (c) or pathologically (p) staged disease (stage IIIA), including those with pN2 disease, trimodal therapy was also frequently practiced in the past and is currently still advocated by large cooperative groups and organizations. Similarly, consolidation CHT provided after concurrent RT-CHT was suggested to be feasible and effective in inoperable stage III NSCLC. Contrasting these practices and suggestions, there is no evidence that trimodal therapy in stage IIIA (clinically or pathologically staged) or consolidation CHT in inoperable stage III NSCLC plays any role in its treatment. In both cases, evidence clearly demonstrates that concurrent RT-CHT is of similar efficacy and less toxic, and it should be considered a standard treatment option for all patients with stage III NSCLC.

  2. p27(kipl) protein expression: an independent prognostic factor in rectal carcinoma stages I-III.

    PubMed

    Pucciarelli; Esposito; Fassina; Alaggio; Masin; Toppan; Chieco-Bianchi; Lise

    1999-11-01

    To evaluate the impact of some molecular markers on lymph node metastases, overall (OS) and disease-free survival (DFS) in rectal cancer. We investigated p27(kip1) , p53, nm23, and vascular endothelial growth factor (VEGF) expression in 109 primary rectal cancer specimens (stage I, n=38; stage II, n=24; stage III, n=20; and stage IV, n=27) from patients operated on between 1990 and 1995 at Clinica Chirurgica II. Tumour differentiation (P=0.0469), depth of rectal wall invasion (T status) (P=0.0000), distant metastases (P=0.0000), vascular invasion (P=0.0000), and p27(kip1) expression (P=0.0022) were associated with lymph node metastases (N status). During follow up (median duration 47 months), 48 patients died, and 25 patients (stages I-III) had recurrences. At multivariate analysis, T and N status, and intratumoural necrosis were independent risk factors for OS. The relative risk (RR) of death for patients with lymph node metastases, advanced T status and intratumoural necrosis was 3.3 (P=0.0002), 2.03 (P=0.0127), and 1.47 (P=0.1935), respectively. When analysis included only stage I-III patients, N status and p27(kip1) protein expression were found to be independent risk factors for OS. The RR of death for patients with lymph node metastases and those without p27(kip1) expression was 2.98 (P=0.0251), and 3.57 (P=0.0231), respectively. At multivariate analysis, N status, p27(kip1) expression, and intratumoural necrosis were independent risk factors for DFS. The RR of recurrence for patients with lymph node metastases, intratumoural necrosis and absence of p27(kip1) expression was 6.29 (P=0.0001), 3.04 (P=0.0168), and 3.25 (P=0.0387), respectively. Absence of p27(kip1) expression is a useful marker of tumour aggressiveness in rectal carcinoma stages I-III, and an independent predictor for OS and DFS.

  3. Address of early stage primary colonic neoplasia by N.O.T.E.S.

    PubMed

    Cahill, R A; Lindsey, I; Cunningham, C

    2009-06-01

    Natural Orifice Translumenal Endoscopic Surgery (N.O.T.E.S.) has the capacity to impact greatly on the practice of colorectal surgery. As much as potentially providing an alternative means of operative approach, its consideration and evolution is already also providing a wealth of instrument innovation that seems likely to greatly enhance the endoscopists' armamentarium for advanced endoluminal intervention. Furthermore, its aspirational concept is greatly advancing the progress of single site incision laparoscopic approaches and is speeding appreciation of translumenal assistance and operation. However, if N.O.T.E.S. is to occupy a distinct role in the surgical management of colorectal disease, it needs a niche indication of its own that constitutes a therapeutic advance with considerable clinical benefit for suitable patients. Conversely, sound development of a specific stream-lined operative strategy for N.O.T.E.S-type operations may exert a reciprocal swash upon conventional specialist practice. Thus spurred by N.O.T.E.S, localized resection may become standard therapy for early stage colonic neoplasia regardless of operative access although considerable clinical study is as yet required. Therefore, as much as ensuring feasibility and accuracy in the replication of conventional surgical maneuvers, the dawn of N.O.T.E.S. should be recognized as an opportunity for the inquisition of prevailing surgical principles and prejudices in order that colorectal operations are further honed towards perfection (above all it should be realized that avoidance of abdominal scarring is not the last barrier before surgical nirvana). This may represent the main legacy of transluminal investigation whether or not pure N.O.T.E.S. operating ever becomes a clinical reality in its own right.

  4. Impact of Diabetes Status and Medication on Presentation, Treatment, and Outcome of Stage II Colon Cancer Patients

    PubMed Central

    Bae, Susie; Wong, Hui-Li; Tie, Jeanne; Desai, Jayesh; Field, Kathryn; Kosmider, Suzanne; Fourlanos, Spiros; Jones, Ian; Skinner, Iain; Gibbs, Peter

    2015-01-01

    Diabetes is a risk factor for colorectal cancer and several reports suggest worse cancer-specific outcomes in diabetes patients. Recent studies in multiple tumour types indicate metformin may positively impact on cancer-specific and overall survival. A population-based series of stage II colorectal cancer patients treated and followed from 2000 to 2013 were analysed for baseline characteristics, treatment, and outcomes. 1116 patients with stage II colon cancer were identified, 55.5% were male and median age was 70.9 years (range 20.5–101.2). The diabetes patients (21.6%, n = 241) were older than nondiabetes patients (median 74.0 versus 69.6, p = 0.0001). There was no impact of diabetes on cancer presentation or pathology. Diabetes patients were less likely to receive adjuvant treatment (13.7 versus 24.8%, p = 0.002) but were equally likely to complete treatment (69.7 versus 67.7%, p = 1.00). Diabetes did not significantly impact cancer recurrence (HR = 1.07, 95% CI 0.71–1.63) or overall survival (HR = 1.23, 95% CI 0.88–1.72), adjusted for age. Diabetes medication did not impact cancer recurrence or survival. Cancer presentation and outcomes in diabetes patients are comparable to those of nondiabetes patients in those with stage II colon cancer. The effect of metformin merits further evaluation in patients with colon cancer. PMID:26074965

  5. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

    PubMed Central

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J.; Strausberg, Robert L.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Gibbs, Peter

    2017-01-01

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence. PMID:27384348

  6. Characterization of a Vibrio fischeri Aminopeptidase and Evidence for Its Influence on an Early Stage of Squid Colonization

    PubMed Central

    Rader, Bethany A.; Gerling, David G.; Gutierrez, Nestor A.; Watkins, Katherine H.; Frey, Michelle West; Nyholm, Spencer V.; Whistler, Cheryl A.

    2012-01-01

    Vibrio fischeri cells are the sole colonists of a specialized light organ in the mantle cavity of the sepiolid squid Euprymna scolopes. The process begins when the bacteria aggregate in mucus secretions outside the light organ. The cells eventually leave the aggregate, enter the light organ, and encounter a rich supply of peptides. The need to dissociate from mucus and presumably utilize peptides led us to hypothesize that protease activity is integral to the colonization process. Protease activity associated with whole cells of Vibrio fischeri strain ES114 was identified as the product of a putative cell membrane-associated aminopeptidase (PepN). To characterize this activity, the aminopeptidase was cloned, overexpressed, and purified. Initial steady-state kinetic studies revealed that the aminopeptidase has broad activity, with a preference for basic and hydrophobic side chains and kcat and Km values that are lower and smaller, respectively, than those of Escherichia coli PepN. A V. fischeri mutant unable to produce PepN is significantly delayed in its ability to colonize squid within the first 12 h, but eventually it establishes a wild-type colonization level. Likewise, in competition with the wild type for colonization, the mutant is outcompeted at 12 h postinoculation but then competes evenly by 24 h. Also, the PepN-deficient strain fails to achieve wild-type levels of cells in aggregates, suggesting an explanation for the initial colonization delay. This study provides a foundation for more studies on PepN expression, localization, and role in the early stages of squid colonization. PMID:22636772

  7. Concurrent Carboplatin/Paclitaxel and Intravaginal Radiation in Surgical Stage I-II Serous Endometrial Cancer

    PubMed Central

    Alektiar, Kaled M.; Makker, Vicky; Abu-Rustum, Nadeem R.; Soslow, Robert A.; Chi, Dennis S.; Barakat, Richard R.; Aghajanian, Carol A.

    2013-01-01

    Objective To report a single institution experience in surgical stage I-II serous endometrial cancer using combined carboplatin/paclitaxel and intravaginal radiation (IVRT). Methods Between 10/00 and 12/06, 25 stage I-II patients with serous endometrial cancer were treated at our institution with surgery, postoperative IVRT, and concurrent chemotherapy (CT). Results The mean age was 67 years old (range, 53-80y). Surgery consisted of hysterectomy (TAH/BSO, 64%, LAVH/BSO, 36%), peritoneal washing, omental biopsy, and pelvic lymph-node dissection (median 14 nodes). Para-aortic nodes sampling was done in 88% (median, 6). IVRT median dose was 21 Gy (range, 18-21 Gy, in 3 fractions) and concurrent CT consisted of carboplatin to AUC = 5 and taxol to 175 mg/m2 given every 3 weeks for 6 cycles. CT was well tolerated with 22/25 (88%) receiving 6 cycles. Three patients received ≤5 cycles; 2 owing to physician preference (3 and 4 cycles) and 1 owing to toxicity (5 cycles). Only 1 patient (4%) had grade 3 toxicity (abscess). Grade 2 neurotoxicity was seen in 5 patients (20%). All patients finished their IVRT as scheduled, and there was no grade 3 toxicity. With a median follow-up of 30 months, the 5-year progression-free and overall survival rate was 88%. None of the patients developed vaginal recurrence. Conclusions Based on this study, surgical staging followed by IVRT and carboplatin/paclitaxel is well tolerated and effective in stage I-II serous endometrial cancer. Confirmation of these results on a larger number of patients with longer follow-up is still needed. PMID:19019418

  8. Concurrent carboplatin/paclitaxel and intravaginal radiation in surgical stage I-II serous endometrial cancer.

    PubMed

    Alektiar, Kaled M; Makker, Vicky; Abu-Rustum, Nadeem R; Soslow, Robert A; Chi, Dennis S; Barakat, Richard R; Aghajanian, Carol A

    2009-01-01

    To report a single institution experience in surgical stage I-II serous endometrial cancer using combined carboplatin/paclitaxel and intravaginal radiation (IVRT). Between 10/00 and 12/06, 25 stage I-II patients with serous endometrial cancer were treated at our institution with surgery, postoperative IVRT, and concurrent chemotherapy (CT). The mean age was 67 years old (range, 53-80 years). Surgery consisted of hysterectomy (TAH/BSO, 64%, LAVH/BSO, 36%), peritoneal washing, omental biopsy, and pelvic lymph-node dissection (median 14 nodes). Para-aortic node sampling was done in 88% (median, 6). IVRT median dose was 21 Gy (range, 18-21 Gy, in 3 fractions) and concurrent CT consisted of carboplatin to AUC=5 and taxol to 175 mg/m(2) given every 3 weeks for 6 cycles. CT was well tolerated with 22/25 (88%) receiving 6 cycles. Three patients received staging followed by IVRT and carboplatin/paclitaxel is well tolerated and effective in stage I-II serous endometrial cancer. Confirmation of these results on a larger number of patients with longer follow-up is still needed.

  9. CD44v6 expression in patients with stage II or stage III sporadic colorectal cancer is superior to CD44 expression for predicting progression

    PubMed Central

    Zhao, LH; Lin, QL; Wei, J; Huai, YL; Wang, KJ; Yan, HY

    2015-01-01

    Background: Currently, it is difficult to predict the prognosis of patients exhibiting stage II or stage III colorectal cancer (CRC) and to identify those patients most likely to benefit from aggressive treatment. The current study was performed to examine the clinicopathological significance of CD44 and CD44v6 protein expression in these patients. Study design: We retrospectively investigated 187 consecutive patients who underwent surgery with curative intent for stage II to III CRC from 2007 to 2013 in the Beijing Civil Aviation Hospital. CD44 and CD44v6 protein expression levels were determined using immunohistochemistry and compared to the clinicopathological data. Results: Using immunohistochemical detection, CD44 expression was observed in 108 (57.75%) of the CRC patients; and its detection was significantly associated with greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological tumor-lymph node-metastasis (TNM) stage. CD44v6 expression was observed in 135 (72.19%) of the CRC patients; and its expression was significantly associated with a poorly differentiated histology, greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological TNM stage. Expression of CD44v6 was higher than that of CD44 in stage II and stage III sporadic CRC. Conclusion: CD44v6 is a more useful marker for predicting a poor prognosis in stage II and stage III sporadic CRC as compared to CD44. PMID:25755763

  10. Radiotherapy for stage II and stage III breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy.

    PubMed

    Le Scodan, Romuald; Selz, Jessica; Stevens, Denise; Bollet, Marc A; de la Lande, Brigitte; Daveau, Caroline; Lerebours, Florence; Labib, Alain; Bruant, Sarah

    2012-01-01

    To evaluate the effect of postmastectomy radiotherapy (PMRT) in Stage II-III breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy (NAC). Of 1,054 breast cancer patients treated with NAC at our institution between 1990 and 2004, 134 had pN0 status after NAC and mastectomy. The demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The effect of PMRT on locoregional recurrence-free survival and overall survival (OS) was evaluated by multivariate analysis, including known prognostic factors. Of the 134 eligible patients, 78 (58.2%) received PMRT and 56 (41.8%) did not. At a median follow-up time of 91.4 months, the 5-year locoregional recurrence-free survival and OS rate was 96.2% and 88.3% with PMRT and 92.5% and 94.3% without PMRT, respectively (p = NS). The corresponding values at 10 years were 96.2% and 77.2% with PMRT and 86.8% and 87.7% without PMRT (p = NS). On multivariate analysis, PMRT had no effect on either locoregional recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.09-1.61; p = .18) or OS (hazard ratio, 2.06; 95% confidence interval, 0.71-6; p = .18). This remained true in the subgroups of patients with clinical Stage II or Stage III disease at diagnosis. A trend was seen toward poorer OS among patients who had not had a pathologic complete in-breast tumor response after NAC (hazard ratio, 6.65; 95% confidence interval, 0.82-54.12; p = .076). The results from the present retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence, or death when PMRT was omitted in breast cancer patients with pN0 status after NAC and mastectomy. Whether the omission of PMRT is acceptable for these patients should be addressed prospectively. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Radiotherapy for Stage II and Stage III Breast Cancer Patients With Negative Lymph Nodes After Preoperative Chemotherapy and Mastectomy

    SciTech Connect

    Le Scodan, Romuald; Selz, Jessica; Stevens, Denise; Bollet, Marc A.; Lande, Brigitte de la; Daveau, Caroline; Lerebours, Florence; Labib, Alain; Bruant, Sarah

    2012-01-01

    Purpose: To evaluate the effect of postmastectomy radiotherapy (PMRT) in Stage II-III breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy (NAC). Patients and Materials: Of 1,054 breast cancer patients treated with NAC at our institution between 1990 and 2004, 134 had pN0 status after NAC and mastectomy. The demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The effect of PMRT on locoregional recurrence-free survival and overall survival (OS) was evaluated by multivariate analysis, including known prognostic factors. Results: Of the 134 eligible patients, 78 (58.2%) received PMRT and 56 (41.8%) did not. At a median follow-up time of 91.4 months, the 5-year locoregional recurrence-free survival and OS rate was 96.2% and 88.3% with PMRT and 92.5% and 94.3% without PMRT, respectively (p = NS). The corresponding values at 10 years were 96.2% and 77.2% with PMRT and 86.8% and 87.7% without PMRT (p = NS). On multivariate analysis, PMRT had no effect on either locoregional recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.09-1.61; p = .18) or OS (hazard ratio, 2.06; 95% confidence interval, 0.71-6; p = .18). This remained true in the subgroups of patients with clinical Stage II or Stage III disease at diagnosis. A trend was seen toward poorer OS among patients who had not had a pathologic complete in-breast tumor response after NAC (hazard ratio, 6.65; 95% confidence interval, 0.82-54.12; p = .076). Conclusions: The results from the present retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence, or death when PMRT was omitted in breast cancer patients with pN0 status after NAC and mastectomy. Whether the omission of PMRT is acceptable for these patients should be addressed prospectively.

  12. Enhanced expression of LINE-1-encoded ORF2 protein in early stages of colon and prostate transformation

    PubMed Central

    De Luca, Chiara; Guadagni, Fiorella; Sinibaldi-Vallebona, Paola; Sentinelli, Steno; Gallucci, Michele; Hoffmann, Andreas; Schumann, Gerald G.; Spadafora, Corrado; Sciamanna, Ilaria

    2016-01-01

    LINE-1 (L1) retrotransposons are a source of endogenous reverse transcriptase (RT) activity, which is expressed as part of the L1-encoded ORF2 protein (L1-ORF2p). L1 elements are highly expressed in many cancer types, while being silenced in most differentiated somatic tissues. We previously found that RT inhibition reduces cell proliferation and promotes differentiation in neoplastic cells, indicating that high endogenous RT activity promotes cancer growth. Here we investigate the expression of L1-ORF2p in several human types of cancer. We have developed a highly specific monoclonal antibody (mAb chA1-L1) to study ORF2p expression and localization in human cancer cells and tissues. We uncover new evidence for high levels of L1-ORF2p in transformed cell lines and staged epithelial cancer tissues (colon, prostate, lung and breast) while no or only basal ORF2p expression was detected in non-transformed cells. An in-depth analysis of colon and prostate tissues shows ORF2p expression in preneoplastic stages, namely transitional mucosa and prostate intraepithelial neoplasia (PIN), respectively. Our results show that L1-ORF2p is overexpressed in tumor and in preneoplastic colon and prostate tissues; this latter finding suggests that ORF2p could be considered as a potential early diagnostic biomarker. PMID:26716650

  13. Effect of modified Davidson's fixative on examined number of lymph nodes and TNM-stage in colon carcinoma.

    PubMed

    Kelder, W; Inberg, B; Plukker, J T M; Groen, H; Baas, P C; Tiebosch, A T M G

    2008-05-01

    We evaluated the effect of modified Davidson's fixative (mDF) on the number of lymph nodes examined and staging in patients with colon carcinoma. The results of two different fixation methods used in the pathological preparation of the resection specimens were analyzed. A traditional formalin preparation with manual dissection of all nodes was performed in 117 colon specimens between January 2003 and July 2004. After July 2004, the resected specimens of 125 patients was fixated in mDF. Differences in the retrieval and number of nodes and size of suspected nodal metastases were measured. All lymph nodes were stained with conventional H&E methods. The median number of examined nodes increased from 5 (0-17) to 13 (0-35) nodes after the introduction of mDF (p<0.001). The type of resection and the T-stage influenced the number of retrieved nodes significantly. The percentage of node-positive cases increased from 30% to 41% (p=0.077) with mDF, the median size of the retrieved lymph nodes decreased from 9 mm before to 6 mm after mDF (p<0.001) and more micrometastases were found (6% vs. 16%, p=0.03). With mDF technique more lymph nodes were retrieved in the resected colon specimens. Smaller nodes and more micrometastases were found, leading to more node positive patients.

  14. Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy can be predicted by molecular subtype

    PubMed Central

    Yun, Seongju; Kim, Won Kyu; Kim, Sora; Paik, Soonmyung; Lee, Hyun Jung; Hong, Sungpil; Kim, Tae Il; Min, Byungsoh; Kim, Hoguen

    2017-01-01

    Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a CMS group, which shows a 79% correlation between the CMS classification and our four molecular subtypes. We found that two of our subtypes showed significantly higher disease-free survival and overall survival than the others. Group 2, in particular, which showed no disease recurrence or death, was characterized by high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21), and right-sided location (12/21); this group strongly correlated with CMS1 (microsatellite instability immune type). We further identified the molecular characteristics of each group and selected 10 potential biomarker genes from each. When these were compared to the previously reported molecular classifier genes, we found that 31 out of 40 selected genes were matched with those previously reported. Our findings indicate that molecular classification can reveal specific molecular subtypes correlating with clinicopathologic features of CRCs and can have predictive value for the prognosis for stage III CRCs with FOLFOX adjuvant chemotherapy. PMID:28455965

  15. Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy can be predicted by molecular subtype.

    PubMed

    Kwon, Yujin; Park, Minhee; Jang, Mi; Yun, Seongju; Kim, Won Kyu; Kim, Sora; Paik, Soonmyung; Lee, Hyun Jung; Hong, Sungpil; Kim, Tae Il; Min, Byungsoh; Kim, Hoguen

    2017-06-13

    Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a CMS group, which shows a 79% correlation between the CMS classification and our four molecular subtypes. We found that two of our subtypes showed significantly higher disease-free survival and overall survival than the others. Group 2, in particular, which showed no disease recurrence or death, was characterized by high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21), and right-sided location (12/21); this group strongly correlated with CMS1 (microsatellite instability immune type). We further identified the molecular characteristics of each group and selected 10 potential biomarker genes from each. When these were compared to the previously reported molecular classifier genes, we found that 31 out of 40 selected genes were matched with those previously reported. Our findings indicate that molecular classification can reveal specific molecular subtypes correlating with clinicopathologic features of CRCs and can have predictive value for the prognosis for stage III CRCs with FOLFOX adjuvant chemotherapy.

  16. Peri-navicular arthrodesis for the Stage III Müller-Weiss disease.

    PubMed

    Cao, Hong-Hui; Tang, Kang-Lai; Xu, Jian-Zhong

    2012-06-01

    We aimed to report our results of peri-navicular arthrodesis with autologous iliac bone graft for Stage III Müller-Weiss disease. Nine cases of Stage III Müller-Weiss disease according to the Maceira classification (four male and five female) with average age of 48.2 (range, 41 to 58) years, had mild or severe midfoot pain with the longitudinal arch collapse. The patients, all of whom had failed conservative treatment for more than 6 months, underwent peri-navicular arthrodesis. All patients were followed up at 3, 6, 9, and 12 months, and then every 6 months with AOFAS ankle-hindfoot scores and radiographic measurements. Mean followup time for radiological and clinical evaluation was 22.4 (rangem 12 to 52) months. All patients were satisfied with their clinical results without pain 12 months after surgery. The mean AOFAS ankle-hindfoot scores improved from 40.1±8.3 preoperatively to 90.9±2.1 at the last followup (p<0.05). A solid fusion was found in all cases at 3 months after surgery by radiographic and clinical evaluation. The average longitudinal arch height increased from 46.1±2.1 mm preoperatively to 53.5±2.3 mm at the last followup (p<0.05) on the lateral weightbearing radiograph. The peri-navicular arthrodesis with autologous iliac bone graft resulted in a good outcome for Stage III Müller-Weiss disease with good clinical outcomes, high fusion rate, and obvious improvement of the longitudinal arch height.

  17. Lack of acute toxicity associated with a multimodality treatment of stage III ovarian epithelial carcinoma

    SciTech Connect

    Belch, R.Z.; Coughlin, C.T.; Cooney, L.C.; Forcier, R.J.; Maurer, L.H. )

    1990-04-01

    Eleven patients with advanced stage III ovarian epithelial carcinoma were treated primarily according to an aggressive multimodality plan utilizing cytoreductive surgery, chemotherapy (high-dose cisplatin and Cytoxan), and consolidative radiation therapy (abdominopelvic bath plus pelvic boost). The treatment was tolerated remarkably well. There was no evidence of progressive disease during treatment, and all patients showed a positive response. There was a notable lack of significant acute morbidity, with the exception of a severe symptomatic peripheral neuropathy associated with cisplatin doses of 200 mg/m2. This was not evident with doses of cisplatin up to 150 mg/m2.

  18. The multimodal approach to the treatment of stage III ovarian carcinoma

    SciTech Connect

    Fuks, Z.; Rizel, S.; Anteby, S.O.; Biran, S.

    1982-05-01

    A multimodal therapy which consists of aggressive sequential surgery, combination chemotherapy, second look laparotomy and whole abdominal radiotherapy is described. Side effects of the irradiation, which was administered in fractionated doses over seven weeks, included nausea, vomiting, diarrhea and a mild and transient leukopenia and thrombocytopenia. One patient developed an obstruction two months after completion of radiotherapy. Third-look laparotomy revealed small bowel adhesions. Actuarial survival at 2.5 years from initiation of chemotherapy was 84%, a significant improvement compared to a control group of Stage III patients treated with adriamycin and cyclophosphamide. (JMT)

  19. [A case of Stage IV sigmoid colon cancer cured with radical combined modality therapy].

    PubMed

    Babaya, Akihito; Fukunaga, Mutsumi; Yamamoto, Tameyoshi; Oda, Kazuyuki; Nakata, Ken; Ohzato, Hiroki

    2013-11-01

    The patient was a 54-year-old man who had undergone resection of the sigmoid colon for unresectable sigmoid colon cancer with multiple liver( H1), lymph node, and lung metastases at the previous hospital. Chemotherapy with 5-fuorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab was initiated after surgery. The outcome was partial response. The patient was introduced to our hospital because he had relocated. Based on the findings of the patient's computed tomography( CT) and positron emission tomography( PET)-CT scans, we decided to perform radical resection. We performed partial hepatectomy( S7 and S8) and pancreatoduodenectomy for metastases to the hepatoduodenal ligament lymph node. After confirming that there was no recurrence, he underwent right partial pneumonectomy. Currently, the patient shows no signs of recurrence. The therapy for colon cancer should include aggressive radical surgery to control metastasis.

  20. Molecular basis of early stages of Clostridium difficile infection: germination and colonization.

    PubMed

    Sarker, Mahfuzur R; Paredes-Sabja, Daniel

    2012-08-01

    Clostridium difficile infections (CDIs) occur when antibiotic therapy disrupts the gastrointestinal flora, favoring infected C. difficile spores to germinate, outgrow, colonize and produce toxins. During CDI, C. difficile vegetative cells initiate the process of sporulation allowing a fraction of the spores to remain adhered to the intestinal surfaces. These spores, which are unaffected by antibiotic therapy commonly used for CDIs, then germinate, outgrow and recolonize the host's GI tract causing relapse of CDI. Consequently, the germination and colonization processes can be considered as the earliest and most essential steps for the development as well as relapse of CDI. The aim of this review is to provide an overview on the molecular basis involved in C. difficile spore germination and colonization.

  1. Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2017-01-18

    Mucosal Melanoma; Recurrent Melanoma; Recurrent Uveal Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  2. Cardiac Rehabilitation Program in Improving Cardiorespiratory Fitness in Stage 0-III Breast Cancer Survivors

    ClinicalTrials.gov

    2017-08-17

    Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  3. PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-11-25

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  4. Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions

    PubMed Central

    Dobkin, Bruce H.

    2014-01-01

    Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot studies of novel rehabilitation interventions Stage 1, consideration-of-concept studies, drawn from animal experiments, theories, and observations, delineate the experimental intervention in a small convenience sample of participants, so the results must be interpreted with caution. Stage 2, development-of-concept pilots, should optimize the components of the intervention, settle on most appropriate outcome measures, and examine dose-response effects. A well-designed study that reveals no efficacy should be published to counterweight the confirmation bias of positive trials. Stage 3, demonstration-of-concept pilots, can build out from what has been learned to test at least 15 participants in each arm, using random assignment and blinded outcome measures. A control group should receive an active practice intervention aimed at the same primary outcome. A third arm could receive a substantially larger dose of the experimental therapy or a combinational intervention. If only 1 site performed this trial, a different investigative group should aim to reproduce positive outcomes based on the optimal dose of motor training. Stage 3 studies ought to suggest an effect size of 0.4 or higher, so that approximately 50 participants in each arm will be the number required to test for efficacy in a stage 4, proof-of-concept MRCT. By developing a consensus around acceptable and necessary practices for each stage, similar to CONSORT recommendations for the publication of phase III clinical trials, better quality pilot studies may move quickly into better designed and more successful MRCTs of experimental interventions. PMID:19240197

  5. Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

    ClinicalTrials.gov

    2016-09-07

    Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx

  6. Survival after recurrence of stage I-III breast, colorectal, or lung cancer.

    PubMed

    Hassett, Michael J; Uno, Hajime; Cronin, Angel M; Carroll, Nikki M; Hornbrook, Mark C; Fishman, Paul; Ritzwoller, Debra P

    2017-08-01

    The experiences of patients with recurrent cancer are assumed to reflect those of patients with de novo stage IV disease; yet, little is truly known because most registries lack recurrence status. Using two databases with excellent recurrence and death information, we examined determinants of survival duration after recurrence of breast (BC), colorectal (CRC), and lung cancers (LC). Recurrence status was abstracted from the medical records of patients who participated in the Cancer Care Outcomes Research and Surveillance study and who received care at two Cancer Research Network sites-the Colorado and Northwest regions of Kaiser Permanente. The analysis included 1653 patients who developed recurrence after completing definitive therapy for stages I-III cancer. Multivariable modeling identified independent determinants of survival duration after recurrence, controlling for other factors. Through 60 months' average follow-up, survival after recurrence for BC, CRC, and LC were 28.4, 23.1 and 16.1 months, respectively. Several factors were independently associated with shorter survival for all three cancers, including higher initial stage (III vs. I: BC -9.9 months; CRC -6.9 months; LC -7.4 months; P≤0.01). Factors associated with shorter survival for selected cancers included: distant/regional recurrence for BC and CRC; current/former smoker for LC; high grade for CRC; and <4-year time-to-recurrence for BC. Initial stage predicts survival duration after recurrence, whereas time-to-recurrence usually does not. The impact of biologic characteristics (e.g., grade, hormone-receptor status) on survival duration after recurrence needs further study. Predictors of survival duration after recurrence may help facilitate patient decision-making. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

    PubMed

    Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

    2015-04-01

    To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Obstructed left colon: one-stage surgery in a developing country.

    PubMed

    Naraynsingh, V; Ariyanayagam, D C

    1990-12-01

    Thirty-two consecutive cases of left-sided colonic obstruction are presented. Thirty cases were managed by primary resection and anastomosis without colostomy. No anastomotic leakage occurred. This procedure allowed significant conservation of material and personnel resources, with minimal patient morbidity.

  9. Distinct stages during colonization of the mouse gastrointestinal tract by Candida albicans

    PubMed Central

    Prieto, Daniel; Pla, Jesús

    2015-01-01

    Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts. This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal status remain to be determined. Using a model of mouse gastrointestinal colonization, we show here that C. albicans stably colonizes the mouse gut in about 3 days starting from a dose as low as 100 cells, reaching steady levels of around 107 cells/g of stools. Using fluorescently labeled strains, we have assessed the competition between isogenic populations from different sources in cohoused animals. We show that long term (15 days) colonizing cells have increased fitness in the gut niche over those grown in vitro or residing in the gut for 1–3 days. Therefore, two distinct states, proliferation and adaptation, seem to exist in the adaptation of this fungus to the mouse gut, a result with potential significance in the prophylaxis and treatment of Candida infections. PMID:26300861

  10. Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy

    SciTech Connect

    Bajetta, E.; Valagussa, P.; Bonadonna, G.; Lattuada, A.; Buzzoni, R.; Rilke, F.; Banfi, A.

    1988-07-01

    This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.

  11. Tumor microRNA-29a expression and the risk of recurrence in stage II colon cancer.

    PubMed

    Weissmann-Brenner, Alina; Kushnir, Michal; Lithwick Yanai, Gila; Aharonov, Ranit; Gibori, Hadas; Purim, Ofer; Kundel, Yulia; Morgenstern, Sara; Halperin, Marissa; Niv, Yaron; Brenner, Baruch

    2012-06-01

    There is emerging evidence for the prognostic role of various microRNA (miRNA) molecules in colon cancer. The aim of this study was therefore to compare the miRNA profiles in the primary tumor of patients with recurrent and non-recurrent colon cancer. The study population included 110 patients, 51 (46%) with stage I and 59 (54%) with stage II disease, who underwent curative colectomies between 1995 and 2005 without adjuvant therapy and for whom reliable miRNA expression data were available. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor samples. Initial profiling, using microarrays, was done in order to identify potential biomarkers of recurrence. The miRNA expression was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 months of surgery (bad prognosis group, n=23, 21%) and those who did not (good prognosis group, n=87, 79%) in the entire group and within each stage. The results showed that in stage I, none of the 903 miRNAs tested showed differential expression between patients with good prognosis compared with those with poor prognosis. In contrast, in stage II, one miRNA, miR-29a, showed a clear differential expression between the groups (p=0.028). High expression of miR-29a was associated with a longer disease-free survival (DFS), on both univariate and multivariate analyses. Using miR-29a, the positive predictive value for non-recurrence was 94% (2 recurrences among 31 patients). The differential expression of miR-29a was verified by qRT-PCR, showing a similar impact of this miR on DFS. In conclusion, this study demonstrated a significant impact of miR-29a on the risk of recurrence in patients with stage II but not in patients with stage I colon cancer. Based on these results, a validation study is planned.

  12. Therapeutic management options for stage III non-small cell lung cancer

    PubMed Central

    Yoon, Stephanie M; Shaikh, Talha; Hallman, Mark

    2017-01-01

    Lung cancer is the leading cause of cancer death worldwide. Majority of newly diagnosed lung cancers are non-small cell lung cancer (NSCLC), of which up to half are considered locally advanced at the time of diagnosis. Patients with locally advanced stage III NSCLC consists of a heterogeneous population, making management for these patients complex. Surgery has long been the preferred local treatment for patients with resectable disease. For select patients, multi-modality therapy involving systemic and radiation therapies in addition to surgery improves treatment outcomes compared to surgery alone. For patients with unresectable disease, concurrent chemoradiation is the preferred treatment. More recently, research into different chemotherapy agents, targeted therapies, radiation fractionation schedules, intensity-modulated radiotherapy, and proton therapy have shown promise to improve treatment outcomes and quality of life. The array of treatment approaches for locally advanced NSCLC is large and constantly evolving. An updated review of past and current literature for the roles of surgery, chemotherapeutic agents, radiation therapy, and targeted therapy for stage III NSCLC patients are presented. PMID:28246582

  13. [STT arthrodesis for treatment of stage III semilunar bone necrosis: functional outcome].

    PubMed

    Tränkle, M; Sauerbier, M; Linsner, G; Bickert, B; Germann, G

    2000-11-01

    Scapho-trapezio-trapezoid arthrodesis for the treatment of Kienböck's disease is recommended as a salvage procedure for Stage III A and B in the Lichtman classification. This study reviews the results of 26 patients with stage III of Kienböck's disease treated by STT-arthrodesis. 26 patients (16 male, 10 female) were treated by STT-arthrodesis between 1993 and 1998. Fusion was established after seven weeks average. All patients were examined, the mean follow-up time was 35 (10 to 72) months. Active range of motion showed 63% of extension/flexion and 51% of radial/ulnar deviation on average, compared to the uninjured hand. Mean preoperative and postoperative pain scores were 58.4 (non-stress) vs. 82.5 (stress) and 16.4 (non-stress) vs. 33.7 (stress), eight patients claimed complete pain relief. Grip strength improved to 71% of the opposite side. Total DASH score reached 24.8. 20 of the 26 patients were satisfied with the final result and would undergo the operation again. We found a significant reduction of pain, a slightly reduced grip strength and a satisfying functional wrist mobility after STT-arthrodesis. Carpal height was unchanged and the carpal collapse did not progress. The mid-term data support that STT-arthrodesis will stand the test of time.

  14. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer.

    PubMed

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer.

  15. Comparative economics of a 12-gene assay for predicting risk of recurrence in stage II colon cancer.

    PubMed

    Alberts, Steven R; Yu, Tiffany M; Behrens, Robert J; Renfro, Lindsay A; Srivastava, Geetika; Soori, Gamini S; Dakhil, Shaker R; Mowat, Rex B; Kuebler, John P; Kim, George P; Mazurczak, Miroslaw A; Hornberger, John

    2014-12-01

    Prior economic analysis that compared the 12-gene assay to published patterns of care predicted the assay would improve outcomes while lowering medical costs for stage II, T3, mismatch-repair-proficient (MMR-P) colon cancer patients. This study assessed the validity of those findings with real-world adjuvant chemotherapy (aCT) recommendations from the US third-party payer perspective. Costs and quality-adjusted life-years (QALYs) were estimated for stage II, T3, MMR-P colon cancer patients using guideline-compliant, state-transition probability estimation methods in a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium provided aCT recommendations before and after knowledge of the 12-gene assay results. Progression and adverse events data with aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2014 Medicare Fee Schedule. Sensitivity analyses evaluated the drivers and robustness of the primary outcomes. After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22 %; fluoropyrimidine monotherapy and FOLFOX recommendations each declined 11 %. Average per-patient drugs, administration, and adverse events costs decreased $US2,339, $US733, and $US3,211, respectively. Average total direct medical costs decreased $US991. Average patient well-being improved by 0.114 QALYs. Savings are expected to persist even if the cost of oxaliplatin drops by >75 % due to generic substitution. This study provides evidence that real-world changes in aCT recommendations due to the 12-gene assay are likely to reduce direct medical costs and improve well-being for stage II, T3, MMR-P colon cancer patients.

  16. Heterogeneity of disease classified as stage III in Wilms tumor: a report from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

    PubMed

    Spreafico, Filippo; Gandola, Lorenza; D'Angelo, Paolo; Terenziani, Monica; Collini, Paola; Bianchi, Maurizio; Provenzi, Massimo; Indolfi, Paolo; Pession, Andrea; Nantron, Marilina; Di Cataldo, Andrea; Marchianò, Alfonso; Catania, Serena; Fossati Bellani, Franca; Piva, Luigi

    2012-01-01

    We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems. Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT). Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% ± 4% and 92% ± 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% ± 7%, as opposed to 98% ± 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% ± 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate. This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Heterogeneity of Disease Classified as Stage III in Wilms Tumor: A Report From the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)

    SciTech Connect

    Spreafico, Filippo; Gandola, Lorenza; Terenziani, Monica; Collini, Paola; Bianchi, Maurizio; Provenzi, Massimo; Indolfi, Paolo; Pession, Andrea; Nantron, Marilina; Di Cataldo, Andrea; Marchiano, Alfonso; Piva, Luigi

    2012-01-01

    Purpose: We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems. Methods and Materials: Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT). Results: Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% {+-} 4% and 92% {+-} 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% {+-} 7%, as opposed to 98% {+-} 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% {+-} 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate. Conclusions: This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed.

  18. Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Carcinoma (Cancer)

    ClinicalTrials.gov

    2013-03-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  19. Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  20. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  1. Microsatellite instability & survival in patients with stage II/III colorectal carcinoma

    PubMed Central

    Srdjan, Markovic; Jadranka, Antic; Ivan, Dimitrijevic; Branimir, Zogovic; Daniela, Bojic; Petar, Svorcan; Velimir, Markovic; Zoran, Krivokapic

    2016-01-01

    Background & objectives: The two key aspects associated with the microsatellite instability (MSI) as genetic phenomenon in colorectal cancer (CRC) are better survival prognosis, and the varying response to 5-fluorouracil (5-FU)-based chemotherapy. This study was undertaken to measure the survival of surgically treated patients with stages II and III CRC based on the MSI status, the postoperative 5-FU treatment as well as clinical and histological data. Methods: A total of 125 consecutive patients with stages II and III (American Joint Committee on Cancer, AJCC staging) primary CRCs, were followed prospectively for a median time of 31 months (January 2006 to December 2009). All patients were assessed, operated and clinically followed. Tumour samples were obtained for cytopathological verification and MSI grading. Results: Of the 125 patients, 21 (20%) had high MSI (MSI-H), and 101 patients (80%) had MSI-L or MSS (low frequency MSI or stable MSI). Patients with MSS CRC were more likely to have recurrent disease (P=0.03; OR=3.2; CI 95% 1-10.2) compared to those with MSI-H CRC. Multi- and univariate Cox regression analysis failed to show a difference between MSI-H and MSS groups with respect to disease-free, disease-specific and overall survival. However, the disease-free survival was significantly lower in patients with MSI-H CRC treated by adjuvant 5-FU therapy (P=0.03). Interpretation & conclusions: MSI-H CRCs had a lower recurrence rate, but the prognosis was worse following adjuvant 5-FU therapy. PMID:27748284

  2. [Cytological finding in the pre- and early stages of cervix carcinoma--a contribution to the evaluation of Papanicolau III].

    PubMed

    Bader, G; Büttner, H H; Neumann, H G; Rhode, E; Beust, M

    1977-01-01

    Cytologic findings and the histologic diagnosis are compared in 326 cervical cones. We have found following ratio of the groups Papanicolaou (Pap) III: Pap IV--in dysplasia 1: 1: 1, in "more dysplasia than carcinoma in situ (CIS)" 1:2:2. The Pap IV dominates in "pure" CIS and in cones with "more CIS than dysplasia". We take out of the Pap III ("with cytologic control") cases named "Pap III with necessity for histologic diagnosis". We have found in this subgroup of Pap III prestages or early stages of cervical carcinoma.

  3. Resveratrol attenuates 1,2-dimethylhydrazine (DMH) induced glycoconjugate abnormalities during various stages of colon carcinogenesis.

    PubMed

    Sengottuvelan, Murugan; Deeptha, Kumaraswamy; Nalini, Namasivayam

    2009-08-01

    Although a myriad of health promoting effects has been attributed to resveratrol (Res) (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin, the most interesting is its anticancer property. The aim of this work was to elucidate the effectiveness of Res against cellular transformation (glycoconjugate alterations) initiated by 1,2-dimethylhydrazine (DMH), a colon specific carcinogen. Group 1 were control rats, group 2 were control rats that received Res (8 mg/kg body weight orally every day), rats in groups 3-6 were treated weekly with DMH (20 mg/kg body weight, subcutaneously x 15 times). In addition, groups 4-6 received Res (as in group 2) in three dietary regimens: initiation (I), post-initiation (PI) and entire period (EP). At the end of the 30 week experimental period in DMH alone exposed rats, altered levels of glycoconjugates (total hexoses, fucose, hexosamine and sialic acid) were observed in liver, intestine and colon tissues. Of the three dietary regimens of Res, the entire period supplementation significantly (p < 0.01) modulated the levels of glycoconjugates and reduced the incidence of adenoma and adenocarcinoma. These findings suggest that Res may extend its chemopreventive effect by restoring the alteration in glycoconjugates that are thought to be involved in the colonic malignant transformation process in this experimental model.

  4. The roles of demography and genetics in the early stages of colonization

    PubMed Central

    Szűcs, Marianna; Melbourne, Brett A.; Tuff, Ty; Hufbauer, Ruth A.

    2014-01-01

    Colonization success increases with the size of the founding group. Both demographic and genetic factors underlie this relationship, yet because genetic diversity normally increases with numbers of individuals, their relative importance remains unclear. Furthermore, their influence may depend on the environment and may change as colonization progresses from establishment through population growth and then dispersal. We tested the roles of genetics, demography and environment in the founding of Tribolium castaneum populations. Using three genetic backgrounds (inbred to outbred), we released individuals of four founding sizes (2–32) into two environments (natal and novel), and measured establishment success, initial population growth and dispersal. Establishment increased with founding size, whereas population growth was shaped by founding size, genetic background and environment. Population growth was depressed by inbreeding at small founding sizes, but growth rates were similar across genetic backgrounds at large founding size, an interaction indicating that the magnitude of the genetic effects depends upon founding population size. Dispersal rates increased with genetic diversity. These results suggest that numbers of individuals may drive initial establishment, but that subsequent population growth and spread, even in the first generation of colonization, can be driven by genetic processes, including both reduced growth owing to inbreeding depression, and increased dispersal with increased genetic diversity. PMID:25143033

  5. Mn(II) Oxidation by the Multicopper Oxidase Complex Mnx: A Coordinated Two-Stage Mn(II)/(III) and Mn(III)/(IV) Mechanism.

    PubMed

    Soldatova, Alexandra V; Romano, Christine A; Tao, Lizhi; Stich, Troy A; Casey, William H; Britt, R David; Tebo, Bradley M; Spiro, Thomas G

    2017-08-23

    The bacterial manganese oxidase MnxG of the Mnx protein complex is unique among multicopper oxidases (MCOs) in carrying out a two-electron metal oxidation, converting Mn(II) to MnO2 nanoparticles. The reaction occurs in two stages: Mn(II) → Mn(III) and Mn(III) → MnO2. In a companion study , we show that the electron transfer from Mn(II) to the low-potential type 1 Cu of MnxG requires an activation step, likely forming a hydroxide bridge at a dinuclear Mn(II) site. Here we study the second oxidation step, using pyrophosphate (PP) as a Mn(III) trap. PP chelates Mn(III) produced by the enzyme and subsequently allows it to become a substrate for the second stage of the reaction. EPR spectroscopy confirms the presence of Mn(III) bound to the enzyme. The Mn(III) oxidation step does not involve direct electron transfer to the enzyme from Mn(III), which is shown by kinetic measurements to be excluded from the Mn(II) binding site. Instead, Mn(III) is proposed to disproportionate at an adjacent polynuclear site, thereby allowing indirect oxidation to Mn(IV) and recycling of Mn(II). PP plays a multifaceted role, slowing the reaction by complexing both Mn(II) and Mn(III) in solution, and also inhibiting catalysis, likely through binding at or near the active site. An overall mechanism for Mnx-catalyzed MnO2 production from Mn(II) is presented.

  6. Postoperative chemoradiotherapy improves survival in patients with stage II–III esophageal squamous cell carcinoma: An analysis of clinical outcomes

    PubMed Central

    Zou, Bingwen; Pang, Jing; Liu, Yongmei; Xu, Yong; Li, Lu; Zhou, Lin; Zhu, Jiang; Huang, Meijuan; Wang, Jin; Ren, Li; Gong, Youlin; Lu, You; Chen, Longqi

    2016-01-01

    Background We compared the efficacy of postoperative chemoradiation (POCRT) and surgery alone (SA) in patients with stage II–III esophageal squamous cell carcinoma (ESCC). Methods We analyzed the records of 265 patients with stage II–III ESCC who had undergone transthoracic esophagectomy and lymphadenectomy; 105 patients received POCRT, while 160 had SA. Results The median disease‐free survival (DFS) of the whole cohort was 22 months (95% confidence interval [CI], 19.2–24.8), while the median overall survival (OS) was 29 months (95% CI 25.5–32.5). The median DFS of the SA group was 21 months (95% CI 17.9–24.0), while that of the POCRT group was 29 months (95% CI 18.8–31.2; P = 0.048). Consistently, patients in the POCRT group had significantly longer median OS than patients in the SA group (34 vs. 26 months, respectively). Subgroup analysis showed that in patients with positive lymph nodes, pathological stage III, T3–4 stage, and poorly differentiated carcinoma, POCRT was apparently more effective than SA at improving OS and decreasing the rates of local recurrence and distant metastasis. Multivariate analysis demonstrated that lymph node involvement and treatment with POCRT were independent prognostic factors. Conclusion Compared with SA, POCRT may be more effective in improving OS and decreasing the rates of local recurrence and distant metastasis, particularly in stage III or positive lymph node stage II–III ESCC patients. PMID:27766781

  7. SU-E-J-269: Tracking of Tumor Regression for Stage III Lung Cancer Using CBCT

    SciTech Connect

    Kang, K; Biswas, T; Podder, T

    2015-06-15

    Purpose: This study is to evaluate the tumor regression over the course of EBRT treatment and to determine the difference of tumor reduction for stage III lung squamous cell cancer (SCC) and adenocarcinoma using CBCT. Methods: Twenty three stage III lung cancer patients treated in our clinic who had daily cone beam CT (CBCT) were selected for this study (16 adenocarcinoma and 7 SCC cases). Patients received prescription dose in the range of 50Gy–71.4Gy (mean =60.3Gy, median =50Gy) at 1.8Gy or 2Gy per fraction. Treatments spanned over a minimum of five weeks. Initial mean volume of the gross tumor volume (GTV) was 123cc (range = 14.7cc–353.3cc). For this study, we choose six sets of CBCTs at an interval of one week, starting from the first fraction of treatment. Daily CBCTs from treatment linac computer were transferred to MIM Software version 6.0. An experienced physician contoured the primary GTV on each slices of the CBCT for these patients. Results: A consistent regression of the GTVs was observed in all patients, except in one patient (adeno case) where GTV did not change. Weekly volumetric reduction was in the range of 11.2%–16.6%. Maximum reductions were noticed in the first two weeks of the treatment cycle; mean overall (for adeno+SCC) reductions were 16.6%, 14.2% in week-1 and week-2, respectively. Mean reduction over five weeks of treatment was 49.8% (range = 0.1%–75.5%). Higher reduction was observed in SCC patients as compare to adenocarcinoma cases (54.9% vs. 47.6%); however, the difference was not statistically significant (p-value > 0.05). Conclusion: Large regression of tumors over the course of EBRT for stage III lung cancer patients was observed. Both SCC and adenocarcinoma responded well; overall reduction for SCC cases was higher. A future study is warranted for determining the co-relation between tumor volume reduction and treatment outcome.

  8. Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III colorectal cancer: a retrospective study

    PubMed Central

    Wang, Yao; Sun, Xin Rong; Feng, Wen Ming; Bao, Ying; Zheng, Yin Yuan

    2016-01-01

    Background Radical resection is the main treatment for colorectal cancer (CRC), but metastasis or recurrence is common in which liver metastasis accounted for 83% of the cases. Therefore, the prognosis of patients with advanced CRC may be improved if liver metastasis is prevented. This study aims to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of stage III CRC patients after curative resection. Methods Between 2002 and 2008, 287 stage III CRC patients who had undergone radical resection were included in this study. According to postoperative adjuvant chemotherapy modality, these patients were divided into two groups. Patients in the combined therapy group received two cycles of HAIC plus four cycles of systemic chemotherapy, while patients in the monotherapy group received six cycles of systemic chemotherapy alone. The HAIC regimen consisted of hepatic arterial infusion of oxaliplatin (OXA, 85 mg/m2) on day 1 and 5-fluorouracil (5-FU, 2,400 mg/m2) on days 2 and 3 followed by a vein infusion of folinic acid (FA, 200 mg/m2) as a 2-hour infusion on days 2 and 3. The systemic chemotherapy regimen consisted of a 2-hour infusion of OXA (85 mg/m2) on day 1 followed by FA (200 mg/m2) as a 2-hour infusion on days 2 and 3, and by 5-FU (2,400 mg/m2) as a 48-hour infusion. This was repeated every 4 weeks. All cases were followed up for 5 years or until death. The 5-year overall survival, disease-free survival, liver metastases-free survival, and the overall liver metastases rates were retrospectively compared. Results Significant differences were found in the 5-year overall survival (combined therapy, 70.71%; monotherapy, 57.14%; P=0.014), disease-free survival (combined therapy, 69.29%; monotherapy, 55.78%; P=0.021), and liver metastases-free survival rates (combined therapy, 70%; monotherapy, 56.46%; P=0.019). Conclusion Prophylactic adjuvant HAIC can prevent metachronous liver metastases and improve the prognosis of patients

  9. Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2017-03-13

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  10. Staging of colon and rectal cancer: from endoscopy to molecular markers.

    PubMed

    Greene, F L

    2006-04-01

    The primary management of colorectal cancer begins with preoperative diagnosis and the ability to stage the extent of the tumor burden clinically. Endoscopic approaches have been pivotal in this management strategy, and have given rise to endoscopic techniques allowing for primary resection and treatment of metastases. This advance has allowed for the continued development of pathologic staging as used in the tumor node metastasis (TNM) system. The next major milestone in the staging of large bowel cancer will be to blend current anatomic staging strategies with specific molecular markers that will refine subsets appropriate for targeted therapy.

  11. DDA1 promotes stage IIB–IIC colon cancer progression by activating NFκB/CSN2/GSK-3β signaling

    PubMed Central

    Sun, Hongcheng; Wen, Yugang; Yu, Fudong; Cui, Feifei; Zhang, Dongyuan; Xue, Yingming; Liu, Chenchen; Yue, Ben; Chen, Jian; Wang, Jingtao; Wang, Xiao; Zhang, Meng; Yu, Yang; Jiang, Weiliang; Liu, Xisheng; Mi, Yushuai; Zhou, Zongguang; Qin, Xuebin; Peng, Zhihai

    2016-01-01

    Conventional high-recurrence risk factors are not sufficient to predict post-operative risk of tumor recurrence or sensitivity to 5-fluorouracil (5-FU)-based chemotherapy for stage II colon cancer. DDA1, an evolutionarily conserved gene located at 19p13.11, may be involved in the activation of nuclear factor kappaB (NFκB). This study aimed to investigate whether DDA1 contributes to tumorigenesis and progression of stage II colon cancer via activation of the NFκB pathway. We found that positive expression of DDA1 alone or in combination with p65 nuclear translocation correlated with increased risk of tumor recurrence in patients with stage IIB–IIC colon cancer. DDA1 overexpression in colon cancer lines promoted cell proliferation, facilitated cell cycle progression, inhibited 5-FU-induced apoptosis, enhanced invasion, and induced the epithelial-mesenchymal transition. Suppression of DDA1 inhibited tumor progression, and reduced tumor growth in vivo. We also demonstrated that DDA1-mediated tumor progression is associated with the activation of the NFκB/COP9 signalosome 2(CSN2)/glycogen synthase kinase3β (GSK3β) pathway. These results indicate that DDA1 promotes colon cancer progression through activation of NFκB/CSN2/GSK3β signaling. DDA1, together with NFκB activation status, may serve as a sensitive biomarker for tumor recurrence risk and prognosis in patients with stage IIB–IIC colon cancers. PMID:26942699

  12. Corneal cross-linking in a 10-year-old child with stage III keratoconus.

    PubMed

    Abbondanza, Marco; Felice, Valentina De; Abbondanza, Gabriele

    2016-07-01

    Keratoconus is a corneal dystrophy characterized by progressive thinning, conical shape of the cornea and irregular astigmatism. It is particularly insidious when it occurs in very young patients. We report the case of a 10-year-old child with an aggressive stage III keratoconus, who was suggested to undergo a Penetrating Keratoplasty. We performed Corneal Collagen Cross-linking with epithelium removal instead, which was successful in arresting the rapid progression of keratoconus. Eighteen months later, Kmax had decreased by 1.3 D, astigmatism by 0.8 D, thinnest pachimetry had improved by 69 μm and CDVA was 20/32. This case confirms that Corneal Collagen Cross-linking is a safe and effective procedure for the treatment of keratoconus even in its aggressive forms. We encourage ophthalmic surgeons to favor conservative treatments when dealing with very young patients. © NEPjOPH.

  13. Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-04-03

    Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Lung Adenocarcinoma, Mixed Subtype; Squamous Cell Lung Carcinoma; Stage III Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  14. Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-10-11

    CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  15. Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Stage III-IVB Head and Neck Cancer Who Cannot Take Cisplatin

    ClinicalTrials.gov

    2017-09-04

    Head and Neck Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  16. A composite measure of personal financial burden among patients with stage III colorectal cancer.

    PubMed

    Veenstra, Christine M; Regenbogen, Scott E; Hawley, Sarah T; Griggs, Jennifer J; Banerjee, Mousumi; Kato, Ikuko; Ward, Kevin C; Morris, Arden M

    2014-11-01

    Despite improved survival with chemotherapy for stage III colorectal cancer (CRC), patients may suffer substantial economic hardship during treatment. Methods for quantifying financial burden in CRC patients are lacking. To derive and validate a novel patient-reported measure of personal financial burden during CRC treatment. Within a population-based survey of patients in the Detroit and Georgia Surveillance, Epidemiology and End Results regions diagnosed with stage III CRC between 2011 and 2013, we asked 7 binary questions assessing effects of disease and treatment on personal finances. We used factor analysis to compute a composite measure of financial burden. We used χ tests to evaluate relationships between individual components of financial burden and chemotherapy use with χ analyses. We used Mantel-Haenszel χ trend tests to examine relationships between the composite financial burden metric and chemotherapy use. Among 956 patient surveys (66% response rate), factor analysis of 7 burden items yielded a single-factor solution. Factor loadings of 6 items were >0.4; these were included in the composite score. Internal consistency was high (Cronbach α=0.79). The mean financial burden score among all respondents was 1.72 (range, 0-6). The 812 (85%) who reported chemotherapy use had significantly higher financial burden scores than those who did not (mean burden score 1.88 vs. 0.88, P<0.001). Financial burden is high among CRC patients, particularly those who use adjuvant chemotherapy. We encourage use of our instrument to validate our measure in the identification of patients in need of additional financial support during treatment.

  17. Chemical analysis of simulated high level waste glasses to support stage III sulfate solubility modeling

    SciTech Connect

    Fox, K. M.

    2016-03-17

    The U.S. Department of Energy (DOE), Office of Environmental Management (EM) is sponsoring an international, collaborative project to develop a fundamental model for sulfate solubility in nuclear waste glass. The solubility of sulfate has a significant impact on the achievable waste loading for nuclear waste forms within the DOE complex. These wastes can contain relatively high concentrations of sulfate, which has low solubility in borosilicate glass. This is a significant issue for low-activity waste (LAW) glass and is projected to have a major impact on the Hanford Tank Waste Treatment and Immobilization Plant (WTP). Sulfate solubility has also been a limiting factor for recent high level waste (HLW) sludge processed at the Savannah River Site (SRS) Defense Waste Processing Facility (DWPF). The low solubility of sulfate in glass, along with melter and off-gas corrosion constraints, dictate that the waste be blended with lower sulfate concentration waste sources or washed to remove sulfate prior to vitrification. The development of enhanced borosilicate glass compositions with improved sulfate solubility will allow for higher waste loadings and accelerate mission completion.The objective of the current scope being pursued by SHU is to mature the sulfate solubility model to the point where it can be used to guide glass composition development for DWPF and WTP, allowing for enhanced waste loadings and waste throughput at these facilities. A series of targeted glass compositions was selected to resolve data gaps in the model and is identified as Stage III. SHU fabricated these glasses and sent samples to SRNL for chemical composition analysis. SHU will use the resulting data to enhance the sulfate solubility model and resolve any deficiencies. In this report, SRNL provides chemical analyses for the Stage III, simulated HLW glasses fabricated by SHU in support of the sulfate solubility model development.

  18. Perceptions of Colon Cancer Screening by Stage of Screening Test Adoption

    PubMed Central

    Menon, Usha; Belue, Rhonda; Skinner, Celette Sugg; Rothwell, B. Erin; Champion, Victoria

    2011-01-01

    Colorectal cancer remains the second leading cause of cancer death in the United States. To fully realize the benefits of early detection of colorectal cancer, screening rates must improve. This study assessed differences in beliefs (from the Health Belief Model) by stage of screening behavior adoption (based on the Transtheoretical Model of Change) as a foundation for intervention development. More people were in the precontemplation stage (not thinking about having the screening test) for fecal occult blood test and sigmoidoscopy versus contemplation (thinking about having the test) or action (adherent with screening). Those in precontemplation stage for fecal occult blood test had lower perceived risk than those in contemplation, lower perceived benefits than those in action, and higher barriers than both those in contemplation and those in action. For sigmoidoscopy stage of readiness, again, precontemplators had lower perceived risk and self-efficacy than contemplators and higher barriers than both contemplators and actors. Given the popularity of the transtheoretical model and the success of stage-based interventions to increase other cancer screening, especially mammography, we should begin to translate such effective interventions to colorectal cancer screening. As such, this study is one of very few to quantify beliefs across stages of colorectal cancer and identify significant differences across stages, laying the foundation for the development and testing of stage-based interventions. PMID:17510580

  19. Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-12-21

    Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  20. Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

    ClinicalTrials.gov

    2017-02-08

    Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC

  1. Local vs regional effects of substratum on early colonization stages of sessile assemblages.

    PubMed

    Guarnieri, Giuseppe; Terlizzi, Antonio; Bevilacqua, Stanislao; Fraschetti, Simonetta

    2009-10-01

    Substratum type and topographic complexity influence the settlement and persistence of benthic organisms. However, the combined effect of these two factors in affecting colonization patterns at different scales has rarely been investigated. A manipulative experiment was conducted to test the interplay of rock type and roughness in affecting the pattern of subtidal assemblages and to provide tests for the generality of effects across a range of spatial scales (centimetres to hundreds of metres). Replicate tiles of four different rock types, with two levels of surface roughness were deployed in rocky subtidal habitats (5 m depth) at two sites (separated by hundreds of metres) at each of three locations (separated by tens of kilometres). Spatial and temporal variation in the colonization patterns over 9 months differed among rock types. However, large-scale processes appeared to be far more important than substratum type or roughness in determining assemblage structure. Predicting the consequences of the introduction of artificial structures into the coastal marine environment is critical as increasingly parts of coastlines are being modified within the Mediterranean and other regions. The results suggest that further investment is needed to manage and mitigate the effects of the deployment of artificial structures in coastal areas.

  2. Applying a stage model of behavior change to colon cancer screening.

    PubMed

    Costanza, Mary E; Luckmann, Roger; Stoddard, Anne M; Avrunin, Jill S; White, Mary Jo; Stark, Jennifer R; Clemow, Lynn; Rosal, Milagros C

    2005-01-01

    There has been limited use of stages of change models in characterizing colorectal cancer (CRC) screening. We assess the applicability of the Precaution Adoption Model (PAPM) by determining the distribution of stages of adoption and by elucidating differences among stages. The study is based on 1394 responses (69%) to a survey mailed in 2002 to patients in a primary care population. Survey measures included: self-reported CRC screening, sociodemographic characteristics, health system characteristics, attitudes and beliefs about CRC screening, perceived vulnerability to CRC, and worry about CRC. The main outcome was PAPM stage of adoption of CRC screening based on the ACS preferred guidelines: colonoscopy every 10 years alone or the combination annual FOBT plus sigmoidoscopy every 5 years. 57% were up-to-date with at least one test; 36% were up-to-date with the ACS preferred guidelines; provider recommendation, positive family history of CRC, and positive decisional balance score were significantly associated with higher compared to lower PAPM stages. The combination of PAPM stage assignment and other factors provides useful information for designing tailored interventions. There are special challenges in developing and interpreting PAPM stage assignments when a guideline offers multiple pathways to adherence and recommends a combination of two tests as a preferred option.

  3. [Is there alternative to FOLFOX adjuvant chemotherapy for stage III colorectal cancer patients?].

    PubMed

    Esch, Anouk; Coriat, Romain; Perkins, Géraldine; Brezault, Catherine; Chaussade, Stanislas

    2012-01-01

    Being the second cancer for men and the third cancer for women in France, colorectal cancer represents a serious public health issue. Its incidence has increased these last years and despite new therapeutics being developed, it still has a bad prognostic. Thanks in part to Hemoccult national mass screening program, its diagnosis is made possible at an earlier stage, which makes a surgical curative resection and the carrying out of adjuvant chemotherapy possible. For stage III colic cancer that has been surgically removed, adjuvant chemotherapy by FOLFOX 4 has to be offered. Nevertheless, because of its toxicities, the patient's high age, important comorbidities or post-surgical complications, this chemotherapy occasionally cannot be done. What are the colorectal cancer prognostic factors which would guide the chemotherapy? TNM classification, number of examined lymph nodes, MSI status, and presence or not of a perforation or a perinervous, lymphatic or venous invasion is recognized prognostic factors. Also, what are the alternatives of FOLFOX 4 regimen as colorectal cancer adjuvant treatment?

  4. Validated competing event model for the stage I-II endometrial cancer population.

    PubMed

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D; Rose, Brent S; Wu, John; Noticewala, Sonal; McHale, Michael T; Yashar, Catheryn M; Vaida, Florin; Mell, Loren K

    2014-07-15

    Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    SciTech Connect

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D.; Rose, Brent S.; Wu, John; Noticewala, Sonal; McHale, Michael T.; Yashar, Catheryn M.; Vaida, Florin; Mell, Loren K.

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  6. The role of induction chemotherapy before radiation therapy in non-operative management of stage III NSCLC.

    PubMed

    Green, M R

    1994-11-01

    Radiation therapy alone has been 'standard' management of patients with Stage III non-small cell lung cancer for several decades. Palliative benefits are routinely achieved but significant survival benefits have not been documented. Patterns of failure in Stage III patients emphasize the need to pursue better treatment for both local macroscopic disease and distant micrometastatic sites. Improved control in both areas will be necessary to meaningfully enhance outcome for the universe of Stage III NSCLC patients. Several randomized trials show a significant survival benefit when cisplatin-containing induction chemotherapy is administered prior to locoregional treatment. In the favorable subset of Stage III patients selected for study by CALGB, the surviving fraction at 2-5 years post-therapy was > or = 2-fold larger in the chemoradiation group than in the cohort treated with radiation alone. The French trial documented a significant decrease in distant metastases rate among the chemotherapy treated patients. In all the trials where patterns of failure are discussed, local disease persistence is the overwhelming rule. Future trials must evaluate improved induction chemotherapy approaches. Stage III patients are an ethical population in which to test induction therapy with new drug combinations randomized against already 'active' regimens for comparative efficacy. End points would be initial response rates, patterns of failure, and overall survival. The feasibility of high-dose chemotherapy regimens with growth factor and hematopoietic support followed by aggressive radiation must be tested. If feasible, trials randomizing high dose versus conventional dose induction programs within the context of sequential multimodality therapy should follow. Intensified radiation approaches such as hyperfractionation or CHART should be paired with active concurrent chemotherapy following induction chemotherapy alone. Pursuit of these approaches over the next several years will

  7. [Adjuvant chemotherapy in colon cancer. About 119 cases].

    PubMed

    Yaich, Asma; Khanfir, Afef; Bayrouti, Mohamed Issam; Frikha, Mounir

    2015-04-01

    colon cancer is a public health problem worldwide and in Tunisia. The prognosis of patients with unresectable colorectal cancer varies according to the stage. The indication for adjuvant chemotherapy is well established in the colon cancer stage III, while it remains a matter of controversy for stage II. The aim of this work is to identify the epidemiological and anatomoclinical assess therapeutic outcomes in terms of overall survival of patients with high-risk stage II and stage III colon cancer treated with surgery and adjuvant chemotherapy. DS: It's a retrospective study based on 119 patients with colon adenocarcinoma from 1996 to 2010. This patients suffering from colon cancer classified stage II and III having them all radical surgery and adjuvant chemotherapy. The average age of our patients was 53 years. The surgery was performed in an emergency situation in 53 patients (44%). Stages II and III, respectively, were observed in 47% and 53% of cases. Three regimens of chemotherapy were used: protocol FUFOL (50%), followed by FOLFOX (34%) and the protocol LV5FU2 (16%). Overall survival of patients all stages combined was 73.4% at 5 years. Stage III of the TNM classification (p = 0.03) and the number of cycles of chemotherapy <6 (p=0.02) were a negative prognostic factors influencing overall survival. Patients stage III treated with FOLFOX chemotherapy type had a better survival than those treated with chemotherapy type LV5FU2 or FUFOL with a significant difference (p= 0.05). Our results are consistent with those in the literature. The prognosis of colon cancer is improving thanks to recent advances that have enabled the integration of new cytogenetic factors in the therapeutic decision.

  8. EFFECT OF REPEATED FREEZING (-185 degrees C.) AND THAWING ON COLON BACILLI, VIRUS III, VACCINE VIRUS, HERPES VIRUS, BACTERIOPHAGE, COMPLEMENT, AND TRYPSIN.

    PubMed

    Rivers, T M

    1927-01-01

    Colon bacilli, Virus III, vaccine virus, herpes virus, bacteriophage, complement, and trypsin are either killed or inactivated by repeated freezing (-185 degrees C.) and thawing. As might be expected, some of the agents are more resistant than others. Hence it may be concluded that destruction or inactivation of an active agent by repeated freezing (-185 degrees C.) and thawing is not proof that it was possessed of life.

  9. EFFECT OF REPEATED FREEZING (–185°C.) AND THAWING ON COLON BACILLI, VIRUS III, VACCINE VIRUS, HERPES VIRUS, BACTERIOPHAGE, COMPLEMENT, AND TRYPSIN

    PubMed Central

    Rivers, T. M.

    1927-01-01

    Colon bacilli, Virus III, vaccine virus, herpes virus, bacteriophage, complement, and trypsin are either killed or inactivated by repeated freezing (–185°C.) and thawing. As might be expected, some of the agents are more resistant than others. Hence it may be concluded that destruction or inactivation of an active agent by repeated freezing (–185°C.) and thawing is not proof that it was possessed of life. PMID:19869231

  10. Lymph Node Negative Colorectal Cancers with Isolated Tumor Deposits Should Be Classified and Treated As Stage III

    PubMed Central

    van Stijn, M. F. M.; Bril, H.; de Lange-de Klerk, E. S. M.; Meijer, G. A.; Meijer, S.; Stockmann, H. B. A. C.

    2010-01-01

    Background The prognostic role of pericolic or perirectal isolated tumor deposits (ITDs) in node-negative colorectal cancer (CRC) patients is unclear. Rules to define ITDs as regional lymph node metastases changed in subsequent editions of the TNM staging without substantial evidence. Aim of this study was to investigate the correlation between ITDs and disease recurrence in stage II and III CRC patients. Materials and Methods The medical files of 870 CRC patients were reviewed. Number, size, shape, and location pattern of all ITDs in node-negative patients were examined in relation to involvement of vascular structures and nerves. The correlation between ITDs and the development of recurrent disease was investigated. Results Disease recurrence was observed in 50.0% of stage II patients with ITDs (13 of 26), compared with 24.4% of stage II patients without ITDs (66 of 270) (P < .01). Disease-free survival of ITD-positive stage II patients was comparable with that of stage III patients. Also within stage III, more recurrences were observed in ITD-positive patients compared with ITD-negative patients (65.1 vs. 39.1%, respectively). No correlation was found between size of ITDs and disease recurrence. More recurrences were seen in patients with irregularly shaped ITDs compared with patients with 1 or more smooth ITDs present. Conclusions Because of the high risk of disease recurrence, all node-negative stage II patients with ITDs, regardless of size and shape, should be classified as stage III, for whom adjuvant chemotherapy should be considered. PMID:20625841

  11. High-Dose Recombinant Interferon Alfa-2B, Ipilimumab, or Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

    ClinicalTrials.gov

    2017-10-02

    Metastatic Non-Cutaneous Melanoma; Non-Cutaneous Melanoma; Recurrent Melanoma of the Skin; Recurrent Non-Cutaneous Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage III Mucosal Melanoma of the Head and Neck AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IVA Mucosal Melanoma of the Head and Neck AJCC v7; Stage IVB Mucosal Melanoma of the Head and Neck AJCC v7; Stage IVC Mucosal Melanoma of the Head and Neck AJCC v7

  12. Lymph node size as a simple prognostic factor in node negative colon cancer and an alternative thesis to stage migration.

    PubMed

    Märkl, Bruno; Schaller, Tina; Kokot, Yuriy; Endhardt, Katharina; Kretsinger, Hallie; Hirschbühl, Klaus; Aumann, Georg; Schenkirsch, Gerhard

    2016-10-01

    Stage migration is an accepted explanation for the association between lymph node (LN) yield and outcome in colon cancer. To investigate whether the alternative thesis of immune response is more likely, we performed a retrospective study. We enrolled 239 cases of node negative cancers, which were categorized according to the number of LNs with diameters larger than 5 mm (LN5) into the groups LN5-very low (0 to 1 LN5), LN5-low (2 to 5 LN5), and LN5-high (≥6 LN5). Significant differences were found in pT3/4 cancers with median survival times of 40, 57, and 71 months (P = .022) in the LN5-very low, LN5-low, and LN5-high groups, respectively. Multivariable analysis revealed that LN5 number and infiltration type were independent prognostic factors. LN size is prognostic in node negative colon cancer. The correct explanation for outcome differences associated with LN harvest is probably the activation status of LNs. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Differentiation of high-risk stage I and II colon tumors based on evaluation of CAV1 gene expression.

    PubMed

    Kitowska, Agnieszka; Wesserling, Martyna; Seroczynska, Barbara; Szutowicz, Andrzej; Ronowska, Anna; Peksa, Rafal; Pawelczyk, Tadeusz

    2015-09-01

    Several molecular markers are currently being investigated for their prognostic or predictive value in colorectal cancer. One of the genes proposed, as a potential molecular marker in CRC is CAV1. The level of CAV1 expression was investigated in low-stage (I and II TNM) colon cancers using Real-Time PCR and immunohistochemistry. The level of CAV1 expression increased in tumors characterized by greater depths of invasiveness. The CAV1 expression level detected in tumors with a depth of invasion at stage T4 was significantly higher compared to that in T2 (P = 0.01) and T3 (P = 0.003) lesions. The length of a patient's survival depended on CAV1 expression level; the 10-year survival rate for patients with elevated expression of CAV1 was ∼59% compared with 91% for patients with reduced or unchanged expression of CAV1 (P = 0.007). The overall survival rate of patients with T3 + T4 lesions was significantly lower (P = 0.006) for patients with tumor displaying elevated CAV1 expression compared with patients with reduced or unchanged CAV1 expression. Evaluation of CAV1 expression offers valuable prognostic information for patients with colorectal cancer, and could be used to select patients with stage I or II disease, who are at increased risk of unfavorable outcomes. © 2015 Wiley Periodicals, Inc.

  14. On the interplay effects with proton scanning beams in stage III lung cancer

    SciTech Connect

    Li, Yupeng; Kardar, Laleh; Liao, Li; Lim, Gino; Li, Xiaoqiang; Li, Heng; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Zhang, Xiaodong; Cao, Wenhua; Chang, Joe Y.; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.

    2014-02-15

    Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite

  15. Preoperative investigations for metastatic staging of colon and rectal cancer across multiple centres--what is current practice?

    PubMed

    Kosmider, S; Stella, D L; Field, K; Moore, M; Ananda, S; Oakman, C; Singh, M; Gibbs, P

    2009-07-01

    The optimal strategy for elective distant staging of colorectal carcinoma (CRC) has yet to be defined, with current guidelines based on small and limited series. One specific issue requiring review is the value of routine computerized tomographic (CT) chest examination. Also lacking is data on current routine clinical practice. A retrospective chart review of consecutive cases of elective surgery for CRC from five hospitals. Two hundred and fifty-seven cases were reviewed, 128 colon and 129 rectal primaries. 164 (64%) of patients overall, ranging from 45% to 88% across the individual centres, had a preoperative serum CEA level performed. CT abdomen/pelvis was performed in 222 (86%) of cases, ranging from 69% to 98% per centre. CT chest was performed in 95 (37%) of cases, 47% of rectal vs 29% of colon cancers (P = 0.004). In 17 cases (18%) CT chest examinations revealed abnormalities suspicious for metastatic disease, leading to a change in management in six (35%) of these cases. Of the 17 cases with an abnormal CT chest, in only 5 of the 14 (36%) where carcinoembryonic antigen (CEA) levels were also recorded was this increased, and in only three (21%) was this markedly (> 10 microg/l) elevated. Substantial variability exists in the preoperative evaluation of patients with CRC. Many patients do not have a CEA and/or abdominal imaging performed. Where performed, CT chest revealed suspicious findings in a significant number of patients, the vast majority of whom had a normal or near normal CEA. Future studies are required to define optimal preoperative staging.

  16. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response. PMID:27622047

  17. Histologic pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

    PubMed Central

    Ko, Jennifer S; Prieto, Victor G; Elson, Paul; Vilain, Ricardo E; Pulitzer, Melissa; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa; Ernstoff, Marc S; Gastman, Brian; Billings, Steven D

    2016-01-01

    Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathologic predictors of outcome were sought. Five metastatic patterns were identified: 1, sheet-like (n=38, 59%); 2, non-solid parafollicular (n=4, 6%); 3, sinusoidal, (n=11, 17%); 4, perivascular hilar (n=1, 2%) and 5, rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21(33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2–5 metastases (p=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. 3 (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. 4 (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph node (1 or 2 versus >2, p<.0001), age (<70 versus ≥70, p=.01), sentinel lymph node metastasis pattern (patterns 2–5 versus 1, p=.02), and immune status (immunocompetent versus suppressed, p=.03) were independent predictors of outcome, and could be used to stratify Stage III patients into 3 groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathologic features

  18. Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases

    PubMed Central

    Balch, Charles M.; Gershenwald, Jeffrey E.; Soong, Seng-jaw; Thompson, John F.; Ding, Shouluan; Byrd, David R.; Cascinelli, Natale; Cochran, Alistair J.; Coit, Daniel G.; Eggermont, Alexander M.; Johnson, Timothy; Kirkwood, John M.; Leong, Stanley P.; McMasters, Kelly M.; Mihm, Martin C.; Morton, Donald L.; Ross, Merrick I.; Sondak, Vernon K.

    2010-01-01

    Purpose To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. Patients and Methods Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed. Results Among all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P < .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P < .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P < .01). Conclusion In this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma. PMID:20368546

  19. Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma

    ClinicalTrials.gov

    2017-10-12

    BRAF NP_004324.2:p.V600X; Metastatic Melanoma; Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  20. Nivolumab and Ipilimumab With or Without Sargramostim in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-10-06

    Recurrent Melanoma of the Skin; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  1. Aldesleukin With or Without Ziv-Aflibercept in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-09-22

    Metastatic Melanoma; Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  2. Eugenia jambolana (Java Plum) Fruit Extract Exhibits Anti-Cancer Activity against Early Stage Human HCT-116 Colon Cancer Cells and Colon Cancer Stem Cells

    PubMed Central

    Charepalli, Venkata; Reddivari, Lavanya; Vadde, Ramakrishna; Walia, Suresh; Radhakrishnan, Sridhar; Vanamala, Jairam K. P

    2016-01-01

    The World Health Organization predicts over a 70% increase in cancer incidents in developing nations over the next decade. Although these nations have limited access to novel therapeutics, they do have access to foods that contain chemopreventive bioactive compounds such as anthocyanins, and as such, consumption of these foods can be encouraged to combat cancer. We and others have previously characterized the anti-colon cancer properties of dietary anthocyanins from different sources. Eugenia jambolana (Java plum) is a tropical medicinal fruit rich in anthocyanins, however, its anti-colon cancer properties are not well characterized. Furthermore, recent evidence suggests that colon cancer stem cells (colon CSCs) promote resistance to chemotherapy, relapse of tumors and contribute to poor prognosis. The objectives of this study were to 1) characterize the anthocyanin profile of Java plum using HPLC-MS; and 2) determine the anti-proliferative (cell counting and MTT) and pro-apoptotic (TUNEL and caspase 3/7 glo assay) properties of Java plum fruit extract (JPE) using HCT-116 colon cancer cell line and colon CSCs (positive for CD 44, CD 133 and ALDH1b1 markers). HPLC-MS analysis showed that JPE contains a variety of anthocyanins including glucosides of delphinidin, cyanidin, petunidin, peonidin and malvidin. JPE anthocyanins suppressed (p < 0.05) proliferation in HCT-116 cells and elevated (p < 0.05) apoptosis in both HCT-116 cells and colon CSCs. JPE also suppressed the stemness in colon CSCs as evaluated using colony formation assay. These results warrant further assessment of the anti-cancer activity of JPE, and its molecular mechanisms using pre-clinical models of colon cancer. PMID:26927179

  3. Primary treatment of stage III ovarian carcinoma with sequential chemotherapy and whole abdominal radiation therapy.

    PubMed

    Reid, G C; Roberts, J A; Hopkins, M P; Schoeppel, S L; Perez-Tamayo, C; Drescher, C; Chamberlain, D; Morley, G W

    1993-06-01

    A prospective phase II clinical treatment trial of 13 patients with previously untreated optimal surgically resected (< or = 1 cm stage III ovarian carcinoma was conducted at the University of Michigan Hospitals. The treatment regimen after surgical resection consisted of chemotherapy followed by whole abdomen and pelvic radiation therapy. Chemotherapy consisted of four cycles of 50 mg/m2 cisplatin and 1000 mg/m2 cytoxan. This was followed by whole abdomen radiation therapy with a planned total dose of 30 Gy to the whole abdomen and then a 20-Gy boost to the pelvis. Six of 13 patients received a paraaortic radiation boost. There was minimal acute toxicity, but delayed toxicity was encountered with 38% of patients developing a bowel obstruction. Nine patients had reassessment laparotomy: 5 second-look laparotomies and 4 laparotomies for bowel obstruction. Two of these 9 patients died of septic complications after surgery. Nine patients died with disease, 1 patient is alive with advanced disease, and only 3 patients are alive with no evidence of disease. Actuarial 3-year survival and progression-free interval was 26 and 20%, respectively. Primary treatment consisting of sequential chemotherapy and whole abdomen radiation in the dose and scheme utilized did not improve the survival over what could be expected utilizing one of these treatments alone. It was associated with increased delayed toxicity.

  4. Trace elements and heavy metals in hair of stage III breast cancer patients.

    PubMed

    Benderli Cihan, Yasemin; Sözen, Selim; Oztürk Yıldırım, Sema

    2011-12-01

    This prospective study was designed to compare the hair levels of 36 elements in 52 patients with stage III breast cancer to those of an equal number of healthy individuals. Principal component and cluster analysis were used for source of identification and apportionment of heavy metals and trace elements in these two groups. A higher average level of iron was found in samples from patients while controls had higher levels of calcium. Both patients and controls had elevated levels of tin, magnesium, zinc, and sodium. Almost all element values in cancer patients showed higher dispersion and asymmetry than in healthy controls. Between the two groups, there were statistically significant differences in the concentrations of silver, arsenic, gold, boron, barium, beryllium, calcium, cadmium, cerium, cobalt, cesium, gadolinium, manganese, nickel, lead, antimony, scandium, selenium, and zinc (p < 0.05). Strong positive correlations were found between lead and gold (r = 0.785) in the cancer group and between palladium and cobalt (r = 0.945) in the healthy individuals. Our results show that there are distinct patterns of heavy metals and trace elements in the hair of breast cancer patients in comparison to healthy controls. These results could be of significance in the diagnosis of breast cancer.

  5. Battling regional (stage III) lung cancer: bumpy road of a cancer survivor in the immunotherapy age.

    PubMed

    Hao, Zhonglin; Biddinger, Paul; Schroeder, Carsten; Tariq, Khurram

    2016-07-07

    A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles. Despite not being eligible for a durvalumab trial because of lack of PD-L1 expression, she had a meaningful response to nivolumab. Once every 2 weeks, infusion of nivolumab resulted in rapid tumour shrinkage in multiple areas. In the next few months, she experienced a variety of side effects, some of which were potentially life-threatening. She had disease progression 9 months into treatment.

  6. Late Closure of a Stage III Idiopathic Macular Hole after Pars Plana Vitrectomy

    PubMed Central

    Afrashi, Filiz; Öztaş, Zafer; Nalçacı, Serhad

    2015-01-01

    A 57-year-old female presented to our hospital with decreased vision in her right eye. Detailed ocular examination was performed, and a macular hole was detected in the right eye. The presence of a full-thickness stage III macular hole was confirmed with optical coherence tomography (OCT) imaging. Pars plana vitrectomy followed by long-acting gas tamponade (C3F8) was performed as treatment. One month after surgery, clinical examination revealed a persistent macular hole, confirmed by an OCT scan. Although the patient was scheduled for reoperation, the surgery was postponed due to personal reasons of the patient. Surprisingly, after five months, a closure pattern with accompanying epiretinal membrane was observed in the macular hole area. The closure of the macular hole was completed without any further intervention 8 months post-surgery. In cases of unclosed macular hole after the first surgery, if a second surgery cannot be performed, follow-up with OCT recommended due to the possibility of spontaneous closure. However, spontaneous closure of a persistent macular hole following PPV is rare, so early diagnosis and surgical repair of unclosed macular holes must remain the primary goal. PMID:27800248

  7. Treatment of stage III carcinoma of the uterine cervix with telecobalt irradiation

    SciTech Connect

    Souhami, L.; Melo, J.A.; Pareja, G.

    1987-11-01

    This is a retrospective analysis of 148 patients with histologically proven carcinoma of the cervix, stage III, treated with irradiation. All patients received external irradiation with cobalt 60 followed by intracavitary radium application. The median age was 55 years. Squamous cell carcinoma was found in 96.5% of the cases. The 8-year actuarial survival rate was 41%. Bilateral parametrial invasion proved to be a strong prognostic factor. Patients with unilateral disease had a survival rate of 43% whereas in those with bilateral involvement it was only 15% (P less than 0.005). The total pelvic failure rate was 29.5%. The overall incidence of distant metastasis was 11%. The complication rate (minor and major complications) was high, with vaginal stenosis (22.5%), proctitis (21.5%), cystitis (13.5%), and fistulae (4%) occurring in 33, 32, 20, and 6 patients, respectively. New treatment modalities are urgently needed for advanced carcinoma of the cervix. Bilateral parametrial involvement is an unfavorable prognostic factor and this should be kept in mind when designing new protocols.

  8. Evaluation of NEXRDA Stage III precipitation data over Sevilleta National Wildlife Refuge: a semiarid region in Central New Mexico

    NASA Astrophysics Data System (ADS)

    Xie, H.; Zhou, X.; Hendrickx, J.; Guan, H.

    2006-05-01

    This study examines NEXRAD Stage III product (hourly, cell size 4 km by 4 km) for its ability in estimating precipitation over Sevilleta National Wildlife Refuge: a semiarid region in Central New Mexico. A GIS-based NEXRAD data processing and visualization method is also presented. A comparison between Stage III and a network of gauge precipitation estimates during 1995 to 2001 indicates that Stage III (1) overestimates the hourly conditional mean precipitation (CM) by 33 percent in monsoon season and 55 percent in non-monsoon season; (2) overestimates the hourly CM for concurrent radar-gauge pairs (non-zero value) by 13 percent in monsoon season and 6 percent in non-monsoon season; (3) overestimates the seasonal precipitation accumulation by 11 to 88 percent in monsoon season and underestimates by 18 to 89 percent in non- monsoon season; and (4) either overestimates annual precipitation accumulation up to 28.2 percent or underestimates it up to 11.9 percent. More caution is suggested in using Stage III data for nonmonsoonal (stratiform) rainfall events (prior to the truncation fixed algorithm deployed in 2002), as the truncation error can be a significant drawback. While overestimates may suppress the truncation caused underestimates in the monsoon seasons.

  9. Georgetown University Integrated Community Energy System (GU-ICES). Phase III, Stage I: feasibility analysis. Final report

    SciTech Connect

    Buck, Victor

    1980-10-01

    Candidate energy alternatives are analyzed in Phase III, Stage I, and the appendices are presented for the feasibility analysis. Information in eight appendices includes the following: detailed statement of work; PEPCO rate schedules; cogeneration schemes; added coal, limestone, and ash storage; hot and cold thermal storage; absorption refrigeration; high temperature heat pumps; and life cycle cost analysis. (MCW)

  10. 125I Seed Permanent Implantation as a Palliative Treatment for Stage III and IV Hypopharyngeal Carcinoma

    PubMed Central

    Li, Lei; Yang, Jie; Li, Xiaojiang; Wang, Xiaoli; Ren, Yanxin; Fei, Jimin; Xi, Yan; Sun, Ruimei; Ma, Jing

    2016-01-01

    Objectives. The aim of this study was to investigate the feasibility and safety of percutaneous 125I seed permanent implantation for advanced hypopharyngeal carcinoma from toxicity, tumor response, and short-term outcome. Methods. 125I seeds implant procedures were performed under computed tomography for 34 patients with advanced hypopharyngeal carcinoma. We observed the local control rate, overall survival, and acute or late toxicity rate. Results. In the 34 patients (stage III, n=6; stage IV, n=28), the sites of origin were pyriform sinus (n=29) and postcricoid area (n=5). All patients also received one to four cycles of chemotherapy after seed implantation. The post-plan showed that the actuarial D90 of 125I seeds ranged from 90 to 158 Gy (median, 127 Gy). The mean follow-up was 12.3 months (range, 3.4 to 43.2 months). The local control was 2.1–31.0 months with a median of 17.7 months (95% confidence interval [CI], 13.4 to 22.0 months). The 1-, 2-, and 3-year local controls were 65.3%, 28.6%, and 9.5% respectively. Twelve patients (35%) died of local recurrence, fourteen patients (41%) died of distant metastases, and three patients (9%) died of recurrence and metastases at the same time. Five patients (15%) still survived to follow-up. At the time of analysis, the median survival time was 12.5 months (95% CI, 9.5 to 15.4 months). The 1-, 2-, and 3-year overall survival rates were 55.2%, 20.3%, and 10.9%, respectively. Five patients (15%) experienced grade 3 toxic events and nine patients (26%) have experienced grade 2 toxic events. Conclusion. This review shows relatively low toxicity for interstitial 125I seed implantation in the patients with advanced stage hypopharyngeal cancer. The high local control results suggest that 125I seed brachytherapy implant as a salvage or palliative treatment for advanced hypopharyngeal carcinoma merit further investigation. PMID:27440132

  11. Site and Timing of First Relapse in Stage III Melanoma Patients: Implications for Follow-Up Guidelines

    PubMed Central

    Romano, Emanuela; Scordo, Michael; Dusza, Stephen W.; Coit, Daniel G.; Chapman, Paul B.

    2010-01-01

    Purpose Stage III melanoma is associated with a high risk of relapse and mortality. Nevertheless, follow-up guidelines have largely been empirical rather than evidence-based. Patients and Methods Clinical records of stage III patients with no evidence of disease seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1992 and 2004, who ultimately relapsed, were reviewed retrospectively to evaluate date of first relapse, time to first relapse, method of first relapse detection, and survival. We also determined overall 5-year relapse-free survival (RFS) of all stage III patients seen at MSKCC during this period. Results The overall 5-year RFS for stage IIIA, IIIB, and IIIIC patients was 63%, 32%, and 11%, respectively. Among relapsing patients, 340 had adequate follow-up to be evaluable for all parameters. Site of first relapse was local/in-transit (28%), regional nodal (21%), or systemic (51%). First relapses were detected by the patient or family, physician, or by screening radiologic tests in 47%, 21%, and 32% of patients, respectively. Multivariate analysis revealed that better overall survival was associated with younger age and first relapse being local/in-transit or nodal, asymptomatic, or resectable. For each substage, we estimated site-specific risk of first relapse. Conclusion Patients detected almost half of first relapses. Our data suggest that routine physical examinations beyond 3 years for stage IIIA, 2 years for stage IIIB, and 1 year for stage IIIC patients and radiologic imaging beyond 3 years for stages IIIA and IIIB and 2 years for stage IIIC patients would be expected to detect few first systemic relapses. PMID:20479405

  12. The proportion cured of patients diagnosed with Stage III-IV cutaneous malignant melanoma in Sweden 1990-2007: A population-based study.

    PubMed

    Eriksson, Hanna; Lyth, Johan; Andersson, Therese M-L

    2016-06-15

    The survival in cutaneous malignant melanoma (CMM) is highly dependent on the stage of the disease. Stage III-IV CMM patients are at high risk of relapse with a heterogeneous outcome, but not all experience excess mortality due to their disease. This group is referred to as the cure proportion representing the proportion of patients who experience the same mortality rate as the general population. The aim of this study was to estimate the cure proportion of patients diagnosed with Stage III-IV CMM in Sweden. From the population-based Swedish Melanoma Register, we included 856 patients diagnosed with primary Stage III-IV CMM, 1990-2007, followed-up through 2013. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by sex, age, tumor site, ulceration status (in Stage III patients) and disease stage. The standardized (over sex, age and site) cure proportion was lower in Stage IV CMMs (0.15, 95% CI 0.09-0.22) than non-ulcerated Stage III CMMs (0.48, 95% CI 0.41-0.55) with a statistically significant difference of 0.33 (95% CI = 0.24-0.41). Ulcerated Stage III CMMs had a cure proportion of 0.27 (95% CI 0.21-0.32) with a statistically significant difference compared to non-ulcerated Stage III CMMs (difference 0.21; 95% CI = 0.13-0.30). The standardized MST of uncured was approximately 9-10 months longer for non-ulcerated versus ulcerated Stage III CMMs. We could demonstrate a significantly better outcome in patients diagnosed with non-ulcerated Stage III CMMs compared to ulcerated Stage III CMMs and Stage IV disease after adjusting for age, sex and tumor site. © 2016 UICC.

  13. Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-12-22

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  14. Direct variable cost of the topical treatment of stages III and IV pressure injuries incurred in a public university hospital.

    PubMed

    Chacon, Julieta M F; Blanes, Leila; Borba, Luis G; Rocha, Luis R M; Ferreira, Lydia M

    2017-05-01

    to estimate the direct variable costs of the topical treatment of stages III and IV pressure injuries of hospitalized patients in a public university hospital, and assess the correlation between these costs and hospitalization time. Forty patients of both sexes who had been admitted to the São Paulo Hospital, São Paulo, SP, Brazil, from 2011 to 2012, with pressure injuries in the sacral, ischial or trochanteric region were included. The patients had a total of 57 pressure injuries in the selected regions, and the lesions were monitored daily until patient release, transfer or death. The quantities and types of materials, as well as the amount of professional labor time spent on each procedure and each patient were recorded. The unit costs of the materials and the hourly costs of the professional labor were obtained from the hospital's purchasing and human resources departments, respectively. Spearman's correlation coefficient and the Mann-Whitney and Kruskal-Wallis tests were used for the statistical analyses. The mean topical treatment costs for stages III and IV PIs were significantly different (US$ 854.82 versus US$ 1785.35; p = 0.004). The mean topical treatment cost of stages III and IV pressure injuries per patient was US$ 1426.37. The mean daily topical treatment cost per patient was US$ 40.83. There was a significant correlation between hospitalization time and the total costs of labor and materials (p < 0.05). There was no significant difference between hospitalization time periods for stages III and IV pressure injuries (40.80 days and 45.01 days, respectively; p = 0.834). The mean direct variable cost of the topical treatment for stages III and IV pressure injuries per patient in this public university hospital was US$ 1426.37. Copyright © 2016. Published by Elsevier Ltd.

  15. Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer.

    PubMed

    Cripps, C; Winquist, E; Devries, M C; Stys-Norman, D; Gilbert, R

    2010-06-01

    What are the benefits associated with the use of anti-epidermal growth factor receptor (anti-EGFR) therapies in squamous cell carcinoma of the head and neck (HNSCC)? Anti-EGFR therapies of interest included cetuximab, gefitinib, lapatinib, zalutumumab, erlotinib, and panitumumab. Head-and-neck cancer includes malignant tumours arising from a variety of sites in the upper aerodigestive tract. The most common histologic type is squamous cell carcinoma, and most common sites are the oral cavity, the oropharynx, the hypopharynx, and the larynx. Worldwide, HNSCC is the sixth most common neoplasm, and despite advances in therapy, long-term survival in HNSCC patients is poor. Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced (stages III-IVB) HNSCC; however, meta-analytic data indicate that the benefit of concurrent platinum-based chemotherapy disappears in patients over the age of 70 years. Cetuximab is a monoclonal antibody approved for use in combination with radiation in the treatment of patients with untreated locally advanced HNSCC and as monotherapy for patients with recurrent or metastatic (stage IVC) HNSCC who have progressed on platinum-based therapy. Given the interest in anti-EGFR agents in advanced HNSCC, the Head and Neck Cancer Disease Site Group (DSG) of Cancer Care Ontario's Program in Evidence-Based Care (PEBC) chose to systematically review the literature pertaining to this topic so as to develop evidence-based recommendations for treatment. Outcomes of interest included overall and progression-free survival, quality of life, tumour response rate and duration, and the toxicity associated with the use of anti-EGFR therapies. The medline, embase, and Cochrane Library databases, the American Society of Clinical Oncology online conference proceedings, the Canadian Medical Association InfoBase, and the National Guidelines Clearinghouse were systematically searched to

  16. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-12-13

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  17. Hartmann's procedure for obstructive carcinoma of the left colon and rectum: a comparative study with one-stage surgery.

    PubMed

    Durán Giménez-Rico, Hipólito; Abril Vega, Carlos; Herreros Rodríguez, José; Concejo Cútoli, Pilar; Paseiro Crespo, Gloria; Sabater Maroto, Cristina; Jadraque Jiménez, Pablo; Durán Sacristán, Hipólito

    2005-08-01

    Despite the criticisms from prestigious expert committees, a high percentage of surgeons continue to use, as the technique-of-choice, Hartmann's procedure for acute malignant intestinal obstruction of the distal colon and rectum, without faecal peritonitis. We have reviewed our results with this technique and compared them with other series of patients in the literature undergoing one-stage surgery (resection with primary anastomosis or sub-total colectomy). A retrospective and descriptive study using clinical histories and, from which, the variables studied were: median hospitalisation stay, morbido-mortality and reconstruction index. Included in the analysis were 44 patients (24 male; 20 female) with an age range between 37 and 87 years (median age: 67.04 years). The median hospitalisation stay was 15.59 days (range: 8-39). In the 10 patients undergoing reconstruction this was 12.8 days (range: 10-17). The overall stay, therefore, was 28.39 days. The median stay in the series of patients having one-stage surgery was 13.9 days. The morbidity using Hartmann's procedure was 43.18% (19/44) and, in the patients with reconstruction, 40% (4/10). The morbidity in the literature series with one-stage surgery was 22.53%. Mortality in our study was 0%. The mortality in the 16 cases from the literature was close to 5%, although in 3 of the studies this was also 0%. The percentage undergoing reconstruction was 22.72% (10 cases). The median age in the non-reconstructed patients was 71.42 years (range: 46-87) compared to a median age of 52.6 (range 37-67) in the group with reconstruction (p < 0.001). The percentages undergoing reconstruction, according to tumour stage, were Dukes B: 36.84%; Dukes C: 23.07%; Dukes D: 0% (p < 0.001). The median waiting-time for a reconstruction was 15.73 months (range: 8-33). Comparisons of our results with the outcomes in the series of patients in the literature with one-stage surgery indicate that "one-stage surgery" is the more suitable but

  18. Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

    ClinicalTrials.gov

    2016-05-24

    Estrogen Receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Male Breast Cancer; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  19. Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia

    ClinicalTrials.gov

    2016-10-24

    Childhood B Acute Lymphoblastic Leukemia; Childhood Burkitt Leukemia; Childhood Diffuse Large Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma

  20. Early postoperative 18F-FDG PET/CT in high-risk stage III colorectal cancer.

    PubMed

    Wasserberg, Nir; Purim, Ofer; Bard, Vyacheslav; Kundel, Yulia; Gordon, Noa; Groshar, David; Goldberg, Natalia; Kashtan, Hanoch; Sulkes, Aaron; Brenner, Baruch

    2015-04-01

    PET/CT may contribute to staging modification in different phases of colorectal cancer (CRC) management. However, it is not routinely indicated for stage III CRC. This study sought to determine the role of early postoperative PET/CT in patients with high-risk stage III CRC. The tumor registry of a tertiary medical center was searched (2004-2011) for all patients with stage III CRC who underwent early postoperative PET/CT because of the presence of high-risk factors for systemic disease. Demographic and clinicopathological characteristics were compared between patients found/not found to have metastatic disease. The cohort included 91 patients with a median age of 67 years (range, 29-90 years). Pathological FDG uptake was observed in 38 (41%). Of these, 14 (15% of the whole cohort) were upstaged with alteration of their treatment protocol, 10 (11%) had local postoperative changes, and 14 (15%) had false-positive findings. The sensitivity and specificity of PET/CT for detecting metastatic disease were 100% and 69%, respectively. Elevated postoperative carcinoembryonic antigen and CA-19.9 levels correlated with a positive PET/CT (P = 0.05 and P = 0.03, respectively). The median follow-up time was 34 months (range, 4-85 months). The estimated 5-year survival rate was significantly higher in patients with a negative than a positive scan (70% vs 42%, P < 0.0006). Findings on early postoperative PET/CT may influence staging and treatment in 15% of selected patients with high-risk stage III CRC. Postoperative levels of carcinoembryonic antigen and CA-19.9 may serve as indications for PET/CT scanning in this setting. Prospective validation is warranted.

  1. Impact of life stage-dependent dispersal on the colonization dynamics of host patches by ticks and tick-borne infectious agents.

    PubMed

    Kada, Sarah; McCoy, Karen D; Boulinier, Thierry

    2017-08-04

    When colonization and gene flow depend on host-mediated dispersal, a key factor affecting vector dispersal potential is the time spent on the host for the blood meal, a characteristic that can vary strongly among life history stages. Using a 2-patch vector-pathogen population model and seabird ticks as biological examples, we explore how vector colonization rates and the spread of infectious agents may be shaped by life stage-dependent dispersal. We contrast hard (Ixodidae) and soft (Argasidae) tick systems, which differ strongly in blood- feeding traits. We find that vector life history characteristics (i.e. length of blood meal) and demographic constraints (Allee effects) condition the colonization potential of ticks; hard ticks, which take a single, long blood meal per life stage, should have much higher colonization rates than soft ticks, which take repeated short meals. Moreover, this dispersal potential has direct consequences for the spread of vector-borne infectious agents, in particular when transmission is transovarial. These results have clear implications for predicting the dynamics of vector and disease spread in the context of large-scale environmental change. The findings highlight the need to include life-stage dispersal in models that aim to predict species and disease distributions, and provide testable predictions related to the population genetic structure of vectors and pathogens along expansion fronts.

  2. ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

    PubMed Central

    Vargas, Teodoro; Moreno-Rubio, Juan; Herranz, Jesús; Cejas, Paloma; Molina, Susana; González-Vallinas, Margarita; Mendiola, Marta; Burgos, Emilio; Aguayo, Cristina; Custodio, Ana B.; Machado, Isidro; Ramos, David; Gironella, Meritxell; Espinosa-Salinas, Isabel; Ramos, Ricardo; Martín-Hernández, Roberto; Risueño, Alberto; De Las Rivas, Javier; Reglero, Guillermo; Yaya, Ricardo; Fernández-Martos, Carlos; Aparicio, Jorge; Maurel, Joan; Feliu, Jaime; de Molina, Ana Ramírez

    2015-01-01

    Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group. PMID:25749516

  3. COMPROMISED MARGINS FOLLOWING MASTECTOMY FOR STAGE I - III INVASIVE BREAST CANCER

    PubMed Central

    Yu, Jennifer; Mushawah, Fatema Al; Taylor, Marie E.; Cyr, Amy E.; Gillanders, William E.; Aft, Rebecca L.; Eberlein, Timothy J.; Gao, Feng; Margenthaler, Julie A.

    2014-01-01

    Background We investigated factors associated with positive margins following mastectomy and the impact on outcomes. Methods We identified 240 patients with stage I-III invasive breast cancer who underwent mastectomy from 1999-2009. Data included patient and tumor characteristics, pathologic margin assessment, and outcomes. Margin positivity was defined as the presence of in situ or invasive malignancy present at any margin. Descriptive statistics were utilized for data summary and were compared using Chi-square. Results Of the 240 patients, 132 (55%) had a simple mastectomy with sentinel lymph node biopsy and 108 (45%) had a modified radical mastectomy. Overall, 21 (9%) patients had positive margins, including 12 (57%) with one positive margin, 3 (14%) with two positive margins, and 6 (29%) with three or more positive margins. The most commonly affected margin was the deep margin (48% of patients). Eight (38%) of the 21 patients received adjuvant chest wall irradiation. There were no differences between patients who had a positive margin versus those who did not with respect to patient age, race, percentage of in situ component, tumor size, tumor grade, lymphovascular invasion, or immunostain profile (p>0.05 for all). None of the patients with positive margins experienced a local recurrence. Conclusions Positive margins following mastectomy occurred in nearly 10% of our patients. No specific patient or tumor characteristics predicted a risk for having a positive margin. Despite the finding that only approximately 40% of patients received adjuvant radiation in the setting of a positive margin, no local recurrences have been observed. PMID:22520579

  4. Compromised margins following mastectomy for stage I-III invasive breast cancer.

    PubMed

    Yu, Jennifer; Al Mushawah, Fatema; Taylor, Marie E; Cyr, Amy E; Gillanders, William E; Aft, Rebecca L; Eberlein, Timothy J; Gao, Feng; Margenthaler, Julie A

    2012-09-01

    We investigated factors associated with positive margins following mastectomy and the impact on outcomes. We identified 240 patients with stage I-III invasive breast cancer who underwent mastectomy from 1999 to 2009. Data included patient and tumor characteristics, pathologic margin assessment, and outcomes. Margin positivity was defined as the presence of in situ or invasive malignancy at any margin. Descriptive statistics were used for data summary and were compared using χ(2). Of the 240 patients, 132 (55%) had a simple mastectomy with sentinel lymph node biopsy and 108 (45%) had a modified radical mastectomy. Overall, 21 patients (9%) had positive margins, including 12 (57%) with one positive margin, 3 (14%) with two positive margins, and 6 (29%) with three or more positive margins. The most commonly affected margin was the deep margin (48% of patients). Eight of the 21 patients (38%) received adjuvant chest wall irradiation. There were no differences between patients who had a positive margin and those who did not with respect to patient age, race, percentage of in situ component, tumor size, tumor grade, lymphovascular invasion, or immunostain profile (P > 0.05 for all). None of the patients with positive margins experienced a local recurrence. Positive margins following mastectomy occurred in nearly 10% of our patients. No specific patient or tumor characteristics predicted a risk for having a positive margin. Despite the finding that only approximately 40% of patients received adjuvant radiation in the setting of a positive margin, no local recurrences have been observed. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival.

    PubMed

    Fink, Stephen P; Myeroff, Lois L; Kariv, Revital; Platzer, Petra; Xin, Baozhong; Mikkola, Debra; Lawrence, Earl; Morris, Nathan; Nosrati, Arman; Willson, James K V; Willis, Joseph; Veigl, Martina; Barnholtz-Sloan, Jill S; Wang, Zhenghe; Markowitz, Sanford D

    2015-10-13

    Genes induced in colon cancer provide novel candidate biomarkers of tumor phenotype and aggressiveness. We originally identified KIAA1199 (now officially called CEMIP) as a transcript highly induced in colon cancer: initially designating the transcript as Colon Cancer Secreted Protein 1. We molecularly characterized CEMIP expression both at the mRNA and protein level and found it is a secreted protein induced an average of 54-fold in colon cancer. Knockout of CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in athymic mice. Tumors that did grow had increased deposition of hyaluronan, linking CEMIP participation in hyaluronan degradation to the modulation of tumor phenotype. We find CEMIP mRNA overexpression correlates with poorer patient survival. In stage III only (n = 31) or in combined stage II plus stage III colon cancer cases (n = 73), 5-year overall survival was significantly better (p = 0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing tumors than those with high CEMIP expressing tumors. These results demonstrate that CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. We present CEMIP as a candidate prognostic marker for colon cancer and a potential therapeutic target.

  6. Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival

    PubMed Central

    Fink, Stephen P.; Myeroff, Lois L.; Kariv, Revital; Platzer, Petra; Xin, Baozhong; Mikkola, Debra; Lawrence, Earl; Morris, Nathan; Nosrati, Arman; Willson, James K. V.; Willis, Joseph; Veigl, Martina; Barnholtz-Sloan, Jill S.; Wang, Zhenghe; Markowitz, Sanford D.

    2015-01-01

    Genes induced in colon cancer provide novel candidate biomarkers of tumor phenotype and aggressiveness. We originally identified KIAA1199 (now officially called CEMIP) as a transcript highly induced in colon cancer: initially designating the transcript as Colon Cancer Secreted Protein 1. We molecularly characterized CEMIP expression both at the mRNA and protein level and found it is a secreted protein induced an average of 54-fold in colon cancer. Knockout of CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in athymic mice. Tumors that did grow had increased deposition of hyaluronan, linking CEMIP participation in hyaluronan degradation to the modulation of tumor phenotype. We find CEMIP mRNA overexpression correlates with poorer patient survival. In stage III only (n = 31) or in combined stage II plus stage III colon cancer cases (n = 73), 5-year overall survival was significantly better (p = 0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing tumors than those with high CEMIP expressing tumors. These results demonstrate that CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. We present CEMIP as a candidate prognostic marker for colon cancer and a potential therapeutic target. PMID:26437221

  7. Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer

    ClinicalTrials.gov

    2017-08-23

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  8. The Presence of Telomere Fusion in Sporadic Colon Cancer Independently of Disease Stage, TP53/KRAS Mutation Status, Mean Telomere Length, and Telomerase Activity

    PubMed Central

    Tanaka, Hiromi; Beam, Matthew J.; Caruana, Kevin

    2014-01-01

    Defects in telomere maintenance can result in telomere fusions that likely play a causative role in carcinogenesis by promoting genomic instability. However, this proposition remains to be fully understood in human colon carcinogenesis. In the present study, the temporal sequence of telomere dysfunction dynamics was delineated by analyzing telomere fusion, telomere length, telomerase activity, hotspot mutations in KRAS or BRAF, and TP53 of tissue samples obtained from 18 colon cancer patients. Our results revealed that both the deficiency of p53 and the shortening of mean telomere length were not necessary for producing telomere fusions in colon tissue. In five cases, telomere fusion was observed even in tissue adjacent to cancerous lesions, suggesting that genomic instability is initiated in pathologically non-cancerous lesions. The extent of mean telomere attrition increased with lymph node invasiveness of tumors, implying that mean telomere shortening correlates with colon cancer progression. Telomerase activity was relatively higher in most cancer tissues containing mutation(s) in KRAS or BRAF and/or TP53 compared to those without these hotspot mutations, suggesting that telomerase could become fully active at the late stage of colon cancer development. Interestingly, the majority of telomere fusion junctions in colon cancer appeared to be a chromatid-type containing chromosome 7q or 12q. In sum, this meticulous correlative study not only highlights the concept that telomere fusion is present in the early stages of cancer regardless of TP53/KRAS mutation status, mean telomere length, and telomerase activity, but also provides additional insights targeting key telomere fusion junctions which may have significant implications for colon cancer diagnoses. PMID:25379018

  9. Predictors of Local Recurrence After Rituximab Based Chemotherapy Alone in Stage III/IV DLBCL: Guiding Decisions for Consolidative Radiation

    PubMed Central

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng; Liu, Yuan; Okwan-Duodu, Derrick; Flowers, Christopher R.; Khan, Mohammad K.

    2015-01-01

    Purpose The role of consolidative radiotherapy (RT) for stage III and IV DLBCL in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials 211 stage III and IV DLBCL patients treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed with local recurrence (LR) as the primary outcome. Results Median follow-up was 43.9 months. 50% experienced LR at 5 years. In multivariate analysis tumor ≥ 5 cm and stage III disease were associated with increased risk of LR. Five year LR free survival for patients with ≥ 5 cm lesions were 47.4% versus 74.7% for patients with < 5cm lesions (p = 0.01). In patients with < 5 cm tumors, SUVmax was ≥15 in all patients with LR. Five year LR free survival was 100% in SUV < 15 versus 68.8% in SUV≥15 (p=0.10). Conclusions Advanced stage DLBCL patients who are stage III or with disease ≥ 5 cm appear to be at an increased risk for LR. Patients with < 5 cm disease and SUVmax≥15 may be at higher risk for LR. These patients may benefit from consolidative RT following chemoimmunotherapy. PMID:25863758

  10. [Ultrasound staging of stage I-II endometrial cancer, analysis of own file in the years 2012-2016].

    PubMed

    Míka, O; Kožnarová, J; Sak, P

    2017-01-01

    The aim of the presented study was to evaluate the accuracy of ultrasound staging of early stage endometrial cancer depending on grading, evaluation of ultrasound examination accuracy growing overtime with gained experience of examiners and comparison of subjective versus objective modalities of deep myometrial invasion assessment in the file of patients who were referred in The Oncogyneacologic Center, Department of Gyneacology and Obstetrics in České Budějovice. Retrospective study. Department of Gyneacology and Obstetrics, Hospital České Budějovice a.s.Methods and the file: In this arcticle we retrospectively evaluate the file of 136 patients with early stage endometrial cancer. The patients underwent diagnostic and therapeutic procedures during the years 2012-2016 in our department. All these patients were able to be compared in different aproaches to deep myometrial invasion assessment using ultrasound examination. Comparing the used methods of deep myometrial invasion assessment with ultrasound examination of early stage endometrial cancer patients the examiner's subjective evaluation seems to be the best approach. After the first year of doing these assessments sensitivity performed 80%, specificity 79% and infiltration of cervix sensitivity 70% and specificity 99%. In case the patients were divided into groups according to the grading, low grade assessed worst sensitivity 64% (high grade l00%), but the best specificity 75% (high grade 56%). The evaluation of objective approaches of ultrasound assement with used cut offs performed the best sensitivity 81% tumour free minimal margin (specificity 67%). On the contrary the best specificity 90% performed the ratio AP (anteroposterior) diameter tumour/AP diameter uterine (senzitivity 54%). Generally in oncological therapy the most important things to put stress on the very accurate staging of oncological disease. In oncogyneacology ultrasound becomes more and more required examination. In our file we proved

  11. Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer

    PubMed Central

    Zeestraten, E C M; Maak, M; Shibayama, M; Schuster, T; Nitsche, U; Matsushima, T; Nakayama, S; Gohda, K; Friess, H; van de Velde, C J H; Ishihara, H; Rosenberg, R; Kuppen, P J K; Janssen, K-P

    2012-01-01

    Background: There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. Methods: In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. Results: Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55–0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ⩾11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44–26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. Conclusion: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer. PMID:22108518

  12. High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

    PubMed Central

    Jørgensen, Stine; Fog, Jacob Ulrik; Søkilde, Rolf; Christensen, Ib Jarle; Hansen, Ulla; Brünner, Nils; Baker, Adam; Møller, Søren; Nielsen, Hans Jørgen

    2010-01-01

    Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06–1.55) in the stage II colon cancer patient group, whereas no significant correlation with disease-free survival was observed in the stage II rectal cancer group. In multivariate analysis both TB and TBR estimates were independent of other clinical parameters (age, gender, total leukocyte count, K-RAS mutational status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which when measured by image analysis identifies a subgroup of stage II colon cancer patients with short disease-free survival. Electronic supplementary material The online version of this article (doi:10.1007/s10585-010-9355-7) contains supplementary material, which is available to authorized users. PMID:21069438

  13. Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Kaneyasu, Yuko Nagai, Nobutaka; Nagata, Yasushi; Hashimoto, Yasutoshi; Yuki, Shintaro; Murakami, Yuji; Kenjo, Masahiro; Kakizawa, Hideaki; Toyota, Naoyuki; Fujiwara, Hisaya; Kudo, Yoshiki; Ito, Katsuhide

    2009-10-01

    Purpose: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. Materials and Methods: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with {sup 192}Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. Results: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade {>=}3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade {>=}3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade {>=}3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. Conclusion: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

  14. Impact of stage III-IV endometriosis on recipients of sibling oocytes: matched case-control study.

    PubMed

    Díaz, I; Navarro, J; Blasco, L; Simón, C; Pellicer, A; Remohí, J

    2000-07-01

    To evaluate the impact of severe endometriosis on IVF-ET outcome in women receiving oocytes from the-same donor. A matched case-control study. Oocyte donation program at the Instituto Valenciano de Infertilidad. Fifty-eight recipients were included in a matched case-control study of IVF-ET in our oocyte donation program. Twenty-five patients were diagnosed by laparoscopy with stage III-IV endometriosis (group I), while the remaining 33 were free of the disease (group II). On the day of retrieval, oocytes from a single donor were donated to recipients from both groups. Some of the donors supplied oocytes for more than 2 patients. Recipients received steroid replacement therapy for endometrial preparation. Ovarian stimulation and oocyte retrieval in donors. Uterine embryo transfer (ET) in recipients after appropriate exogenous hormone replacement therapy (HRT). Pregnancy, implantation, miscarriage, and live birth rates. The number of oocytes donated and fertilized, as well as the number of available and transferred embryos, was not statistically different between the two groups. Pregnancy, implantation, and miscarriage rates were not affected by stage III-IV endometriosis when compared with the control group. The live birth rate was 28.0% in the group with endometriosis and 27.2% in the control group. These results show that implantation is not affected by stage III-IV endometriosis. Given the contemporary methods of endometrial preparation for transfer of embryos derived from donor oocytes, any potential negative effect of severe endometriosis on the uterine environment is undetectable.

  15. Totally laparoscopic associating liver tourniquet and portal vein occlusion for staged hepatectomy combined with simultaneous left hemicolectomy for bilateral liver metastases of the primary colon cancer

    PubMed Central

    Xu, Hong-wei; Li, Hong-yu; Liu, Fei; Wei, Yong-gang; Li, Bo

    2017-01-01

    Abstract Background: Resection of the liver is often limited to the insufficient future liver remnant (FLR). To address this problem, the modification surgical technique “associating liver tourniquet and portal vein occlusion for staged hepatectomy” (ALTPS) was developed and led to quick hypertrophy in a short interval. In some colorectal cancer patients with multiple and bilobar metastases, the resection of the primary is often protracted immensely to the unpredictable postoperative complications for whom is to be treated with a liver-first approach. To overcome this problem, a simultaneous resection of the primary tumor and totally laparoscopic ALTPS for bilateral liver metastases of the primary colon cancer were performed. Case summary: A 63-year-old female patient with left colon cancer and synchronous bilateral colorectal liver metastases underwent a totally laparoscopic ALTPS and simultaneous left hemicolectomy because of the small FLR. The operative times were 460 minutes for the first stage and 240 minutes for the second stage without the need for blood transfusions. The recoveries after the first and the second operations were uneventful, and the patient was discharged on postoperative day 11 of the second stage operation. Conclusion: Our case shows the totally laparoscopic ALTPS and simultaneous left hemicolectomy at step 1 for bilobar liver metastases of the primary colon cancer with no severe postoperative complications. If a resection of the primary tumor does not compromise the split procedure, the combination of pure laparoscopic ALTPS and primary resection is feasible and safe. PMID:28296776

  16. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

    PubMed Central

    Sanoff, Hanna K.; Stitzenberg, Karyn B.; Baron, John A.; Lund, Jennifer L.; Sandler, Robert S.

    2017-01-01

    Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n = 6, 862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50) and older (age 50–69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50–69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years. PMID:28239395

  17. A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

    PubMed

    Zang, Yong; Lee, J Jack

    2017-01-15

    We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    PubMed

    Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

    2015-06-01

    For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice.

  19. The local treatment modalities in FIGO stage I-II small-cell carcinoma of the cervix are determined by disease stage and lymph node status.

    PubMed

    Zhou, Juan; Yang, Hong-Yi; Wu, San-Gang; He, Zhen-Yu; Lin, Huan-Xin; Sun, Jia-Yuan; Li, Qun; Guo, Zhan-Wen

    2016-06-01

    The purpose of this study was to identify the optimal local treatment modalities for International Federation of Gynecology and Obstetrics (FIGO) stage I-II small-cell carcinoma of the cervix (SCCC), including cancer-directed surgery (CDS) and/or radiotherapy (RT). The Surveillance Epidemiology and End Results (SEER) database was used to identify SCCC patients from 1988 to 2012, and analyzed using Kaplan-Meier survival and Cox regression proportional hazard methods to determine factors significant for cause-specific survival (CSS) and overall (OS). A total of 208 patients of SCCC were enrolled. The median follow-up time was 31 months. Fifty-eight (27.9%) patients were treated with primary CDS, 88 (42.3%) patients underwent CDS combined with RT, and 62 (29.8%) patients were treated with primary RT. Univariate and multivariate analyses showed that local treatment modalities were independent prognostic factors for CSS and OS. Patients who had undergone CDS had better CSS and OS, compared with patients who had been treated with combined CDS and RT or RT alone. The 5-year CSS and OS of entire group was 49.8% and 46.4%, respectively. The 5-year CSS in the groups of patients receiving CDS, CDS combined with RT, and RT alone were 67.9%, 49.7%, and 32.6%, respectively (P < 0.001). The 5-year OS in patients treated with CDS, CDS combined with RT, and RT alone were 64.9%, 46.2%, and 28.8% (P < 0.001). Primary surgery was associated with improved CSS and OS for FIGO stage I and lymph node negative disease. Primary surgery is the most effective local treatment for FIGO stage I-II SCCC, as adjuvant RT or radical RT does not improve survival compared to radical surgery, especially in patients with FIGO stage I and lymph node negative disease.

  20. A prospective, randomized, multisite clinical evaluation of a transparent absorbent acrylic dressing and a hydrocolloid dressing in the management of Stage II and shallow Stage III pressure ulcers.

    PubMed

    Brown-Etris, Marie; Milne, Catherine; Orsted, Heather; Gates, Judy L; Netsch, Debra; Punchello, Marion; Couture, Nancy; Albert, Martine; Attrell, Edie; Freyberg, Julie

    2008-04-01

    To compare clinical performance of a transparent absorbent acrylic dressing (3M Tegaderm Absorbent Clear Acrylic Dressing ]TAAD[; 3M Company, St Paul, MN) and a hydrocolloid dressing (HD ]DuoDERM CGF, ConvaTec, ER Squibb & Sons, Princeton, NJ[) in the management of Stage II and shallow Stage III pressure ulcers. Prospective, open-label, randomized, comparative, multisite clinical evaluation. Patients were followed up for a maximum of 56 days or until their ulcer healed. At weekly intervals, investigators conducted wound assessments and dressing performance evaluations. Wound care clinics, home care, and long-term care. Thirty-five patients received the TAAD, and 37 received the HD. Dressing performance assessments, patient comfort, dressing wear time, and wound healing were measured. The majority of investigator assessments favored the TAAD. Considerations given included the ability to center dressings over the ulcer (P = .005), ability to assess the ulcer before (P < .001) and after (P < .001) absorption, barrier properties (P = .039), patient comfort during removal (P < .001), overall patient comfort (P = .048), conformability before (P = .026) and after (P = .001) absorption, ease of removal (P < .001), nonadherence to wound bed (P < .001), residue in the wound (P = .002), residue on periwound skin (P < .001), and odor after absorption (P = .016). Overall satisfaction favored the TAAD (P < .001), and a high value was placed on its transparent feature (P < .001). Mean (SD) wear time for the TAAD was 5.7 (2.55) days compared with 4.7 (2.29) days for the HD (P = .086). This 1-day difference in wear time was clinically noticeable by the investigators (P = .035). Wound closure for the 2 dressing groups was nearly identical (P = .9627). Performance results favored the TAAD over the HD as standard treatment for Stage II and shallow Stage III pressure ulcers.

  1. Experimental Investigation of a Five-stage Axial-flow Research Compressor with Transonic Rotors in All Stages III : Interstage Data and Individual Stage Performance Characteristics

    NASA Technical Reports Server (NTRS)

    Sandercock, Donald M; Kovach, Karl

    1956-01-01

    For use in computing the detailed performance parameters of individual blade rows of a multistage compressor, radial distributions of total pressure, total temperature, static pressure and air-flow angle are tabulated. The data cover a range of air flow from choke to the approximate surge limit for equivalent rotor speeds from 70 to 100 percent of design. Equivalent stage performance curves determined from the radial survey measurements indicate both the individual performance and the matching of the stages at the speeds investigated.

  2. Anti-FIRs (PUF60) auto-antibodies are detected in the sera of early-stage colon cancer patients

    PubMed Central

    Kobayashi, Sohei; Hoshino, Tyuji; Hiwasa, Takaki; Satoh, Mamoru; Rahmutulla, Bahityar; Tsuchida, Sachio; Komukai, Yuji; Tanaka, Tomoaki; Matsubara, Hisahiro; Shimada, Hideaki; Nomura, Fumio; Matsushita, Kazuyuki

    2016-01-01

    Anti-PUF60, poly(U)-binding-splicing factor, autoantibodies are reported to be detected in the sera of dermatomyositis and Sjogren's syndrome that occasionally associated with malignancies. PUF60 is identical with far-upstream element-binding protein-interacting repressor (FIR) that is a transcriptional repressor of c-myc gene. In colorectal cancers, a splicing variant of FIR that lacks exon2 (FIRΔexon2) is overexpressed as a dominant negative form of FIR. In this study, to reveal the presence and the significance of anti-FIRs (FIR/FIRΔexon2) antibodies in cancers were explored in the sera of colorectal and other cancer patients. Anti-FIRs antibodies were surely detected in the preoperative sera of 28 colorectal cancer patients (32.2% of positive rates), and the detection rate was significantly higher than that in healthy control sera (Mann–Whitney U test, p < 0.01). The level of anti-FIRs antibodies significantly decreased after the operation (p < 0.01). Anti-FIRs antibodies were detected in the sera of early-stage and/or recurrent colon cancer patients in which anti-p53 antibodies, CEA, and CA19-9 were not detected as well as in the sera of other cancer patients. Furthermore, the area under the curve of receiver operating characteristic for anti-FIRs antibodies was significantly larger (0.85) than that for anti-p53 antibodies or CA19-9. In conclusions, the combination of anti-FIRs antibodies with other clinically available tumor markers further improved the specificity and accuracy of cancer diagnosis. PMID:27756887

  3. CYTOLOGICAL ASPECTS OF ANTIMICROBIAL ANTIBIOSIS. III. CYTOLOGICALLY DISTINGUISHABLE STAGES IN ANTIBIOTIC ACTION OF COLISTIN SULFATE ON ESCHERICHIA COLI.

    PubMed

    KAYE, J J; CHAPMAN, G B

    1963-09-01

    Kaye, Jeremy J. (Cornell University Medical College, New York, N.Y.) and George B. Chapman. Cytological aspects of antimicrobial antibiosis. III. Cytologically distinguishable stages in antibiotic action of colistin sulfate on Escherichia coli. J. Bacteriol. 86:536-543. 1963.-Broth cultures of Escherichia coli were subjected to a constant concentration of colistin sulfate for varying periods of time. Controls and treated cells were fixed, dehydrated, and embedded in methacrylate, and ultrathin sections were examined in an electron microscope. Three stages in the antibiotic process were discerned. Stage 1 was characterized by a disruption of the axial orientation of the nuclear material and by an invasion of nuclear areas by tufts of material presumably of cytoplasmic origin; no loss of cellular contents could be detected cytologically. Stage 2 was characterized by the loss of nuclear material and by a loss of typical cytoplasmic granularity, an increase in cytoplasmic electron density, and an agglomeration of the cytoplasm into packed tufts of material; in contrast to the nuclear material, there was no loss of cytoplasmic material in this stage. Stage 3 was characterized by the loss of the altered cytoplasmic material but with the persistence of mesosomes, plasma membrane, and cell wall. Speculation that each and all of these changes might have resulted from an altered intracellular milieu secondary to a primary effect of the antibiotic on the plasma membrane is presented.

  4. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  5. Trametinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-09-12

    KRAS Activating Mutation; Recurrent Non-Small Cell Lung Carcinoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7

  6. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.

    PubMed

    Turner, Natalie; Wong, Hui-Li; Templeton, Arnoud; Tripathy, Sagarika; Whiti Rogers, Te; Croxford, Matthew; Jones, Ian; Sinnathamby, Mathuranthakan; Desai, Jayesh; Tie, Jeanne; Bae, Susie; Christie, Michael; Gibbs, Peter; Tran, Ben

    2016-02-01

    In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.

  7. Identification of high-risk factors as indicators for adjuvant therapy in stage II colon cancer patients treated at a single institution

    PubMed Central

    YAMAGUCHI, KEIZO; OGATA, YUTAKA; AKAGI, YOSHITO; SHIROUZU, KAZUO

    2013-01-01

    Although post-operative adjuvant chemotherapy (ACT) is only recommended for patients with stage II colon cancer who are at a high risk of recurrence, the definition of high risk remains unclear. The present study aimed to identify the risk factors for recurrence, which may also be indicators for adjuvant therapy, using a retrospective analysis of clinicopathological data obtained from stage II colon cancer patients who had undergone a curative resection. The present study also investigated the effects of ACT in patients who displayed the risk factors for recurrence. Univariate and multivariate analyses of the data collected from 377 stage II colon cancer patients, treated at Kurume University Hospital (Fukuoka, Japan) between 1982 and 2005, was conducted in order to determine and compare the risk factors for recurrence between the 163 patients who had undergone adjuvant therapy and the 214 patients who had not undergone adjuvant therapy. The risk factors for recurrence in patients who had not undergone adjuvant therapy were a serum carcinoembryonic antigen (CEA) level that was twice the cut-off value and pre-operative bowel obstruction. Adjuvant therapy provided no benefit to patients who presented with neither risk factor, but significantly decreased the recurrence rate in patients presenting with one or both risk factors. Based on these findings, serum CEA levels of twice the cut-off value and pre-operative bowel obstruction were proposed as indicators in the assessment for adjuvant chemotherapy following a curative resection for stage II colon cancer. These results warrant further clinical study of ACT in patients with one or both risk factors. PMID:24137386

  8. Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

    ClinicalTrials.gov

    2017-03-21

    Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  9. A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery.

    PubMed

    Peng, Jian-Hong; Fang, Yu-Jing; Li, Cai-Xia; Ou, Qing-Jian; Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De Sen

    2016-04-19

    Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.

  10. Audit of the association between length of time spent on diagnostic work-up and tumour stage in patients with symptomatic colon cancer.

    PubMed

    Tiong, Jimmy; Gray, Andrew; Jackson, Christopher; Thompson-Fawcett, Mark; Schultz, Michael

    2017-03-01

    Colorectal cancer is one of the most incident cancers in New Zealand. Due to resource limitations, some patients experienced protracted wait times before reaching a definitive diagnosis. We analysed the relationship between time to diagnosis and clinical stage and reviewed the length of time for components of the diagnostic work-up to identify priority areas for service improvement. We benchmarked our timeliness against introduced standards. This retrospective study included all patients with colonic (not rectal) cancer between October 2007 and September 2009. Patients were stratified into an early and advanced group. Types of delay were calculated from the onset of symptoms to the administration of treatment. The compliance with target waiting times was assessed. Fifty-eight patients were included in the early group and 83 patients in the advanced group. There were no significant differences in demographics or symptoms. The work-up was longer than international benchmarks, but with wide variations. There was no statistical difference between lengths of work-up in the groups. The advanced group had increased utilization of private and emergency investigations. Forty-four per cent met the diagnostic colonoscopy target waiting time of 42 days with a trend in favour of the advanced group and 21% received treatment within 62 days (non-significant). Current systems are not sophisticated enough to predict the stage of colon cancer. Here, long waiting times were not associated with cancer stage in symptomatic patients. Resources need to be directed to diagnostic colonic imaging. © 2014 Royal Australasian College of Surgeons.

  11. A phase I study of nedaplatin, pemetrexed and thoracic intensity-modulated radiotherapy for inoperable stage III lung adenocarcinoma.

    PubMed

    Lu, Yiyu; Gu, Weiguang; Deng, Jin; Yang, Hua; Yang, Wen

    2016-10-07

    Concurrent chemotherapy and radiation is the standard treatment for unresectable stage III Lung adenocarcinoma. However, no optimal concurrent chemotherapeutic regimen has been described. This study aimed to assess concurrent pemetrexed, nedaplatin and thoracic intensity-modulated radiotherapy followed by consolidation pemetrexed/nedaplatin for unresectable Stage IIIA/B lung adenocarcinoma. Patients with unresectable stage III lung adenocarcinoma received thoracic intensity-modulated radiotherapy at 60-64 Gy in 30-32 fractions, concurrently with two cycles of 500 mg/m(2) pemetrexed, with nedaplatin doses escalating from 60 mg/m(2) (level 1) to 70 mg/m(2) (level 2) and 80 mg/m(2) (level 3). Consolidation consisted of three pemetrexed/nedaplatin (500 mg/m(2), 60 mg/m(2)) cycles every 3 weeks after concurrent therapy. The primary objective of the safety was to determine the maximum-tolerated dose (MTD). The secondary endpoints included response rate, PFS and OS. Fifteen patients were enrolled, including 3, 6 and 6 individuals in the first, second, and third dose levels, respectively. Three cases of dose-limiting toxicities (grade 3 hepatitis, pneumonitis, and grade 4 thrombocytopenia), including one and two patients at levels 2 and 3, respectively, were observed and resulted in discontinued/delayed treatment. Response rates were 86.7 % (95 % confidence interval [CI], 64.2-97.8 %) and 64.3 % (95 % CI, 38.3-85.4 %) at chemoradiation and treatment completions, respectively. Median OS was 30.0 months (95 % CI, 16.4-43.6 months); 2-year OS was 44.0 % (95 % CI, 18.7-69.2 %). Median PFS was 12.0 months (95 % CI, 6.9-17.0 months), and the 2-year PFS 27.0 % (95 % CI, 4.7-49.3 %). Full dose 500 mg/m(2) of pemetrexed and nedaplatin 70 mg/m(2) could be used safely with thoracic intensity-modulated radiotherapy for inoperable stage III lung adenocarcinoma. Further evaluation of stage III lung adenocarcinoma management is warranted. This study was

  12. Clinical significance of detecting lymphatic and blood vessel invasion in stage II colon cancer using markers D2-40 and CD34 in combination.

    PubMed

    Lai, Jin-Huo; Zhou, Yong-Jian; Bin, Du; Qiangchen; Wang, Shao-Yuan

    2014-01-01

    This research was conducted to compare differences in colon cancer lymphatic vessel invasion (LVI) with D2-40 antibody labeling and regular HE staining, blood vessel invasion (BVI) with CD34 antibody labeling and HE staining and to assess the possibility of using D2-40-LVI/CD34-BVI in combination for predicting stage II colon cancer prognosis and guiding adjuvant chemotherapy.Anti-D2-40 and anti-CD34 antibodies were applied to tissue samples of 220 cases of stage II colon cancer to label lymphatic vessels and small blood vessels, respectively. LVI and BVI were assessed and multivariate COX regression analysis was performed for associations with colon cancer prognosis. Regular HE staining proved unable to differentiate lymphatic vessels from blood vessels, while D2-40 selectively labeled lymphatic endothelial cell cytosol and CD34 was widely expressed in large and small blood vessels of tumors as well as normal tissues. Compared to regular HE staining, D2-40-labeling for LVI and CD34-labeling for BVI significantly increased positive rate (22.3% vs 10.0% for LVI, and 19.1% vs 9.1% for BVI). Multivariate analysis indicated that TNM stage, pathology tissue type, post-surgery adjuvant chemotherapy, D2-40-LVI, and CD34-BVI were independent factors affecting whole group colon cancer prognosis, while HE staining-BVI, HE staining-LVI were not significantly related. When CD34-BVI/D2-40-LVI were used in combination for detection, the risk of death for patients with two or one positive results was 5.003 times that in the LVI(-)andBVI(-) group (95% CI 2.365 - 9.679). D2-40 antibody LVI labeling and CD34 antibody BVI labeling have higher specificity and accuracy than regular HE staining and can be used as molecular biological indicators for prognosis prediction and guidance of adjuvant chemotherapy for stage II colon cancer.

  13. Non-digestible fraction of beans (Phaseolus vulgaris L.) modulates signalling pathway genes at an early stage of colon cancer in Sprague-Dawley rats.

    PubMed

    Haydé, Vergara-Castañeda; Ramón, Guevara-González; Lorenzo, Guevara-Olvera; Dave, Oomah B; Rosalía, Reynoso-Camacho; Paul, Wiersma; Guadalupe, Loarca-Piña

    2012-08-01

    Colorectal cancer is one of the most common causes of morbidity and mortality in Western countries, the second cause of cancer mortality in the USA and a major public health problem in Mexico. A diet rich in legumes is directly related to the prevention of colon cancer, showing an inverse relationship with the development of colorectal adenomas in human subjects. The present study shows the results of molecular changes involved in the Tp53 pathway at an early stage in the distal colon tissue of azoxymethane (AOM)-induced colon cancer in rats evaluated by PCR array after exposure to diets containing the non-digestible fraction (NDF) of cooked bean (cultivar Bayo Madero). Significant differences were detected in seventy-two genes of the Tp53-mediated signalling pathway involved in apoptosis, cell-cycle regulation and arrest, inhibition of proliferation and inflammation, and DNA repair. Tp53, Gadd45a, Cdkn1a and Bax were highly expressed (9·3-, 18·3-, 5·5- and 3·5-fold, respectively) in the NDF+AOM group, whereas Cdc25c, Ccne2, E2f1 and Bcl2 were significantly suppressed ( - 9·2-, - 2·6-, - 18·4- and - 3·5-fold, respectively), among other genes, compared with the AOM group, suggesting that chemoprevention of aberrant crypt foci results from a combination of cell-cycle arrest in G1/S and G2/M phases and cell death by apoptotic induction. We demonstrate that the NDF from common bean modulates gene expression profiles in the colon tissue of AOM-induced rats, contributing to the chemoprotective effect of common bean on early-stage colon cancer.

  14. Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

    ClinicalTrials.gov

    2015-12-18

    Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

  15. Role of Surgery in Stages II and III Pediatric Abdominal Non-Hodgkin Lymphoma: A 5-Years Experience.

    PubMed

    Ali, Amany M; Sayd, Heba A; Hamza, Hesham M; Salem, Mohamed A

    2011-03-29

    Abdominal Non-Hodgkin lymphomas (NHL) are the most common extra nodal presentation of pediatric NHL. Our aim is to assess the role of surgery as a risk factor and to evaluate the impact of risk-adjusted systemic chemotherapy on survival of patients with stages II and III disease. This study included 35 pediatric patients with abdominal NHL treated over five years at South Egypt Cancer Institute (SECI), Assiut University, between January 2005 and January 2010. The data of every patient included: Age, sex, and presentation, staging work up to determine extent of the disease and the type of resection performed, histopathological examination, details of chemotherapy, disease free survival and overall survival. The study included 25 boys and 10 girls with a median age of six years (range: 2.5:15). Thirty patients (86%) presented with abdominal pain, 23 patients (66%) presented with abdominal mass and distention, 13 patients (34%) presented with weight loss, and intestinal obstruction occurred in six patients (17%). The ileo-cecal region and abdominal lymph nodes were the commonest sites (48.5%, 21% respectively). Burkitt's lymphoma was the most common histological type in 29 patients (83%). Ten (28.5%) stage II (group A) and 25 (71.5%) stage III (group B). Complete resections were performed in 10 (28.5%), debulking in 6 (17%) and imaging guided biopsy in 19 (54%). A11 patients received systemic chemotherapy. The median follow up duration was 63 months (range 51-78 months). The parameters that significantly affect the overall survival were stage at presentation complete resection for localized disease. In conclusion, the extent of disease at presentation is the most important prognostic factor in pediatric abdominal NHL. Surgery is restricted to defined situations such as; abdominal emergencies, diagnostic biopsy and total tumor extirpation in localized disease. Chemotherapy is the cornerstone in the management of pediatric abdominal NHL.

  16. Comparison of the Antiproliferative Activity of Two Antitumour Ruthenium(III) Complexes With Their Apotransferrin and Transferrin-Bound Forms in a Human Colon Cancer Cell Line

    PubMed Central

    Keppler, B. K.; Hartmann, M.; Messori, L.; Berger, M. R.

    1996-01-01

    Two ruthenium(III) complexes, namely trans-indazolium[tetrachlorobis(indazole)- ruthenate(III)], HInd[RuInd2Cl4] and trans-imidazolium[tetrachlorobis(imidazole)- ruthenate(III)], HIm[RuIm2Cl4] exhibit high anticancer activity in an autochthonous colorectal carcinoma model in rats. Recently, it has been shown that both complexes bind specifically to human serum apotransferrin and the resulting adducts have been studied through spectroscopic and chromatographic techniques with the ultimate goal of preparing adducts with good selectivity for cancer cells due to the fact that tumour cells express high amounts of transferrin receptors on their cell surface. In order to investigate whether the cellular uptake of the complexes was mediated by apotransferrin or transferrin, we compared the antiproliferative efficacy of HInd[RuInd2Cl4] and HIm[RuIm2Cl4] with its apotransferrin- and transferrin-bound form in the human colon cancer cell line SW707 using the microculture tetrazolium test (MTT). Our results show that especially the transferrin-bound forms exhibit high antiproliferative activity, which exceeds that of the free complex, indicating that this protein can act as a carrier of the ruthenium complexes into the tumor cell. PMID:18472789

  17. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Harris, Jeremy P.; Murphy, James D.; Hanlon, Alexandra L.; Le, Quynh-Thu; Loo, Billy W.; Diehn, Maximilian

    2014-03-15

    Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

  18. Serum protein profiling using an aptamer array predicts clinical outcomes of stage IIA colon cancer: A leave-one-out crossvalidation

    PubMed Central

    Huh, Jung Wook; Kim, Sung Chun; Sohn, Insuk; Jung, Sin-Ho; Kim, Hee Cheol

    2016-01-01

    Background In this study, we established and validated a model for predicting prognosis of stage IIA colon cancer patients based on expression profiles of aptamers in serum. Methods Bloods samples were collected from 227 consecutive patients with pathologic T3N0M0 (stage IIA) colon cancer. We incubated 1,149 serum molecule-binding aptamer pools of clinical significance with serum from patients to obtain aptamers bound to serum molecules, which were then amplified and marked. Oligonucleotide arrays were constructed with the base sequences of the 1,149 aptamers, and the marked products identified above were reacted with one another to produce profiles of the aptamers bound to serum molecules. These profiles were organized into low- and high-risk groups of colon cancer patients based on clinical information for the serum samples. Cox proportional hazards model and leave-one-out cross-validation (LOOCV) were used to evaluate predictive performance. Results During a median follow-up period of 5 years, 29 of the 227 patients (11.9%) experienced recurrence. There were 212 patients (93.4%) in the low-risk group and 15 patients (6.6%) in the high-risk group in our aptamer prognosis model. Postoperative recurrence significantly correlated with age and aptamer risk stratification (p = 0.046 and p = 0.001, respectively). In multivariate analysis, aptamer risk stratification (p < 0.001) was an independent predictor of recurrence. Disease-free survival curves calculated according to aptamer risk level predicted through a LOOCV procedure and age showed significant differences (p < 0.001 from permutations). Conclusion Aptamer risk stratification can be a valuable prognostic factor in stage II colon cancer patients. PMID:26908450

  19. Functional Magnetic Resonance Imaging in Assessing Affect Reactivity and Regulation in Patients With Stage 0-III Breast Cancer

    ClinicalTrials.gov

    2017-02-27

    Healthy Subject; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  20. Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-10-10

    Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  1. Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Tribius, Silke; Yekebas, Emre F.; Bahrehmand, Roia; Wildfang, Ingeborg; Kilic, Ergin; Muellerleile, Ulrich; Gross, Eberhard; Schild, Steven E.; Alberti, Winfried

    2006-06-01

    Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

  2. Transforming growth factor-beta suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis.

    PubMed

    Tang, Yi; Katuri, Varalakshmi; Srinivasan, Radhika; Fogt, Franz; Redman, Robert; Anand, Girish; Said, Anan; Fishbein, Thomas; Zasloff, Michael; Reddy, E Premkumar; Mishra, Bibhuti; Mishra, Lopa

    2005-05-15

    Although transforming growth factor-beta (TGF-beta) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a beta-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation of TGF-beta to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition. Analysis of development of colon cancer in (adult) elf+/-/Smad4+/-, elf+/-, Smad4+/-, and gut epithelial cells from elf-/- mutant mouse embryos pinpoints the defect to hyperplasia/adenoma transition. Further analysis of the role of ELF in human colorectal cancer confirms reduced expression of ELF in Dukes' B1 stage tissues (P < 0.05) and of Smad4 in advanced colon cancers (P < 0.05). This study indicates that by modulating Smad 4, ELF has a key role in TGF-beta signaling in the suppression of early colon cancer.

  3. Reducing Length of Hospital Stay Does Not Increase Readmission Rates in Early-Stage Gastric, Colon, and Lung Cancer Surgical Cases in Japanese Acute Care Hospitals.

    PubMed

    Kunisawa, Susumu; Fushimi, Kiyohide; Imanaka, Yuichi

    2016-01-01

    The Japanese government has worked to reduce the length of hospital stay by introducing a per-diem hospital payment system that financially incentivizes the timely discharge of patients. However, there are concerns that excessively reducing length of stay may reduce healthcare quality, such as increasing readmission rates. The objective of this study was to investigate the temporal changes in length of stay and readmission rates as quality indicators in Japanese acute care hospitals. We used an administrative claims database under the Diagnosis Procedure Combination Per-Diem Payment System for Japanese hospitals. Using this database, we selected hospitals that provided data continuously from July 2010 to March 2014 to enable analyses of temporal changes in length of stay and readmission rates. We selected stage I (T1N0M0) gastric, colon, and lung cancer surgical patients who had been discharged alive from the index hospitalization. The outcome measures were length of stay during the index hospitalization and unplanned emergency readmissions within 30 days after discharge. From among 804 hospitals, we analyzed 42,585, 15,467, and 40,156 surgical patients for gastric, colon, and lung cancer, respectively. Length of stay was reduced by approximately 0.5 days per year. In contrast, readmission rates were generally stable at approximately 2% or had decreased slightly over the 4-year period. In early-stage gastric, colon, and lung cancer surgical patients in Japan, reductions in length of stay did not result in increased readmission rates.

  4. Reducing Length of Hospital Stay Does Not Increase Readmission Rates in Early-Stage Gastric, Colon, and Lung Cancer Surgical Cases in Japanese Acute Care Hospitals

    PubMed Central

    Kunisawa, Susumu; Fushimi, Kiyohide; Imanaka, Yuichi

    2016-01-01

    Background The Japanese government has worked to reduce the length of hospital stay by introducing a per-diem hospital payment system that financially incentivizes the timely discharge of patients. However, there are concerns that excessively reducing length of stay may reduce healthcare quality, such as increasing readmission rates. The objective of this study was to investigate the temporal changes in length of stay and readmission rates as quality indicators in Japanese acute care hospitals. Methods We used an administrative claims database under the Diagnosis Procedure Combination Per-Diem Payment System for Japanese hospitals. Using this database, we selected hospitals that provided data continuously from July 2010 to March 2014 to enable analyses of temporal changes in length of stay and readmission rates. We selected stage I (T1N0M0) gastric, colon, and lung cancer surgical patients who had been discharged alive from the index hospitalization. The outcome measures were length of stay during the index hospitalization and unplanned emergency readmissions within 30 days after discharge. Results From among 804 hospitals, we analyzed 42,585, 15,467, and 40,156 surgical patients for gastric, colon, and lung cancer, respectively. Length of stay was reduced by approximately 0.5 days per year. In contrast, readmission rates were generally stable at approximately 2% or had decreased slightly over the 4-year period. Conclusions In early-stage gastric, colon, and lung cancer surgical patients in Japan, reductions in length of stay did not result in increased readmission rates. PMID:27832182

  5. Recurrences and toxicity after adjuvant vaginal brachytherapy in Stage I-II endometrial cancer: A monoinstitutional experience.

    PubMed

    Perrucci, Elisabetta; Lancellotta, Valentina; Bini, Vittorio; Zucchetti, Claudio; Mariucci, Cristina; Montesi, Giampaolo; Saccia, Stefano; Palumbo, Isabella; Aristei, Cynthia

    2016-01-01

    To evaluate the incidences of vaginal recurrence and toxicity after vaginal brachytherapy in Stage I-II endometrial cancer. Between 2003 and 2012, 150 high-intermediate-risk Stage I and 7 Stage II patients, median age 64 years, underwent surgery, with or without lymphadenectomy, and 3D brachytherapy: 7 Gy, at 5 mm depth from applicator surface, for 3-week fractions. The effects of age, grading, number of excised lymph nodes and pathologic stage on loco-regional relapse (LRR), metastases, and tumor-related death were investigated. Vaginal toxicity was evaluated during followup visits. At 83 months of median followup, 144 patients were disease free, 2 in relapse, 7 deceased from disease, and 4 from other causes. One vaginal (0.6%), five nodal (3.2%), three pelvic over the vaginal cuff (1.9%), and one distant recurrences were seen (0.6%). The 5-year probability of LRR-free, distant metastasis-free and cause-specific survivals for all patients were 93.6% (95% confidence interval [CI]: 88.1-96.7), 97.8% (95% CI: 93.2-99.3), and 96.5% (95% CI: 93.5-99.5) and for Stage I 95.7% (95% CI: 92.2-9.1), 99.3% (95% CI: 98.0-100), and 97.7% (95% CI: 95.2-100), respectively. At multivariate analysis, Stage II disease and more than 12 lymph nodes sampled were associated with LRR (hazard ratio [HR]: 3.88; 95% CI: 1.390-10.878; p = 0.010 and HR: 6.952; 95% CI: 1.591-30.385; p = 0.010) and Stage II with metastasis and tumor-related death (HR: 23.057; 95% CI: 2.296-231.485; p = 0.008 and HR: 4.324; 95% CI: 1.223-15.290; p = 0.023). Vaginal acute and chronic toxicity was 16% and 55.4%, respectively, all only Grades 1-2. For high-to-intermediate-risk Stage I endometrial cancer, 3D vaginal brachytherapy achieved good local control and low toxicity. In Stage II, patients brachytherapy could be administered after complete surgical staging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  6. The Type III secretion system of Xanthomonas fuscans subsp. fuscans is involved in the phyllosphere colonization process and in transmission to seeds of susceptible beans.

    PubMed

    Darsonval, A; Darrasse, A; Meyer, D; Demarty, M; Durand, K; Bureau, C; Manceau, C; Jacques, M-A

    2008-05-01

    Understanding the survival, multiplication, and transmission to seeds of plant pathogenic bacteria is central to study their pathogenesis. We hypothesized that the type III secretion system (T3SS), encoded by hrp genes, could have a role in host colonization by plant pathogenic bacteria. The seed-borne pathogen Xanthomonas fuscans subsp. fuscans causes common bacterial blight of bean (Phaseolus vulgaris). Directed mutagenesis in strain CFBP4834-R of X. fuscans subsp. fuscans and bacterial population density monitoring on bean leaves showed that strains with mutations in the hrp regulatory genes, hrpG and hrpX, were impaired in their phyllospheric growth, as in the null interaction with Escherichia coli C600 and bean. In the compatible interaction, CFBP4834-R reached high phyllospheric population densities and was transmitted to seeds at high frequencies with high densities. Strains with mutations in structural hrp genes maintained the same constant epiphytic population densities (1 x 10(5) CFU g(-1) of fresh weight) as in the incompatible interaction with Xanthomonas campestris pv. campestris ATCC 33913 and the bean. Low frequencies of transmission to seeds and low bacterial concentrations were recorded for CFBP4834-R hrp mutants and for ATCC 33913, whereas E. coli C600 was not transmitted. Moreover, unlike the wild-type strain, strains with mutations in hrp genes were not transmitted to seeds by vascular pathway. Transmission to seeds by floral structures remained possible for both. This study revealed the involvement of the X. fuscans subsp. fuscans T3SS in phyllospheric multiplication and systemic colonization of bean, leading to transmission to seeds. Our findings suggest a major contribution of hrp regulatory genes in host colonization processes.

  7. Evaluation of cisplatin and DTIC in inoperable stage III and IV melanoma. A Southwest Oncology Group study.

    PubMed

    Fletcher, W S; Daniels, D S; Sondak, V K; Dana, B; Townsend, R; Hynes, H E; Hutchins, L F; Pancoast, J R

    1993-08-01

    The Southwest Oncology Group entered 62 patients with Stage IV or inoperable Stage III (one patient) melanoma into SWOG protocol 8804 and treated them with cisplatin 100 mg/m2 and DTIC 750 mg/m2 i.v. infusion over 15-30 minutes. There were 18 patients with brain metastases and four ocular primaries. Five patients, all without bain metastases, were ineligible. Responses of 8 patients could not be determined, and 11 patients received only one course of treatment. Of the eligible patients, 46 (81%) had some hematologic toxicities, with 31 of these (67%) having grade III or worse. There were 23 patients (40%) with renal toxicities. The miscellaneous toxicities were muscle weakness, flu-like symptoms, and fatigue. Five patients died while on treatment. There were no complete responses. Eight patients had partial responses ranging from 1.5 to 10.5 months, although two patients were still alive at 30.4 and 30.9 months. The estimated response rate for patients with brain metastases was 11%. The estimated response rate for patients without brain metastases was 13%. If one unconfirmed partial response is included, the overall response rate is 14% with a 95% confidence interval of 6% to 26%. It is concluded that DTIC and cisplatin have definite activity in melanoma, but, at least in this population, the toxicity is treatment-limiting and requires close attention to patient care.

  8. Prognostic value of tumor infiltrating NK cells and macrophages in stage II+III esophageal cancer patients

    PubMed Central

    Zheng, Xiao; Shi, Liangrong; Wu, Changping; Jiang, Jingting

    2016-01-01

    The detailed understanding of the immunobiology of tumor microenvironment has recently translated into new therapeutic approach against human cancers. Besides the role of immune cells mediating adaptive immune responses, the tumor infiltrating components of the innate immune system including, neutrophils, mast cells, NK cells, and macrophages, also role importantly in anti-tumor immunity. In our present study, we retrospectively analyzed the prognostic value of the densities of tumor infiltrating NK cells and macrophages in esophageal cancer tissues derived from stage II+III patients. Our results showed that the density of the infiltrating NK cells in tumor stroma was significantly associated with nodal status. In addition, the densities of the infiltrating NK cells in tumor nest, and the infiltrating macrophages in tumor nest as well as in tumor stroma, were significantly associated with patients' postoperative prognoses. Furthermore, the combination of infiltrating NK cells in tumor nest and stroma, or the combination of infiltrating macrophages in tumor nest and stroma, could also be used as important prognostic tool in predicting the survival of the stage II+III esophageal cancer patients. PMID:27736796

  9. Intra-Abdominal Complications after Curative Gastrectomies Worsen Prognoses of Patients with Stage II–III Gastric Cancer

    PubMed Central

    A.T.M. Abdul, Kader; Murakami, Yuki; Yoshimoto, Miwa; Onishi, Kazunari; Kuroda, Hirohiko; Matsunaga, Tomoyuki; Fukumoto, Yoji; Takano, Shuichi; Tokuyasu, Naruo; Osaki, Tomohiro; Saito, Hiroaki; Ikeguchi, Masahide

    2016-01-01

    Background Postoperative complications have been shown to worsen prognoses of various cancer types. Methods We retrospectively analyzed 265 patients with stage II-III gastric cancer who underwent curative gastrectomies between 1991 and 2010 at Tottori University Hospital to determine the effect of postoperative intra-abdominal complication (IAC) on prognosis. Results Of the 265 patients, 38 (14.3%) developed postoperative IACs of grade ≥ 2, of whom significantly more patients were male. Patients in the IAC group were significantly older than patients in the non-complication (NC) group. The NC group had significantly better survival than did the IAC group (P < 0.0001). Within the IAC group, 5-year survival rates did not significantly differ between patients with infectious complication subgroup (24.6%) and the non-infectious subgroup (46.2%). Grade of complication was not related to prognosis. Lengths of time before starting adjuvant chemotherapy (AC) after surgery were significantly longer for the IAC group (55.3 ± 34.7 days) than for the NC group: (26.6 ± 11.9 days; P = 0.0023). Prognosis of patients who took AC within 6 weeks after surgery tended to be better than that of patients who took AC > 6 weeks after surgery (P = 0.071). In multivariate analysis, IAC was an independent predictor of prognosis, as were age, invasion depth, and lymph node metastasis. Conclusion Postoperative IACs were related to poorer survival for patients with stage II–III gastric cancer. PMID:27708536

  10. Dosimetric evaluation of a simple planning method for improving intensity-modulated radiotherapy for stage III lung cancer

    PubMed Central

    Lu, Jia-Yang; Lin, Zhu; Zheng, Jing; Lin, Pei-Xian; Cheung, Michael Lok-Man; Huang, Bao-Tian

    2016-01-01

    This study aimed to evaluate the dosimetric outcomes of a base-dose-plan-compensation (BDPC) planning method for improving intensity-modulated radiotherapy (IMRT) for stage III lung cancer. For each of the thirteen included patients, three types of planning methods were applied to obtain clinically acceptable plans: (1) the conventional optimization method (CO); (2) a split-target optimization method (STO), in which the optimization objectives were set higher dose for the target with lung density; (3) the BDPC method, which compensated for the optimization-convergence error by further optimization based on the CO plan. The CO, STO and BDPC methods were then compared regarding conformity index (CI), homogeneity index (HI) of the target, organs at risk (OARs) sparing and monitor units (MUs). The BDPC method provided better HI/CI by 54%/7% on average compared to the CO method and by 38%/3% compared to the STO method. The BDPC method also spared most of the OARs by up to 9%. The average MUs of the CO, STO and BDPC plans were 890, 937 and 1023, respectively. Our results indicated that the BDPC method can effectively improve the dose distribution in IMRT for stage III lung cancer, at the expense of more MUs. PMID:27009235

  11. Treatment of Severe (Stage III and IV) Chronic Pressure Ulcers Using Pulsed Radio Frequency Energy in a Quadriplegic Patient

    PubMed Central

    Porreca, Eugene G.; Giordano-Jablon, Gina M.

    2008-01-01

    Objective: To report an adjuvant treatment to basic wound care of stage III and IV pressure ulcers in a patient with quadriplegia. Methods: Pulsed radio frequency energy was used as an adjunct to basic wound care of 3 large, long-standing (6 years) stage III and IV pressure ulcers that were unresponsive to conventional therapy in a 59-year-old man with quadriplegia. Results: The ulcers (on right foot, left heel, and sacrum) markedly decreased in size (16.7, 28.5, and 13.1 mm2 per day, respectively). The ulcer on the right foot healed within 4 weeks, the left heel ulcer reduced in size by 95% at 7 months, and the large sacral ulcer healed to closure in 11 months. Conclusion: Pulsed radio frequency energy treatment with basic wound care, if administered early in the course of pressure ulcer therapy, might avoid the lengthy hospitalizations and repeated surgical procedures necessary for treatment of uncontrolled ulcers, reducing the overall cost of treatment and improving the quality of life for chronically ill or injured patients. PMID:19008935

  12. Distribution of Resistant Esophageal Adenocarcinoma in the Resected Specimens of Clinical Stage III Patients After Chemoradiation: Its Clinical Implications

    PubMed Central

    Neishaboori, Nastaran; Wadhwa, Roopma; Nogueras-González, Graciela M.; Elimova, Elena; Shiozaki, Hironori; Sudo, Kazuki; Charalampakis, Nikolaos; Hiremath, Adarsh; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Blum, Mariela A.; Rogers, Jane E.; Garris, Jeana L.; Rice, David C.; Komaki, Ritsuko; Swisher, Stephen G.; Skinner, Heath D.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2015-01-01

    Background We have limited knowledge of the geographic distribution of resistant EAC in the resected specimen and its clinical importance can be enormous. Method We selected patients with baseline stage III EAC who had chemoradiation followed by surgery, and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (% of resistant EAC, anatomic distribution). Results 100 clinical stage III patients were studied. 90% had an R0 resection. 99% had either moderate or poorly differentiated EAC. 12% had >50% residual cancer, 31% had 11–50% residual cancer, 53% had 1–10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa=66%, muscularis propria=76%, serosa=62%, and all=35%. Lack of EAC (meaning response) was observed in mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery had no EAC in 79% of patients, in the surgical specimen, however, resistant EAC was frequent (66%) in mucosa/submucosa. Conclusion Contrary to our belief that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the post-chemoradiation biopsies are misleading and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients. PMID:25765719

  13. ColoFinder: a prognostic 9-gene signature improves prognosis for 871 stage II and III colorectal cancer patients

    PubMed Central

    He, Jianmin

    2016-01-01

    Colorectal cancer (CRC) is a heterogeneous disease with a high mortality rate and is still lacking an effective treatment. Our goal is to develop a robust prognosis model for predicting the prognosis in CRC patients. In this study, 871 stage II and III CRC samples were collected from six gene expression profilings. ColoFinder was developed using a 9-gene signature based Random Survival Forest (RSF) prognosis model. The 9-gene signature recurrence score was derived with a 5-fold cross validation to test the association with relapse-free survival, and the value of AUC was gained with 0.87 in GSE39582(95% CI [0.83–0.91]). The low-risk group had a significantly better relapse-free survival (HR, 14.8; 95% CI [8.17–26.8]; P < 0.001) than the high-risk group. We also found that the 9-gene signature recurrence score contributed more information about recurrence than standard clinical and pathological variables in univariate and multivariate Cox analyses when applied to GSE17536(p = 0.03 and p = 0.01 respectively). Furthermore, ColoFinder improved the predictive ability and better stratified the risk subgroups when applied to CRC gene expression datasets GSE14333, GSE17537, GSE12945and GSE24551. In summary, ColoFinder significantly improves the risk assessment in stage II and III CRC patients. The 9-gene prognostic classifier informs patient prognosis and treatment response. PMID:26989635

  14. Who benefits from chemoradiation in stage III-IVA endometrial cancer? An analysis of the National Cancer Data Base.

    PubMed

    Lester-Coll, Nataniel H; Park, Henry S; Rutter, Charles E; Corso, Christopher D; Young, Melissa R; Ratner, Elena S; Litkouhi, Babak; Decker, Roy H; Yu, James B; Damast, Shari

    2016-07-01

    Adjuvant therapy for advanced endometrial cancer (AEC) is not standardized. We investigated whether regional radiotherapy with chemotherapy (CRT) compared to chemotherapy alone (CT) was associated with improved overall survival (OS) in an AEC cohort and among subgroups by stage and histologic grade. Women who received CT or CRT after hysterectomy and bilateral salpingo-oophorectomy for FIGO stage III-IVA AEC diagnosed in 2004-2012 were identified in the National Cancer Data Base. Multilevel modeling was used to identify covariates associated with treatment selection. OS was compared using Kaplan-Meier estimates, the log-rank test, Cox proportional hazards regression, and propensity score matching. We identified 9837 patients, of whom 6358 (65%) received CT and 3479 (35%) received CRT. Median follow-up was 59.6months. OS was higher in patients receiving CRT compared to CT (70% v 55% at 5years, log-rank P<0.001). Controlling for stage, histologic grade, tumor size, age, comorbidity and race, CRT remained independently associated with improved OS (HR 0.63, 95% CI 0.57-0.70, P<0.001). When stratified by stage and histologic grade, there was a significant OS benefit for stage IIIA, IIIB, IIIC, grade 2, and grade 3 (all P<0.001), a trend for stage IVA (P=0.06), but no benefit for grade 1 (P=0.91). On multivariable subgroup analyses, these findings persisted, including lack of benefit in grade 1 patients (HR 0.72, P=0.14). These results were further confirmed after propensity score matching. Adjuvant CRT for AEC was associated with improved OS, except for patients with well-differentiated disease, who fared equally well with CT alone. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Perioperative and postoperative complications of intracavitary radiation for FIGO stage I-III carcinoma of the cervix.

    PubMed

    Jhingran, A; Eifel, P J

    2000-03-15

    To evaluate perioperative and postoperative complications of low-dose-rate (LDR) intracavitary radiation therapy in patients with FIGO Stage I-III carcinoma of the uterine cervix. We retrospectively reviewed the medical and radiotherapy records of all patients treated with radiation between 1960 and 1992 at The University of Texas M. D. Anderson Cancer Center for FIGO I-III carcinomas of the cervix. Patients who had had initial hysterectomy or whose treatment did not include intracavitary irradiation were excluded. The final study included 4043 patients who had undergone 7662 intracavitary procedures. Eleven (0. 3%) patients had documented or suspected cases of thromboembolism resulting in 4 deaths. Of these 11 patients, 8 had clinical or radiographic evidence of tumor involving pelvic nodes or fixed pelvic wall. The risk of postoperative thromboembolism did not decrease significantly with the routine use of mini-dose heparin prophylaxis (p = 0.3). Other life-threatening perioperative complications included myocardial infarction (1 death in 5 patients), cerebrovascular accident (2 patients), congestive heart failure or atrial fibrillation (3 patients), and halothane liver toxicity (2 deaths in 2 patients). Intraoperative complications included uterine perforation (2.8%) and vaginal laceration (0.3%), which occurred more frequently in patients >/= 60 years old (p < 0.01). Fourteen percent of patients had a temperature >/= 101 degrees F during at least one hospital stay. The only correlation between minor intraoperative complications and disease-specific survival was found in patients who had Stage III disease and uterine perforation; survival was significantly (p = 0.01) decreased in these patients. Fatal or life-threatening complications of intracavitary treatment were very rare. Deep venous thrombosis (DVT) and pulmonary embolism (PE) did not occur in otherwise healthy patients with early disease and were rare even when disease was more advanced. Minor

  16. Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits.

    PubMed

    Seledtsova, Galina V; Shishkov, Alexey A; Kaschenko, Erika A; Goncharov, Andrey G; Gazatova, Natalya D; Seledtsov, Victor I

    2016-04-01

    New therapies for melanoma have yielded promising results, but their application is limited because of serious side-effects and only moderate impact on patient survival. Vaccine therapies may offer some hope by targeting tumor-specific responses, considering the immunogenic nature of melanomas. To investigate the safety profile and efficiency of a xenogeneic cell-based vaccine therapy in stage III melanoma patients and evaluate the survival rate in treated patients. Twenty-seven stage III melanoma patients were immunized with a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells. Neither grade III/IV toxicities, nor clinically significant changes in blood and biochemical parameters were noted after an induction course of 10 XPV subcutaneous immunizations. No laboratory or clinical signs of systemic autoimmunity were documented. Following 10 vaccinations, a relative increase in the numbers of circulating memory CD4+CD45RO+ T cells (but not CD8+ CD45RO+ T cells) was observed. Peripheral blood mononuclear cells obtained from XPV-treated patients demonstrated increased proliferative responses to human BRO melanoma-associated antigens and marked increases in serum levels of IFN-γ and IL-8. Serum levels of TNF-α, IL-4 and IL-6 were not affected. The overall five-year survival rate in the treated patients was significantly higher than that in 27 control patients with matched clinical and prognostic characteristics (55% vs 18%). XPV-based immunotherapy could be maximally effective when started as early as possible before or after surgical excision of the primary tumor and local metastases, i.e. when tumor-mediated suppressive effects on immunity are minimal.

  17. Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

    ClinicalTrials.gov

    2013-02-26

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer; Stage IVA Rectal Cancer; Stage IVB Rectal Cancer

  18. Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses.

    PubMed

    Mitchell, P; Thatcher, N; Socinski, M A; Wasilewska-Tesluk, E; Horwood, K; Szczesna, A; Martín, C; Ragulin, Y; Zukin, M; Helwig, C; Falk, M; Butts, C; Shepherd, F A

    2015-06-01

    Tecemotide is a MUC1-antigen-specific cancer immunotherapy. The phase III START study did not meet its primary end point but reported notable survival benefit with tecemotide versus placebo in an exploratory analysis of the predefined patient subgroup treated with concurrent chemoradiotherapy. Here, we attempted to gain further insight into the effects of tecemotide in START. START recruited patients who did not progress following frontline chemoradiotherapy for unresectable stage III non-small-cell lung cancer. We present updated overall survival (OS) data and exploratory analyses of OS for baseline biomarkers: soluble MUC1 (sMUC1), antinuclear antibodies (ANA), neutrophil/lymphocyte ratio (NLR), lymphocyte count, and HLA type. Updated OS data are consistent with the primary analysis: median 25.8 months (tecemotide) versus 22.4 months (placebo) (HR 0.89, 95% CI 0.77-1.03, P = 0.111), with ∼20 months additional median follow-up time compared with the primary analysis. Exploratory analysis of the predefined subgroup treated with concurrent chemoradiotherapy revealed clinically relevant prolonged OS with tecemotide versus placebo (29.4 versus 20.8 months; HR 0.81, 95% CI 0.68-0.98, P = 0.026). No improvement was seen with sequential chemoradiotherapy. High sMUC1 and ANA correlated with a possible survival benefit with tecemotide (interaction P = 0.0085 and 0.0022) and might have future value as biomarkers. Interactions between lymphocyte count, NLR, or prespecified HLA alleles and treatment effect were not observed. Updated OS data support potential treatment benefit with tecemotide in patients treated with concurrent chemoradiotherapy. Exploratory biomarker analyses suggest that elevated sMUC1 or ANA levels correlate with tecemotide benefit. NCT00409188. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. [A case of multiple liver metastases from colon cancer treated with complete resection via two-stage hepatectomy after regeneration of the liver].

    PubMed

    Sugishita, Toshiya; Ganno, Hideaki; Hataji, Kenichiro; Ami, Katunori; Nagahama, Takeo; Fukuda, Akira; Ando, Masayuki; Arai, Kuniyoshi

    2015-01-01

    A 55-year-old woman underwent low anterior resection for sigmoid colon cancer with multiple bilobar metastases. She then received 23 courses of Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX) plus bevacizumab and 13 courses of Leucovorin, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab as down staging chemotherapy. A two-stage hepatectomy was planned to avoid the risk of hepatic failure due to radial resection of bilobar metastases. Therefore, a right lobectomy was performed, and curative resection was achieved 54 days after the first hepatectomy. Two-stage hepatectomy as well as a combination of induction chemotherapy and portal vein embolization may have contributed to the improved prognosis of the initially unresectable multiple bilobar liver metastases.

  20. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097, Paclitaxel, and Carboplatin Before Surgery in Treating Patients With Stage II or Stage III Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2015-09-03

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  1. Ultrasound-guided umbilical cord occlusion using bipolar diathermy for Stage III/IV twin-twin transfusion syndrome.

    PubMed

    Taylor, M J O; Shalev, E; Tanawattanacharoen, S; Jolly, M; Kumar, S; Weiner, E; Cox, P M; Fisk, N M

    2002-01-01

    To evaluate bipolar diathermy as a technique for selective fetocide in the treatment of advanced (Stage III/IV) twin-twin transfusion syndrome (TTTS). A prospective observational study in two tertiary referral fetal medicine centres: Queen Charlotte's Hospital, London, UK and Haemek Hospital, Afula, Israel. Fifteen cases of TTTS (14 twins and one triplet pregnancy) were treated by selective occlusion of either the donor (n=8) or recipient's (n=7) umbilical cord using ultrasound-guided bipolar diathermy. Following each procedure, patients were scanned serially for fetal growth, liquor volume and umbilical Doppler measurements. Procedural complications and obstetric outcome were recorded. Postnatal placental injection studies were performed. Overall co-twin survival in Stage III/IV TTTS was 13/14 (93%). There were no treatment failures. The incidence of preterm prelabour rupture of membranes (PPROM) within 3 weeks of the procedure was 3/15 (20%). In those cases where pre-procedure umbilical artery Dopplers were abnormal, the Doppler findings normalised post-procedure in all non-cord-occluded fetuses. Growth velocities of surviving donors were similar to those of surviving recipients. Bipolar diathermy appears an effective technique for the selective reduction of monochorionic twins complicated by severe as well as preterminal TTTS, with recipient and donor fetuses being equally appropriate choices for fetocide. We suggest that for advanced-stage disease where the parents can contemplate this option, cord occlusion as a single preemptive procedure maximises the opportunity for intact survival of a single survivor. Copyright 2002 John Wiley & Sons, Ltd.

  2. Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-09-29

    AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma

  3. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also obser