Science.gov

Sample records for rectal cancer combined

  1. Immunoscore in Rectal Cancer

    ClinicalTrials.gov

    2016-03-28

    Cancer of the Rectum; Neoplasms, Rectal; Rectal Cancer; Rectal Tumors; Rectal Adenocarcinoma; Melanoma; Breast Cancer; Renal Cell Cancer; Lung Cancer; Bladder Cancer; Head and Neck Cancer; Ovarian Cancer; Thyroid Cancer

  2. Drug Combinations in Preoperative Chemoradiation for Rectal Cancer.

    PubMed

    Glynne-Jones, Rob; Carvalho, Carlos

    2016-07-01

    Preoperative radiotherapy has an accepted role in reducing the risk of local recurrence in locally advanced resectable rectal cancer, particularly when the circumferential resection margin is breached or threatened, according to magnetic resonance imaging. Fluoropyrimidine-based chemoradiation can obtain a significant down-sizing response and a curative resection can then be achieved. Approximately, 20% of the patients can also obtain a pathological complete response, which is associated with less local recurrences and increased survival. Patients who achieve a sustained complete clinical response may also avoid radical surgery. In unresectable or borderline resectable tumors, around 20% of the patients still fail to achieve a sufficient down-staging response with the current chemoradiation schedules. Hence, investigators have aspired to increase pathological complete response rates, aiming to improve curative resection rates, enhance survival, and potentially avoid mutilating surgery. However, adding additional cytotoxic or biological agents have not produced dramatic improvements in outcome and often led to excess surgical morbidity and higher levels of acute toxicity, which effects on compliance and in the global efficacy of chemoradiation. PMID:27238473

  3. Association between obesity and local control of advanced rectal cancer after combined surgery and radiotherapy

    PubMed Central

    Choi, Yunseon; Lee, Yun-Han; Park, Sung Kwang; Cho, Heunglae; Ahn, Ki Jung

    2016-01-01

    Purpose: The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). Materials and Methods: We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2–3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ≥25 kg/m2) in local control was evaluated. Results: The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of 25.6 kg/m2 as a cutoff value. Conclusion: Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted. PMID:27306771

  4. Tolerability of Combined Modality Therapy for Rectal Cancer in Elderly Patients Aged 75 Years and Older

    SciTech Connect

    Margalit, Danielle N.; Mamon, Harvey J.; Ryan, David P.; Blaszkowsky, Lawrence S.; Clark, Jeffrey; Willett, Christopher G.; Hong, Theodore S.

    2011-12-01

    Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham and Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability. Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed {>=}4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0). Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of

  5. Rectal cancer: a review

    PubMed Central

    Fazeli, Mohammad Sadegh; Keramati, Mohammad Reza

    2015-01-01

    Rectal cancer is the second most common cancer in large intestine. The prevalence and the number of young patients diagnosed with rectal cancer have made it as one of the major health problems in the world. With regard to the improved access to and use of modern screening tools, a number of new cases are diagnosed each year. Considering the location of the rectum and its adjacent organs, management and treatment of rectal tumor is different from tumors located in other parts of the gastrointestinal tract or even the colon. In this article, we will review the current updates on rectal cancer including epidemiology, risk factors, clinical presentations, screening, and staging. Diagnostic methods and latest treatment modalities and approaches will also be discussed in detail. PMID:26034724

  6. Drugs Approved for Colon and Rectal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  7. Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost

    SciTech Connect

    Jakobsen, Anders . E-mail: andjac@vgs.vejleamt.dk; Mortensen, John P.; Bisgaard, Claus; Lindebjerg, Jan; Hansen, Johnny W.; Rafaelsen, Soren R.

    2006-02-01

    Purpose: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. Methods and Materials: The study included 50 patients with rectal adenocarcinoma. All patients had T3 tumor with a circumferential margin 0-5 mm on a magnetic resonance imaging scan. The radiotherapy was delivered by a technique including two planning target volumes. Clinical target volume 1 (CTV1) received 60 Gy/30 fractions, and CTV2 received 48.6 Gy/27 fractions. The tumor dose was raised to 65 Gy with endorectal brachytherapy 5 Gy/1 fraction to the tumor bed. On treatment days, the patients received uracil and tegafur 300 mg/m2 concurrently with radiotherapy. Results: Forty-eight patients underwent operation. Histopathologic tumor regression was assessed by the Tumor Regression Grade (TRG) system. TRG1 was recorded in 27% of the patients, and a further 27% were classified as TRG2. TRG3 was found in 40%, and 6% had TRG4. The toxicity was low. Conclusion: The results indicate that high-dose radiation with concurrent chemotherapy and endorectal brachytherapy is feasible with a high rate of complete response, but further trials are needed to define its possible role as treatment option.

  8. General Information about Rectal Cancer

    MedlinePlus

    ... Research Rectal Cancer Treatment (PDQ®)–Patient Version General Information About Rectal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  9. Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

    PubMed Central

    Verstraete, M; Debucquoy, A; Dekervel, J; van Pelt, J; Verslype, C; Devos, E; Chiritescu, G; Dumon, K; D'Hoore, A; Gevaert, O; Sagaert, X; Van Cutsem, E; Haustermans, K

    2015-01-01

    Background: This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT). Methods: From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with α-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for circulating angiogenic proteins. Markers were related with the pathological response of patients. Results: One dose of bevacizumab changed the expression of 14 genes and led to a significant decrease in microvessel density and in the proportion of pericyte-covered blood vessels, and a small but nonsignificant increase in hypoxia. Alterations in angiogenic processes after bevacizumab delivery were only detected in responding tumours. Lower PDGFA expression and PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression were found after bevacizumab treatment only in patients with pathological complete response. Conclusions: We could not support the ‘normalization hypothesis' and suggest a role for PDGFA, PDGF-BB, CA-IX and α-SMA. Validation in larger patient groups is needed. PMID:25867261

  10. Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model.

    PubMed

    Yan, Yang; Xu, Yingxin; Zhao, Yunshan; Li, Li; Sun, Peiming; Liu, Hailiang; Fan, Qinghao; Liang, Kai; Liang, Wentao; Sun, Huiwei; Du, Xiaohui; Li, Rong

    2014-02-01

    Due to the anatomical structure of the rectum, the treatment of rectal cancer remains challenging. Ad-E2F, an oncolytic adenovirus containing the E2F-1 promoter, can selectively replicate within and kill cancer cells derived from solid tumors. Thus, this virus provides a novel approach for the treatment of rectal cancer. Given the poor efficacy and possible adverse reactions that arise from the use of oncolytic virus alone and the results of our analysis of the efficacy of Ad-E2F in the treatment of rectal cancer, we investigated the use of oncolytic adenovirus in combination with adoptive immunotherapy using cytokine-induced killer (CIK) cells as a therapeutic treatment for rectal cancer. Our results illustrated that E2F-1 gene expression is higher in rectal cancer tissue than in normal tissue. Furthermore, the designed oncolytic adenovirus Ad-E2F is capable of selectively killing colorectal cell lines but has no significant effect on CIK cells. The results of in vitro and in vivo experiments demonstrated that combined therapy with Ad-E2F and CIK cells produce stronger antitumor effects than the administration of Ad-E2F or CIK cells alone. For low rectal cancers that are suitable for intratumoral injection, local injections of oncolytic viruses in combination with CIK cell-based adoptive immunotherapy may be suitable as a novel comprehensive therapeutic approach. PMID:24037896

  11. Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer.

    PubMed

    Doi, Hiroshi; Beppu, Naohito; Odawara, Soichi; Tanooka, Masao; Takada, Yasuhiro; Niwa, Yasue; Fujiwara, Masayuki; Kimura, Fumihiko; Yanagi, Hidenori; Yamanaka, Naoki; Kamikonya, Norihiko; Hirota, Shozo

    2013-11-01

    The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials. PMID:23658415

  12. [A patient with unresectable progressive advanced rectal cancer maintained in a state of remission by using combination therapy].

    PubMed

    Kuwabara, Hiroshi; Yamamoto, Yohei; Baba, Hironobu; Mitsuoka, Akito; Nakamura, Hiroshi; Sanada, Takahiro; Baba, Hiroyuki; Goseki, Narihide; Hodotsuka, Masanori; Sano, Tomohiko

    2012-11-01

    We report the case of a patient with unresectable progressive advanced rectal cancer, who has been able to maintain a good quality of life because of combination therapy, including chemoradiotherapy. A 52-year-old woman was diagnosed with progressive locally advanced rectal cancer and invasion of the adnexa of the uterus and the left ureter. No distant metastasis was detected. Colostomy was performed, followed by chemoradiotherapy combined with S-1; then, mFOLFOX6 +bevacizumab (BV) therapy was administered. Aggravation of bilateral hydronephrosis was detected upon completion of 2 courses of treatment, and therefore, percutaneous nephrostomy of the right kidney was performed. After the patient underwent 20 courses of treatment, imaging showed a reduction in the size of the lesion, and the CEA level returned to normal. Later, remission was sustained by sLV5FU2+BV therapy and oral administration of S-1. As a result, we were able to remove the nephrostomy tube from the right kidney in February 2011. Four years after initiation of the treatment, the patient has shown no indication of recurrence. PMID:23267933

  13. Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

    SciTech Connect

    Mohiuddin, Mohammed; Paulus, Rebecca; Mitchell, Edith; Hanna, Nader; Yuen, Albert; Nichols, Romaine; Yalavarthi, Salochna; Hayostek, Cherie; Willett, Christopher

    2013-07-01

    Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m{sup 2} per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m{sup 2} per day, Monday to Friday, plus irinotecan, 50 mg/m{sup 2} once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.

  14. Chemoradiation of rectal cancer.

    PubMed

    Arrazubi, V; Suárez, J; Novas, P; Pérez-Hoyos, M T; Vera, R; Martínez Del Prado, P

    2013-02-01

    The treatment of locally advanced rectal cancer is a challenge. Surgery, chemotherapy and radiotherapy comprise the multimodal therapy that is administered in most cases. Therefore, a multidisciplinary approach is required. Because this cancer has a high rate of local recurrence, efforts have been made to improve clinical outcomes while minimizing toxicity and maintaining quality of life. Thus, total mesorectal excision technique was developed as the standard surgery, and chemotherapy and radiotherapy have been established as neoadjuvant treatment. Both approaches reduce locoregional relapse. Two neoadjuvant treatments have emerged as standards of care: short-course radiotherapy and long-course chemoradiotherapy with fluoropyrimidines; however, long-course chemoradiotherapy might be more appropriate for low-lying neoplasias, bulky tumours or tumours with near-circumferential margins. If neoadjuvant treatment is not administered and locally advanced stage is demonstrated in surgical specimens, adjuvant chemoradiotherapy is recommended. The addition of chemotherapy to the treatment regimen confers a significant benefit. Adjuvant chemotherapy is widely accepted despite scarce evidence of its benefit. The optimal time for surgery after neoadjuvant therapy, the treatment of low-risk T3N0 neoplasms, the convenience of avoiding radiotherapy in some cases and tailoring treatment to pathological response have been recurrent subjects of debate that warrant more extensive research. Adding new drugs, changing the treatment sequence and selecting the treatment based on prognostic or predictive factors other than stage remain experimental. PMID:23584263

  15. Drugs Approved for Colon and Rectal Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Colon and Rectal Cancer This page ... and rectal cancer that are not listed here. Drugs Approved for Colon Cancer Avastin (Bevacizumab) Bevacizumab Camptosar ( ...

  16. Magnetic Resonance Imaging (MRI) with retrograde intralumen contrast enhancement of the rectum in diagnostics of rectovaginal fistulas after combination therapy of rectal cancer. Experience of application

    NASA Astrophysics Data System (ADS)

    Usova, A.; Frolova, I.; Afanasev, S.; Tarasova, A.; Molchanov, S.

    2016-02-01

    Experiment of use of MRI in diagnostics of rectovaginal fistulas after combination therapy of rectal cancer is shown on clinical examples. We used retrograde contrasting of a rectum with 150ml ultrasonic gel to make MRI more informative in case of low diagnostic efficiency of ultrasound, colonoscopy and gynecological examination.

  17. Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Rectal Cancer

    ClinicalTrials.gov

    2013-01-09

    Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Rectum; 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

  18. [Rectal cancer and adjuvant chemotherapy: which conclusions?].

    PubMed

    Bachet, J-B; Rougier, P; de Gramont, A; André, T

    2010-01-01

    Adenocarcinoma of the rectum represents about a third of cases of colorectal cancer, with an annual incidence of 12,000 cases in France. On the contrary of colon cancer, the benefice of adjuvant chemotherapy in rectal cancer has not been definitively proved, more because this question was assessed in few recent studies than because negative results. Preoperative radiochemotherapy is now the reference treatment for mid and lower rectal cancers, and allow to increase the local control without improvement of progression free survival and overall survival. The data of the "historical studies" of adjuvant treatment in rectal cancer published before 1990, of the meta-analysis of adjuvant trials in rectal cancer and of the QUASAR study suggest that adjuvant chemotherapy with fluoropyrimidines (intravenous or oral), in absence of pre-operative treatment, decrease the risk of metastatic relapse after curative surgery for a rectal cancer of stage II or III. This benefice seems similar to the one observed in colon cancer. In the EORTC radiotherapy group trial 22921, an adjuvant chemotherapy with 5-fluorouracil and low dose of leucovorin was not associated with a significantly improvement of overall survival but, despite the fact that only 42.9% of patients received all planed cycles, the progression free survival was increased (not significantly) in groups receiving adjuvant chemotherapy. The French recommendations are to discuss the indication of adjuvant chemotherapy by fluoropyrimidines in cases of stage III rectal cancer on histopathologic reports and no chemotherapy in case of stade II. Despite the fact that none study have assessed a combination of fluoropyrimidines and oxaliplatin in adjuvant setting in rectal cancer, like in colon cancer, the Folfox4, modified Folfox6 or Xelox regimens are valid options in stage III (experts opinion). In cases of pathologic complete remission or in absence of involved nodes, the benefice of adjuvant chemotherapy is not assessed. In

  19. 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

  20. Preoperative diagnosis and staging of rectal cancer using diffusion-weighted and water imaging combined with dynamic contrast-enhanced scanning

    PubMed Central

    ZHAO, QILI; LIU, LIJIAN; WANG, QIUYAN; LIANG, ZEXIA; SHI, GAOFENG

    2014-01-01

    The aim of the present study was to evaluate the value of diffusion-weighted imaging (DWI) and water imaging combined with dynamic contrast-enhanced scanning for the preoperative diagnosis and staging of rectal cancer. In total, 72 patients with pathologically confirmed rectal cancer were selected for examination using magnetic resonance imaging (MRI) with phased-array coils, DWI, water imaging and dynamic contrast-enhanced scanning. The patients were divided into two groups, experimental (simple enhanced scanning plus diffusion combined with water imaging) and control (simple enhanced scanning), for the pathological observations. The sensitivity, specificity and accuracy for the T staging of the carcinomas using scan enhancement with DWI and the evaluation of cancer using water imaging were 98.5% (65/66), 66.7% (4/6) and 95.8% (69/72), respectively, and the accuracy for N staging was 89%. Whereas, the sensitivity, specificity and accuracy for the T staging of the carcinomas using simple scan enhancement were 85.7% (42/49), 78.3% (18/23) and 83.3% (60/72), respectively, and the accuracy for N staging was 61%. Therefore, the combination of multiple MRI techniques may be of high value for the early diagnosis and exact staging of rectal cancer. PMID:25360178

  1. Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

    SciTech Connect

    Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J. )

    1993-04-02

    The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily [times] 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs.

  2. Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

    ClinicalTrials.gov

    2015-10-24

    Mucinous Adenocarcinoma of the Rectum; 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

  3. Fournier gangrene: rare complication of rectal cancer

    PubMed Central

    Ossibi, Pierlesky Elion; Souiki, Tarik; Majdoub, Karim Ibn; Toughrai, Imane; Laalim, Said Ait; Mazaz, Khalid; Tenkorang, Somuah; Farih, My Hassan

    2015-01-01

    Fournier's Gangrene is a rare complication of rectal cancer. Its discovery is often delayed. It's incidence is about 0.3/100 000 populations in Western countries. We report a patient with peritoneal perforation of rectal cancer revealed by scrotal and perineal necrotizing fasciitis. PMID:26161211

  4. Progress in Rectal Cancer Treatment

    PubMed Central

    Ceelen, Wim P.

    2012-01-01

    The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a “wait and see” approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer. PMID:22970381

  5. Treatment delay in rectal cancer.

    PubMed

    Law, C W; Roslani, A C; Ng, L L C

    2009-06-01

    Early diagnosis of rectal cancer is important for prompt treatment and better outcome. Little data exists for comparison or to set standards. The primary objective of this study is to identify factors resulting in delays in treatment of rectal cancer, the correlation between the disease stage and diagnosis waiting time, treatment waiting time and duration of symptoms. A five year retrospective audit was undertaken in University of Malaya Medical Centre (UMMC). There were 137 patients recruited and the median time to diagnosis was nine days after the first UMMC Surgical Unit consultation with a mean of 18.7 days. Some 11% had to wait more than four weeks for diagnosis. The median time from confirmation of diagnosis to surgery was 11 days with a mean of 18.6 days. Sixty-two percent of patients were operated upon within two weeks of diagnosis and more than 88% by four weeks. However, 10% of them had delayed surgery done four weeks after diagnosis. Long colonoscopy waiting time was the main cause for delay in diagnosis while delay in staging CTs were the main reason for treatment delays. PMID:20058579

  6. Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2015-09-03

    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

  7. Rectal Cancer, Version 2.2015.

    PubMed

    Benson, Al B; Venook, Alan P; Bekaii-Saab, Tanios; Chan, Emily; Chen, Yi-Jen; Cooper, Harry S; Engstrom, Paul F; Enzinger, Peter C; Fenton, Moon J; Fuchs, Charles S; Grem, Jean L; Grothey, Axel; Hochster, Howard S; Hunt, Steven; Kamel, Ahmed; Kirilcuk, Natalie; Leong, Lucille A; Lin, Edward; Messersmith, Wells A; Mulcahy, Mary F; Murphy, James D; Nurkin, Steven; Rohren, Eric; Ryan, David P; Saltz, Leonard; Sharma, Sunil; Shibata, David; Skibber, John M; Sofocleous, Constantinos T; Stoffel, Elena M; Stotsky-Himelfarb, Eden; Willett, Christopher G; Gregory, Kristina M; Freedman-Cass, Deborah

    2015-06-01

    The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease. PMID:26085388

  8. Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer

    SciTech Connect

    Hofheinz, Ralf-Dieter . E-mail: ralf.hofheinz@med3.ma.uni-heidelberg.de; Horisberger, Karoline; Woernle, Christoph; Wenz, Frederik; Kraus-Tiefenbacher, Uta; Kaehler, Georg; Dinter, Dietmar; Grobholz, Rainer; Heeger, Steffen; Post, Stefan; Hochhaus, Andreas; Willeke, Frank

    2006-12-01

    Purpose: To establish the feasibility and efficacy of chemotherapy with capecitabine, weekly irinotecan, cetuximab, and pelvic radiotherapy for patients with locally advanced rectal cancer. Methods and materials: Twenty patients with rectal cancer (clinical Stage uT3-T4 or N+) received a standard dosing regimen of cetuximab (400 mg/m{sup 2} on Day 1 and 250 mg/m{sup 2} on Days 8, 15, 22, and 29) and escalating doses of irinotecan and capecitabine according to phase I methods: dose level I, irinotecan 40 mg/m{sup 2} on Days 1, 8, 15, 22, and 29 and capecitabine 800 mg/m{sup 2} on Days 1-38; dose level II, irinotecan 40 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}; and dose level III, irinotecan 50 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}. Radiotherapy was given to a dose of 50.4 Gy (45 Gy plus 5.4 Gy). Resection was scheduled 4-5 weeks after termination of chemoradiotherapy. Results: On dose level I, no dose-limiting toxicities occurred; however, Grade 3 diarrhea affected 1 of 6 patients on dose level II. Of 5 patients treated at dose level III, 2 exhibited dose-limiting toxicity (diarrhea in 2 and nausea/vomiting in 1). Therefore, dose level II was determined as the recommended dose for future studies. A total of 10 patients were treated on dose level II and received a mean relative dose intensity of 100% of cetuximab, 94% of irinotecan, and 95% of capecitabine. All patients underwent surgery. Five patients had a pathologically complete remission and six had microfoci of residual tumor only. Conclusion: Preoperative chemoradiotherapy with cetuximab, capecitabine, and weekly irinotecan is feasible and well tolerated. The preliminary efficacy is very promising. Larger phase II trials are ongoing.

  9. Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

    PubMed Central

    Ippolito, Davide; Fior, Davide; Trattenero, Chiara; Ponti, Elena De; Drago, Silvia; Guerra, Luca; Franzesi, Cammillo Talei; Sironi, Sandro

    2015-01-01

    AIM: To assess the clinical diagnostic value of functional imaging, combining quantitative parameters of apparent diffusion coefficient (ADC) and standardized uptake value (SUV)max, before and after chemo-radiation therapy, in prediction of tumor response of patients with rectal cancer, related to tumor regression grade at histology. METHODS: A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study. All patients underwent a whole body 18FDG positron emission tomography (PET)/computed tomography (CT) scan and a pelvic magnetic resonance (MR) examination including diffusion weighted (DW) imaging for staging (PET1, RM1) and after completion (6.6 wk) of neoadjuvant treatment (PET2, RM2). Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings. The MR scanning, performed on 1.5 T magnet (Philips, Achieva), included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm²/s. On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2. The percentage decrease of SUVmax (ΔSUV) and ADC (ΔADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade (Mandard’s criteria; TRG1 = complete regression, TRG5 = no regression). RESULTS: After completion of therapy, all the patients were submitted to surgery. According to the Mandard’s criteria, 22 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; 9 tumors were classified as non responders (TRG3, 4 and 5). Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2 (P < 0.001), whereas the mean ADC values was lower in RM1 than RM2 (P < 0.001), with a ΔSUV and ΔADC respectively of 60.2% and 66.8%. The best predictors for TRG response were SUV2 (threshold of 4.4) and ADC2 (1.29 × 10-3 mm2/s) with high

  10. Transanal total mesorectal excision for rectal cancer.

    PubMed

    Hasegawa, Suguru; Takahashi, Ryo; Hida, Koya; Kawada, Kenji; Sakai, Yoshiharu

    2016-06-01

    Although laparoscopic surgery for rectal cancer has been gaining acceptance with the gradual accumulation of evidence, it remains a technically demanding procedure in patients with a narrow pelvis, bulky tumors, or obesity. To overcome the technical difficulties associated with laparoscopic rectal dissection and transection, transanal endoscopic rectal dissection, which is also referred to as transanal (reverse, bottom-up) total mesorectal excision (TME), has recently been introduced. Its potential advantages include the facilitation of the dissection of the anorectum, regardless of the patient body habitus, and a clearly defined safe distal margin and transanal extraction of the specimen. This literature review shows that this approach seems to be feasible with regard to the operative and short-term postoperative outcomes. In experienced hands, transanal TME is a promising method for the resection of mid- and low-rectal cancers. Further investigations are required to clarify the long-term oncological and functional outcomes. PMID:26055500

  11. Cetuximab in Combination With Capecitabine, Irinotecan, and Radiotherapy for Patients With Locally Advanced Rectal Cancer: Results of a Phase II MARGIT Trial

    SciTech Connect

    Horisberger, Karoline; Treschl, Anne; Mai, Sabine; Barreto-Miranda, Manuel; Kienle, Peter; Stroebel, Philipp; Erben, Philipp; Woernle, Christoph; Dinter, Dietmar; Kaehler, Georg; Hochhaus, Andreas; Post, Stefan; Willeke, Frank; Wenz, Frederik

    2009-08-01

    Purpose: To evaluate the safety and efficacy of preoperative radiotherapy (RT) in combination with cetuximab, capecitabine, and irinotecan in patients with locally advanced rectal cancer. Methods and Materials: Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive cetuximab (400 mg/m{sup 2} Day 1, 250 mg/m{sup 2} Days 8, 15, 22, 29) in combination with weekly irinotecan 40 mg/m{sup 2} and capecitabine 500 mg/m{sup 2} twice daily (Days 1-38). RT was given to a dose of 50.4 Gy (45 + 5.4 Gy). Primary endpoint was toxicity, and antitumor activity as assessed by the pathologic complete remission (pCR) rate was a secondary endpoint. Results: Fifty patients were enrolled; 88% showed T3 or T4 and 76% nodal-positive tumors with a median distance from the anal verge of 7.5 cm. The actual dose intensity was as follows (median/mean, %): cetuximab 100/92, irinotecan 100/91, capecitabine 100/89). Main adverse events Grades 2/3/4 were (National Cancer Institute common toxicity criteria version 3.0, %): leukocytopenia 6/2/2, nausea/vomiting 4/2/0, diarrhea 34/30/0, proctitis 26/2/0, elevation of liver transaminases 8/10/0, and acnelike skin rash 46/6/0. All patients underwent surgery, and no postoperative deaths occurred. Eighty-four percent underwent low-anterior resection, and 68% of the specimen exhibited moderate or good tumor regression, but only 4 patients had a pCR. Conclusion: Preoperative chemoradiation with cetuximab-CapIri-RT has manageable toxicity, with diarrhea being the most commonly observed adverse event. Nevertheless, the efficacy of this regimen with a pCR rate of only 8% was significantly lower than that observed in a previous Phase I trial.

  12. Only Half of Rectal Cancer Patients Get Recommended Treatment

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158339.html Only Half of Rectal Cancer Patients Get Recommended Treatment: ... therapy for rectal cancer in the United States, only slightly more than half of patients receive it, ...

  13. Phase I Study of Oxaliplatin in Combination With Capecitabine and Radiotherapy as Postoperative Treatment for Stage II and III Rectal Cancer

    SciTech Connect

    Jin Jing

    2008-11-01

    Purpose: A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin (OXA) combined with capecitabine and radiotherapy as adjuvant treatment in patients with operable rectal cancer. Patients and Methods: A total of 21 patients with Stage II or III rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks. OXA was administered at a dosage of 40 (n = 6), 50 (n = 3),60 (n = 3), 70 (n = 3), or 80 mg/m{sup 2} (n = 6) once a week for 2 weeks (first cycle) followed by a second cycle after a 7-day break. Capecitabine at a fixed dose of 1,300 mg/m{sup 2}/d was administered orally at the same schedule as for OXA. DLT was defined as Grade 3 or 4 hematologic and nonhematologic toxicity. Results: Grade 1-3 leukopenia, diarrhea, and nausea/vomiting were the most common toxic side effects, and most were Grade 1-2. A DLT was first observed in 1 of 3 patients at 40 mg/m{sup 2} (Grade 3 diarrhea) but was not observed in the next 3 patients at the same level or in patients who received a dose level of 50-70 mg/m{sup 2}. At 80 mg/m{sup 2}, DLT occurred in 3 of 6 patients (1 Grade 4 leukopenia and 2 Grade 3 diarrhea). Conclusions: OXA combined with a fixed dose of capecitabine at 625 mg/m{sup 2} twice daily by mouth plus radiotherapy in the adjuvant setting was tolerable and clinically feasible. The maximal tolerated dose of OXA in this setting was 80 mg/m{sup 2}, comparable to the maximal tolerated dose of OXA in the neoadjuvant setting.

  14. 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

  15. [Novel techniques in the treatment of rectal cancer].

    PubMed

    Rautio, Tero; Kairaluoma, Matti; Sand, Juhani

    2016-01-01

    Rectal cancer is the eighth and tenth most common kind of cancer in men and women, respectively, with an increasing frequency of occurrence. Together with cancer of the large intestine it forms the third most common cancer entity. Surgical therapy is the most important form of treatment of rectal cancer; in combination with adjuvant therapy it will cure a significant proportion of the patients and provide relief for tumor-induced hemorrhagic and obstructive symptoms. The operation has usually been conducted as an open surgery with the use of simple instruments. In recent times, the operative techniques have become more versatile, and mini-invasive techniques have resulted in quicker recovery of the patients from the operation. PMID:27483632

  16. Quality of care indicators in rectal cancer.

    PubMed

    Demetter, P; Ceelen, W; Danse, E; Haustermans, K; Jouret-Mourin, A; Kartheuser, A; Laurent, S; Mollet, G; Nagy, N; Scalliet, P; Van Cutsem, E; Van Den Eynde, M; Van de Stadt, J; Van Eycken, E; Van Laethem, J L; Vindevoghel, K; Penninckx, F

    2011-09-01

    Quality of health care is a hot topic, especially with regard to cancer. Although rectal cancer is, in many aspects, a model oncologic entity, there seem to be substantial differences in quality of care between countries, hospitals and physicians. PROCARE, a Belgian multidisciplinary national project to improve outcome in all patients with rectum cancer, identified a set of quality of care indicators covering all aspects of the management of rectal cancer. This set should permit national and international benchmarking, i.e. comparing results from individual hospitals or teams with national and international performances with feedback to participating teams. Such comparison could indicate whether further improvement is possible and/or warranted. PMID:22103052

  17. A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer

    PubMed Central

    Willeke, F; Horisberger, K; Kraus-Tiefenbacher, U; Wenz, F; Leitner, A; Hochhaus, A; Grobholz, R; Willer, A; Kähler, G; Post, S; Hofheinz, R-D

    2007-01-01

    We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan (50 mg m−2 weekly) and capecitabine (500 mg m−2 bid days 1–38) with a concurrent RT dose of 50.4 Gy. Surgery was scheduled 4–6 weeks after the completion of chemoradiation. A total of 36 patients (median age 62 years; m/f: 27:9) including three patients with local recurrence were enclosed onto the trial. The median distance of the tumour from the anal verge was 5 cm. The main toxicity observed was (NCI-CTC grades 1/2/3/4 (n)): Anaemia 23/9/−/−; leucocytopenia 12/7/7/2, diarrhoea 13/15/4/−, nausea/vomiting 9/10/2/−, and increased activity of transaminases 3/3/1/−. One patient had a reversible episode of ventricular fibrillation during chemoradiation, most probably caused by capecitabine. The relative dose intensity was (median/mean (%)): irinotecan 95/91, capecitabine 100/92). Thirty-four patients underwent surgery (anterior resection n=25; abdomino-perineal resection n=6; Hartmann's procedure n=3). R0-resection was accomplished in all patients. Two patients died in the postoperative course from septic complications. Pathological complete remission was observed in five out of 34 resected patients (15%), and nine patients showed microfoci of residual tumour (26%). After a median follow-up of 28 months one patient had developed a local recurrence, and five patients distant metastases. Three-year overall survival for all patients with surgery (excluding three patients treated for local relapse or with primary metastatic disease) was 80%. In summary, preoperative chemoradiation with CapIri-RT exhibits promising efficacy whereas showing managable toxicity. The local recurrence and distant failure rates observed after

  18. 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

    2016-06-10

    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

  19. Current status of laparoscopy for the treatment of rectal cancer

    PubMed Central

    Shussman, Noam; Wexner, Steven D

    2014-01-01

    Surgery for rectal cancer in complex and entails many challenges. While the laparoscopic approach in general and specific to colon cancer has been long proven to have short term benefits and to be oncologically safe, it is still a debatable topic for rectal cancer. The attempt to benefit rectal cancer patients with the known advantages of the laparoscopic approach while not compromising their oncologic outcome has led to the conduction of many studies during the past decade. Herein we describe our technique for laparoscopic proctectomy and assess the current literature dealing with short term outcomes, immediate oncologic measures (such as lymph node yield and specimen quality) and long term oncologic outcomes of laparoscopic rectal cancer surgery. We also briefly evaluate the evolving issues of robotic assisted rectal cancer surgery and the current innovations and trends in the minimally invasive approach to rectal cancer surgery. PMID:25386061

  20. MicroRNA in rectal cancer

    PubMed Central

    Azizian, Azadeh; Gruber, Jens; Ghadimi, B Michael; Gaedcke, Jochen

    2016-01-01

    In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters. PMID:27190581

  1. Efficiency of Non-Contrast-Enhanced Liver Imaging Sequences Added to Initial Rectal MRI in Rectal Cancer Patients

    PubMed Central

    Kwon, Gene-hyuk; Kim, Kyung Ah; Hwang, Seong Su; Park, Soo Youn; Kim, Hyun A.; Choi, Sun Young; Kim, Ji Woong

    2015-01-01

    Purpose The purpose of this study was to estimate the value of addition of liver imaging to initial rectal magnetic resonance imaging (MRI) for detection of liver metastasis and evaluate imaging predictors of a high risk of liver metastasis on rectal MRI. Methods We enrolled 144 patients who from October 2010 to May 2013 underwent rectal MRI with T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) (b values = 50, 500, and 900 s/mm2) of the liver and abdominopelvic computed tomography (APCT) for the initial staging of rectal cancer. Two reviewers scored the possibility of liver metastasis on different sets of liver images (T2WI, DWI, and combined T2WI and DWI) and APCT and reached a conclusion by consensus for different analytic results. Imaging features from rectal MRI were also analyzed. The diagnostic performances of CT and an additional liver scan to detect liver metastasis were compared. Multivariate logistic regression to determine independent predictors of liver metastasis among rectal MRI features and tumor markers was performed. This retrospective study was approved by the Institutional Review Board, and the requirement for informed consent was waived. Results All sets of liver images were more effective than APCT for detecting liver metastasis, and DWI was the most effective. Perivascular stranding and anal sphincter invasion were statistically significant for liver metastasis (p = 0.0077 and p = 0.0471), while extramural vascular invasion based on MRI (mrEMVI) was marginally significant (p = 0.0534). Conclusion The addition of non-contrast-enhanced liver imaging, particularly DWI, to initial rectal MRI in rectal cancer patients could facilitate detection of liver metastasis without APCT. Perivascular stranding, anal sphincter invasion, and mrEMVI detected on rectal MRI were important imaging predictors of liver metastasis. PMID:26348217

  2. Importance of surgical margins in rectal cancer.

    PubMed

    Mukkai Krishnamurty, Devi; Wise, Paul E

    2016-03-01

    Distal resection margin (DRM) and circumferential resection margin (CRM) are two important considerations in rectal cancer management. Although guidelines recommend a 2 cm DRM, studies have shown that a shorter DRM is adequate, especially in patients receiving neoadjuvant chemoradiation. Standardization of total mesorectal excision has greatly improved quality of CRM. Although more patients are undergoing sphincter-saving procedures, abdominoperineal resection is indicated for very distal tumors, and pelvic exenteration is often necessary for tumors involving pelvic organs. PMID:27094456

  3. The Great Pretender: Rectal Syphilis Mimic a Cancer

    PubMed Central

    Pisani Ceretti, Andrea; Virdis, Matteo; Maroni, Nirvana; Arena, Monica; Masci, Enzo; Magenta, Alberto; Opocher, Enrico

    2015-01-01

    Rectal syphilis is a rare expression of the widely recognised sexual transmitted disease, also known as the great imitator for its peculiarity of being confused with mild anorectal diseases because of its vague symptoms or believed rectal malignancy, with the concrete risk of overtreatment. We present the case of a male patient with primary rectal syphilis, firstly diagnosed as rectal cancer; the medical, radiological, and endoscopic features are discussed below. PMID:26451271

  4. Irinotecan and radiosensitization in rectal cancer.

    PubMed

    Illum, Henrik

    2011-04-01

    Neoadjuvant radiation therapy with concurrent 5-fluorouracil-based chemotherapy is currently considered the standard of care for locally advanced rectal cancer. Pathologically complete response is a desirable outcome and has been associated with increased disease-free survival. There is a need to improve on this approach given that only approximately 10% achieve a pathologically complete response. Irinotecan has an established role in the treatment of metastatic rectal cancer. Both in-vitro and in-vivo data have shown promising radiosensitization properties. This study provides an overview of the published clinical trials evaluating the role of irinotecan as a radiosensitizer in the management of locally advanced rectal cancer. Although early-phase clinical trials initially showed promising results, this did not translate into improved outcome in a larger randomized phase II trial. Increased topoisomerase I expression has recently been identified as a possible predictive marker for improved response to irinotecan-based radiosensitization. This finding could help identify a subset of patients more likely to benefit from the addition of irinotecan in future trials. PMID:21160419

  5. [Preoperative chemoradiotherapy for resectable lower rectal cancer].

    PubMed

    Takase, Shiro; Kamigaki, Takashi; Yamashita, Kimihiro; Nakamura, Tetsu; Nishimura, Hideki; Sasaki, Ryohei

    2009-11-01

    To suppress local recurrence and preserve sphincter function, we performed preoperative chemoradiotherapy( CRT) of rectal cancer. Sixteen patients with lower advanced rectal cancer received tegafur/uracil/calcium folinate+RT followed by curative resection with lateral lymph node dissection 2-8 weeks later. The male/female ratio was found to be 11:5 (41-75 years old) and the CRT was feasible for all patients. There were 11-PR and 5-SD according to RECIST criteria, and lower isotope accumulation was observed for all primary tumors in FDG-PET study. After CRT, all patients received R0 curative resection (11 APR, 2 LAR, 1 Hartmann and 1 ISR). On pathological study, 3 patients showed complete response. Surgical complications including pelvic infection, delayed a wound healing and deep venous thrombosis, etc. In conclusion, preoperative CRT of advanced rectal cancer could potentially be useful for local control and sphincter saving, however, it is necessary to manage specific surgical complications due to radiation. PMID:20037306

  6. A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer

    SciTech Connect

    Navarro, Matilde . E-mail: mnavarrogarcia@ico.scs.es; Dotor, Emma; Rivera, Fernando; Sanchez-Rovira, Pedro; Vega-Villegas, Maria Eugenia; Cervantes, Andres; Garcia, Jose Luis; Gallen, Manel; Aranda, Enrique

    2006-09-01

    Purpose: The aim of this study was to evaluate the efficacy and tolerance of preoperative chemoradiotherapy (CRT) with irinotecan (CPT-11) and 5-fluorouracil (5-FU) in patients with resectable rectal cancer. Methods and Materials: Patients with resectable T3-T4 rectal cancer and Eastern Cooperative Oncology Group performance status <2 were included. CPT-11 (50 mg/m{sup 2} weekly) and 5-FU (225 mg/m{sup 2}/day continuous infusion, 5 days/week) were concurrently administered with radiation therapy (RT) (45 Gy, 1.8 Gy/day, 5 days/week), during 5 weeks. Results: A total of 74 patients were enrolled: mean age, 59 years (20-74 years; SD, 11.7). Planned treatment was delivered to most patients (median relative dose intensity for both drugs was 100%). Grade 3/4 lymphocytopenia occurred in 35 patients (47%), neutropenia in 5 (7%), and anemia in 2 (3%). Main Grade 3 nonhematologic toxicities were diarrhea (14%), asthenia (9%), rectal mucositis (8%), and abdominal pain (8%). Of the 73 resected specimens, 13.7% (95% confidence interval [CI], 6.8-23.7) had a pathologic complete response and 49.3% (95% CI, 37.4-61.3) were downstaged. Additionally, 66.7% (95% CI, 51.1-80.0) of patients with ultrasound staged N1/N2 disease had no pathologic evidence of nodal involvement after CRT. Conclusions: This preoperative CRT schedule has been shown to be effective and feasible in a large population of patients with resectable rectal cancer.

  7. Rectal cancer: An evidence-based update for primary care providers

    PubMed Central

    Gaertner, Wolfgang B; Kwaan, Mary R; Madoff, Robert D; Melton, Genevieve B

    2015-01-01

    Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers. PMID:26167068

  8. Immunological Landscape and Clinical Management of Rectal Cancer

    PubMed Central

    Pérez-Ruiz, Elísabeth; Berraondo, Pedro

    2016-01-01

    The clinical management of rectal cancer and colon cancer differs due to increased local relapses in rectal cancer. However, the current molecular classification does not differentiate rectal cancer and colon cancer as two different entities. In recent years, the impact of the specific immune microenvironment in cancer has attracted renewed interest and is currently recognized as one of the major determinants of clinical progression in a wide range of tumors. In colorectal cancer, the density of lymphocytic infiltration is associated with better overall survival. Due to the need for biomarkers of response to conventional treatment with chemoradiotherapy in rectal tumors, the immune status of rectal cancer emerges as a useful tool to improve the management of patients. PMID:26941741

  9. The influence of hormone therapies on colon and rectal cancer.

    PubMed

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels; Løkkegaard, Ellen; Kjær, Susanne Krüger

    2016-05-01

    Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0.83, 0.72-0.96 and 0.89, 0.80-1.00), compared to never users. Transdermal estrogen-only therapy implied more protection than oral administration, while no significant influence was found of regimen, progestin type, nor of tibolone. The benefit of HT was stronger for long-term hormone users; and hormone users were at lower risk of advanced stage of colorectal cancer, which seems supportive for a causal association between hormone therapy and colorectal cancer. PMID:26758900

  10. HOSPITAL VARIATION IN SPHINCTER PRESERVATION FOR ELDERLY RECTAL CANCER PATIENTS

    PubMed Central

    Dodgion, Christopher M.; Neville, Bridget A; Lipsitz, Stuart R.; Schrag, Deborah; Breen, Elizabeth; Zinner, Michael J.; Greenberg, Caprice C.

    2014-01-01

    Purpose To evaluate hospital variation in the use of low anterior resection (LAR), local excision (LE) and abdominoperineal resection (APR) in the treatment of rectal cancer in elderly patients. Methods Using SEER-Medicare linked data, we identified 4,959 stage I–III rectal cancer patients over age 65 diagnosed from 2000–2005 who underwent operative intervention at one of 370 hospitals. We evaluated the distribution of hospital-specific procedure rates and used generalized mixed models with random hospital effects to examine the influence of patient characteristics and hospital on operation type, using APR as a reference. Results The median hospital performed APR on 33% of elderly rectal cancer patients. Hospital was a stronger predictor of LAR receipt than any patient characteristic, explaining 32% of procedure choice, but not a strong predictor of LE, explaining only 3.8%. Receipt of LE was primarily related to tumor size and tumor stage, which, combined, explained 31% of procedure variation. Conclusions Receipt of local excision is primarily determined by patient characteristics. In contrast, the hospital where surgery is performed significantly influences whether a patient undergoes an LAR or APR. Understanding the factors that cause this institutional variation is crucial to ensuring equitable availability of sphincter preservation. PMID:24750983

  11. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  12. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  13. Evidence-based treatment of patients with rectal cancer

    PubMed Central

    ZHANG, QIANG; YANG, JIE; QIAN, QUN

    2016-01-01

    Rectal cancer is a worldwide disease whose incidence has increased significantly. Evidence-based medicine is a category of medicine that optimizes decision making by using evidence from well-designed and conducted research. Evidence-based medicine can be used to formulate a reasonable treatment plan for newly diagnosed rectal cancer patients. The current review focuses on the application of evidence-based treatment on patients with rectal cancer. The relationship between perioperative blood transfusion and recurrence of rectal cancer after surgery, the selection between minimally invasive laparoscopic surgery and traditional laparotomy, choice of chemotherapy for patients with rectal cancer prior to surgery, selection between stapled and hand-sewn methods for colorectal anastomosis during rectal cancer resection, and selection between temporary ileostomy and colostomy during the surgery were addressed. Laparoscopy is considered to have more advantages but is time-consuming and has high medical costs. In addition, laparoscopic rectal cancer radical resection is preferred to open surgery. In radical resection surgery, use of a stapling device for anastomosis can reduce postoperative anastomotic fistula, although patients should be informed of possible anastomotic stenosis. PMID:26998054

  14. Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-09-10

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  15. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  16. Anterior-only Partial Sacrectomy for en bloc Resection of Locally Advanced Rectal Cancer

    PubMed Central

    Roldan, Hector; Perez-Orribo, Luis F.; Plata-Bello, Julio M.; Martin-Malagon, Antonio I.; Garcia-Marin, Victor M.

    2014-01-01

    Study Design Case report. Objective The usual procedure for partial sacrectomies in locally advanced rectal cancer combines a transabdominal and a posterior sacral route. The posterior approach is flawed with a high rate of complications, especially infections and wound-healing problems. Anterior-only approaches have indirectly been mentioned within long series of rectal cancer surgery. We describe a case of partial sacrectomy for en bloc resection of a locally advanced rectal cancer with invasion of the low sacrum through a combined transabdominal and perineal approach without any posterior incision. Methods Through a midline laparotomy, the tumor was dissected and the sacral osteotomy was performed. Once the sacrum was mobile, the muscular attachments to its posterior wall were cut through the perineal approach. This latter route was also used to remove the whole specimen. Results The postoperative period was uneventful in terms of infection and wound healing, but the patient developed right foot dorsiflexion paresis that completely disappeared in 1 month. Resection margins were negative. After a follow-up of 18 months, the patient has no local recurrence but presented lung and liver metastases. Conclusion In cases of rectal cancer involving the low sacrum, the combination of a transabdominal and a perineal route to carry out the partial sacrectomy is a feasible approach that avoids changes of surgical positioning and the morbidity related to posterior incisions. This strategy should be considered when deciding on undertaking partial sacrectomy in locally advanced rectal cancer. PMID:25396109

  17. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    PubMed Central

    Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

    2014-01-01

    Background Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III “pain ladder” drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient’s refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures), and to evaluate the effect of the mode of administration (intrathecal versus rectal) on the bupivacaine plasma concentration. Cases We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours). The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 mL every 4.5–11 hours). Methods Total bupivacaine plasma concentrations were determined using the high-performance liquid chromatography-ultraviolet method. Results Effective pain control was achieved with intrathecal bupivacaine (0.077–0.154 mg·kg−1) and bupivacaine in enema (1.820 mg·kg−1). Intrathecal bupivacaine (0.5%, 2 mL) caused a drop in blood pressure; other side effects were absent in both cases. Total plasma bupivacaine concentrations following intrathecal and rectal bupivacaine application did not exceed 317.2 ng·mL−1 and 235.7 ng·mL−1, respectively. Bupivacaine elimination was

  18. Orbital metastasis as the inaugural presentation of occult rectal cancer

    PubMed Central

    Cherif, Eya; Ben Hassine, Lamia; Azzabi, Samira; Khalfallah, Narjess

    2014-01-01

    Orbital metastasis is uncommon and occurs in 2–3% of patients with cancer. It is rarely the initial manifestation of a systemic malignancy. It usually indicates extensive haematogenous dissemination of a primary cancer and is associated with poor prognosis. Breast, lungs and prostate cancers are the most common primary cancers leading to orbital metastasis. However, orbital tumour revealing a rectal adenocarcinoma is exceptional. We describe a case of orbital tumour in a 67-year-old man with no history of systemic cancer while presenting with ophthalmic symptoms. Investigations revealed rectal adenocarcinoma as the primary malignant tumour. PMID:24481014

  19. Patterns of metastasis in colon and rectal cancer.

    PubMed

    Riihimäki, Matias; Hemminki, Akseli; Sundquist, Jan; Hemminki, Kari

    2016-01-01

    Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis. PMID:27416752

  20. Patterns of metastasis in colon and rectal cancer

    PubMed Central

    Riihimäki, Matias; Hemminki, Akseli; Sundquist, Jan; Hemminki, Kari

    2016-01-01

    Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis. PMID:27416752

  1. Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

    SciTech Connect

    Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G.

    2013-08-01

    Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following

  2. Secondary Cancers After Radiation Therapy for Primary Prostate or Rectal Cancer.

    PubMed

    Lee, Yen-Chien; Hsieh, Chung-Cheng; Li, Chung-Yi; Chuang, Jen-Pin; Lee, Jenq-Chang

    2016-04-01

    Literature about the risk of secondary cancer after radiation therapy (RT) of prostate and rectal cancer reveals contradictory results. We conducted a meta-analysis to examine whether the RT induces secondary rectal or prostate cancer in patients, respectively, with prostate or rectal cancer. All studies published in Medline or Pubmed up to March 3, 2015, containing RT of primary rectal or prostate cancer, and providing risk estimates of secondary prostate or rectal cancer were considered as eligible. Relative risk (RR) and standardized incidence ratios (SIR) were calculated using the random-effects model. Twenty studies met the inclusion criteria. 12 of them were from the Surveillance, Epidemiology, and End Results (SEER) database. For prostate cancer patients, pooled adjusted RRs or SIRs did not show an effect on the risk of secondary rectal cancer. However, notwithstanding the limitations of SEER-based studies, the subgroup of prostate cancer patients receiving external beam radiation therapy (EBRT) showed an increased risk of rectal cancer. For rectal cancer patients, pooled adjusted RR of prostate cancer was 1.12 (95 % CI, 0.44-2.8) and SIR was 0.40 (95 % CI, 0.29-0.55). All studies included in the SIR analysis of rectal cancer were derived from the SEER data source. Based on current evidence, RT for prostate cancer patients had no effect on rectal cancer incidence, except for patients who received EBRT therapy. However, compared with the general population, RT for rectal cancer is associated with a decreased prostate cancer risk as found in SEER-based studies. PMID:26711638

  3. Surgical strategy for low rectal cancers.

    PubMed

    Dumont, F; Mariani, A; Elias, D; Goéré, D

    2015-02-01

    The two goals of surgery for lower rectal cancer surgery are to obtain clear "curative" margins and to limit post-surgical functional disorders. The question of whether or not to preserve the anal sphincter lies at the center of the therapeutic choice. Histologically, tumor-free distal and circumferential margins of>1mm allow a favorable oncologic outcome. Whether such margins can be obtained depends of TNM staging, tumor location, response to chemoradiotherapy and type of surgical procedure. The technique of intersphincteric resection relies on these narrow margins to spare the sphincter. This procedure provides satisfactory oncologic outcome with a rate of circumferential margin involvement ranging from 5% to 11%, while good continence is maintained in half of the patients. The extralevator abdominoperineal resection provides good oncologic results, however this procedure requires a permanent colostomy. A permanent colostomy alters several domains of quality of life when located at the classical abdominal site but not when brought out at the perineal site as a perineal colostomy. PMID:25455959

  4. Toward Restored Bowel Health in Rectal Cancer Survivors.

    PubMed

    Steineck, Gunnar; Schmidt, Heike; Alevronta, Eleftheria; Sjöberg, Fei; Bull, Cecilia Magdalena; Vordermark, Dirk

    2016-07-01

    As technology gets better and better, and as clinical research provides more and more knowledge, we can extend our ambition to cure patients from cancer with restored physical health among the survivors. This increased ambition requires attention to grade 1 toxicity that decreases quality of life. It forces us to document the details of grade 1 toxicity and improve our understanding of the mechanisms. Long-term toxicity scores, or adverse events as documented during clinical trials, may be regarded as symptoms or signs of underlying survivorship diseases. However, we lack a survivorship nosology for rectal cancer survivors. Primarily focusing on radiation-induced side effects, we highlight some important observations concerning late toxicity among rectal cancer survivors. With that and other data, we searched for a preliminary survivorship-disease nosology for rectal cancer survivors. We disentangled the following survivorship diseases among rectal cancer survivors: low anterior resection syndrome, radiation-induced anal sphincter dysfunction, gut wall inflammation and fibrosis, blood discharge, excessive gas discharge, excessive mucus discharge, constipation, bacterial overgrowth, and aberrant anatomical structures. The suggested survivorship nosology may form the basis for new instruments capturing long-term symptoms (patient-reported outcomes) and professional-reported signs. For some of the diseases, we can search for animal models. As an end result, the suggested survivorship nosology may accelerate our understanding on how to prevent, ameliorate, or eliminate manifestations of treatment-induced diseases among rectal cancer survivors. PMID:27238476

  5. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  6. Low Rectal Cancer Study (MERCURY II)

    ClinicalTrials.gov

    2016-03-11

    Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

  7. Sexual Function in Males After Radiotherapy for Rectal Cancer

    SciTech Connect

    Bruheim, Kjersti; Guren, Marianne G.; Dahl, Alv A.; Skovlund, Eva; Balteskard, Lise; Carlsen, Erik; Fossa, Sophie D.; Tveit, Kjell Magne

    2010-03-15

    Purpose: Knowledge of sexual problems after pre- or postoperative radiotherapy (RT) with 50 Gy for rectal cancer is limited. In this study, we aimed to compare self-rated sexual functioning in irradiated (RT+) and nonirradiated (RT-) male patients at least 2 years after surgery for rectal cancer. Methods and Materials: Patients diagnosed with rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Male patients without recurrence at the time of the study. The International Index of Erectile Function, a self-rated instrument, was used to assess sexual functioning, and serum levels of serum testosterone were measured. Results: Questionnaires were returned from 241 patients a median of 4.5 years after surgery. The median age was 67 years at survey. RT+ patients (n = 108) had significantly poorer scores for erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction with sex life compared with RT- patients (n = 133). In multiple age-adjusted analysis, the odds ratio for moderate-severe erectile dysfunction in RT+ patients was 7.3 compared with RT- patients (p <0.001). Furthermore, erectile dysfunction of this degree was associated with low serum testosterone (p = 0.01). Conclusion: RT for rectal cancer is associated with significant long-term effects on sexual function in males.

  8. Voiding Dysfunction after Total Mesorectal Excision in Rectal Cancer

    PubMed Central

    Kim, Jae Heon; Noh, Tae Il; Oh, Mi Mi; Park, Jae Young; Lee, Jeong Gu; Um, Jun Won; Min, Byung Wook

    2011-01-01

    Purpose The aim of this study was to assess the voiding dysfunction after rectal cancer surgery with total mesorectal excision (TME). Methods This was part of a prospective study done in the rectal cancer patients who underwent surgery with TME between November 2006 and June 2008. Consecutive uroflowmetry, post-voided residual volume, and a voiding questionnaire were performed at preoperatively and postoperatively. Results A total of 50 patients were recruited in this study, including 28 male and 22 female. In the comparison of the preoperative data with the postoperative 3-month data, a significant decrease in mean maximal flow rate, voided volume, and post-voided residual volume were found. In the comparison with the postoperative 6-month data, however only the maximal flow rate was decreased with statistical significance (P=0.02). In the comparison between surgical methods, abdominoperineal resection patients showed delayed recovery of maximal flow rate, voided volume, and post-voided residual volume. There was no significant difference in uroflowmetry parameters with advances in rectal cancer stage. Conclusions Voiding dysfunction is common after rectal cancer surgery but can be recovered in 6 months after surgery or earlier. Abdominoperineal resection was shown to be an unfavorable factor for postoperative voiding. Larger prospective study is needed to determine the long-term effect of rectal cancer surgery in relation to male and female baseline voiding condition. PMID:22087426

  9. Recent advances in robotic surgery for rectal cancer.

    PubMed

    Ishihara, Soichiro; Otani, Kensuke; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Junichiro; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Kazama, Shinsuke; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2015-08-01

    Robotic technology, which has recently been introduced to the field of surgery, is expected to be useful, particularly in treating rectal cancer where precise manipulation is necessary in the confined pelvic cavity. Robotic surgery overcomes the technical drawbacks inherent to laparoscopic surgery for rectal cancer through the use of multi-articulated flexible tools, three-dimensional stable camera platforms, tremor filtering and motion scaling functions, and greater ergonomic and intuitive device manipulation. Assessments of the feasibility and safety of robotic surgery for rectal cancer have reported similar operation times, blood loss during surgery, rates of postoperative morbidity, and circumferential resection margin involvement when compared with laparoscopic surgery. Furthermore, rates of conversion to open surgery are reportedly lower with increased urinary and male sexual functions in the early postoperative period compared with laparoscopic surgery, demonstrating the technical advantages of robotic surgery for rectal cancer. However, long-term outcomes and the cost-effectiveness of robotic surgery for rectal cancer have not been fully evaluated yet; therefore, large-scale clinical studies are required to evaluate the efficacy of this new technology. PMID:26059248

  10. Treatment of rectal cancer by low anterior resection with coloanal anastomosis.

    PubMed Central

    Paty, P B; Enker, W E; Cohen, A M; Lauwers, G Y

    1994-01-01

    OBJECTIVE: Our institution's experience with low anterior resection in combination with coloanal anastomosis (LAR/CAA) for primary rectal cancer was reviewed (1) to determine cancer treatment results, 2) to identify risk factors for pelvic recurrence, and 3) to assess the long-term success of sphincter preservation. SUMMARY BACKGROUND DATA: Use of sphincter-preserving resection for mid-rectal and selected distal-rectal cancers continues to increase. As surgical techniques and adjuvant therapy evolve, treatment results must be carefully assessed. METHODS: One hundred thirty-four patients treated for primary rectal cancer by LAR/CAA between 1977 and 1990 were studied retrospectively. All pathologic slides were reviewed. Median follow-up was 4 years. RESULTS: Actuarial 5-year survival for all patients was 73%. Among 36 patients who relapsed, distant metastatic disease had developed at the time of first clinical relapse in most (86%). Pelvic recurrence was detected in 13 patients, an actuarial rate of 11% at 5 years. Mesenteric implants, positive microscopic resection margin, T3 tumor, perineural invasion, blood vessel invasion, and high tumor grade were associated with increased risk for pelvic recurrence. Eleven patients ultimately required permanent colostomy, and in eight instances the cause was pelvic recurrence. CONCLUSIONS: Low anterior resection combined with coloanal anastomosis provides good treatment for mid-rectal cancers and for some distal rectal cancers. Pelvic recurrence is not associated with short distal resection margins but is correlated with the presence of histopathologic markers of aggressive disease in the primary tumor. Long-term preservation of anal sphincter function depends primarily on control of pelvic tumor and can be achieved in more than 90% of patients. Images Figure 1. Figure 3. PMID:8161262

  11. [Palliative Care for Rectal Cancer Complicated with Gastric Cancer].

    PubMed

    Furukawa, Takeshi; Takahashi, Hitoshi; Tanaka, Kei; Muto, Takaaki

    2015-11-01

    Medical advancements have led to an increase in the number of elderly people. However, standard treatments may sometimes be difficult to use in elderly people. Here, we report the case of an elderly patient with rectal and gastric cancer who refused radical surgery. The patient was an 83-year-old man who had type-2 diabetes, hypertension, hyperuricemia, mitral valve regurgitation, and mild dementia. Furthermore, he was blind in both eyes owing to glaucoma. He first visited our hospital in 2005. In 2010, he was diagnosed with anemia, but he refused a thorough examination; however, he did consent to take iron supplements. In July 2011, he consulted our hospital for symptoms of frequent diarrhea, and agreed to an examination. After colonoscopy, he was diagnosed with rectal cancer that was becoming obstructive. There were no metastases to other organs, but he was also diagnosed with gastric cancer. As he and his family refused radical surgery, a stoma was constructed. After the operation, he received palliative care but died in September 2013. PMID:26805335

  12. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  13. Current Status of Minimally Invasive Surgery for Rectal Cancer.

    PubMed

    Fleshman, James

    2016-05-01

    Recent randomized controlled data have shown possible limitations to laparoscopic treatment of rectal cancer. The retrospective data, used as the basis for designing the trials, and which showed no problems with the technique, are discussed. The design of the randomized trials is discussed relative to the future meta-analysis of the recent data. The implications of the current findings on practice are discussed as surgeons try to adjust their practice to the new findings. The possible next steps for clinical and research innovations are put into perspective as new technology is considered to compensate for newly identified limitations in the laparoscopic treatment of rectal cancer. PMID:26831061

  14. Which Patients With Rectal Cancer Do Not Need Radiotherapy?

    PubMed

    Joye, Ines; Haustermans, Karin

    2016-07-01

    According to current guidelines, the standard treatment for locally advanced rectal cancer patients is preoperative (chemo)radiotherapy followed by total mesorectal excision surgery and adjuvant chemotherapy. Improvements in surgical techniques, imaging modalities, chemotherapy regimens, and radiotherapy delivery have reduced local recurrence rates to less than 10%. The current challenge in rectal cancer treatment lies in the prevention of distant metastases, which still occur in more than 25% of the patients. The decrease in local recurrence rates, the need for more effective systemic treatments, and the increased awareness of treatment-induced toxicity raise the question as to whether a more selective use of radiotherapy is advocated. PMID:27238471

  15. Minimally invasive surgery for rectal cancer: Are we there yet?

    PubMed Central

    Champagne, Bradley J; Makhija, Rohit

    2011-01-01

    Laparoscopic colon surgery for select cancers is slowly evolving as the standard of care but minimally invasive approaches for rectal cancer have been viewed with significant skepticism. This procedure has been performed by select surgeons at specialized centers and concerns over local recurrence, sexual dysfunction and appropriate training measures have further hindered widespread acceptance. Data for laparoscopic rectal resection now supports its continued implementation and widespread usage by expeienced surgeons for select patients. The current controversies regarding technical approaches have created ambiguity amongst opinion leaders and are also addressed in this review. PMID:21412496

  16. Robotic Surgery for Rectal Cancer: An Update in 2015

    PubMed Central

    Kwak, Jung Myun; Kim, Seon Hahn

    2016-01-01

    During the last decade, robotic surgery for rectal cancer has rapidly gained acceptance among colorectal surgeons worldwide, with well-established safety and feasibility. The lower conversion rate and better surgical specimen quality of robotic compared with laparoscopic surgery potentially improves survival. Earlier recovery of voiding and sexual function after robotic total mesorectal excision is another favorable outcome. Long-term survival data are sparse with no evidence that robotic surgery offers major benefits in oncological outcomes. Although initial reports are promising, more rigorous scientific evaluation in multicenter, randomized clinical trials should be performed to definitely determine the advantages of robotic rectal cancer surgery. PMID:26875201

  17. The role of endoscopic ultrasound in the evaluation of rectal cancer

    PubMed Central

    Siddiqui, Ali A; Fayiga, Yomi; Huerta, Sergio

    2006-01-01

    Accurate staging of rectal cancer is essential for selecting patients who can undergo sphincter-preserving surgery. It may also identify patients who could benefit from neoadjuvant therapy. Clinical staging is usually accomplished using a combination of physical examination, CT scanning, MRI and endoscopic ultrasound (EUS). Transrectal EUS is increasingly being used for locoregional staging of rectal cancer. The accuracy of EUS for the T staging of rectal carcinoma ranges from 80-95% compared with CT (65-75%) and MR imaging (75-85%). In comparison to CT, EUS can potentially upstage patients, making them eligible for neoadjuvant treatment. The accuracy to determine metastatic nodal involvement by EUS is approximately 70-75% compared with CT (55-65%) and MR imaging (60-70%). EUS guided FNA may be beneficial in patients who appear to have early T stage disease and suspicious peri-iliac lymphadenopathy to exclude metastatic disease. PMID:17049086

  18. [Research hotspot and progress of preoperative chemoradiotherapy for rectal cancer].

    PubMed

    Peng, Jianhong; Pan, Zhizhong

    2016-06-01

    Preoperative chemoradiotherapy (CRT) has become an important component of comprehensive treatment for rectal cancer. Although local recurrent risk has been remarkably reduced by CRT, distant metastasis remains the main cause of therapeutic failure. Therefore, more and more studies focused on controlling distant metastasis in order to prolong long-term survival. Recently, CRT has achieved certain progression in rectal cancer: (1)Patients with stage T3 should be classified into specific subgroups to formulate individualized treatment regimen. For stage T3a, it is feasible to perform surgery alone or administrate low intensity preoperative CRT; for stage T3b and T3c, conventional preoperative CRT should be performed in order to reduce the risk of recurrence postoperatively. (2)With regard to combined regimen for chemotherapy, oral capecitabine superiors to intravenous bolus 5-fluorouracil (5-FU) and is comparable to continuous intravenous infusion 5-FU with a better safety. Therefore, capecitabine is recommended for older patients and those with poor tolerance to chemotherapy. Compared to single 5-FU concurrent CRT, addition of oxaliplatin into preoperative CRT may result in a higher survival benefit in Chinese patients. As to the application of irinotecan, bevacizumab or cetuximab, unless there are more evidence to confirm their efficacy and safety from randomized controlled trial, they should not be recommended for adding to preoperative CRT routinely. (3)On the optimization in CRT pattern, the application values of induction chemotherapy before concurrent CRT, consolidation chemotherapy after concurrent CRT, neoadjuvant sandwich CRT, neoadjuvant chemotherapy alone and short-course preoperative radiotherapy remain further exploration. (4)On the treatment strategy for clinical complete response (cCR) after CRT, whether "wait and see" strategy is able to be adopted, it is still a hot topic with controversy. PMID:27353093

  19. Comparative analysis of radiosensitizers for K-RAS mutant rectal cancers.

    PubMed

    Kleiman, Laura B; Krebs, Angela M; Kim, Stephen Y; Hong, Theodore S; Haigis, Kevin M

    2013-01-01

    Approximately 40% of rectal cancers harbor activating K-RAS mutations, and these mutations are associated with poor clinical response to chemoradiotherapy. We aimed to identify small molecule inhibitors (SMIs) that synergize with ionizing radiation (IR) ("radiosensitizers") that could be incorporated into current treatment strategies for locally advanced rectal cancers (LARCs) expressing mutant K-RAS. We first optimized a high-throughput assay for measuring individual and combined effects of SMIs and IR that produces similar results to the gold standard colony formation assay. Using this screening platform and K-RAS mutant rectal cancer cell lines, we tested SMIs targeting diverse signaling pathways for radiosensitizing activity and then evaluated our top hits in follow-up experiments. The two most potent radiosensitizers were the Chk1/2 inhibitor AZD7762 and the PI3K/mTOR inhibitor BEZ235. The chemotherapeutic agent 5-fluorouracil (5-FU), which is used to treat LARC, synergized with AZD7762 and enhanced radiosensitization by AZD7762. This study is the first to compare different SMIs in combination with IR for the treatment of K-RAS mutant rectal cancer, and our findings suggest that Chk1/2 inhibitors should be evaluated in new clinical trials for LARC. PMID:24349411

  20. Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report.

    PubMed

    Kim, Kyungsuk; Lee, Sanghun

    2016-01-01

    Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang-tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients. PMID:27198037

  1. The Molecular Basis of Rectal Cancer

    PubMed Central

    Shiller, Michelle; Boostrom, Sarah

    2015-01-01

    The majority of rectal carcinomas are sporadic in nature, and relevant testing for driver mutations to guide therapy is important. A thorough family history is necessary and helpful in elucidating a potential hereditary predilection for a patient's carcinoma. The adequate diagnosis of a heritable tendency toward colorectal carcinoma alters the management of a patient disease and permits the implementation of various surveillance algorithms as preventive measures. PMID:25733974

  2. How to identify rectal sub-regions likely involved in rectal bleeding in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Dréan, G.; Acosta, O.; Ospina, J. D.; Voisin, C.; Rigaud, B.; Simon, A.; Haigron, P.; de Crevoisier, R.

    2013-11-01

    Nowadays, the de nition of patient-speci c constraints in prostate cancer radiotherapy planning are solely based on dose-volume histogram (DVH) parameters. Nevertheless those DVH models lack of spatial accuracy since they do not use the complete 3D information of the dose distribution. The goal of the study was to propose an automatic work ow to de ne patient-speci c rectal sub-regions (RSR) involved in rectal bleeding (RB) in case of prostate cancer radiotherapy. A multi-atlas database spanning the large rectal shape variability was built from a population of 116 individuals. Non-rigid registration followed by voxel-wise statistical analysis on those templates allowed nding RSR likely correlated with RB (from a learning cohort of 63 patients). To de ne patient-speci c RSR, weighted atlas-based segmentation with a vote was then applied to 30 test patients. Results show the potentiality of the method to be used for patient-speci c planning of intensity modulated radiotherapy (IMRT).

  3. Hyperthermotherapy for postoperative local recurrences of rectal cancer.

    PubMed

    Kuroda, M; Hizuta, A; Iwagaki, H; Makihata, E; Asaumi, J; Nishikawa, K; Gao, X S; Nakagawa, T; Togami, I; Takeda, Y

    1993-08-01

    Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected. PMID:8213219

  4. Role of Peroxiredoxin I in Rectal Cancer and Related to p53 Status

    SciTech Connect

    Chen, Miao-Fen; Lee, Kuan-Der; Yeh, Chung-Hung; Chen, Wen-Cheng; Huang, Wen-Shih; Chin, Chih-Chien; Lin, Paul- Yang; Wang, Jeng-Yi

    2010-11-01

    Background: Neoadjuvant chemoradiotherapy is widely accepted for the treatment of localized rectal cancer. Although peroxiredoxin I (PrxI) and p53 have been implicated in carcinogenesis and cancer treatment, the role of PrxI and its interaction with p53 in the prognosis and treatment response of rectal cancer remain relatively unstudied. Methods and Materials: In the present study, we examined the levels of PrxI and p53 in rectal cancer patients using membrane arrays and compared them with normal population samples. To demonstrate the biologic changes after manipulation of PrxI expression, we established stable transfectants of HCT-116 (wild-type p53) and HT-29 (mutant p53) cells with a PrxI silencing vector. The predictive capacities of PrxI and p53 were also assessed by relating the immunohistochemical staining of a retrospective series of rectal cancer cases to the clinical outcome. Results: The membrane array and immunochemical staining data showed that PrxI, but not p53, was significantly associated with the tumor burden. Our immunochemistry findings further indicated that PrxI positivity was linked to a poor response to neoadjuvant therapy and worse survival. In cellular and animal experiments, the inhibition of PrxI significantly decreased tumor growth and sensitized the tumor to irradiation, as indicated by a lower capacity to scavenge reactive oxygen species and more extensive DNA damage. The p53 status might have contributed to the difference between HCT-116 and HT-29 after knockdown of PrxI. Conclusion: According to our data, the level of PrxI combined with the p53 status is relevant to the prognosis and the treatment response. We suggested that PrxI might be a new biomarker for rectal cancer.

  5. The Prognostic Value of Circumferential Resection Margin Involvement in Patients with Extraperitoneal Rectal Cancer.

    PubMed

    Shin, Dong Woo; Shin, Jin Yong; Oh, Sung Jin; Park, Jong Kwon; Yu, Hyeon; Ahn, Min Sung; Bae, Ki Beom; Hong, Kwan Hee; Ji, Yong Il

    2016-04-01

    The prognostic influence of circumferential resection margin (CRM) status in extraperitoneal rectal cancer probably differs from that of intraperitoneal rectal cancer because of its different anatomical and biological behaviors. However, previous reports have not provided the data focused on extraperitoneal rectal cancer. Therefore, the aim of this study was to examine the prognostic significance of the CRM status in patients with extraperitoneal rectal cancer. From January 2005 to December 2008, 248 patients were treated for extraperitoneal rectal cancer and enrolled in a prospectively collected database. Extraperitoneal rectal cancer was defined based on tumors located below the anterior peritoneal reflection, as determined intraoperatively by a surgeon. Cox model was used for multivariate analysis to examine risk factors of recurrence and mortality in the 248 patients, and multivariate logistic regression analysis was performed to identify predictors of recurrence and mortality in 135 patients with T3 rectal cancer. CRM involvement for extraperitoneal rectal cancer was present in 29 (11.7%) of the 248 patients, and was the identified predictor of local recurrence, overall recurrence, and death by multivariate Cox analysis. In the 135 patients with T3 cancer, CRM involvement was found to be associated with higher probability of local recurrence and mortality. In extraperitoneal rectal cancer, CRM involvement is an independent risk factor of recurrence and survival. Based on the results of the present study, it seems that CRM involvement in extraperitoneal rectal cancer is considered an indicator for (neo)adjuvant therapy rather than conventional TN status. PMID:27097629

  6. Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

    ClinicalTrials.gov

    2016-01-22

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  7. Intravoxel Incoherent Motion-derived Histogram Metrics for Assessment of Response after Combined Chemotherapy and Radiation Therapy in Rectal Cancer: Initial Experience and Comparison between Single-Section and Volumetric Analyses.

    PubMed

    Nougaret, Stephanie; Vargas, Hebert Alberto; Lakhman, Yulia; Sudre, Romain; Do, Richard K G; Bibeau, Frederic; Azria, David; Assenat, Eric; Molinari, Nicolas; Pierredon, Marie-Ange; Rouanet, Philippe; Guiu, Boris

    2016-08-01

    Purpose To determine the diagnostic performance of intravoxel incoherent motion (IVIM) parameters and apparent diffusion coefficient (ADC) to assess response to combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer by using histogram analysis derived from whole-tumor volumes and single-section regions of interest (ROIs). Materials and Methods The institutional review board approved this retrospective study of 31 patients with rectal cancer who underwent magnetic resonance (MR) imaging before and after CRT, including diffusion-weighted imaging with 34 b values prior to surgery. Patient consent was not required. ADC, perfusion-related diffusion fraction (f), slow diffusion coefficient (D), and fast diffusion coefficient (D*) were calculated on MR images acquired before and after CRT by using biexponential fitting. ADC and IVIM histogram metrics and median values were obtained by using whole-tumor volume and single-section ROI analyses. All ADC and IVIM parameters obtained before and after CRT were compared with histopathologic findings by using t tests with Holm-Sidak correction. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of IVIM parameters derived from whole-tumor volume and single-section ROIs for prediction of histopathologic response. Results Extreme values aside, results of histogram analysis of ADC and IVIM were equivalent to median values for tumor response assessment (P > .06). Prior to CRT, none of the median ADC and IVIM diffusion metrics correlated with subsequent tumor response (P > .36). Median D and ADC values derived from either whole-volume or single-section analysis increased significantly after CRT (P ≤ .01) and were significantly higher in good versus poor responders (P ≤ .02). Median IVIM f and D* values did not significantly change after CRT and were not associated with tumor response to CRT (P > .36). Interobserver agreement was excellent for whole-tumor volume

  8. A case of capecitabine-induced coronary microspasm in a patient with rectal cancer

    PubMed Central

    Arbea, Leire; Coma-Canella, Isabel; Martinez-Monge, Rafael; García-Foncillas, Jesús

    2007-01-01

    5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed. PMID:17465463

  9. Correlation of Chromosomal Instability, Telomere Length and Telomere Maintenance in Microsatellite Stable Rectal Cancer: A Molecular Subclass of Rectal Cancer

    PubMed Central

    Boardman, Lisa A.; Johnson, Ruth A.; Viker, Kimberly B.; Hafner, Kari A.; Jenkins, Robert B.; Riegert-Johnson, Douglas L.; Smyrk, Thomas C.; Litzelman, Kristin; Seo, Songwon; Gangnon, Ronald E.; Engelman, Corinne D.; Rider, David N.; Vanderboom, Russell J.; Thibodeau, Stephen N.; Petersen, Gloria M.; Skinner, Halcyon G.

    2013-01-01

    Introduction Colorectal cancer (CRC) tumor DNA is characterized by chromosomal damage termed chromosomal instability (CIN) and excessively shortened telomeres. Up to 80% of CRC is microsatellite stable (MSS) and is historically considered to be chromosomally unstable (CIN+). However, tumor phenotyping depicts some MSS CRC with little or no genetic changes, thus being chromosomally stable (CIN-). MSS CIN- tumors have not been assessed for telomere attrition. Experimental Design MSS rectal cancers from patients ≤50 years old with Stage II (B2 or higher) or Stage III disease were assessed for CIN, telomere length and telomere maintenance mechanism (telomerase activation [TA]; alternative lengthening of telomeres [ALT]). Relative telomere length was measured by qPCR in somatic epithelial and cancer DNA. TA was measured with the TRAPeze assay, and tumors were evaluated for the presence of C-circles indicative of ALT. p53 mutation status was assessed in all available samples. DNA copy number changes were evaluated with Spectral Genomics aCGH. Results Tumors were classified as chromosomally stable (CIN-) and chromosomally instable (CIN+) by degree of DNA copy number changes. CIN- tumors (35%; n=6) had fewer copy number changes (<17% of their clones with DNA copy number changes) than CIN+ tumors (65%; n=13) which had high levels of copy number changes in 20% to 49% of clones. Telomere lengths were longer in CIN- compared to CIN+ tumors (p=0.0066) and in those in which telomerase was not activated (p=0.004). Tumors exhibiting activation of telomerase had shorter tumor telomeres (p=0.0040); and tended to be CIN+ (p=0.0949). Conclusions MSS rectal cancer appears to represent a heterogeneous group of tumors that may be categorized both on the basis of CIN status and telomere maintenance mechanism. MSS CIN- rectal cancers appear to have longer telomeres than those of MSS CIN+ rectal cancers and to utilize ALT rather than activation of telomerase. PMID:24278232

  10. Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival.

    PubMed

    Sexe, R; Miedema, B W

    1993-07-01

    The risk of malignant disease arising in rectal mucosa is high. Surgery is the most effective form of treatment but results in cure in only 50% of patients. Adjuvant preoperative radiation therapy reduces the likelihood of local recurrence but does not improve survival rates. Fluorouracil is the most effective agent for adjuvant chemotherapy and slightly improves survival when given after surgery. Combining radiation therapy with chemotherapy appears to have a synergistic effect, and recent studies show that providing this combination after surgery improves survival. Future trends in the treatment of rectal cancer are expected to include expanded use of local excision to preserve anal sphincter function, preoperative use of a combination of radiation therapy and chemotherapy, perioperative use of chemotherapy combined with immunostimulating therapy, and use of tumor antibodies for diagnostic and therapeutic purposes. PMID:8321771

  11. Dietary intake of folate and co-factors in folate metabolism, MTHFR polymorphisms, and reduced rectal cancer.

    PubMed

    Murtaugh, Maureen A; Curtin, Karen; Sweeney, Carol; Wolff, Roger K; Holubkov, Richard; Caan, Bette J; Slattery, Martha L

    2007-03-01

    Little is known about the contribution of polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and the folate metabolism pathway in rectal cancer alone. Data were from participants in a case-control study conducted in Northern California and Utah (751 cases and 979 controls). We examined independent associations and interactions of folate, B vitamins, methionine, alcohol, and MTHFR polymorphisms (MTHFR C677T and A1298C) with rectal cancer. Dietary folate intake was associated with a reduction in rectal cancer OR 0.66, 95% CI 0.48-0.92 (>475 mcg day compared to < or = 322 mcg) as was a combination of nutrient intakes contributing to higher methyl donor status (OR 0.79, 95% CI 0.66-0.95). Risk was reduced among women with the 677 TT genotype (OR 0.54, 95% CI 0.30-0.9), but not men (OR 1.11, 95% CI 0.70-1.76) and with the 1298 CC genotype in combined gender analysis (OR 0.67, 95% CI 0.46-0.98). These data are consistent with a protective effect of increasing dietary folate against rectal cancer and suggest a protective role of the MTHFR 677 TT genotype in women and 1298 CC in men and women. Folate intake, low methyl donor status, and MTHFR polymorphisms may play independent roles in the etiology of rectal cancer. PMID:17245555

  12. Critical appraisal of laparoscopic vs open rectal cancer surgery

    PubMed Central

    Tan, Winson Jianhong; Chew, Min Hoe; Dharmawan, Angela Renayanti; Singh, Manraj; Acharyya, Sanchalika; Loi, Carol Tien Tau; Tang, Choong Leong

    2016-01-01

    AIM: To evaluate the long-term clinical and oncological outcomes of laparoscopic rectal resection (LRR) and the impact of conversion in patients with rectal cancer. METHODS: An analysis was performed on a prospective database of 633 consecutive patients with rectal cancer who underwent surgical resection. Patients were compared in three groups: Open surgery (OP), laparoscopic surgery, and converted laparoscopic surgery. Short-term outcomes, long-term outcomes, and survival analysis were compared. RESULTS: Among 633 patients studied, 200 patients had successful laparoscopic resections with a conversion rate of 11.1% (25 out of 225). Factors predictive of survival on univariate analysis include the laparoscopic approach (P = 0.016), together with factors such as age, ASA status, stage of disease, tumor grade, presence of perineural invasion and vascular emboli, circumferential resection margin < 2 mm, and postoperative adjuvant chemotherapy. The survival benefit of laparoscopic surgery was no longer significant on multivariate analysis (P = 0.148). Neither 5-year overall survival (70.5% vs 61.8%, P = 0.217) nor 5-year cancer free survival (64.3% vs 66.6%, P = 0.854) were significantly different between the laparoscopic group and the converted group. CONCLUSION: LRR has equivalent long-term oncologic outcomes when compared to OP. Laparoscopic conversion does not confer a worse prognosis. PMID:27358678

  13. Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Smith, J. Joshua; Garcia-Aguilar, Julio

    2015-01-01

    Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

  14. Neoadjuvant-intensified treatment for rectal cancer: Time to change?

    PubMed Central

    Musio, Daniela; De Felice, Francesca; Bulzonetti, Nadia; Guarnaccia, Roberta; Caiazzo, Rossella; Bangrazi, Caterina; Raffetto, Nicola; Tombolini, Vincenzo

    2013-01-01

    AIM: To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer. METHODS: Between January 2007 and December 2011, 80 patients with histologically confirmed rectal adenocarcinoma were enrolled. Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes. Patients received intensified combined modality treatment, consisting of neoadjuvant radiation therapy (50.4-54.0 Gy) and infusional chemotherapy (oxaliplatin 50 mg/m2) on the first day of each week, plus five daily continuous infusions of fluorouracil (200 mg/m2 per die) from the first day of radiation therapy until radiotherapy completion. Patients received five or six cycles of oxaliplatin based on performance status, clinical lymph node involvement, and potential risk of a non-sphincter-conserving surgical procedure. Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment; adjuvant chemotherapy treatment was left to the oncologist’s discretion and was recommended in patients with positive lymph nodes. After treatment, all patients were monitored every three months for the first year and every six months for the subsequent years. RESULTS: Of the 80 patients enrolled, 75 patients completed the programmed neoadjuvant radiochemotherapy treatment. All patients received the radiotherapy prescribed total dose; five patients suspended chemotherapy indefinitely because of chemotherapy-related toxicity. At least five cycles of oxaliplatin were administered to 73 patients. Treatment was well tolerated with high compliance and a good level of toxicity. Most of the acute toxic effects observed were classified as grades 1-2. Proctitis grade 2 was the most common symptom (63.75%) and the earliest manifestation of acute toxicity. Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three

  15. Treatment of rectal cancer metastases to the thyroid gland: report of two cases.

    PubMed

    Cheung, Winson Y; Brierley, James; Mackay, Helen J

    2008-07-01

    Rectal cancer rarely metastasizes to the thyroid gland. When it does, however, it poses particular problems with regard to diagnosis and management. Case reports to date support a first-line surgical approach alone or in combination with radiation therapy. Despite the use of these treatment modalities, the presence of thyroid metastasis is associated with a very poor prognosis and significant morbidity. Herein, we review the literature and report on 2 cases of rectal carcinoma metastatic to the thyroid gland that were treated with oxaliplatin-containing chemotherapy regimens. In both cases, the patients responded well to combination chemotherapy up front or after previous surgery and chemoradiation. The favorable survival and symptom benefits observed in these patients suggest that combination chemotherapy should be considered in the management of these very rare cases. PMID:18650197

  16. Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: results of the branch trial

    PubMed Central

    Avallone, Antonio; Pecori, Biagio; Bianco, Franco; Aloj, Luigi; Tatangelo, Fabiana; Romano, Carmela; Granata, Vincenza; Marone, Pietro; Leone, Alessandra; Botti, Gerardo; Petrillo, Antonella; Caracò, Corradina; Iaffaioli, Vincenzo R.; Muto, Paolo; Romano, Giovanni; Comella, Pasquale; Budillon, Alfredo; Delrio, Paolo

    2015-01-01

    Background We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy. Patients and methods This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate. Results The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%–65%). Neutropenia was the most common grade ≥3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%–89%) and 85% (95%CI, 69%–93%), respectively, for the sequential-schedule. Conclusions These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC. PMID:26320185

  17. Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

    PubMed Central

    Glynne-Jones, R; Grainger, J; Harrison, M; Ostler, P; Makris, A

    2006-01-01

    Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered

  18. Watch and wait approach to rectal cancer: A review.

    PubMed

    Pozo, Marcos E; Fang, Sandy H

    2015-11-27

    In 2014, there were an estimated 136800 new cases of colorectal cancer, making it the most common gastrointestinal malignancy. It is the second leading cause of cancer death in both men and women in the United States and over one-third of newly diagnosed patients have stage III (node-positive) disease. For stage II and III colorectal cancer patients, the mainstay of curative therapy is neoadjuvant therapy, followed by radical surgical resection of the rectum. However, the consequences of a proctectomy, either by low anterior resection or abdominoperineal resection, can lead to very extensive comorbidities, such as the need for a permanent colostomy, fecal incontinence, sexual and urinary dysfunction, and even mortality. Recently, trends of complete regression of the rectal cancer after neoadjuvant chemoradiation therapy have been confirmed by clinical and radiographic evaluation-this is known as complete clinical response (cCR). The "watch and wait" approach was first proposed by Dr. Angelita Habr-Gama in Brazil in 2009. Those patients with cCR are followed with close surveillance physical examinations, endoscopy, and imaging. Here, we review management of rectal cancer, the development of the "watch and wait" approach and its outcomes. PMID:26649153

  19. Quality of life in rectal cancer surgery: What do the patient ask?

    PubMed Central

    De Palma, Giovanni D; Luglio, Gaetano

    2015-01-01

    Rectal cancer surgery has dramatically changed with the introduction of the total mesorectal excision (TME), which has demonstrated to significantly reduce the risk of local recurrence. The combination of TME with radiochemotherapy has led to a reduction of local failure to less than 5%. On the other hand, surgery for rectal cancer is also impaired by the potential for a significant loss in quality of life. This is a new challenge surgeons should think about nowadays: If patients live more, they also want to live better. The fight against cancer cannot only be based on survival, recurrence rate and other oncological endpoints. Patients are also asking for a decent quality of life. Rectal cancer is probably a paradigmatic example: Its treatment is often associated with the loss or severe impairment of faecal function, alteration of body anatomy, urogenital problems and, sometimes, intractable pain. The evolution of laparoscopic colorectal surgery in the last decades is an important example, which emphasizes the importance that themes like scar, recovery, pain and quality of life might play for patients. The attention to quality of life from both patients and surgeons led to several surgical innovations in the treatment of rectal cancer: Sphincter saving procedures, reservoir techniques (pouch and coloplasty) to mitigate postoperative faecal disorders, nerve-sparing techniques to reduce the risk for sexual dysfunction. Even more conservative procedures have been proposed alternatively to the abdominal-perineal resection, like the local excisions or transanal endoscopic microsurgery, till the possibility of a wait and see approach in selected cases after radiation therapy. PMID:26730279

  20. [Effect of preserving left colic artery during radical operation of rectal cancer on anastomotic leakage and operation time].

    PubMed

    Zang, Lu; Ma, Junjun; Zheng, Minhua

    2016-04-01

    Surgical treatment for rectal cancer has changed radically in recent years since the introduction of the principle of total mesorectal excision (TME) and technique of laparoscopic approach. The emphasis of management for vessels in laparoscopic TME surgery for rectal cancer is mainly focused on the inferior mesenteric artery (IMA) and its branches. Two alternatives of the level to execute the IMA are high ligation(without preservation of left colic artery, LCA) and low ligation (with preservation of LCA). In this article, we review the latest literature from China and foreign countries concerning this issue, and combine with our own experience to investigate the effect of LCA preserving on anastomotic leakage and operation time, which may provide a reference for proper choice of the management of IMA in rectal cancer surgery. PMID:27112468

  1. Pan FGFR Kinase Inhibitor BGJ398 and Combination Chemotherapy in Treating Patients With Untreated Metastatic Pancreatic Cancer

    ClinicalTrials.gov

    2016-05-19

    Colon Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Rectal Adenocarcinoma; Stage III Pancreatic 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 IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  2. Surgery for Locally Recurrent Rectal Cancer: Tips, Tricks, and Pitfalls.

    PubMed

    Warrier, Satish K; Heriot, Alexander G; Lynch, Andrew Craig

    2016-06-01

    Rectal cancer can recur locally in up to 10% of the patients who undergo definitive resection for their primary cancer. Surgical salvage is considered appropriate in the curative setting as well as select cases with palliative intent. Disease-free survival following salvage resection is dependent upon achieving an R0 resection margin. A clear understanding of applied surgical anatomy, appropriate preoperative planning, and a multidisciplinary approach to aggressive soft tissue, bony, and vascular resection with appropriate reconstruction is necessary. Technical tips, tricks, and pitfalls that may assist in managing these cancers are discussed and the roles of additional boost radiation and intraoperative radiation therapy in the management of such cancers are also discussed. PMID:27247536

  3. Infusional 5-Fluorouracil and ZD1839 (Gefitinib-Iressa) in Combination With Preoperative Radiotherapy in Patients With Locally Advanced Rectal Cancer: A Phase I and II Trial (1839IL/0092)

    SciTech Connect

    Valentini, Vincenzo; De Paoli, Antonino; Gambacorta, Maria Antonietta Mantini, Giovanna; Ratto, Carlo; Vecchio, Fabio Maria; Barbaro, Brunella; Innocente, Roberto; Rossi, Carlo; Boz, Giovanni; Barba, Maria Cristina; Frattegiani, Alessandro; Lupattelli, Marco; Doglietto, Giovan Battista

    2008-11-01

    Purpose: To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. Methods and Materials: Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. Results: A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). Conclusions: Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.

  4. Successful treatment of rectal cancer with perineal invasion: Three case reports

    PubMed Central

    KITAHARA, TOMOHIRO; UEMURA, MAMORU; HARAGUCHI, NAOTSUGU; NISHIMURA, JUNICHI; SHINGAI, TATSUSHI; HATA, TAISHI; TAKEMASA, ICHIRO; MIZUSHIMA, TSUNEKAZU; DOKI, YUICHIRO; MORI, MASAKI; YAMAMOTO, HIROFUMI

    2014-01-01

    Rectal cancer occasionally invades adjacent organs. However, rectal cancer with perineal invasion is uncommon and difficult to treat. Locally advanced colorectal cancer may be clinically treated with neoadjuvant therapy, followed by en bloc resection. Skin invasion may lead to tumor dissemination via cutaneous blood flow and lymphatic routes. There is currently no firm evidence regarding the treatment of these significantly advanced rectal cancers. In this study, we report 3 cases of rectal cancer with perineal invasion, successfully managed by multimodality treatment. Case 1 is a 52-year-old man with rectal cancer that had invaded the perineum; case 2 is a 38-year-old man with rectal cancer infiltrating the perineal skin and liver metastasis; and case 3 is a 50-year-old woman with rectal cancer and perineal invasion. All the cases were treated with radical excision. No severe complications were observed in the perioperative period. Case 2, in particular, was confirmed to remain alive 5 years after the surgery. Our experience suggests that multimodality treatment, including extended radical surgery, may be a feasible approach to the treatment of rectal cancer with perineal skin invasion. PMID:24940483

  5. Role of Magnetic Resonance Imaging in Primary Rectal Cancer-Standard Protocol and Beyond.

    PubMed

    Gourtsoyianni, Sofia; Papanikolaou, Nickolas

    2016-08-01

    New-generation magnetic resonance imaging (MRI) scanners with optimal phased-array body coils have contributed to obtainment of high-resolution T2-weighted turbo spin echo images in which visualization of anatomical details such as the mesorectal fascia and the bowel wall layers is feasible. Preoperative, locoregional staging of rectal cancer with MRI, considered standard of care nowadays, relies on these images for stratification of high-risk patients for local recurrence, patients most likely to benefit from neoadjuvant therapy, as well as patients who exhibit imaging features indicative of a high risk of metastatic disease. Functional imaging, including optimized for rectal cancer diffusion-weighted imaging and more recently use of dynamic contrast-enhanced MRI, combined with radiologists׳ rising level of familiarity regarding the assessment of reactive changes postchemoradiation treatment, have shown to increase MRI staging accuracy after neoadjuvant treatment. Our intention is to review already established standard protocols for primary rectal cancer and go through potential additional promising imaging tools. PMID:27342896

  6. Molecular Markers Predict Distant Metastases After Adjuvant Chemoradiation for Rectal Cancer

    SciTech Connect

    Kim, Jun Won; Kim, Yong Bae; Choi, Jun Jeong; Koom, Woong Sub; Kim, Hoguen; Kim, Nam-Kyu; Ahn, Joong Bae; Lee, Ikjae; Cho, Jae Ho; Keum, Ki Chang

    2012-12-01

    Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant

  7. Rectal wall sparing by dosimetric effect of rectal balloon used during Intensity-Modulated Radiation Therapy (IMRT) for prostate cancer

    SciTech Connect

    Teh, Bin S.

    2005-03-31

    The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-LokTM bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2 x 2-cm field size. The dose beyond the

  8. Generic Planning Target Margin for Rectal Cancer Treatment Setup Variation

    SciTech Connect

    Robertson, John M. Campbell, Jonathon P.; Yan Di

    2009-08-01

    Purpose: To calculate the generic planning target margin (GPTM) for patients receiving radiation therapy (RT) for rectal cancer placed in a prone position with a customized cradle for small-bowel exclusion. Methods and Materials: A total of 25 consecutive rectal cancer patients were treated for 25 or 28 fractions in a prone position using a cradle to maximize small bowel exclusion. Treatment planning computed tomography (CT) scans were used to create orthogonally digitally reconstructed radiographs (DRRs) for portal image registration, which were compared with daily portal images from an electronic portal-imaging device (EPID). Translation values needed to align the DRRs and EPIDs were recorded for the superior to inferior (SI), right to left (RL), and anterior to posterior (AP) directions, and used to calculate the GPTM using the four-parameter model. Age, weight, and body mass index were tested compared with the setup variation using a Pearson correlation and a t test for significance. Gender versus setup variation was compared with a t test. Results: A total of 1,723 EPID images were reviewed. The GPTM was 10 mm superior, 8 mm inferior, 7 mm RL and 10 mm AP. Age and gender were unrelated to setup variation. Weight was significantly associated with systematic AP variation (p < 0.05). BMI was significantly associated with systematic SI (p < 0.05) and AP (p < 0.01) variation and random RL variation (p < 0.05). Conclusions: The GPTM for rectal cancer is asymmetric with a maximum of 10 mm in the superior, anterior and posterior dimensions. Body mass index may effect setup variation. Research using advanced treatment planning should include these margins in the planning target volume definition.

  9. New approach to adjuvant radiotherapy in rectal cancer

    SciTech Connect

    Mohiuddin, M.; Dobelbower, R.R.; Kramer, S.

    1980-02-01

    A sandwich technique of adjuvant radiotherapy was used to treat twenty-three patients with rectal cancer. In this technique, low dose preoperative irradiation (500 rad in one treatment) was given to all patients followed by immediate surgery (usually an A-P resection); on the basis of histopathological findings, patients with stage B/sub 2/ and C rectal cancer were selectively given 4500 rad post-operative irradiation in 5 weeks. Nine patients had early lesions (stage A and B/sub 1/) and did not receive postoperative irradiation. Thirteen patients had stage B/sub 2/ and C disease and hence received the full course of postoperative irradiation. One patient was found to have liver metastasis at the time of surgery, and hence received only palliative therapy. Follow-up of these twenty-three patients ranges from 10 months to 24 months with a median follow-up of 15 months. Treatment was well-tolerated with few side effects. Only two of the twenty-two patients who were treated for cure have failed to date. Both patients had stage C/sub 2/ disease; one patient developed an anterior abdominal wall recurrence in the surgical scar 3 months post-treatment and the second patient developed brain and bone metastases. No patients have failed in the pelvis. We feel this technique of adjuvant therapy is a logical approach to the treatment of rectal cancer and has potential for improving survival. The rationale for this approach to adjuvant radiotherapy is discussed together with implications for survival.

  10. Causes and outcomes of emergency presentation of rectal cancer.

    PubMed

    Comber, Harry; Sharp, Linda; de Camargo Cancela, Marianna; Haase, Trutz; Johnson, Howard; Pratschke, Jonathan

    2016-09-01

    Emergency presentation of rectal cancer carries a relatively poor prognosis, but the roles and interactions of causative factors remain unclear. We describe an innovative statistical approach which distinguishes between direct and indirect effects of a number of contextual, patient and tumour factors on emergency presentation and outcome of rectal cancer. All patients diagnosed with rectal cancer in Ireland 2004-2008 were included. Registry information, linked to hospital discharge data, provided data on patient demographics, comorbidity and health insurance; population density and deprivation of area of residence; tumour type, site, grade and stage; treatment type and optimality; and emergency presentation and hospital caseload. Data were modelled using a structural equation model with a discrete-time survival outcome, allowing us to estimate direct and mediated effects of the above factors on hazard, and their inter-relationships. Two thousand seven hundred and fifty patients were included in the analysis. Around 12% had emergency presentations, which increased hazard by 80%. Affluence, private patient status and being married reduced hazard indirectly by reducing emergency presentation. Older patients had more emergency presentations, while married patients, private patients or those living in less deprived areas had fewer than expected. Patients presenting as an emergency were less likely to receive optimal treatment or to have this in a high caseload hospital. Apart from stage, emergency admission was the strongest determinant of poor survival. The factors contributing to emergency admission in this study are similar to those associated with diagnostic delay. The socio-economic gradient found suggests that patient education and earlier access to endoscopic investigation for public patients could reduce emergency presentation. PMID:27087482

  11. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    PubMed Central

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  12. Rectal metastasis from Breast cancer: A rare entity

    PubMed Central

    Ng, Cho Ee; Wright, Lucie; Pieri, Andrew; Belhasan, Anas; Fasih, Tarannum

    2015-01-01

    Introduction Breast cancer metastases occurs in around 50% of all presentation. It is the second most common type of cancer to metastasise to the GI tract but this only occurs in less than 1% of cases. Presentation of case We report a case that underwent treatment for invasive lobular cancer (ILC) of the breast and 5 years later was found to have rectal and peritoneal metastasis. She is currently receiving palliative management including chemotherapy in the form of weekly Paclitaxel (Taxol®) and stenting to relieve obstruction. Conclusion There should be high clinical suspicion of bowel metastasis in patients presenting with positive faecal occult blood with or without bowel symptoms even if the incidence is less <1% of metastases, particularly in cases where the initial breast tumour was large, with positive axillary nodes. PMID:26188979

  13. Local excision for early rectal cancer: transanal endoscopic microsurgery and beyond

    PubMed Central

    Althumairi, Azah A.

    2015-01-01

    The goal of treatment for early stage rectal cancer is to optimize oncologic control while minimizing the long-term impact of treatment on quality of life. The standard of care treatment for most stage I and II rectal cancers is radical surgery alone, specifically total mesorectal excision (TME). For early rectal cancers, this procedure is usually curative but can have a substantial impact on quality of life, including the possibility of permanent colostomy and the potential for short and long-term bowel, bladder, and sexual dysfunction. Given the morbidity associated with radical surgery, alternative approaches to management of early rectal cancer have been explored, including local excision (LE) via transanal excision (TAE) or transanal endoscopic microsurgery (TEM) and transanal minimally invasive surgery (TAMIS). Compared to the gold standard of radical surgery, local procedures for strictly selected early rectal cancers should lead to identical oncological results and even better outcomes regarding morbidity, mortality, and quality of life. PMID:26029457

  14. Pelvic intraoperative neuromonitoring during robotic-assisted low anterior resection for rectal cancer.

    PubMed

    Grade, Marian; Beham, Alexander W; Schüler, P; Kneist, Werner; Ghadimi, B Michael

    2016-06-01

    While the oncological outcome of patients with rectal cancer has been considerably improved within the last decades, anorectal, urinary and sexual functions remained impaired at high levels, regardless of whether radical surgery was performed open or laparoscopically. Consequently, intraoperative monitoring of the autonomic pelvic nerves with simultaneous electromyography of the internal anal sphincter and manometry of the urinary bladder has been introduced to advance nerve-sparing surgery and to improve functional outcome. Initial results suggested that pelvic neuromonitoring may result in better functional outcomes. Very recently, it has also been demonstrated that minimally invasive neuromonitoring is technically feasible. Because, to the best of our knowledge, pelvic neuromonitoring has not been performed during robotic surgery, we report the first case of robotic-assisted low anterior rectal resection combined with intraoperative monitoring of the autonomic pelvic nerves. PMID:26705113

  15. [A Case of Advanced Rectal Cancer Resected Successfully after Induction Chemotherapy with Modified FOLFOX6 plus Panitumumab].

    PubMed

    Yukawa, Yoshimi; Uchima, Yasutake; Kawamura, Minori; Takeda, Osami; Hanno, Hajime; Takayanagi, Shigenori; Hirooka, Tomoomi; Dozaiku, Toshio; Hirooka, Takashi; Aomatsu, Naoki; Hirakawa, Toshiki; Iwauchi, Takehiko; Nishii, Takafumi; Morimoto, Junya; Nakazawa, Kazunori; Takeuchi, Kazuhiro

    2016-05-01

    We report a case of advanced colon cancer that was effectively treated with mFOLFOX6 plus panitumumab combination chemotherapy. The patient was a 54-year-old man who had type 2 colon cancer of the rectum. An abdominal CT scan demonstrated rectal cancer with bulky lymph node metastasis and 1 hepatic node(rectal cancer SI[bladder retroperitoneum], N2M0H1P0, cStage IV). He was treated with mFOLFOX6 plus panitumumab as neoadjuvant chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and regional metastatic lymph nodes had reduced in size(rectal cancer A, N1H1P0M0, cStage IV). Anterior rectal resection with D3 nodal dissection and left lateral segmentectomy of the liver was performed. The histological diagnosis was tubular adenocarcinoma(tub2-1), int, INF a, pMP, ly0, v0, pDM0, pPM0, R0. He was treated with 4 courses of mFOLFOX6 after surgery. The patient has been in good health without a recurrence for 2 years and 5 months after surgery. This case suggests that induction chemotherapy with mFOLFOX6 plus panitumumab is a potentially effective regimen for advanced colon cancer. PMID:27210100

  16. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer

    SciTech Connect

    Rich, T.A.; Skibber, J.M.; Ajani, J.A.

    1995-07-15

    To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m{sup 2}/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. Posttreatment tumor stages were T1-2, N0 in 35%, T3, N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further. 22 refs., 2 figs., 3 tabs.

  17. Intra-tumor Genetic Heterogeneity in Rectal Cancer

    PubMed Central

    Hardiman, Karin M.; Ulintz, Peter J.; Kuick, Rork; Hovelson, Daniel H.; Gates, Christopher M.; Bhasi, Ashwini; Grant, Ana Rodrigues; Liu, Jianhua; Cani, Andi K.; Greenson, Joel; Tomlins, Scott; Fearon, Eric R.

    2015-01-01

    Colorectal cancer arises in part from the cumulative effects of multiple gene lesions. Recent studies in selected cancer types have revealed significant intra-tumor genetic heterogeneity and highlighted its potential role in disease progression and resistance to therapy. We hypothesized the existence of significant intra-tumor genetic heterogeneity in rectal cancers involving variations in localized somatic mutations and copy number abnormalities. Two or three spatially disparate regions from each of six rectal tumors were dissected and subjected to next-generation whole exome DNA sequencing, Oncoscan SNP arrays, and targeted confirmatory sequencing and analysis. The resulting data were integrated to define subclones using SciClone. Mutant-allele tumor heterogeneity (MATH) scores, mutant allele frequency correlation, and mutation percent concordance were calculated, and copy number analysis including measurement of correlation between samples was performed. Somatic mutations profiles in individual cancers were similar to prior studies, with some variants found in previously reported significantly mutated genes and many patient-specific mutations in each tumor. Significant intra-tumor heterogeneity was identified in the spatially disparate regions of individual cancers. All tumors had some heterogeneity but the degree of heterogeneity was quite variable in the samples studied. We found that 67–97% of exonic somatic mutations were shared among all regions of an individual’s tumor. The SciClone computational method identified 2 to 8 shared and unshared subclones in the spatially disparate areas in each tumor. MATH scores ranged from 7 to 41. Allele frequency correlation scores ranged from R2 = 0.69 to 0.96. Measurements of correlation between samples for copy number changes varied from R2 = 0.74 to 0.93. All tumors had some heterogeneity, but the degree was highly variable in the samples studied. The occurrence of significant intra-tumor heterogeneity may allow

  18. Prostatic irradiation is not associated with any measurable increase in the risk of subsequent rectal cancer

    SciTech Connect

    Kendal, Wayne S. . E-mail: wkendal@ottawahospital.on.ca; Eapen, Libni; MacRae, Robert; Malone, Shawn; Nicholas, Garth

    2006-07-01

    Purpose: To investigate a putative increased risk of rectal cancer subsequent to prostatic radiotherapy. Methods and Materials: In an analysis of the Surveillance, Epidemiology, and End Results registry, we compared men who had radiotherapy for prostatic carcinoma with those treated surgically and those treated with neither modality. Kaplan-Meier analyses for the time to failure from rectal cancer were performed between age-matched subgroups of the three cohorts. Cox proportional hazards analyses were performed to ascertain what influences might affect the incidence of subsequent rectal cancer. Results: In all, 33,831 men were irradiated, 167,607 were treated surgically, and 36,335 received neither modality. Rectal cancers developed in 243 (0.7%) of those irradiated (mean age, 70.7 years), 578 (0.3%) of those treated surgically (68.7 years), and 227 (0.8%) of those treated with neither modality (74.2 years). When age effects and the differences between the surgical and untreated cohorts were controlled for, we were unable to demonstrate any significant increased incidence of rectal cancer in men irradiated for prostatic cancer. Conclusions: An increased frequency of rectal cancer after prostatic irradiation, apparent on crude analysis, could be attributed to age confounding and other unmeasured confounders associated with prostate cancer treatment and rectal cancer risk.

  19. Early and late toxicity of radiotherapy for rectal cancer.

    PubMed

    Joye, Ines; Haustermans, Karin

    2014-01-01

    With the implementation of total mesorectal excision surgery and neoadjuvant (chemo) radiotherapy, the outcome of rectal cancer patients has improved and a substantial proportion of them have become long-term survivors. These advances come at the expense of radiation- and chemotherapy-related toxicity which remains an underestimated problem. Radiation-induced early toxicity in rectal cancer treatment mainly includes diarrhea, cystitis, and perineal dermatitis, while bowel dysfunction, fecal incontinence, bleeding, and perforation, genitourinary dysfunction, and pelvic fractures constitute the majority of late toxicity. It is now generally accepted that short-course radiotherapy (SCRT) and immediate surgery is associated with less early toxicity compared to conventionally fractionated chemoradiotherapy with delayed surgery. There are no significant differences in late toxicity between both treatment regimens. While there is hardly an increase in early toxicity after preoperative SCRT with immediate surgery, late toxicity is substantial compared to surgery alone. Early toxicity is more frequent when a longer interval between SCRT and surgery is used and is comparable to the toxicity observed with conventionally fractionated radiotherapy except that it occurs after the end of the radiotherapy. So far, randomized phase III trials failed to demonstrate a substantial gain in tumoural response when oxaliplatin or molecular agents are added to the multimodality treatment. Moreover, the addition of these drugs increases toxicity and remains therefore experimental. PMID:25103006

  20. Pilot Study of a Clinical Pathway Implementation in Rectal Cancer

    PubMed Central

    Uña, Esther; López-Lara, Francisco

    2010-01-01

    Background: Rectal cancer is a highly prevalent disease which needs a multidisciplinary approach to be treated. The absence of specific protocols implies a significant and unjustifiable variability among the different professionals involved in this disease. The purpose is to develop a clinical pathway based on the analysis process and aims to reduce this variability and to reduce unnecessary costs. Methods: We created a multidisciplinary team with contributors from every clinical area involved in the diagnosis and treatment in this disease. We held periodic meetings to agree on a protocol based on the best available clinical practice guidelines. Once we had agreed on the protocol, we implemented its use as a standard in our institution. Every patient older than 18 years who was diagnosed with rectal cancer was considered a candidate to be treated via the pathway. Results: We evaluated 48 patients during the course of this study. Every parameter measured was improved after the implementation of the pathway, except the proportion of patients with 12 nodes or more analysed. The perception that our patients had about this project was very good. Conclusions: Clinical pathways are needed to improve the quality of health care. This kind of project helps reduce hospital costs and optimizes the use of limited resources. On the other hand, unexplained variability is also reduced, with consequent benefits for the patients. PMID:21151842

  1. Robotic Versus Laparoscopic Resection for Mid and Low Rectal Cancers

    PubMed Central

    Salman, Bulent; Yuksel, Osman

    2016-01-01

    Background and Objectives: The current study was conducted to determine whether robotic low anterior resection (RLAR) has real benefit over laparoscopic low anterior resection (LLAR) in terms of surgical and early oncologic outcomes. Methods: We retrospectively analyzed data from 35 RLARs and 28 LLARs, performed for mid and low rectal cancers, from January 2013 through June 2015. Results: A total of 63 patients were included in the study. All surgeries were performed successfully. The clinicopathologic characteristics were similar between the 2 groups. Compared with the laparoscopic group, the robotic group had less intraoperative blood loss (165 vs. 120 mL; P < .05) and higher mean operative time (252 vs. 208 min; P < .05). No significant differences were observed in the time to flatus passage, length of hospital stay, and postoperative morbidity. Pathological examination of total mesorectal excision (TME) specimens showed that both circumferential resection margin and transverse (proximal and distal) margins were negative in the RLAR group. However, 1 patient each had positive circumferential resection margin and positive distal transverse margin in the LLAR group. The mean number of harvested lymph nodes was 27 in the RLAR group and 23 in the LLAR group. Conclusions: In our study, short-term outcomes of robotic surgery for mid and low rectal cancers were similar to those of laparoscopic surgery. The quality of TME specimens was better in the patients who underwent robotic surgery. However, the longer operative time was a limitation of robotic surgery. PMID:27081292

  2. Cutaneous Metastasis of Rectal Cancer: A Case Report and Literature Review

    PubMed Central

    Dehal, Ahmed; Patel, Sunal; Kim, Sean; Shapera, Emanuel; Hussain, Farabi

    2016-01-01

    Cutaneous metastasis of rectal cancer is rare. It typically indicates widespread disease and poor prognosis. We report an exceedingly rare case of rectal cancer with metastasis to the skin and review the literature on cutaneous metastasis of rectal cancer. A 47-year-old man presented with stage IV unresectable adenocarcinoma of the rectum and received palliative chemoradiation for local pain control. About a year later he developed extensive skin lesions involving the genital area, bilateral groin, and perineum. Biopsy specimen showed mucinous adenocarcinoma compatible with rectal origin. Palliative treatment with radiation therapy was initiated. The patient responded well to treatment and is still alive more than a year after diagnosis of cutaneous metastasis. Surgeons should maintain strong suspicion of cutaneous metastases when patients with rectal cancer have new or evolving skin lesions. PMID:26824966

  3. Proteogenomic characterization of human colon and rectal cancer

    SciTech Connect

    Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri; Wang, Sean; Wang, Pei; Kinsinger, Christopher; Rivers, Robert; Rodriguez, Henry; Townsend, Reid; Ellis, Matthew; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert; Liebler, Daniel

    2014-09-18

    We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.

  4. Rectal cancer and Fournier’s gangrene - current knowledge and therapeutic options

    PubMed Central

    Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

    2015-01-01

    Fournier’s gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects. PMID:26290629

  5. Heterogeneity of KRAS Mutation Status in Rectal Cancer

    PubMed Central

    Jo, Peter; König, Alexander; Schirmer, Markus; Kitz, Julia; Conradi, Lena-Christin; Azizian, Azadeh; Bernhardt, Markus; Wolff, Hendrik A.; Grade, Marian; Ghadimi, Michael; Ströbel, Philipp; Schildhaus, Hans-Ulrich; Gaedcke, Jochen

    2016-01-01

    Introduction Anti-EGFR targeted therapy is of increasing importance in advanced colorectal cancer and prior KRAS mutation testing is mandatory for therapy. However, at which occasions this should be performed is still under debate. We aimed to assess in patients with locally advanced rectal cancer whether there is intra-specimen KRAS heterogeneity prior to and upon preoperative chemoradiotherapy (CRT), and if there are any changes in KRAS mutation status due to this intervention. Materials and Methods KRAS mutation status analyses were performed in 199 tumor samples from 47 patients with rectal cancer. To evaluate the heterogeneity between different tumor areas within the same tumor prior to preoperative CRT, 114 biopsies from 34 patients (mean 3 biopsies per patient) were analyzed (pre-therapeutic intratumoral heterogeneity). For the assessment of heterogeneity after CRT residual tumor tissue (85 samples) from 12 patients (mean 4.2 tissue samples per patient) were analyzed (post-therapeutic intratumoral heterogeneity) and assessment of heterogeneity before and after CRT was evaluated in corresponding patient samples (interventional heterogeneity). Primer extension method (SNaPshot™) was used for initial KRAS mutation status testing for Codon 12, 13, 61, and 146. Discordant results by this method were reevaluated by using the FDA-approved KRAS Pyro Kit 24, V1 and the RAS Extension Pyro Kit 24, V1 Kit (therascreen® KRAS test). Results For 20 (43%) out of the 47 patients, a KRAS mutation was detected. With 12 out of 20, the majority of these mutations affected codon 35. We did not obtained evidence that CRT results in changes of the KRAS mutation pattern. In addition, no intratumoral heterogeneity in the KRAS mutational status could be proven. This was true for both the biopsies prior to CRT and the resection specimens thereafter. The discrepancy observed in some samples when using the SNaPshot™ assay was due to insufficient sensitivity of this technique upon

  6. Combination Chemotherapy and Bevacizumab With or Without RO4929097 in Treating Patients With Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2013-10-07

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  7. Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  8. Analysis of tumor-infiltrating gamma delta T cells in rectal cancer

    PubMed Central

    Rong, Liang; Li, Ke; Li, Rui; Liu, Hui-Min; Sun, Rui; Liu, Xiao-Yan

    2016-01-01

    AIM: To investigate the regulatory effect of Vδ1 T cells and the antitumor activity of Vδ2 T cells in rectal cancer. METHODS: Peripheral blood, tumor tissues and para-carcinoma tissues from 20 rectal cancer patients were collected. Naïve CD4 T cells from the peripheral blood of rectal cancer patients were purified by negative selection using a Naive CD4+ T Cell Isolation Kit II (Miltenyi Biotec). Tumor tissues and para-carcinoma tissues were minced into small pieces and digested in a triple enzyme mixture containing collagenase type IV, hyaluronidase, and deoxyribonuclease for 2 h at room temperature. After digestion, the cells were washed twice in RPMI1640 and cultured in RPMI1640 containing 10% human serum supplemented with L-glutamine and 2-mercaptoethanol and 1000 U/mL of IL-2 for the generation of T cells. Vδ1 T cells and Vδ2 T cells from tumor tissues and para-carcinoma tissues were expanded by anti-TCR γδ antibodies. The inhibitory effects of Vδ1 T cells on naïve CD4 T cells were analyzed using the CFSE method. The cytotoxicity of Vδ2 T cells on rectal cancer lines was determined by the LDH method. RESULTS: The percentage of Vδ1 T cells in rectal tumor tissues from rectal cancer patients was significantly increased, and positively correlated with the T stage. The percentage of Vδ2 T cells in rectal tumor tissues from rectal cancer patients was significantly decreased, and negatively correlated with the T stage. After culture for 14 d with 1 μg/mL anti-TCR γδ antibodies, the percentage of Vδ1 T cells from para-carcinoma tissues was 21.45% ± 4.64%, and the percentage of Vδ2 T cells was 38.64% ± 8.05%. After culture for 14 d, the percentage of Vδ1 T cells from rectal cancer tissues was 67.45% ± 11.75% and the percentage of Vδ2 T cells was 8.94% ± 2.85%. Tumor-infiltrating Vδ1 T cells had strong inhibitory effects, and tumor-infiltrating Vδ2 T cells showed strong cytolytic activity. The inhibitory effects of Vδ1 T cells from para

  9. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Hong, Theodore S.; Moughan, Jennifer; Garofalo, Michael C.; Bendell, Johanna; Berger, Adam C.; Oldenburg, Nicklas B.E.; Anne, Pramila Rani; Perera, Francisco; Jabbour, Salma K.; Nowlan, Adam; DeNittis, Albert; Crane, Christopher

    2015-09-01

    Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

  10. Current treatment of rectal cancer adapted to the individual patient

    PubMed Central

    Cerezo, Laura; Ciria, Juan Pablo; Arbea, Leire; Liñán, Olga; Cafiero, Sergio; Valentini, Vincenzo; Cellini, Francesco

    2013-01-01

    Preoperative radiochemotherapy and total mesorectal excision surgery is a recommended standard therapy for patients with locally advanced rectal cancer. However, some subgroups of patients benefit more than others from this approach. In order to avoid long-term complications of radiation and chemotherapy, efforts are being made to subdivide T3N0 stage using advanced imaging techniques, and to analyze prognostic factors that help to define subgroup risk patients. Long-course radiochemotherapy has the potential of downsizing the tumor before surgery and may increase the chance of sphincter preservation in some patients. Short-course radiotherapy (SCRT), on the other hand, is a practical schedule that better suits patients with intermediated risk tumors, located far from the anal margin. SCRT is also increasingly being used among patients with disseminated disease, before resection of the rectal tumor. Improvements in radiation technique, such as keeping the irradiation target below S2/S3 junction, and the use of IMRT, can reduce the toxicity associated with radiation, specially long-term small bowel toxicity. PMID:24416579

  11. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer.

    PubMed

    Gollins, S; Sebag-Montefiore, D

    2016-02-01

    Improved surgical technique plus selective preoperative radiotherapy have decreased rectal cancer pelvic local recurrence from, historically, 25% down to about 5-10%. However, this improvement has not reduced distant metastatic relapse, which is the main cause of death and a key issue in rectal cancer management. The current standard is local pelvic treatment (surgery ± preoperative radiotherapy) followed by adjuvant chemotherapy, depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline magnetic resonance imaging, downstaging long-course preoperative chemoradiation (LCPCRT) is generally used. However, for non-CRM-threatened disease, varying approaches are currently adopted in the UK, including straight to surgery, short-course preoperative radiotherapy and LCPCRT. Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating preoperative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full-dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse. Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy-based schedules. Although several measures of neoadjuvant treatment response assessment based on imaging or pathology are promising predictive biomarkers for long-term survival, none has been validated in prospective phase III studies. The phase III setting will enable this, also providing translational opportunities to examine molecular predictors of response and survival. PMID:26645661

  12. Total mesorectal excision for the treatment of rectal cancer

    PubMed Central

    Zedan, Ali; Salah, Tareq

    2015-01-01

    Introduction In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. Methods This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan’s technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. Results One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan’s technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was

  13. Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

    ClinicalTrials.gov

    2013-05-01

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; 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 IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  14. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    PubMed

    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. PMID:27103578

  15. Advancing Techniques of Radiation Therapy for Rectal Cancer.

    PubMed

    Patel, Sagar A; Wo, Jennifer Y; Hong, Theodore S

    2016-07-01

    Since the advent of radiation therapy for rectal cancer, there has been continual investigation of advancing technologies and techniques that allow for improved dose conformality to target structures while limiting irradiation of surrounding normal tissue. For locally advanced disease, intensity modulated and proton beam radiation therapy both provide more highly conformal treatment volumes that reduce dose to organs at risk, though the clinical benefit in terms of toxicity reduction is unclear. For early stage disease, endorectal contact therapy and high-dose rate brachytherapy may be a definitive treatment option for patients who are poor operative candidates or those with low-lying tumors that desire sphincter-preservation. Finally, there has been growing evidence that supports stereotactic body radiotherapy as a safe and effective salvage treatment for the minority of patients that locally recur following trimodality therapy for locally advanced disease. This review addresses these topics that remain areas of active clinical investigation. PMID:27238474

  16. Adjuvant chemotherapy for rectal cancer: Is it needed?

    PubMed Central

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  17. Radiofrequency thermal treatment with chemoradiotherapy for advanced rectal cancer

    PubMed Central

    SHOJI, HISANORI; MOTEGI, MASAHIKO; OSAWA, KIYOTAKA; OKONOGI, NORIYUKI; OKAZAKI, ATSUSHI; ANDOU, YOSHITAKA; ASAO, TAKAYUKI; KUWANO, HIROYUKI; TAKAHASHI, TAKEO; OGOSHI, KYOJI

    2016-01-01

    We previously reported that patients with a clinical complete response (CR) following radiofrequency thermal treatment exhibit significantly increased body temperature compared with other groups, whereas patients with a clinical partial response or stable disease depended on the absence or presence of output limiting symptoms. The aim of this study was to evaluate the correlation among treatment response, Hidaka radiofrequency (RF) output classification (HROC: termed by us) and changes in body temperature. From December 2011 to January 2014, 51 consecutive rectal cancer cases were included in this study. All patients underwent 5 RF thermal treatments with concurrent chemoradiation. Patients were classified into three groups based on HROC: with ≤9, 10–16, and ≥17 points, calculated as the sum total points of five treatments. Thirty-three patients received surgery 8 weeks after treatment, and among them, 32 resected specimens were evaluated for histological response. Eighteen patients did not undergo surgery, five because of progressive disease (PD) and 13 refused because of permanent colostomy. We demonstrated that good local control (ypCR + CR + CRPD) was observed in 32.7% of cases in this study. Pathological complete response (ypCR) was observed in 15.7% of the total 51 patients and in 24.2% of the 33 patients who underwent surgery. All ypCR cases had ≥10 points in the HROC, but there were no patients with ypCR among those with ≤9 points in the HROC. Standardization of RF thermal treatment was performed safely, and two types of patients were identified: those without or with increased temperatures, who consequently showed no or some benefit, respectively, for similar RF output thermal treatment. We propose that the HROC is beneficial for evaluating the efficacy of RF thermal treatment with chemoradiation for rectal cancer, and the thermoregulation control mechanism in individual patients may be pivotal in predicting the response to RF thermal treatment

  18. MRI for evaluation of treatment response in rectal cancer.

    PubMed

    Blazic, Ivana M; Campbell, Naomi M; Gollub, Marc J

    2016-08-01

    MRI plays an increasingly pivotal role in the clinical staging of rectal cancer in the baseline and post-treatment settings. An accurate evaluation of response to neoadjuvant treatment is crucial because of its major influence on patient management and quality of life. However, evaluation of treatment response is challenging for both imaging and clinical assessments owing to treatment-related inflammation and fibrosis. At one end of the spectrum are clinical yT4 rectal cancers, wherein precise post-treatment MRI evaluation of tumour spread is particularly important for avoiding unnecessary exenterative surgery. At the other extreme, for tumours with clinical near-complete response or clinical complete response to neoadjuvant treatment, less invasive treatment may be suitable instead of the standard surgical approach such as, for example, a "Watch and Wait" approach or perhaps local excision. Ideally, the goal of post-treatment MRI evaluation would be to identify these subgroups of patients so that they might be spared unnecessary surgical intervention. It is known that post-chemoradiation therapy restaging using conventional MR sequences is less accurate than baseline staging, particularly in confirming T0 disease, largely owing to the difficulty in distinguishing fibrosis, oedema and normal mucosa from small foci of residual tumour. However, there is a growing utilization of multiparametric MRI, which has superseded other types of evaluations and requires review and periodic re-evaluation. This commentary discusses the current status of multiparametric MRI in the post-treatment setting and the challenges facing imaging in general in the accurate determination of treatment response. PMID:27331883

  19. Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer*

    PubMed Central

    Kerns, Sarah L.; Stock, Richard; Stone, Nelson N.; Blacksburg, Seth R.; Rath, Lynda; Vega, Ana; Fachal, Laura; Gómez-Caamaño, Antonio; De Ruysscher, Dirk; Lammering, Guido; Parliament, Matthew; Blackshaw, Michael; Sia, Michael; Cesaretti, Jamie; Terk, Mitchell; Hixson, Rosetta; Rosenstein, Barry S.; Ostrer, Harry

    2013-01-01

    Background and Purpose Rectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict for rectal bleeding, and genetic factors may be important. Materials and Methods A genome-wide association study (GWAS) was performed to identify SNPs associated with development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites. Results rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined p-values 5.4×10−8 and 6.9×10−7 respectively). Several other SNPs had p-values trending towards genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers’ d = 5.0×10−12 in the replication cohort). Conclusions This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified. PMID:23719583

  20. Severe rectal injury following radiation for prostatic cancer

    SciTech Connect

    Green, N.; Goldberg, H.; Goldman, H.; Lombardo, L.; Skaist, L.

    1984-04-01

    Between 1970 and 1981, 348 patients underwent definitive irradiation. Of these patients 6 (1.7 per cent) sustained severe rectal injury as manifest by major rectal bleeding, rectal stricture, rectal mucosal slough and rectal ulceration. Severe rectal injury was observed in 0 of 13 patients (0 per cent) treated with 125iodine, 3 of 329 (1 per cent) treated with 6,400 to 6,800 rad external irradiation, 2 of 39 (5 per cent) treated with 7,000 to 7,300 rad external irradiation, and 1 of 7 (14 per cent) treated with 198gold and external irradiation. The impact of radiation dose, radiation therapy technique and surgical trauma was assessed. Rectal injury was managed by supportive measures in 2 patients and by diverting colostomy in 3 with benefit. One patient underwent abdominoperineal resection. A small bowel fistula and an intra-abdominal abscess developed, and the patient died.

  1. Quality of life after surgery for rectal cancer.

    PubMed

    Gavaruzzi, Teresa; Giandomenico, Francesca; Del Bianco, Paola; Lotto, Lorella; Perin, Alessandro; Pucciarelli, Salvatore

    2014-01-01

    Patients' health-related quality of life (HRQoL) is now considered a relevant clinical outcome. This study systematically reviewed articles published in the last 5 years, focusing on the impact of rectal cancer treatment on patients' HRQoL. Of the 477 articles retrieved, 56 met the inclusion criteria. The most frequently reported comparisons were between surgical procedures (21 articles), especially between sphincter-preserving and non-sphincter preserving surgery or between stoma and stoma-free patients (13 articles), and between multimodality therapies (11 articles). Additionally, twelve articles compared patients' and healthy controls' HRQoL as primary or secondary aim. The majority of the studies were observational (84 %), controlled (66 %), cross-sectional (54 %), prospective (100 %), with a sample of more than 100 patients (59 %), and with more than 60 % of patients treated with neoadjuvant therapy (50 %). The most frequently used instruments were the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30), its colorectal cancer specific module QLQ-CR38, and the Medical Outcomes Study Short-Form 36 items questionnaire. Findings from the included articles are summarised and commented, with a special focus on the comparison between surgical treatments, between irradiated and not-irradiated patients, and between patients and the general population. PMID:25103003

  2. Application of Laparoscopic Extralevator Abdominoperineal Excision in Locally Advanced Low Rectal Cancer

    PubMed Central

    Wang, Yan-Lei; Dai, Yong; Jiang, Jin-Bo; Yuan, Hui-Yang; Hu, San-Yuan

    2015-01-01

    Background: When compared with conventional abdominoperineal resection (APR), extralevator abdominoperineal excision (ELAPE) has been demonstrated to reduce the risk of local recurrence for the treatment of locally advanced low rectal cancer. Combined with the laparoscopic technique, laparoscopic ELAPE (LELAPE) has the potential to reduce invasion and hasten postoperative recovery. In this study, we aim to investigate the advantages of LELAPE in comparison with conventional APR. Methods: From October 2010 to February 2013, 23 patients with low rectal cancer (T3–4N0–2M0) underwent LELAPE; while during the same period, 25 patients were treated with conventional APR. The patient characteristics, intraoperative data, postoperative complications, and follow-up results were retrospectively compared and analyzed. Results: The basic patient characteristics were similar; but the total operative time for the LELAPE was longer than that of the conventional APR group (P = 0.014). However, the operative time for the perineal portion was comparable between the two groups (P = 0.328). The LELAPE group had less intraoperative blood loss (P = 0.022), a lower bowel perforation rate (P = 0.023), and a positive circumferential margin (P = 0.028). Moreover, the patients, who received the LELAPE, had a lower postoperative Visual Analog Scale, quicker recovery of bowel function (P = 0.001), and a shorter hospital stay (P = 0.047). However, patients in the LELAPE group suffered more chronic perineal pain (P = 0.002), which may be related to the coccygectomy (P = 0.033). Although the metastasis rate and mortality rate were similar between the two groups, the local recurrence rate of the LELAPE group was statistically improved (P = 0.047). Conclusions: When compared with conventional APR, LELAPE has the potential to reduce the risk of local recurrence, and decreases operative invasion for the treatment of locally advanced low rectal cancer. PMID:25963355

  3. Evaluation of preoperative serum markers for individual patient prognosis in stage I-III rectal cancer.

    PubMed

    Giessen, Clemens; Nagel, Dorothea; Glas, Maria; Spelsberg, Fritz; Lau-Werner, Ulla; Modest, Dominik Paul; Michl, Marlies; Heinemann, Volker; Stieber, Petra; Schulz, Christoph

    2014-10-01

    Several independent serum biomarkers have been proposed as prognostic and/or predictive markers for colorectal cancer (CRC). To this date, carcinoembryonic antigen (CEA) remains the only recommended serological CRC biomarker. The present retrospective analysis investigates the prognostic value of several serum markers. A total of 256 patients with rectal cancer underwent surgery for curative intent in a university cancer center between January 1988 and June 2007. Preoperative serum was retrospectively analyzed for albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin, bilirubin, CA 125, cancer antigen 19-9, cancer antigen 72-4 (CA 72-4), CEA, CRP, CYFRA 21-1, ferritin, gamma-glutamyl transpeptidase, glutamate oxaloacetate transanunase, glutamate pyruvate transaminase, hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate-dehydrogenase, serum amyloid A (SAA), and 25-hydroxyvitamin D. Cancer-specific survival (CSS) and disease-free survival (DFS) were estimated. Median follow-up time was 8.4 years. Overall 3- and 5-year CSS was 88.6 and 78.9 %, respectively. DFS rates were 72.8 % (3 years) and 67.5 % (5 years). Univariate analysis of CSS indicated aP, CA 72-4, CEA, and SAA as prognostic factors, while aP, CEA, and SAA were also prognostic with regard to DFS. Multivariate analysis confirmed SAA together with T and N stage as prognostic factors. According to UICC stage, CEA and SAA add prognostic value in stages II and III with regard to DFS and CSS, respectively. The combined use of CEA and SAA is able to identify patients with favorable and poor prognosis. In addition to tumor baseline parameters, routine analysis of SAA together with CEA provided markedly improved prognostic value on CSS and DFS in resected rectal cancer. PMID:25027407

  4. Multidisciplinary treatment of rectal cancer in 2014: where are we going?

    PubMed

    Vignali, Andrea; De Nardi, Paola

    2014-08-28

    In the present review we discuss the recent developments and future directions in the multimodal treatment of locally advanced rectal cancer, with respect to staging and re-staging modalities, to the current role of neoadjuvant chemo-radiation and to the conservative and more limited surgical approaches based on tumour response after neoadjuvant combined therapy. When initial tumor staging is considered a high accuracy has been reported for T pre-treatment staging, while preoperative lymph node mapping is still suboptimal. With respect to tumour re-staging, all the current available modalities still present a limited accuracy, in particular in defining a complete response. The role of short vs long-course radiotherapy regimens as well as the optimal time of surgery are still unclear and under investigation by means of ongoing randomized trials. Observational management or local excision following tumour complete response are promising alternatives to total mesorectal excision, but need further evaluation, and their use outside of a clinical trial is not recommended. The preoperative selection of patients who will benefit from neoadjuvant radiotherapy or not, as well as the proper identification of a clinical complete tumour response after combined treatment modalities,will influence the future directions in the treatment of locally advanced rectal cancer. PMID:25170209

  5. [Secondary retroperitoneal fibrosis in a 39-year-old man after rectal cancer].

    PubMed

    Jarosch, A; Tiller, M; Rohrbach, H; Leimbach, T; Schepp, W

    2016-05-01

    A 39-year-old man had been treated for rectal cancer 6 years ago by lower anterior resection of the rectum and perioperative radiochemotherapy. Since then follow-up had been unremarkable but now the patient presented with unspecific lower abdominal pain. The cause of the pain was identified as paraneoplastic retroperitoneal fibrosis secondary to metachronous pulmonary metastases of the rectal cancer. PMID:26895316

  6. Implementation of a Hospital-Based Quality Assessment Program for Rectal Cancer

    PubMed Central

    Hendren, Samantha; McKeown, Ellen; Morris, Arden M.; Wong, Sandra L.; Oerline, Mary; Poe, Lyndia; Campbell, Darrell A.; Birkmeyer, Nancy J.

    2014-01-01

    Purpose: Quality improvement programs in Europe have had a markedly beneficial effect on the processes and outcomes of rectal cancer care. The quality of rectal cancer care in the United States is not as well understood, and scalable quality improvement programs have not been developed. The purpose of this article is to describe the implementation of a hospital-based quality assessment program for rectal cancer, targeting both community and academic hospitals. Methods: We recruited 10 hospitals from a surgical quality improvement organization. Nurse reviewers were trained to abstract rectal cancer data from hospital medical records, and abstracts were assessed for accuracy. We conducted two surveys to assess the training program and limitations of the data abstraction. We validated data completeness and accuracy by comparing hospital medical record and tumor registry data. Results: Nine of 10 hospitals successfully performed abstractions with ≥ 90% accuracy. Experienced nurse reviewers were challenged by the technical details in operative and pathology reports. Although most variables had less than 10% missing data, outpatient testing information was lacking from some hospitals' inpatient records. This implementation project yielded a final quality assessment program consisting of 20 medical records variables and 11 tumor registry variables. Conclusion: An innovative program linking tumor registry data to quality-improvement data for rectal cancer quality assessment was successfully implemented in 10 hospitals. This data platform and training program can serve as a template for other organizations that are interested in assessing and improving the quality of rectal cancer care. PMID:24839288

  7. Evolution of imaging in rectal cancer: multimodality imaging with MDCT, MRI, and PET.

    PubMed

    Raman, Siva P; Chen, Yifei; Fishman, Elliot K

    2015-04-01

    Magnetic resonance imaging (MRI), multidetector computed tomography (MDCT), and positron emission tomography (PET) are complementary imaging modalities in the preoperative staging of patients with rectal cancer, and each offers their own individual strengths and weaknesses. MRI is the best available radiologic modality for the local staging of rectal cancers, and can play an important role in accurately distinguishing which patients should receive preoperative chemoradiation prior to total mesorectal excision. Alternatively, both MDCT and PET are considered primary modalities when performing preoperative distant staging, but are limited in their ability to locally stage rectal malignancies. This review details the role of each of these three modalities in rectal cancer staging, and how the three imaging modalities can be used in conjunction. PMID:25830037

  8. Evolution of imaging in rectal cancer: multimodality imaging with MDCT, MRI, and PET

    PubMed Central

    Chen, Yifei; Fishman, Elliot K.

    2015-01-01

    Magnetic resonance imaging (MRI), multidetector computed tomography (MDCT), and positron emission tomography (PET) are complementary imaging modalities in the preoperative staging of patients with rectal cancer, and each offers their own individual strengths and weaknesses. MRI is the best available radiologic modality for the local staging of rectal cancers, and can play an important role in accurately distinguishing which patients should receive preoperative chemoradiation prior to total mesorectal excision. Alternatively, both MDCT and PET are considered primary modalities when performing preoperative distant staging, but are limited in their ability to locally stage rectal malignancies. This review details the role of each of these three modalities in rectal cancer staging, and how the three imaging modalities can be used in conjunction. PMID:25830037

  9. The effect of a combination of rectal diclofenac and caudal bupivacaine on postoperative analgesia in children.

    PubMed

    Gadiyar, V; Gallagher, T M; Crean, P M; Taylor, R H

    1995-09-01

    Both caudal anaesthesia and non-steroidal anti-inflammatory drugs have been used in the management of postoperative pain in children. The aim of the present study was to evaluate the combination of caudal analgesia and rectally administered diclofenac in the treatment of pain following minor surgery in children. Thirty-nine, ASA grade 1 or 2, children undergoing inguinal or penoscrotal surgery were randomly assigned to receive either a caudal block using 0.125% bupivacaine with adrenaline or a similar caudal block in combination with rectally administered diclofenac 1 mg.kg-1. Children given a caudal block alone were more likely to need analgesia in the first 24 h postoperatively. It would appear that the combination of a caudal block and rectal diclofenac in children undergoing minor lower abdominal surgery reduces the need for subsequent analgesia. PMID:7573879

  10. FXYD-3 expression in relation to local recurrence of rectal cancer

    PubMed Central

    Arbman, Gunnar; Sun, Xiao-Feng; Edler, David; Syk, Erik; Hallbook, Olof

    2016-01-01

    Purpose In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. Materials and Methods FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81). Results Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without. Conclusion Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence. PMID:27104167

  11. Radiofrequency thermal treatment with chemoradiotherapy for advanced rectal cancer.

    PubMed

    Shoji, Hisanori; Motegi, Masahiko; Osawa, Kiyotaka; Okonogi, Noriyuki; Okazaki, Atsushi; Andou, Yoshitaka; Asao, Takayuki; Kuwano, Hiroyuki; Takahashi, Takeo; Ogoshi, Kyoji

    2016-05-01

    We previously reported that patients with a clinical complete response (CR) following radiofrequency thermal treatment exhibit significantly increased body temperature compared with other groups, whereas patients with a clinical partial response or stable disease depended on the absence or presence of output limiting symptoms. The aim of this study was to evaluate the correlation among treatment response, Hidaka radiofrequency (RF) output classification (HROC: termed by us) and changes in body temperature. From December 2011 to January 2014, 51 consecutive rectal cancer cases were included in this study. All patients underwent 5 RF thermal treatments with concurrent chemoradiation. Patients were classified into three groups based on HROC: with ≤9, 10-16, and ≥17 points, calculated as the sum total points of five treatments. Thirty-three patients received surgery 8 weeks after treatment, and among them, 32 resected specimens were evaluated for histological response. Eighteen patients did not undergo surgery, five because of progressive disease (PD) and 13 refused because of permanent colostomy. We demonstrated that good local control (ypCR + CR + CRPD) was observed in 32.7% of cases in this study. Pathological complete response (ypCR) was observed in 15.7% of the total 51 patients and in 24.2% of the 33 patients who underwent surgery. All ypCR cases had ≥10 points in the HROC, but there were no patients with ypCR among those with ≤9 points in the HROC. Standardization of RF thermal treatment was performed safely, and two types of patients were identified: those without or with increased temperatures, who consequently showed no or some benefit, respectively, for similar RF output thermal treatment. We propose that the HROC is beneficial for evaluating the efficacy of RF thermal treatment with chemoradiation for rectal cancer, and the thermoregulation control mechanism in individual patients may be pivotal in predicting the response to RF

  12. Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer

    PubMed Central

    Andersen, Rikke Fredslund; Nielsen, Boye Schnack; Sørensen, Flemming Brandt; Appelt, Ane Lindegaard; Jakobsen, Anders; Hansen, Torben Frøstrup

    2016-01-01

    Introduction An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. Materials and Methods The expression of the investigated miRNAs was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27 patients with T3-4 rectal cancer. From each tumour, tissue from three different luminal localisations was examined. Inter- and intra-patient variability was assessed by calculating intraclass correlation coefficients (ICCs). Correlations between RT-qPCR and ISH were evaluated using Spearman’s correlation. Results ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%. The ICCmean (mean of three samples from each patient) was higher than 50% for miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH), miRNA-630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients, comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to 0.325 for the mean value from each patient, and from -0.085 to 0.515 in the section including the deepest part of the tumour. Conclusion Intratumoral heterogeneity may influence the measurement of miRNA expression and consequently the number of samples needed for representative estimates. Our findings with two different methods suggest that one sample is sufficient for adequate assessment of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of miRNA-125b, miRNA-145, and miRNA-630

  13. Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results

    SciTech Connect

    Czito, Brian G. . E-mail: czito001@mc.duke.edu; Bendell, Johanna C.; Willett, Christopher G.; Morse, Michael A.; Blobe, Gerard C.; Tyler, Douglas S.; Thomas, John; Ludwig, Kirk A.; Mantyh, Christopher R.; Ashton, Jill; Yu Daohai; Hurwitz, Herbert I.

    2007-06-01

    Purpose: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. Methods and Materials: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. Results: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m{sup 2} weekly, and capecitabine 625 mg/m{sup 2} bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. Conclusions: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further

  14. Use of Molecular Imaging to Predict Clinical Outcome in Patients With Rectal Cancer After Preoperative Chemotherapy and Radiation

    SciTech Connect

    Konski, Andre Li Tianyu; Sigurdson, Elin; Cohen, Steven J.; Small, William; Spies, Stewart; Yu, Jian Q.; Wahl, Andrew; Stryker, Steven; Meropol, Neal J.

    2009-05-01

    Purpose: To correlate changes in 2-deoxy-2-[18F]fluoro-D-glucose (18-FDG) positron emission tomography (PET) (18-FDG-PET) uptake with response and disease-free survival with combined modality neoadjuvant therapy in patients with locally advanced rectal cancer. Methods and Materials: Charts were reviewed for consecutive patients with ultrasound-staged T3x to T4Nx or TxN1 rectal adenocarcinoma who underwent preoperative chemoradiation therapy at Fox Chase Cancer Center (FCCC) or Robert H. Lurie Comprehensive Cancer Center of Northwestern University with 18-FDG-PET scanning before and after combined-modality neoadjuvant chemoradiation therapy . The maximum standardized uptake value (SUV) was measured from the tumor before and 3 to 4 weeks after completion of chemoradiation therapy preoperatively. Logistic regression was used to analyze the association of pretreatment SUV, posttreatment SUV, and % SUV decrease on pathologic complete response (pCR), and a Cox model was fitted to analyze disease-free survival. Results: A total of 53 patients (FCCC, n = 41, RLCCC, n = 12) underwent pre- and postchemoradiation PET scanning between September 2000 and June 2006. The pCR rate was 31%. Univariate analysis revealed that % SUV decrease showed a marginally trend in predicting pCR (p = 0.08). In the multivariable analysis, posttreatment SUV was shown a predictor of pCR (p = 0.07), but the test results did not reach statistical significance. None of the investigated variables were predictive of disease-free survival. Conclusions: A trend was observed for % SUV decrease and posttreatment SUV predicting pCR in patients with rectal cancer treated with preoperative chemoradiation therapy. Further prospective study with a larger sample size is warranted to better characterize the role of 18-FDG-PET for response prediction in patients with rectal cancer.

  15. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    SciTech Connect

    Kuremsky, Jeffrey G.; Tepper, Joel E.; McLeod, Howard L. Phar

    2009-07-01

    Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.

  16. The role of the robotic technique in minimally invasive surgery in rectal cancer

    PubMed Central

    Bianchi, Paolo Pietro; Luca, Fabrizio; Petz, Wanda; Valvo, Manuela; Cenciarelli, Sabine; Zuccaro, Massimiliano; Biffi, Roberto

    2013-01-01

    Laparoscopic rectal surgery is feasible, oncologically safe, and offers better short-term outcomes than traditional open procedures in terms of pain control, recovery of bowel function, length of hospital stay, and time until return to working activity. Nevertheless, laparoscopic techniques are not widely used in rectal surgery, mainly because they require a prolonged and demanding learning curve that is available only in high-volume and rectal cancer surgery centres experienced in minimally invasive surgery. Robotic surgery is a new technology that enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, promising to overcome some of the technical difficulties associated with standard laparoscopy. The aim of this review is to summarise the current data on clinical and oncological outcomes of minimally invasive surgery in rectal cancer, focusing on robotic surgery, and providing original data from the authors’ centre. PMID:24101946

  17. Selection Criteria for the Radical Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Davies, Mansel Leigh; Harris, Dean; Davies, Mark; Lucas, Malcolm; Drew, Peter; Beynon, John

    2011-01-01

    There are over 14,000 newly diagnosed rectal cancers per year in the United Kingdom of which between 50 and 64 percent are locally advanced (T3/T4) at presentation. Pelvic exenterative surgery was first described by Brunschwig in 1948 for advanced cervical cancer, but early series reported high morbidity and mortality. This approach was later applied to advanced primary rectal carcinomas with contemporary series reporting 5-year survival rates between 32 and 66 percent and to recurrent rectal carcinoma with survival rates of 22–42%. The Swansea Pelvic Oncology Group was established in 1999 and is involved in the assessment and management of advanced pelvic malignancies referred both regionally and UK wide. This paper will set out the selection, assessment, preparation, surgery, and outcomes from pelvic exenterative surgery for locally advanced primary rectal carcinomas. PMID:22312517

  18. Genotype and Phenotype Factors as Determinants for Rectal Stump Cancer in Patients With Familial Adenomatous Polyposis

    PubMed Central

    Bertario, Lucio; Russo, Antonio; Radice, Paolo; Varesco, Liliana; Eboli, Marco; Spinelli, Pasquale; Reyna, Arturo; Sala, Paola

    2000-01-01

    Objective To identify factors influencing the occurrence of cancer in the rectal remnant in patients with familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA). Summary Background Data The risk for rectal cancer in patients with FAP after colectomy and IRA remains a major concern. Methods Between 1955 and 1997, 371 patients (206 men, 165 women) from the Registry of Hereditary Colorectal Tumors underwent colectomy and IRA as a primary surgical procedure. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard models were fitted to assess the relative excess risk of rectal cancer and to control for confounding factors. A multivariate analysis was performed to assess the relation between cancer risk in the rectum and sex, age, number of rectal polyps, colon cancer, and APC germline mutation. Results Median follow-up was 81 months. Eighty-nine patients (24%) had colon cancer at the time of surgery. The APC mutation was found in 200 patients. In 27 patients, cancer developed in the retained rectum 1 to 26 years after surgery. The incidence of rectal carcinoma appears to increase with time: at 10, 15, and 20 years after surgery, the cumulative risk was 7.7%, 13.1%, and 23.0%, respectively. Multivariate analysis identified as independent predictors the presence of colon cancer at IRA and a mutation occurring between codons 1250 and 1464; both factors increased the risk nine times. Conclusions The presence of cancer at IRA and APC mutation type are the most important risk factors for the future development of cancer in the rectal remnant in patients with FAP. PMID:10749615

  19. Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Leenders, Max; Siersema, Peter D; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Bastide, Nadia; Fagherazzi, Guy; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Klinaki, Eleni; Masala, Giovanna; Grioni, Sara; Santucci De Magistris, Maria; Tumino, Rosario; Ricceri, Fulvio; Peeters, Petra H M; Lund, Eiliv; Skeie, Guri; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Navarro, Carmen; Ardanaz, Eva; Ohlsson, Bodil; Jirström, Karin; Van Guelpen, Bethany; Wennberg, Maria; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Romieu, Isabelle; Huybrechts, Inge; Cross, Amanda J; Murphy, Neil; Riboli, Elio; Bueno-de-Mesquita, H Bas

    2015-12-01

    Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely. PMID:26077137

  20. The radiation-induced changes in rectal mucosa: Hyperfractionated vs. hypofractionated preoperative radiation for rectal cancer

    SciTech Connect

    Starzewski, Jacek J.; Pajak, Jacek T.; Pawelczyk, Iwona; Lange, Dariusz; Golka, Dariusz . E-mail: dargolka@wp.pl; Brzeziska, Monika; Lorenc, Zbigniew

    2006-03-01

    Purpose: The purpose of the study was the qualitative and quantitative evaluation of acute radiation-induced rectal changes in patients who underwent preoperative radiotherapy according to two different irradiation protocols. Patients and Methods: Sixty-eight patients with rectal adenocarcinoma underwent preoperative radiotherapy; 44 and 24 patients underwent hyperfractionated and hypofractionated protocol, respectively. Fifteen patients treated with surgery alone served as a control group. Five basic histopathologic features (meganucleosis, inflammatory infiltrations, eosinophils, mucus secretion, and erosions) and two additional features (mitotic figures and architectural glandular abnormalities) of radiation-induced changes were qualified and quantified. Results: Acute radiation-induced reactions were found in 66 patients. The most common were eosinophilic and plasma-cell inflammatory infiltrations (65 patients), erosions, and decreased mucus secretion (54 patients). Meganucleosis and mitotic figures were more common in patients who underwent hyperfractionated radiotherapy. The least common were the glandular architectural distortions, especially in patients treated with hypofractionated radiotherapy. Statistically significant differences in morphologic parameters studied between groups treated with different irradiation protocols were found. Conclusion: The system of assessment is a valuable tool in the evaluation of radiation-induced changes in the rectal mucosa. A greater intensity of regenerative changes was found in patients treated with hyperfractionated radiotherapy.

  1. Rectal cancer: future directions and priorities for treatment, research and policy in New Zealand.

    PubMed

    Jackson, Christopher; Ehrenberg, Nieves; Frizelle, Frank; Sarfati, Diana; Balasingam, Adrian; Pearse, Maria; Parry, Susan; Print, Cristin; Findlay, Michael; Bissett, Ian

    2014-06-01

    New Zealand has one of the highest incidences of rectal cancer in the world, and its optimal management requires a multidisciplinary approach. A National Rectal Cancer Summit was convened in August 2013 to discuss management of rectal cancer in the New Zealand context, to highlight controversies and discuss domestic priorities for the future. This paper summarises the priorities for treatment, research and policy for rectal cancer services in New Zealand identified as part of the Summit in August. The following priorities were identified: - Access to high-quality information for service planning, review of outcomes, identification of inequities and gaps in provision, and quality improvement; - Engagement with the entire sector, including private providers; - Focus on equity; - Emerging technologies; - Harmonisation of best practice; - Importance of multidisciplinary team meetings. In conclusion, improvements in outcomes for patients with rectal cancer in New Zealand will require significant engagement between policy makers, providers, researchers, and patients in order to ensure equitable access to high quality treatment, and strategic incorporation of emerging technologies into clinical practice. A robust clinical information framework is required in order to facilitate monitoring of quality improvements and to ensure that equitable care is delivered. PMID:24929694

  2. [Three Cases of Stage Ⅳ Low Rectal Cancer with Lateral Pelvic Lymph Node Metastasis].

    PubMed

    Tamura, Hiroshi; Shimada, Yoshifumi; Yagi, Ryoma; Tajima, Yosuke; Okamura, Takuma; Nakano, Masato; Ishikawa, Takashi; Sakata, Jun; Kobayashi, Takashi; Kameyama, Hitoshi; Kosugi, Shin-ichi; Wakai, Toshifumi; Nogami, Hitoshi; Maruyama, Satoshi; Takii, Yasumasa

    2015-11-01

    Case 1: A 61-year-old man who had a diagnosis of low rectal cancer with lateral pelvic lymph node (LPLN) metastasis and multiple liver metastases underwent low anterior resection with LPLN dissection. The initial surgery was followed by chemotherapy, and then an extended right hepatectomy with partial resection of the liver was performed. Subsequently, a lung metastasis was detected, and the lung was partially resected. The patient was alive 9 years and 6 months after the initial operation. Case 2: A 53-year-old man had a diagnosis of low rectal cancer. After 5 courses of mFOLFOX6 plus bevacizumab, he underwent low anterior resection with LPLN dissection and resection of the peritoneal metastasis. The patient was alive 6 years and 3 months after the surgery without any signs of recurrence. Case 3: A 48-year-old man had a diagnosis of low rectal cancer and multiple liver metastases. He underwent low anterior resection with LPLN dissection and right hepatic lobectomy. He subsequently showed liver and lung metastases. The patient received systemic chemotherapy, and is alive with recurrent disease. We report 3 cases of Stage Ⅳ low rectal cancer with LPLN metastasis, and propose that LPLN dissection is important as a part of R0 resection for Stage Ⅳ low rectal cancer. PMID:26805345

  3. Technical feasibility of laparoscopic extended surgery beyond total mesorectal excision for primary or recurrent rectal cancer

    PubMed Central

    Akiyoshi, Takashi

    2016-01-01

    Relatively little is known about the oncologic safety of laparoscopic surgery for advanced rectal cancer. Recently, large randomized clinical trials showed that laparoscopic surgery was not inferior to open surgery, as evidenced by survival and local control rates. However, patients with T4 tumors were excluded from these trials. Technological advances in the instrumentation and techniques used by laparoscopic surgery have increased the use of laparoscopic surgery for advanced rectal cancer. High-definition, illuminated, and magnified images obtained by laparoscopy may enable more precise laparoscopic surgery than open techniques, even during extended surgery for T4 or locally recurrent rectal cancer. To date, the quality of evidence regarding the usefulness of laparoscopy for extended surgery beyond total mesorectal excision has been low because most studies have been uncontrolled series, with small sample sizes, and long-term data are lacking. Nevertheless, laparoscopic extended surgery for rectal cancer, when performed by specialized laparoscopic colorectal surgeons, has been reported safe in selected patients, with significant advantages, including a clear visual field and less blood loss. This review summarizes current knowledge on laparoscopic extended surgery beyond total mesorectal excision for primary or locally recurrent rectal cancer. PMID:26811619

  4. Slug expression enhances tumor formation in a non-invasive rectal cancer model

    PubMed Central

    Camp, E. Ramsay; Findlay, Victoria J.; Vaena, Silvia G.; Walsh, Jarret; Lewin, David N.; Turner, David P.; Watson, Dennis K

    2011-01-01

    Background Epithelial-to-mesenchymal transition (EMT) is a series of molecular changes allowing epithelial cancer cells to acquire properties of mesenchymal cells: increased motility and invasion and protection from apoptosis. Transcriptional regulators such as Slug mediate EMT, working in part to repress E-cadherin transcription. We report a novel, non-invasive in vivo rectal cancer model to explore the role of Slug in colorectal cancer (CRC) tumor development. Methods For the generation of DLD-1 cells overexpressing Slug (Slug DLD-1), a Slug or empty (Empty DLD-1) pCMV-3Tag-1 (kanamycin resistant) vector was used for transfection. Cells were evaluated for Slug and E-cadherin expression, and cell migration and invasion. For the in vivo study, colon cancer cells (parental DLD-1, Slug DLD-1, empty DLD-1, and HCT-116) were submucosally injected into the posterior rectum of nude mice using endoscopic guidance. After 28 days, tumors were harvested and tissue was analyzed. Results Slug expression in our panel of colon cancer cell lines was inversely correlated with E-cadherin expression and enhanced migration/invasion. Slug DLD-1 cells demonstrated a 21-fold increased Slug and 19-fold decreased E-cadherin expression compared with empty DLD-1. Similarly, the Slug DLD-1 cells had significantly enhanced cellular migration and invasion. In the orthotopic rectal cancer model, Slug DLD-1 cells formed rectal tumors in 9/10 (90%) of the mice (mean volume = 458 mm3) compared with only 1/10 (10%) with empty DLD-1 cells. Conclusion Slug mediates EMT with enhanced in vivo rectal tumor formation. Our non-invasive in vivo model enables researchers to explore the molecular consequences of altered genes in a clinically relevant rectal cancer in an effort to develop novel therapeutic approaches for patients with rectal cancer. PMID:21470622

  5. The Role of Dual-Time Combined 18-Fluorideoxyglucose Positron Emission Tomography and Computed Tomography in the Staging and Restaging Workup of Locally Advanced Rectal Cancer, Treated With Preoperative Chemoradiation Therapy and Radical Surgery

    SciTech Connect

    Capirci, Carlo Rubello, Domenico; Pasini, Felice; Galeotti, Fabrizio; Bianchini, Enzo; Del Favero, Giuseppe; Panzavolta, Riccardo; Crepaldi, Giorgio; Rampin, Lucia; Facci, Enzo; Gava, Marcello; Banti, Elena; Marano, Gianfranco

    2009-08-01

    Purpose: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. Methods and Materials: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300mg/m{sup 2}/day) followed 8-10 weeks later by surgery. All patients underwent [{sup 18}F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUV{sub max}), and percentage of SUV{sub max} difference (Response Index = RI) between pre- and post-CRT [{sup 18}F]FDG-PET scans were evaluated. Results: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUV{sub max} was significantly higher than post-CRT (15.8, vs 5.9; p < 0.001). The mean RI was significantly higher in responders than in nonresponder patients (71.3% vs 38%; p = 0.0038). Using a RI cut-off of 65% for defining response to therapy, the following parameters have been obtained: 84.5% sensitivity, 80% specificity, 81.4% positive predictive value, 84.2% negative predictive value, and 81% overall accuracy. Conclusion: These results suggest the potential role of [{sup 18}F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.

  6. Study shows colon and rectal tumors constitute a single type of cancer

    Cancer.gov

    The pattern of genomic alterations in colon and rectal tissues is the same regardless of anatomic location or origin within the colon or the rectum, leading researchers to conclude that these two cancer types can be grouped as one, according to The Cancer

  7. Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

    SciTech Connect

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed; Safran, Howard

    2012-01-01

    Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

  8. Diagnosis of rectal cancer by Tissue Resonance Interaction Method

    PubMed Central

    2010-01-01

    Background Since population screening has the potential to reduce mortality from rectal cancer (RC), novel methods with improved cost-effectiveness warrant consideration. In a previous pilot study, we found that the rapid, inexpensive and non-invasive electromagnetic detection of RC is a highly specific and sensitive technique. The aim of the present prospective study was to evaluate the prediction accuracy of electromagnetic detection of RC. Methods 304 eligible subjects were consecutively enrolled in our Institute and subjected to electromagnetic detection followed by colonoscopy and histopathologic analysis of biopsies. A putative RC carrier status was attributed to subjects showing an electromagnetic signal < 50 units (U). Results RC patients showed a significantly lower electromagnetic signal (40.9 ± 0.9 U; mean ± S.E.) than did non-RC subjects (79.2 ± 1.4 U; P < 2.2e-16). At a threshold < 50 U, electromagnetic detection identified 103 putative patients, whereas colonoscopy detected 108 patients, with an overlap of 91 patients between the two methods. The 15.7% false-negative rate by electromagnetic detection was brought to zero by raising the threshold value to 70 U; on the other hand, such a threshold increased the false-positive rate to 30%. Conclusion Electromagnetic detection of RC at a signal threshold < 70 U appears to eliminate false-negative results. Although colonoscopy would still be required in examining the false-positives associated with the < 70 U electromagnetic threshold, the need for this method would be reduced. Thus, electromagnetic detection represents a new accurate, rapid, simple, and inexpensive tool for early detection of RC that merits testing in large population-based programs. PMID:20462445

  9. Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

    PubMed

    Lim, S H; Chua, W; Henderson, C; Ng, W; Shin, J-S; Chantrill, L; Asghari, R; Lee, C S; Spring, K J; de Souza, P

    2015-10-01

    Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response. PMID:26032919

  10. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients

    PubMed Central

    Clavo, Bernardino; Santana-Rodriguez, Norberto; Llontop, Pedro; Gutierrez, Dominga; Ceballos, Daniel; Méndez, Charlin; Rovira, Gloria; Suarez, Gerardo; Rey-Baltar, Dolores; Garcia-Cabrera, Laura; Martínez-Sánchez, Gregorio; Fiuza, Dolores

    2015-01-01

    Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52–119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7–14) g/dL to 13 (10–15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation. PMID:26357522

  11. Transanal Total Mesorectal Excision With Single-Incision Laparoscopy for Rectal Cancer

    PubMed Central

    Foo, Dominic Chi-chung; Choi, Hok Kwok; Wei, Rockson; Yip, Jeremy

    2016-01-01

    Background and Objectives: There has been great enthusiasm for the technique of transanal total mesorectal excision. Coupled with this procedure, we performed single-incision laparoscopic surgery for left colon mobilization. This is a description of our initial experience with the combined approach. Methods: Patients with distal or mid rectal cancer were included. The operation was performed by 2 teams: one team performed the single-incision mobilization of the left colon via the right lower quadrant ileostomy site, and the other team performed the total mesorectal excision with a transanal platform. Results: During the study period, 10 patients (5 men) with cancer of the rectum underwent the surgery. The mean age was 62.2 ± 11.1 years, and the mean body mass index was 23.4 ± 3.2 kg/m2. The tumor's mean distance from the anal verge was 5.1 ± 2.5 cm. The median operating time was 247.5 minutes (range, 188–462 minutes). The mean estimated blood loss was 124 ± 126 mL (range, 10–188 mL). Conversion to multiport laparoscopy was needed in one case (10%). Postoperative pain, as reflected by the pain score, was minimal. The mean number of lymph nodes harvested was 15.6 ± 3.8. All specimens had clear distal and circumferential radial margins. The overall complication rate was 10%. Conclusion: Our experience showed transanal total mesorectal excision with single-incision laparoscopy to be a feasible option for rectal cancer. Patients reported minimal postoperative pain. Further studies on the long-term outcome are warranted. PMID:27186068

  12. Phase II Study of Preoperative Helical Tomotherapy With a Simultaneous Integrated Boost for Rectal Cancer

    SciTech Connect

    Engels, Benedikt; Tournel, Koen; Everaert, Hendrik; Hoorens, Anne; Sermeus, Alexandra; Christian, Nicolas; Storme, Guy; Verellen, Dirk; De Ridder, Mark

    2012-05-01

    Purpose: The addition of concomitant chemotherapy to preoperative radiotherapy is considered the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control (LC), but has no impact on survival or the incidence of distant metastases. In addition, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively, preoperative helical tomotherapy with a simultaneous integrated boost (SIB). Methods and Materials: A total of 108 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. Patients with an anticipated circumferential resection margin (CRM) of less than 2 mm, based on magnetic resonance imaging, received a SIB to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: A total of 102 patients presented with cT3-4 tumors; 57 patients entered the boost group and 51 the no-boost group. One patient in the no-boost group developed a radio-hypersensitivity reaction, resulting in a complete tumor remission, a Grade 3 acute and Grade 5 late enteritis. No other Grade {>=}3 acute toxicities occurred. With a median follow-up of 32 months, Grade {>=}3 late gastrointestinal and urinary toxicity were observed in 6% and 4% of the patients, respectively. The actuarial 2-year LC, progression-free survival and overall survival were 98%, 79%, and 93%. Conclusions: Preoperative helical tomotherapy displays a favorable acute toxicity profile in patients with cT3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and resulted in a promising LC.

  13. Surgery for Locally Advanced T4 Rectal Cancer: Strategies and Techniques.

    PubMed

    Helewa, Ramzi M; Park, Jason

    2016-06-01

    Locally advanced T4 rectal cancer represents a complex clinical condition that requires a well thought-out treatment plan and expertise from multiple specialists. Paramount in the management of patients with locally advanced rectal cancer are accurate preoperative staging, appropriate application of neoadjuvant and adjuvant treatments, and, above all, the provision of high-quality, complete surgical resection in potentially curable cases. Despite the advanced nature of this disease, extended and multivisceral resections with clear margins have been shown to result in good oncological outcomes and offer patients a real chance of cure. In this article, we describe the assessment, classification, and multimodality treatment of primary locally advanced T4 rectal cancer, with a focus on surgical planning, approaches, and outcomes. PMID:27247535

  14. A tensor-based population value decomposition to explain rectal toxicity after prostate cancer radiotherapy

    PubMed Central

    Ospina, Juan David; Commandeur, Frédéric; Ríos, Richard; Dréan, Gaël; Correa, Juan Carlos; Simon, Antoine; Haigron, Pascal; De Crevoisier, Renaud; Acosta, Oscar

    2013-01-01

    In prostate cancer radiotherapy the association between the dose distribution and the occurrence of undesirable side-effects is yet to be revealed. In this work a method to perform population analysis by comparing the dose distributions is proposed. The method is a tensor-based approach that generalises an existing method for 2D images and allows for the highlighting of over irradiated zones correlated with rectal bleeding after prostate cancer radiotherapy. Thus, the aim is to contribute to the elucidation of the dose patterns correlated with rectal toxicity. The method was applied to a cohort of 63 patients and it was able to build up a dose pattern characterizing the difference between patients presenting rectal bleeding after prostate cancer radiotherapy and those who did not. PMID:24579164

  15. [A Case of Lateral Lymph Node Recurrence Five-Years after Curative Surgery for Rectal Cancer].

    PubMed

    Hagihara, Kiyotaka; Miyake, Masakazu; Uemura, Mamoru; Miyazaki, Michihiko; Ikeda, Masataka; Maeda, Sakae; Yamamoto, Kazuyoshi; Hama, Naoki; Miyamoto, Atsushi; Omiya, Hideyasu; Nishikawa, Kazuhiro; Hirao, Motohiro; Takami, Koji; Nakamori, Shoji; Sekimoto, Mitsugu

    2015-11-01

    A 62-year-old woman had undergone laparoscopic abdominoperineal resection for rectal cancer in February 2008. The pathological diagnosis was pT2, pN0, M0, pStageⅠ. At her request, she took UFT for 5 years as adjuvant chemotherapy. A CT examination revealed lateral lymph node swelling in January 2014. She was referred to our hospital after a diagnosis of lateral lymph node recurrence. She was administered 6 courses of FOLFIRI plus Cmab as neoadjuvant chemotherapy, after which the tumor size reduced by 62%. The treatment effect was rated as a PR. Laparoscopic right intrapelvic lymph node dissection was performed in July 2014, and the pathological diagnosis was recurrence of rectal cancer in the lateral lymph nodes. We report a case of dissection of lymph node recurrence 5 years after curative surgery for rectal cancer, along with a literature review. PMID:26805111

  16. Definition and delineation of the clinical target volume for rectal cancer

    SciTech Connect

    Roels, Sarah; Duthoy, Wim; Haustermans, Karin . E-mail: Karin.Haustermans@uzleuven.be; Penninckx, Freddy; Vandecaveye, Vincent; Boterberg, Tom; Neve, Wilfried de

    2006-07-15

    Purpose: Optimization of radiation techniques to maximize local tumor control and to minimize small bowel toxicity in locally advanced rectal cancer requires proper definition and delineation guidelines for the clinical target volume (CTV). The purpose of this investigation was to analyze reported data on the predominant locations and frequency of local recurrences and lymph node involvement in rectal cancer, to propose a definition of the CTV for rectal cancer and guidelines for its delineation. Methods and Materials: Seven reports were analyzed to assess the incidence and predominant location of local recurrences in rectal cancer. The distribution of lymphatic spread was analyzed in another 10 reports to record the relative frequency and location of metastatic lymph nodes in rectal cancer, according to the stage and level of the primary tumor. Results: The mesorectal, posterior, and inferior pelvic subsites are most at risk for local recurrences, whereas lymphatic tumor spread occurs mainly in three directions: upward into the inferior mesenteric nodes; lateral into the internal iliac lymph nodes; and, in a few cases, downward into the external iliac and inguinal lymph nodes. The risk for recurrence or lymph node involvement is related to the stage and the level of the primary lesion. Conclusion: Based on a review of articles reporting on the incidence and predominant location of local recurrences and the distribution of lymphatic spread in rectal cancer, we defined guidelines for CTV delineation including the pelvic subsites and lymph node groups at risk for microscopic involvement. We propose to include the primary tumor, the mesorectal subsite, and the posterior pelvic subsite in the CTV in all patients. Moreover, the lateral lymph nodes are at high risk for microscopic involvement and should also be added in the CTV.

  17. Improved outcomes for rectal cancer in the era of preoperative chemoradiation and tailored mesorectal excision: a series of 338 consecutive cases.

    PubMed

    Pacelli, Fabio; Sanchez, Alejandro M; Covino, Marcello; Tortorelli, Antonio P; Bossola, Maurizio; Valentini, Vincenzo; Gambacorta, Maria A; Doglietto, Giovanni B

    2013-02-01

    Neoadjuvant chemoradiation (CRT), tailored mesorectal excision, and intraoperative radiotherapy (IORT) have become the leading measures for rectal cancer treatment. The objective of this study was to evaluate early and long-term results of a multimodal treatment model for rectal cancer followed by curative surgery. Prospectively collected hospital records of 338 patients surgically treated for rectal cancer between January 1998 and December 2008 were retrospectively reviewed. Patients with high rectum level cancers and those with middle and low rectum cancers with clinical stage T1 to T2 underwent surgery, whereas those with T3 to T4 and N+ disease at the middle and low rectum received neoadjuvant CRT in 96.2 per cent of cases. Short-course neoadjuvant radiotherapy was not considered for neoadjuvant treatment. Postoperative major complications and mortality rates were 12.7 and 2.3 per cent, respectively. Overall 5-year disease-specific and disease-free survival were 80 and 73.1 per cent, respectively, whereas local recurrence rate was 6.1 per cent. At multivariate analysis, nodal status and circumferential margin status were independently associated with poor survival; local recurrence rates were independently affected by nodal and marginal status and tumor stage. The extent of mesorectal excision should be tailored depending on tumor location and the use of neoadjuvant chemotherapy, combined with IORT in advanced middle and low rectal cancer, leading to remarkable tumor downstaging with excellent prognosis in responding patients. PMID:23336654

  18. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  19. Oxidative balance and colon and rectal cancer: interaction of lifestyle factors and genes.

    PubMed

    Slattery, Martha L; Lundgreen, Abbie; Welbourn, Bill; Wolff, Roger K; Corcoran, Christopher

    2012-06-01

    Pro-oxidant and anti-oxidant genetic and lifestyle factors can contribute to an individual's level of oxidative stress. We hypothesize that diet, lifestyle and genetic factors work together to influence colon and rectal cancer through an oxidative balance mechanism. We evaluated nine markers for eosinophil peroxidase (EPX), two for myeloperoxidase (MPO), four for hypoxia-inducible factor-1A (HIFIA), and 16 for inducible nitric oxide synthase (NOS2A) in conjunction with dietary antioxidants, aspirin/NSAID use, and cigarette smoking. We used data from population-based case-control studies (colon cancer n=1555 cases, 1956 controls; rectal cancer n=754 cases, 959 controls). Only NOS2A rs2297518 was associated with colon cancer (OR 0.86 95% CI 0.74, 0.99) and EPX rs2302313 and MPO rs2243828 were associated with rectal cancer (OR 0.75 95% CI 0.59, 0.96; OR 0.81 95% CI 0.67, 0.99 respectively) for main effects. However, after adjustment for multiple comparisons we observed the following significant interactions for colon cancer: NOS2A and lutein, EPX and aspirin/NSAID use, and NOS2A (4 SNPs) and cigarette smoking. For rectal cancer we observed the following interactions after adjustment for multiple comparisons: HIF1A and vitamin E, NOS2A (3SNPs) with calcium; MPO with lutein; HIF1A with lycopene; NOS2A with selenium; EPX and NOS2A with aspirin/NSAID use; HIF1A, MPO, and NOS2A (3 SNPs) with cigarette smoking. We observed significant interaction between a composite oxidative balance score and a polygenic model for both colon (p interaction 0.0008) and rectal cancer (p=0.0018). These results suggest the need to comprehensively evaluate interactions to assess the contribution of risk from both environmental and genetic factors. PMID:22531693

  20. Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity in Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Ippolito, Edy; Massaccesi, Mariangela; Digesu, Cinzia; Deodato, Francesco; Macchia, Gabriella; Pirozzi, Giuseppe Antonio; Cilla, Savino; Cuscuna, Daniele; Di Lallo, Alessandra; Mattiucci, Gian Carlo; Mantini, Giovanna; Pacelli, Fabio; Valentini, Vincenzo; Cellini, Numa; Ingrosso, Marcello; Morganti, Alessio Giuseppe

    2012-06-01

    Purpose: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Methods and Materials: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. Results: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade {>=}2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade {>=}2 clinical rectal late toxicity was higher in patients with grade {>=}2 (32% vs. 15 %, p = 0.02) or grade {>=}3 VRS telangiectasia (47% vs. 17%, p {<=} 0.01) and an overall VRS score of {>=}2 (31% vs. 16 %, p = 0.04) or {>=}3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Conclusions: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

  1. Preoperative CT versus diffusion weighted magnetic resonance imaging of the liver in patients with rectal cancer; a prospective randomized trial

    PubMed Central

    Løgager, Vibeke B.; Skjoldbye, Bjørn; Møller, Jakob M.; Lorenzen, Torben; Rasmussen, Vera L.; Thomsen, Henrik S.; Mollerup, Talie H.; Okholm, Cecilie; Rosenberg, Jacob

    2016-01-01

    Introduction. Colorectal cancer is one of the most frequent cancers in the world and liver metastases are seen in up to 19% of patients with colorectal cancers. Detection of liver metastases is not only vital for sufficient treatment and survival, but also for a better estimation of prognosis. The aim of this study was to evaluate the feasibility of diffusion weighted MRI of the liver as part of a combined MR evaluation of patients with rectal cancers and compare it with the standard preoperative evaluation of the liver with CT. Methods. Consecutive patients diagnosed with rectal cancers were asked to participate in the study. Preoperative CT and diffusion weighted MR (DWMR) were compared to contrast enhanced laparoscopic ultrasound (CELUS). Results. A total of 35 patients were included, 15 patients in Group-1 having the standard CT evaluation of the liver and 20 patients in Group-2 having the standard CT evaluation of the liver and DWMR of the liver. Compared with CELUS, the per-patient sensitivity/specificity was 50/100% for CT, and for DWMR: 100/94% and 100/100% for Reader 1 and 2, respectively. The per-lesion sensitivity of CT and DWMR were 17% and 89%, respectively compared with CELUS. Furthermore, one patient had non-resectable metastases after DWMR despite being diagnosed with resectable metastases after CT. Another patient was diagnosed with multiple liver metastases during CELUS, despite a negative CT-scan. Discussion. DWMR is feasible for preoperative evaluation of liver metastases. The current standard preoperative evaluation with CT-scan results in disadvantages like missed metastases and futile operations. We recommend that patients with rectal cancer, who are scheduled for MR of the rectum, should have a DWMR of the liver performed at the same time. PMID:26793420

  2. Preliminary experience of a predictive model to define rectal volume and rectal dose during the treatment of prostate cancer

    PubMed Central

    Falco, M D; D'Andrea, M; Fedele, D; Barbarino, R; Benassi, M; Giudice, E; Hamoud, E; Ingrosso, G; Ladogana, P; Santarelli, F; Tortorelli, G; Santoni, R

    2011-01-01

    Objectives The aim of this study was to define a method to evaluate the total dose delivered to the rectum during the whole treatment course in six patients undergoing irradiation for prostate cancer using an offline definition of organ motion with images from a cone beam CT (CBCT) scanner available on a commercial linear accelerator. Methods Patient set-up was verified using a volumetric three-dimensional CBCT scanner; 9–14 CBCT scans were obtained for each patient. Images were transferred to a commercial treatment planning system for offline organ motion analysis. The shape of the rectums were used to obtain a mean dose–volume histogram (), which was the average of the DVHs of the rectums as they appeared in each verification CBCT. A geometric model of an average rectum (AR) was produced using the rectal contours delineated on the CBCT scans (DVHAR). To check whether the first week of treatment was representative of the whole treatment course, we evaluated the DVHs related to only the first five CBCT scans ( and DVHAR5). Finally, the influence of a dietary protocol on the goodness of our results was considered. Results In all six patients the original rectal DVH for the planning CT scan showed higher values than all DVHs. Conclusion Although the application of the model to a larger set of patients is necessary to confirm this trend, reconstruction of a representative volume of the rectum throughout the entire treatment course seems feasible. PMID:21849366

  3. [Conversion Therapy of Initially Unresectable Rectal Cancer with Perforation via FOLFOX4 Chemotherapy].

    PubMed

    Yamada, Chizu; Ishikawa, Fumihiko; Nitta, Hiroshi; Fujita, Yoshihisa; Omoto, Hideyuki; Kamata, Shigeyuki; Ito, Hiroshi

    2015-11-01

    We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence. PMID:26805353

  4. New technique of transanal proctectomy with completely robotic total mesorrectal excision for rectal cancer.

    PubMed

    Gómez Ruiz, Marcos; Palazuelos, Carlos Manuel; Martín Parra, José Ignacio; Alonso Martín, Joaquín; Cagigas Fernández, Carmen; del Castillo Diego, Julio; Gómez Fleitas, Manuel

    2014-05-01

    Anterior resection with total mesorectal excision is the standard method of rectal cancer resection. However, this procedure remains technically difficult in mid and low rectal cancer. A robotic transanal proctectomy with total mesorectal excision and laparoscopic assistance is reported in a 57 year old male with BMI 32 kg/m2 and rectal adenocarcinoma T2N1M0 at 5 cm from the dentate line. Operating time was 420 min. Postoperative hospital stay was 6 days and no complications were observed. Pathological report showed a 33 cm specimen with ypT2N0 adenocarcinoma at 2 cm from the distal margin, complete TME and non affected circumferential resection margin. Robotic technology might reduce some technical difficulties associated with TEM/TEO or SILS platforms in transanal total mesorectal excision. Further clinical trials will be necessary to assess this technique. PMID:24589418

  5. Priapism secondary to penile metastasis of rectal cancer

    PubMed Central

    Park, Ji Chan; Lee, Wook Hyun; Kang, Min Kyu; Park, Suk Young

    2009-01-01

    Metastatic penile carcinoma is rare and usually originates from genitourinary tumors. The presenting symptoms or signs have been described as nonspecific except for priapism. Rectal adenocarcinoma is a very unusual source of metastatic penile carcinoma. We report a case of metastatic penile carcinoma that originated from the rectum. Symptomatic improvement occurred with palliative radiotherapy. PMID:19725161

  6. Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy

    SciTech Connect

    Pachkoria, Ketevan; Zhang Hong; Adell, Gunnar; Jarlsfelt, Ingvar; Sun Xiaofeng . E-mail: xiao-feng.sun@ibk.liu.se

    2005-11-01

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p {<=} 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors.

  7. Preoperative chemoradiotherapy followed by transanal local excision for T3 distal rectal cancer: A case report

    PubMed Central

    YEO, SEUNG-GU

    2016-01-01

    Local excision (LE) for rectal cancer is currently indicated for selected T1 stage tumors. However, preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves local disease control, but also leads to a decrease in the stage and size of the primary mural tumor, along with a decrease in the risk of regional lymphadenopathy. The present study reports the outcome of a patient with T3N0M0 rectal cancer who was treated with LE following preoperative CRT. The distal pole of the tumor was located 2 cm from the anal verge. Preoperative pelvic radiotherapy of 50.4 Gy was administered in 28 fractions. Chemotherapy using 5-fluorouracil and leucovorin was administered during the first and last weeks of radiotherapy. The tumor response to CRT, was found to be marked at 7 weeks after CRT completion, and a complete response was presumed clinically. Transanal full-thickness LE was performed, and pathological examination revealed the absence of residual cancer cells. After 30 months of close follow-up, the patient was alive with no evidence of disease, and treatment-associated severe toxicities were not observed. Although a longer follow-up period is required, this case report suggests that LE may also be a feasible alternative treatment for T3 rectal cancer, which exhibits a marked response to preoperative CRT, particularly in elderly and comorbid patients contraindicated for radical surgery, or patients who are reluctant to undergo sphincter-ablation surgery. PMID:27073466

  8. Increased number of negative lymph nodes is associated with improved cancer specific survival in pathological IIIB and IIIC rectal cancer treated with preoperative radiotherapy

    PubMed Central

    Li, Qingguo; Zhuo, Changhua; Cai, Guoxiang; Li, Dawei; Liang, Lei; Cai, Sanjun

    2014-01-01

    Preoperative radiation significantly decreases the number of retrieved lymph nodes (LNs) in rectal cancer, but little is known with respect to the prognostic significance of negative LN (NLN) counts under these circumstances. In this study, Surveillance, Epidemiology, and End Results Program (SEER)-registered ypIII stage rectal cancer patients, and patients from Fudan University Shanghai Cancer Center (FDSCC) were combined and analyzed. The results showed that the survival rate of patients with n (cutoff) or more NLNs increased gradually when n ranged from two to nine. After n reached 10 or greater, survival rates were approximately equivalent. Furthermore, the optimal cutoff value of 10 was validated as an independent prognostic factor in stage ypIIIB and ypIIIC patients by both univariate and multivariate analysis (P < 0.001); the number of NLNs could also stratify the prognosis of ypN(+) patients in more detail. Patients in the FDSCC set validated these findings and confirmed that NLN count was not decreased in the good tumor regression group relative to the poor tumor regression group. These results suggest that NLN count is an independent prognostic factor for ypIIIB and ypIIIC rectal cancer patients, and, together with the number of positive LNs, this will provide better prognostic information than the number of positive LNs alone. PMID:25514596

  9. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

    PubMed

    Di Valentin, T; Asmis, T; Asselah, J; Aubin, F; Aucoin, N; Berry, S; Biagi, J; Booth, C M; Burkes, R; Coburn, N; Colwell, B; Cripps, C; Dawson, L A; Dorreen, M; Frechette, D; Goel, R; Gray, S; Hammad, N; Jonker, D; Kavan, P; Maroun, J; Nanji, S; Roberge, D; Samson, B; Seal, M; Shabana, W; Simunovic, M; Snow, S; Tehfe, M; Thirlwell, M; Tsvetkova, E; Vickers, M; Vuong, T; Goodwin, R

    2016-02-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer. PMID:26966404

  10. Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers

    PubMed Central

    Di Valentin, T.; Asmis, T.; Asselah, J.; Aubin, F.; Aucoin, N.; Berry, S.; Biagi, J.; Booth, C.M.; Burkes, R.; Coburn, N.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Frechette, D.; Goel, R.; Gray, S.; Hammad, N.; Jonker, D.; Kavan, P.; Maroun, J.; Nanji, S.; Roberge, D.; Samson, B.; Seal, M.; Shabana, W.; Simunovic, M.; Snow, S.; Tehfe, M.; Thirlwell, M.; Tsvetkova, E.; Vickers, M.; Vuong, T.; Goodwin, R.

    2016-01-01

    The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17–19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer. PMID:26966404

  11. An individual patient data meta-analysis of adjuvant therapy with uracil–tegafur (UFT) in patients with curatively resected rectal cancer

    PubMed Central

    Sakamoto, J; Hamada, C; Yoshida, S; Kodaira, S; Yasutomi, M; Kato, T; Oba, K; Nakazato, H; Saji, S; Ohashi, Y

    2007-01-01

    Uracil–Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70–0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63–0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer. PMID:17375049

  12. Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

    PubMed

    Lascano, V; Hahne, M; Papon, L; Cameron, K; Röeder, C; Schafmayer, C; Driessen, L; van Eenennaam, H; Kalthoff, H; Medema, J P

    2015-01-01

    We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan-Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16-2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79-1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression. PMID:25622308

  13. Anastomotic leakage after anterior resection for rectal cancer with mesorectal excision: incidence, risk factors, and management.

    PubMed

    Tortorelli, Antonio Pio; Alfieri, Sergio; Sanchez, Alejandro Martin; Rosa, Fausto; Papa, Valerio; Di Miceli, Dario; Bellantone, Chiara; Doglietto, Giovanni Battista

    2015-01-01

    We investigated risk factors and prognostic implications of symptomatic anastomotic leakage after anterior resection for rectal cancer, and the influence of a diverting stoma. Our retrospective review of prospective collected data analyzed 475 patients who underwent anterior resection for rectal cancer. Uni- and multivariate analysis was made between anastomotic leakage and patient, tumor, and treatment variables, either for the overall group (n = 475) and in the midlow rectal cancer subgroup (n = 291). Overall rate of symptomatic leakage was 9 per cent (43 of 475) with no related postoperative mortality. At univariate analysis, significant factors for leak were a tumor less than 6 cm from the anal verge (13.7 vs 6.6%; P = 0.011) and intraoperative transfusions (16.9 vs 4.3%; P = 0.001). Similar results were observed in the midlow rectal cancer subgroup. At multivariate analysis, no parameter resulted in being an independent prognostic factor for risk of leakage. In patients with a leakage, a temporary enterostomy considerably reduced the need for reoperation (12.5 vs 77.8%; P < 0.0001) and the risk of a permanent stoma (18.7 vs 28.5%; P = 0.49). The incidence of anastomotic failure increases for lower tumors, whereas it is not influenced by radiotherapy. Defunctioning enterostomy does not influence the leak rate, but it mitigates clinical consequences. PMID:25569064

  14. Optimal Total Mesorectal Excision for Rectal Cancer: the Role of Robotic Surgery from an Expert's View

    PubMed Central

    Kang, Jeonghyun

    2010-01-01

    Total mesorectal excision (TME) has gained worldwide acceptance as a standard surgical technique in the treatment of rectal cancer. Ever since laparoscopic surgery was first applied to TME for rectal cancer, with increasing penetration rates, especially in Asia, an unstable camera platform, the limited mobility of straight laparoscopic instruments, the two-dimensional imaging, and a poor ergonomic position for surgeons have been regarded as limitations. Robotic technology was developed in an attempt to reduce the limitations of laparoscopic surgery. The robotic system has many advantages, including a more ergonomic position, stable camera platform and stereoscopic view, as well as elimination of tremor and subsequent improved dexterity. Current comparison data between robotic and laparoscopic rectal cancer surgery show similar intraoperative results and morbidity, postoperative recovery, and short-term oncologic outcomes. Potential benefits of a robotic system include reduction of surgeon's fatigue during surgery, improved performance and safety for intracorporeal suture, reduction of postoperative complications, sharper and more meticulous dissection, and completion of autonomic nerve preservation techniques. However, the higher cost for a robotic system still remains an obstacle to wide application, and many socioeconomic issues remain to be solved in the future. In addition, we need more concrete evidence regarding the merits for both patients and surgeons, as well as the merits compared to conventional laparoscopic techniques. Therefore, we need large-scale prospective randomized clinical trials to prove the potential benefits of robot TME for the treatment of rectal cancer. PMID:21221237

  15. Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

    SciTech Connect

    Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Bernard, Johnny R.; Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J.

    2014-04-01

    Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.

  16. Collaborative case conferences in rectal cancer: case series in a tertiary care centre

    PubMed Central

    Eskicioglu, C.; Forbes, S.; Tsai, S.; Francescutti, V.; Coates, A.; Grubac, V.; Sonnadara, R.; Simunovic, M.

    2016-01-01

    Background In many hospitals, resource barriers preclude the use of preoperative multidisciplinary cancer conferences (mccs) for consecutive patients with cancer. Collaborative cancer conferences (cccs) are modified mccs that might overcome such barriers. Methods We established a ccc at an academic tertiary care centre to review preoperative plans for patients with rectal cancer. Attendees included only surgeons who perform colorectal cancer procedures and a radiologist with expertise in cross-sectional imaging. Individual reviews began with the primary surgeon presenting the case information and initial treatment recommendations. Cross-sectional images were then reviewed, the case was discussed, and consensus on ccc-treatment recommendations was achieved. Outcomes for the present study were changes in treatment recommendations defined as “major” (that is, redirection of patient to preoperative radiation from straight-to-surgery or uncertain plan, or redirection of the patient to straight-to-surgery from preoperative radiation or plan uncertain) or as “minor” (that is, referral to a multidisciplinary cancer clinic, request additional tests, change type of neoadjuvant therapy, change type of surgery). Chart reviews provided relevant patient, tumour, and treatment information. Results Between September 2011 and September 2012, 101 rectal cancer patients were discussed at a ccc. Of the 35 management plans (34.7%) that were changed as a result, 8 had major changes, and 27 had minor changes. Available patient and tumour factors did not predict for a change in treatment recommendation. Conclusions Preoperative cccs at a tertiary-care centre changed treatment recommendations for one third of patients with rectal cancer. Given that no specific factor predicted for a treatment plan change, it is likely prudent that all rectal cancer patients undergo some form of collaborative review. PMID:27122982

  17. Ileorectal fistula due to a rectal cancer-A case report.

    PubMed

    Takahashi, Minoru; Fukuda, Takahiro

    2011-01-01

    A 51-year-old man was seen at our hospital because of diarrhea. Barium enema and colonoscopy revealed a cancer in the lower rectum and fistula formation from the site to ileum. Resection of the rectal cancer and ileorectal fistula was performed. Histologically, the resected lesion was mucinous adenocarcinoma with contiguous invasion from the rectum to the ileum. The patient is alive with no sign of recurrence 120 months after operation. Fistula formation between the colon and other gastrointestinal tract organs is very rare, especially for rectal cancer. Fistula-forming colorectal cancers are rarely found to have metastatic lesions in the liver, peritoneum and lymph nodes despite their invasive behavior; accordingly, curative resection involving partial resection of the intestine with fistula is expected. PMID:22096678

  18. Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

    SciTech Connect

    Das, Prajnan; Eng, Cathy; Rodriguez-Bigas, Miguel A.; Chang, George J.; Skibber, John M.; You, Y. Nancy; Maru, Dipen M.; Munsell, Mark F.; Clemons, Marilyn V.; Kopetz, Scott E.; Garrett, Christopher R.; Shureiqi, Imad; Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H.

    2014-02-01

    Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m{sup 2} to 825 mg/m{sup 2} orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

  19. [Current status and novel approach of robotic surgery for rectal cancer].

    PubMed

    Du, Xiaohui

    2015-08-01

    With the development of minimally invasive surgery, laparoscopic technique is now widely used in rectal surgery because of its advantages in terms of pain control, recovery of bowel function, length of hospital stay, short- and long-term outcomes. Total mesorectal excision(TME) is recommended as the standard procedure for rectal cancer. Laparoscopic TME, however, can be challenging due to its two-dimensional vision, restricted instrument movements, and a prolonged learning curve. Robotic surgery overcomes these intrinsic limitations by superior three-dimensional magnified optics, stable retraction platform, and 7 degrees of freedom of instrument movements, and offers an easier operation and shorter learning curve. This review summarizes the advantages as well as the current status of robotic rectal surgery, and explores the novel approach and new techniques with the related literature and the author's own experience. PMID:26303685

  20. Bevacizumab, Capecitabine, Amifostine, and Preoperative Hypofractionated Accelerated Radiotherapy (HypoArc) for Rectal Cancer: A Phase II Study

    SciTech Connect

    Koukourakis, Michael I.; Tsoutsou, Pelagia; Chloropoulou, Pelagia A.; Manolas, Kostantinos; Sivridis, Efthimios

    2011-06-01

    Purpose: Bevacizumab has established therapeutic activity in patients with metastatic colorectal cancer, and anti-vascular endothelial growth factor therapy enhances the activity of radiotherapy in experimental models. We assessed the feasibility and efficacy of preoperative radiochemotherapy combined with bevacizumab in patients with rectal cancer. Methods and Materials: Nineteen patients with radiologic T3 and/or N+ rectal carcinoma were treated with preoperative conformal hypofractionated accelerated radiotherapy (3.4 Gy in 10 consecutive fractions) supported with amifostine (500-1,000 mg daily), capecitabine (600 mg/m{sup 2} twice daily, 5 days per week), and bevacizumab (5 mg/kg every 2 weeks for 2 cycles). Surgery followed 6 weeks after the end of radiotherapy. A cohort of 14 sequential patients treated with the same regimen without bevacizumab was available for comparison. Results: Grade 2 or 3 diarrhea was noted in 7 of 19 patients (36.8%), which was statistically worse than patients receiving the same regimen without bevacizumab (p = 0.01). A higher incidence of Grade 2 or 3 proctalgia was also noted (21.1%) (p = 0.03). Bladder and skin toxicity was negligible. All toxicities regressed completely within 2 weeks after the end of therapy. Pathologic complete and partial response was noted in 7 of 19 cases (36.8%) and 8 of 19 cases (42.1%). Within a median follow-up of 21 months, none of the patients has had late complications develop and only 1 of 18 evaluable cases (5.5%) has had locoregional relapse. Conclusions: Bevacizumab can be safely combined with hypofractionated radiotherapy and capecitabine as a preoperative radiochemotherapy regimen for patients with rectal cancer. The high pathologic complete response rates urges the testing of bevacizumab in randomized studies.

  1. Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changes in rectal cancer

    SciTech Connect

    Lussanet, Quido G. de . E-mail: qdlu@rdia.azm.nl; Backes, Walter H.; Griffioen, Arjan W.; Padhani, Anwar R.; Baeten, Coen I.; Baardwijk, Angela van; Lambin, Philippe; Beets, Geerard L.; Engelshoven, Jos van; Beets-Tan, Regina G.H.

    2005-12-01

    Purpose: Dynamic contrast-enhanced T1-weighted magnetic resonance imaging (DCE-MRI) allows noninvasive evaluation of tumor microvasculature characteristics. This study evaluated radiation therapy related microvascular changes in locally advanced rectal cancer by DCE-MRI and histology. Methods and Materials: Dynamic contrast-enhanced-MRI was performed in 17 patients with primary rectal cancer. Seven patients underwent 25 fractions of 1.8 Gy radiation therapy (RT) (long RT) before DCE-MRI and 10 did not. Of these 10, 3 patients underwent five fractions of 5 Gy RT (short RT) in the week before surgery. The RT treated and nontreated groups were compared in terms of endothelial transfer coefficient (K{sup PS}, measured by DCE-MRI), microvessel density (MVD) (scored by immunoreactivity to CD31 and CD34), and tumor cell and endothelial cell proliferation (scored by immunoreactivity to Ki67). Results: Tumor K{sup PS} was 77% (p = 0.03) lower in the RT-treated group. Histogram analyses showed that RT reduced both magnitude and intratumor heterogeneity of K{sup PS} (p = 0.01). MVD was significantly lower (37%, p 0.03) in tumors treated with long RT than in nonirradiated tumors, but this was not the case with short RT. Endothelial cell proliferation was reduced with short RT (81%, p = 0.02) just before surgery, but not with long RT (p > 0.8). Tumor cell proliferation was reduced with both long (57%, p < 0.001) and short RT (52%, p = 0.002). Conclusion: Dynamic contrast-enhanced-MRI-derived K{sup PS} values showed significant radiation therapy related reductions in microvessel blood flow in locally advanced rectal cancer. These findings may be useful in evaluating effects of radiation combination therapies (e.g., chemoradiation or RT combined with antiangiogenesis therapy), to account for effects of RT alone.

  2. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients

    PubMed Central

    Agostini, Marco; Zangrando, Andrea; Pastrello, Chiara; D'Angelo, Edoardo; Romano, Gabriele; Giovannoni, Roberto; Giordan, Marco; Maretto, Isacco; Bedin, Chiara; Zanon, Carlo; Digito, Maura; Esposito, Giovanni; Mescoli, Claudia; Lavitrano, Marialuisa; Rizzolio, Flavio; Jurisica, Igor; Giordano, Antonio; Pucciarelli, Salvatore; Nitti, Donato

    2015-01-01

    Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer. PMID:26023803

  3. Exacerbation of Dermatomyositis with Recurrence of Rectal Cancer: A Case Report

    PubMed Central

    Nagano, Yuka; Inoue, Yasuhiro; Shimura, Tadanobu; Fujikawa, Hiroyuki; Okugawa, Yoshinaga; Hiro, Junichiro; Toiyama, Yuji; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2015-01-01

    Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by cutaneous and muscle manifestations. The association between DM and malignancy has been well recognized for many years. The clinical course of paraneoplastic DM may be affected by malignancies, although the cause and effect relationship between exacerbation of DM and cancer progression is uncertain. Herein, we report a 44-year-old woman who presented with progressive DM associated with rectal cancer. After curative resection of rectal cancer, DM symptoms resolved. Three months after surgery, blood test surveillance showed elevation of serum carcinoembryonic antigen levels, although the patient remained asymptomatic. One month later she had a DM flare-up, and multiple lung and liver metastases were found. She immediately underwent cancer chemotherapy with prednisolone therapy for DM. However, her condition deteriorated and she was unable to swallow. Percutaneous endoscopic gastrostomy was constructed, allowing alimentation and oral delivery, which made it possible to keep her on chemotherapy. She had remarkable response for unresectable metastases 8 weeks after the administration of chemotherapy. Seven months after onset of recurrence, her condition improved considerably and she had stable disease. Moreover, she can now eat food of soft consistency. Our case provides further support for the clinical importance of cancer chemotherapy for patients who have progressive DM and unresectable rectal cancer. PMID:26668568

  4. Exacerbation of Dermatomyositis with Recurrence of Rectal Cancer: A Case Report.

    PubMed

    Nagano, Yuka; Inoue, Yasuhiro; Shimura, Tadanobu; Fujikawa, Hiroyuki; Okugawa, Yoshinaga; Hiro, Junichiro; Toiyama, Yuji; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2015-01-01

    Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by cutaneous and muscle manifestations. The association between DM and malignancy has been well recognized for many years. The clinical course of paraneoplastic DM may be affected by malignancies, although the cause and effect relationship between exacerbation of DM and cancer progression is uncertain. Herein, we report a 44-year-old woman who presented with progressive DM associated with rectal cancer. After curative resection of rectal cancer, DM symptoms resolved. Three months after surgery, blood test surveillance showed elevation of serum carcinoembryonic antigen levels, although the patient remained asymptomatic. One month later she had a DM flare-up, and multiple lung and liver metastases were found. She immediately underwent cancer chemotherapy with prednisolone therapy for DM. However, her condition deteriorated and she was unable to swallow. Percutaneous endoscopic gastrostomy was constructed, allowing alimentation and oral delivery, which made it possible to keep her on chemotherapy. She had remarkable response for unresectable metastases 8 weeks after the administration of chemotherapy. Seven months after onset of recurrence, her condition improved considerably and she had stable disease. Moreover, she can now eat food of soft consistency. Our case provides further support for the clinical importance of cancer chemotherapy for patients who have progressive DM and unresectable rectal cancer. PMID:26668568

  5. Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

    SciTech Connect

    Ospina, Juan D.; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B.; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C.; and others

    2014-08-01

    Purpose: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Methods and Materials: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). Results: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. Conclusions: The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models.

  6. Cancer-initiating cells derived from human rectal adenocarcinoma tissues carry mesenchymal phenotypes and resist drug therapies.

    PubMed

    Fan, C-W; Chen, T; Shang, Y-N; Gu, Y-Z; Zhang, S-L; Lu, R; OuYang, S-R; Zhou, X; Li, Y; Meng, W-T; Hu, J-K; Lu, Y; Sun, X-F; Bu, H; Zhou, Z-G; Mo, X-M

    2013-01-01

    Accumulating evidence indicates that cancer-initiating cells (CICs) are responsible for cancer initiation, relapse, and metastasis. Colorectal carcinoma (CRC) is typically classified into proximal colon, distal colon, and rectal cancer. The gradual changes in CRC molecular features within the bowel may have considerable implications in colon and rectal CICs. Unfortunately, limited information is available on CICs derived from rectal cancer, although colon CICs have been described. Here we identified rectal CICs (R-CICs) that possess differentiation potential in tumors derived from patients with rectal adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R-CICs and their immediate progenies carried potential epithelial-mesenchymal transition characteristics. These R-CICs generated tumors similar to their tumor of origin when injected into immunodeficient mice, differentiated into rectal epithelial cells in vitro, and were capable of self-renewal both in vitro and in vivo. More importantly, subpopulations of R-CICs resisted both 5-fluorouracil/calcium folinate/oxaliplatin (FolFox) and cetuximab treatment, which are the most common therapeutic regimens used for patients with advanced or metastatic rectal cancer. Thus, the identification, expansion, and properties of R-CICs provide an ideal cellular model to further investigate tumor progression and determine therapeutic resistance in these patients. PMID:24091671

  7. Automatically-generated rectal dose constraints in intensity-modulated radiation therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Hwang, Taejin; Kim, Yong Nam; Kim, Soo Kon; Kang, Sei-Kwon; Cheong, Kwang-Ho; Park, Soah; Yoon, Jai-Woong; Han, Taejin; Kim, Haeyoung; Lee, Meyeon; Kim, Kyoung-Joo; Bae, Hoonsik; Suh, Tae-Suk

    2015-06-01

    The dose constraint during prostate intensity-modulated radiation therapy (IMRT) optimization should be patient-specific for better rectum sparing. The aims of this study are to suggest a novel method for automatically generating a patient-specific dose constraint by using an experience-based dose volume histogram (DVH) of the rectum and to evaluate the potential of such a dose constraint qualitatively. The normal tissue complication probabilities (NTCPs) of the rectum with respect to V %ratio in our study were divided into three groups, where V %ratio was defined as the percent ratio of the rectal volume overlapping the planning target volume (PTV) to the rectal volume: (1) the rectal NTCPs in the previous study (clinical data), (2) those statistically generated by using the standard normal distribution (calculated data), and (3) those generated by combining the calculated data and the clinical data (mixed data). In the calculated data, a random number whose mean value was on the fitted curve described in the clinical data and whose standard deviation was 1% was generated by using the `randn' function in the MATLAB program and was used. For each group, we validated whether the probability density function (PDF) of the rectal NTCP could be automatically generated with the density estimation method by using a Gaussian kernel. The results revealed that the rectal NTCP probability increased in proportion to V %ratio , that the predictive rectal NTCP was patient-specific, and that the starting point of IMRT optimization for the given patient might be different. The PDF of the rectal NTCP was obtained automatically for each group except that the smoothness of the probability distribution increased with increasing number of data and with increasing window width. We showed that during the prostate IMRT optimization, the patient-specific dose constraints could be automatically generated and that our method could reduce the IMRT optimization time as well as maintain the

  8. [A patient with recurrent rectal cancer in whom pulmonary metastasis disappeared by FOLFOX 4 therapy].

    PubMed

    Fujisawa, Minoru; Ono, Seigo; Nakayama, Yoshimi; Nitta, Shingo; Ishiyama, Shun; Shinjou, Kunihiro; Machida, Michio; Kitabatake, Toshiaki; Ishibiki, Yoshirou; Urao, Masahiko; Kojima, Kuniaki

    2007-11-01

    We performed FOLFOX 4 therapy in a patient with lung metastasis (a 62-year-old woman) after surgery for rectal cancer and observed both normalization of tumor markers and disappearance of the metastasis. Low anterior resection was performed for progressive rectal cancer, and treatment with UFT and folinate was started one month after surgery. However, tumor markers increased after 2 months of treatment and CT scans showed metastases to both lungs. FOLFOX 4 therapy was started, and tumor markers became normal after four courses, while the lung metastases disappeared after 10 courses. The dosage of FOLFOX 4 was reduced after three courses due to neutropenia and diarrhea. This treatment appeared to be effective for the inhibition of lung metastasis associated with colorectal cancer. PMID:18030029

  9. Increased expression of FERM domain-containing 4A protein is closely associated with the development of rectal cancer

    PubMed Central

    FAN, YONGTIAN; LI, DECHUAN; QIAN, JUN; LIU, YONG; FENG, HAIYANG; LI, DECHUAN

    2016-01-01

    The aim of the present study was to detect the expression levels of FERM domain-containing 4A (FRMD4A) in rectal cancer tissues and peripheral blood and to investigate the correlation between FRMD4A and cancer development. A total of 78 consecutive patients were enrolled in this study. Thirty healthy individuals were used as the control group. The expression of FRMD4A in rectal cancer and the corresponding normal adjacent tissues was detected by immunohistochemistry and western blotting. The expression of FRMD4A mRNA in peripheral blood was detected by reverse transcription-quantitative polymerase chain reaction. The expression of FRMD4A in rectal cancer tissues was found to be negatively correlated with the degree of differentiation, depth of invasion and Dukes' stage. A negative correlation was identified between FRMD4A and epithelial cadherin expression. The expression of FRMD4A in the peripheral blood of patients with rectal cancer was significantly increased compared with that in the control group (P<0.05). Expression of FRMD4A in the peripheral blood in the patients with lymph node metastasis was significantly increased compared with that in the patients without lymph node metastasis (P<0.05). These results indicate that the expression of FRMD4A is significantly increased in rectal cancer tissues and the peripheral blood of patients with rectal cancer, and the expression levels of FRMD4A are closely associated with differentiation, invasion of rectal cancer and Dukes' stage. In conclusion, the findings of the present study suggest that FRMD4A may be used as a target for the diagnosis and treatment of rectal cancer. PMID:26893625

  10. [Endoluminal echography in rectal cancer--preoperative staging and postoperative control].

    PubMed

    Tankova, L; Kadnian, Kh; Draganov, V; Damianov, D; Damianov, N; Penchev, P; Gegova, A

    2003-01-01

    The aim of this study is to determine the diagnostic potential of endoluminal echography and the pitfalls sources in the preoperative staging and postoperative follow-up in patients with rectal cancer. 245 patients with rectal carcinoma are evaluated during 10 years period (Jan. 1993-Jan. 2002 years). 96 patients are monitored in the early and late postoperative periods for the early detection of local recurrence as well as for the anorectal physiology assessment after low anterior rectal resection or coloanal anastomosis. Lineal transducer UST-657-5MHz (Aloka 620) and 10MHz miniprobe are applied. The accuracy for T-staging is 84% and for N-staging is 82%. The local recurrence is detected in 21 patients, on average 12.6 months after curative surgery. The local recurrence is more often in cases of lymph node involvement as well as if some specific echographic features for extramural vascular invasion are present. Endoluminal echography provides individual therapeutic management and postoperative control in patients with rectal cancer. PMID:15641546

  11. [Laparoscopic Surgery for Adult Intussusception Due to Rectal Cancer--A Case Report].

    PubMed

    Ishikawa, Akira; Higuchi, Ichiro; Akiyama, Yosuke; Tanigawa, Takahiko; Hasuike, Yasunori

    2015-11-01

    An 87-year-old woman with the chief complaint of bloody stool was referred to our hospital from an institution for the aged. The abdomen was soft and flat, and a tumor was not palpable on digital rectal examination. Tumor markers were within normal ranges. Abdominal enhanced CT scan showed a multiple concentric ring sign at the rectum. Colonoscopic and barium examination led to a diagnosis of rectal intussusception due to rectal cancer. We first tried to reposition it preoperatively, but it was impossible. She fortunately had no symptoms of ileus; therefore, we chose to perform laparoscopic surgery. We achieved the reposition intraoperatively and performed Hartmann's operation with D2 lymph node dissection because she was a very elderly patient with high-risk comorbidities. The pathological diagnosis was as follows: RS, 40×40 mm, type 2, tub2, pT3 (SS), pN0, ly0, v0, pStageⅡ, R0, Cur A. Adult intussusception due to rectal cancer is extremely rare. We report that in this case that laparoscopic surgery was possible, along with a review of the relevant literature. PMID:26805342

  12. Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer

    PubMed Central

    Azizian, Azadeh; Epping, Ingo; Kramer, Frank; Jo, Peter; Bernhardt, Markus; Kitz, Julia; Salinas, Gabriela; Wolff, Hendrik A.; Grade, Marian; Beißbarth, Tim; Ghadimi, B. Michael; Gaedcke, Jochen

    2016-01-01

    Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients’ prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options. Methods: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage. Quantitative real-time polymerase chain reaction (qPCR) was performed on an independent set of 147 rectal cancer patients to validate relevant miRNAs. Results: In the microarray screen, 14 microRNAs were significantly correlated to overall survival. Five microRNAs were included from previous work. Finally, 19 miRNAs were evaluated by qPCR. miR-515-5p, miR-573, miR-579 and miR-802 demonstrated significant correlation with overall survival and cancer-specific survival (p < 0.05). miR-573 was also significantly correlated with the tumor regression grade after preoperative chemoradiotherapy. miR-133b showed a significant correlation with distant-metastasis-free survival. miR-146b expression levels showed a significant correlation with nodal stage. Conclusion: Specific microRNAs can be used as biomarkers to predict prognosis of patients with rectal cancer and possibly stratify patients’ therapy if validated in a prospective study. PMID:27092493

  13. Magnetic resonance imaging of rectal cancer: staging and restaging evaluation.

    PubMed

    Moreno, Courtney C; Sullivan, Patrick S; Kalb, Bobby T; Tipton, Russell G; Hanley, Krisztina Z; Kitajima, Hiroumi D; Dixon, W Thomas; Votaw, John R; Oshinski, John N; Mittal, Pardeep K

    2015-10-01

    Magnetic resonance imaging is used to non-invasively stage and restage rectal adenocarcinomas. Accurate staging is important as the depth of tumor extension and the presence or absence of lymph node metastases determines if an individual will undergo preoperative neoadjuvant chemoradiation. Accurate description of tumor location is important for presurgical planning. The relationship of the tumor to the anal sphincter in addition to the depth of local invasion determines the surgical approach used for resection. High-resolution T2-weighted imaging is the primary sequence used for initial staging. The addition of diffusion-weighted imaging improves accuracy in the assessment of treatment response on restaging scans. Approximately 10%-30% of individuals will experience a complete pathologic response following chemoradiation with no residual viable tumor found in the resected specimen at histopathologic assessment. In some centers, individuals with no residual tumor visible on restaging MR who are thought to be at high operative risk are monitored with serial imaging and a "watch and wait" approach in lieu of resection. Normal rectal anatomy, MR technique utilized for staging and restaging scans, and TMN staging are reviewed. An overview of surgical techniques used for resection including newer, minimally invasive endoluminal techniques is included. PMID:25759246

  14. The effect of preoperative chemoradiotherapy on lymph nodes harvested in TME for rectal cancer

    PubMed Central

    2013-01-01

    Background Adequate lymph nodes resection in rectal cancer is important for staging and local control. This retrospective analysis single center study evaluated the effect of neoadjuvant chemoradiation on the number of lymph nodes in rectal carcinoma, considering some clinicopathological parameters. Methods A total of 111 patients undergone total mesorectal excision for rectal adenocarcinoma from July 2005 to May 2012 in our center were included. No patient underwent any prior pelvic surgery or radiotherapy. Chemoradiotherapy was indicated in patients with rectal cancer stage II or III before chemoradiation. Results One-hundred and eleven patients were considered. The mean age was 67.6 yrs (range 36 – 84, SD 10.8). Fifty (45.0%) received neoadjuvant therapy before resection. The mean number of removed lymph nodes was 13.6 (range 0–39, SD 7.3). In the patients who received neoadjuvant therapy the number of nodes detected was lower (11.5, SD 6.5 vs. 15.3, SD 7.5, p = 0.006). 37.4% of patients with preoperative chemoradiotherapy had 12 or more lymph nodes in the specimen compared to the 63.6% of those who had surgery at the first step (p: 0.006). Other factors associated in univariate analysis with lower lymph nodes yield included stage (p 0.005) and grade (p 0.0003) of the tumour. Age, sex, tumor site, type of operation, surgeons and pathologists did not weight upon the number of the removed lymph nodes. Conclusion In TME surgery for rectal cancer, preoperative CRT results into a reduction of lymph nodes yield in univariate analisys and linear regression. PMID:24246069

  15. Quality of Life After a Low Anterior Resection for Rectal Cancer in Elderly Patients

    PubMed Central

    Walma, Marieke S.; de Roos, Marnix A.J.; Boerma, Djamila; van Westreenen, Henderik L.

    2016-01-01

    Purpose Fecal incontinence is a major concern, and its incidence increases with age. Quality of life may decrease due to fecal incontinence after both sphincter-saving surgery and a rectal resection with a permanent stoma. This study investigated quality of life, with regard to fecal incontinency, in elderly patients after rectal-cancer surgery. Methods All patients who underwent elective rectal surgery with anastomosis for rectal cancer between December 2008 and June 2012 at two Dutch hospitals were eligible for inclusion. The Wexner and the fecal incontinence quality of life (FIQoL) scores were collected. Young (<70 years of age) and elderly (≥70 years of age) patients were compared. Results Seventy-nine patients were included, of whom 19 were elderly patients (24.1%). All diverting stomas that had been placed (n = 60, 75.9%) had been closed at the time of the study. There were no differences in Wexner or FIQoL scores between the young and the elderly patients. Also, there were no differences between patients without a diverting stoma and patients in whom bowel continuity had been restored. Elderly females had significantly worse scores on the FIQoL subscales of coping/behavior (P = 0.043) and depression/self-perception (P = 0.004) than young females. Elderly females scored worse on coping/behavior (P = 0.010) and depression/self-perception (P = 0.036) than elderly males. Young and elderly males had comparable scores. Conclusion Quality of life with regard to fecal incontinency is worse in elderly females after sphincter-preserving surgery for rectal cancer. Patients should be informed of this impact, and a definite stoma may be considered in this patient group. PMID:26962533

  16. Laparoscopic vs open abdominoperineal resection in the multimodality management of low rectal cancers

    PubMed Central

    Wang, Yu-Wei; Huang, Li-Yong; Song, Cheng-Li; Zhuo, Chang-Hua; Shi, De-Bing; Cai, Guo-Xiang; Xu, Ye; Cai, San-Jun; Li, Xin-Xiang

    2015-01-01

    .7 d vs 2.7 ± 0.6 d, P < 0.001), earlier first flatus (57.3 ± 7.9 h vs 63.5 ± 9.2 h, P < 0.001), shorter urinary drainage time (6.5 ± 3.4 d vs 7.8 ± 1.3 d, P < 0.001), and shorter postoperative admission (11.2 ± 4.7 d vs 12.6 ± 4.0 d, P = 0.014). With regard to APR-specific complications (perineal wound complications and parastomal hernia), there were no significant differences between the two groups. Similar results were found in the 26 pairs of patients administered neoadjuvant chemoradiation in subgroup analysis. During the follow-up period, no port site recurrences were observed. CONCLUSION: Laparoscopic abdominoperineal resection for multidisciplinary management of rectal cancer is safe, and is associated with earlier recovery and shorter admission time in combination with neoadjuvant chemoradiation. PMID:26401082

  17. Elevated Platelet Count as Predictor of Recurrence in Rectal Cancer Patients Undergoing Preoperative Chemoradiotherapy Followed by Surgery

    PubMed Central

    Toiyama, Yuji; Inoue, Yasuhiro; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Saigusa, Susumu; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2015-01-01

    The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer. PMID:25692418

  18. Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study

    PubMed Central

    Miki, Yoshitaka; Maeda, Kiyoshi; Hosono, Masako; Nagahara, Hisashi; Hirakawa, Kosei; Shimatani, Yasuhiko; Tsutsumi, Shinichi; Miki, Yukio

    2014-01-01

    The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m2 twice daily at Dose Level 1, with a planned escalation to 900 mg/m2 twice daily at Dose Level 2. Within 6.1–10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m2 twice daily. PMID:25129557

  19. Postoperative Irradiation for Rectal Cancer Increases the Risk of Small Bowel Obstruction After Surgery

    PubMed Central

    Baxter, Nancy N.; Hartman, Lacey K.; Tepper, Joel E.; Ricciardi, Rocco; Durham, Sara B.; Virnig, Beth A.

    2007-01-01

    Objective: To determine the risk of small bowel obstruction (SBO) after irradiation (RT) for rectal cancer Background: SBO is a frequent complication after standard resection of rectal cancer. Although the use of RT is increasing, the effect of RT on risk of SBO is unknown. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results cancer registry data linked to Medicare claims data to determine the effect of RT on risk of SBO. Patients 65 years of age and older diagnosed with nonmetastatic invasive rectal cancer treated with standard resection from 1986 through 1999 were included. We determined whether patients had undergone RT and evaluated the effect of RT and timing of RT on the incidence of admission to hospital for SBO, adjusting for potential confounders using a proportional hazards model. Results: We identified a total of 5606 patients who met our selection criteria: 1994 (36%) underwent RT, 74% postoperatively. Patients were followed for a mean of 3.8 years. A total of 614 patients were admitted for SBO over the study period; 15% of patients in the RT group and 9% of patients in the nonirradiated group (P < 0.001). After controlling for age, sex, race, diagnosis year, type of surgery, and stage, we found that patients who underwent postoperative RT were at higher risk of SBO, hazard ratio 1.69 (95% CI, 1.3–2.1). However, the long-term risk associated with preoperative irradiation was not statistically significant (hazard ratio, 0.89; 95% CI, 0.55–1.46). Conclusions: Postoperative but not preoperative RT after standard resection of rectal cancer results in an increased risk of SBO over time. PMID:17414603

  20. Prognostic significance of neutrophil-to-lymphocyte ratio in rectal cancer: a meta-analysis

    PubMed Central

    Dong, Yi-wei; Shi, Yan-qiang; He, Li-wen; Su, Pei-zhu

    2016-01-01

    Background Inflammatory responses play decisive roles in tumor development, immune surveillance, and responses to therapy. High neutrophil-to-lymphocyte ratio (NLR), as an inflammation index, has been reported to be a predictor for poor prognosis of various cancers. The purpose of this meta-analysis was to evaluate the prognostic value of NLR in patients with rectal cancer. Methods A comprehensive search of the literature was conducted through PubMed and EMBASE. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the association between NLR and three outcomes: overall survival, disease-free survival, and recurrence-free survival. Results Seven cohorts involving 959 patients were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was associated with poor overall survival (HR: 13.41, 95% CI: 4.90–36.72), disease-free survival (HR: 4.37, 95% CI: 2.33–8.19), and recurrence-free survival (HR: 3.64, 95% CI: 1.88–7.05). Conclusion An elevated NLR is a valuable and easily available prognostic marker for rectal cancer. It is associated with unfavorable overall survival, disease-free survival, and recurrence-free survival. NLR could be a useful candidate factor for making treatment decisions for individual patients with rectal cancer. PMID:27307753

  1. [Two Cases of Curative Resection of Locally Advanced Rectal Cancer after Preoperative Chemotherapy].

    PubMed

    Mitsuhashi, Noboru; Shimizu, Yoshiaki; Kuboki, Satoshi; Yoshitomi, Hideyuki; Kato, Atsushi; Ohtsuka, Masayuki; Shimizu, Hiroaki; Miyazaki, Masaru

    2015-11-01

    Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46-year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub-intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case. PMID:26805302

  2. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    SciTech Connect

    Katz, Matthew S.; Minsky, Bruce D. . E-mail: minskyb@mskcc.org; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-08-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  3. Digital rectal exam

    MedlinePlus

    ... Elsevier Saunders; 2012:chap 99. Read More Colon cancer Prostate cancer Update Date 11/1/2015 Updated by: ... Health Topics Anal Disorders Enlarged Prostate (BPH) Prostate Cancer Prostate Cancer Screening Prostate Diseases Rectal Disorders Browse the ...

  4. Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-11-01

    Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.

  5. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    SciTech Connect

    Appelt, Ane L.; Ploen, John; Vogelius, Ivan R.; Bentzen, Soren M.; Jakobsen, Anders

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

  6. Interstitial curietherapy in the conservative treatment of anal and rectal cancers

    SciTech Connect

    Papillon, J.; Montbarbon, J.F.; Gerard, J.P.; Chassard, J.L.; Ardiet, J.M. )

    1989-12-01

    Conservative treatment has become a valid alternative to radical surgery in most cases of cancer of the anal canal and in selected cases of cancer of the low rectum. In this strategy interstitial curietherapy has an appreciable role to play. The results of a series of 369 patients followed more than 3 years indicate that implantation of Iridium-192 is effective not as sole treatment but as a booster dose 2 months after a course of external beam or intracavitary irradiation. The dose delivered did not exceed 20 to 30 Gy and the implantations were always performed in one plane using either a plastic template or a steel fork. Three groups of cases must be considered: (a) among 221 patients with epidermoid carcinoma of the anal canal, the rate of death related to treatment failures was 20% and among the patients cured more than 90% retained normal sphincter function. (b) In 90 patients with T1-T2 invasive adenocarcinoma of the rectum, Iridium-192 was carried out after four applications of contact X ray therapy. The rate of control was 84%. (c) In 62 elderly, poor risk patients with T2-T3 tumor of the low rectum initially suitable for an abdomino-perineal resection, a tentative extension of the field of conservation was made using a split-course protocol combining a short course of external beam irradiation at a dose of 30-35 Gy in 10 fractions over 12 days and an Iridium-192 implant. The rate of death due to treatment failures was 14.5% and among the patients controlled 97% had a normal anal function. These results show that implantations of Iridium-192 may contribute to the control of anal and rectal cancers and may spare many patients a permanent colostomy, but the treatment requires great care in patient selection, treatment protocol, technical details, and follow-up. This treatment policy must be conceived as a team work of radiation oncologists and surgeons.

  7. Late rectal and bladder toxicity following radiation therapy for prostate cancer: Predictive factors and treatment results

    PubMed Central

    Fuentes-Raspall, Rafael; Inoriza, José Maria; Rosello-Serrano, Alvaro; Auñón-Sanz, Carmen; Garcia-Martin, Pilar; Oliu-Isern, Gemma

    2013-01-01

    Aim This study aimed at investigating factors associated to late rectal and bladder toxicity following radiation therapy and the effectiveness of Hyperbaric Oxygen Therapy (HBOT) when toxicity is grade ≥2. Background Radiation is frequently used for prostate cancer, but a 5–20% incidence of late radiation proctitis and cystitis exists. Some clinical and dosimetric factors have been defined without a full agreement. For patients diagnosed of late chronic proctitis and/or cystitis grade ≥2 treatment is not well defined. Hyperbaric Oxygen Therapy (HBOT) has been used, but its effectiveness is not well known. Materials and methods 257 patients were treated with radiation therapy for prostate cancer. Clinical, pharmacological and dosimetric parameters were collected. Patients having a grade ≥2 toxicity were treated with HBOT. Results of the intervention were measured by monitoring toxicity by Common Toxicity Criteria v3 (CTCv3). Results Late rectal toxicity was related to the volume irradiated, i.e. V50 > 53.64 (p = 0.013); V60 > 38.59% (p = 0.005); V65 > 31.09% (p = 0.002) and V70 > 22.81% (p = 0.012). We could not correlate the volume for bladder. A total of 24 (9.3%) patients experienced a grade ≥2. Only the use of dicumarinic treatment was significant for late rectal toxicity (p = 0.014). A total of 14 patients needed HBOT. Final percentage of patients with a persistent toxicity grade ≥2 was 4.5%. Conclusion Rectal volume irradiated and dicumarinic treatment were associated to late rectal/bladder toxicity. When toxicity grade ≥2 is diagnosed, HBOT significantly ameliorate symptoms. PMID:24416567

  8. CoReCG: a comprehensive database of genes associated with colon-rectal cancer

    PubMed Central

    Agarwal, Rahul; Kumar, Binayak; Jayadev, Msk; Raghav, Dhwani; Singh, Ashutosh

    2016-01-01

    Cancer of large intestine is commonly referred as colorectal cancer, which is also the third most frequently prevailing neoplasm across the globe. Though, much of work is being carried out to understand the mechanism of carcinogenesis and advancement of this disease but, fewer studies has been performed to collate the scattered information of alterations in tumorigenic cells like genes, mutations, expression changes, epigenetic alteration or post translation modification, genetic heterogeneity. Earlier findings were mostly focused on understanding etiology of colorectal carcinogenesis but less emphasis were given for the comprehensive review of the existing findings of individual studies which can provide better diagnostics based on the suggested markers in discrete studies. Colon Rectal Cancer Gene Database (CoReCG), contains 2056 colon-rectal cancer genes information involved in distinct colorectal cancer stages sourced from published literature with an effective knowledge based information retrieval system. Additionally, interactive web interface enriched with various browsing sections, augmented with advance search facility for querying the database is provided for user friendly browsing, online tools for sequence similarity searches and knowledge based schema ensures a researcher friendly information retrieval mechanism. Colorectal cancer gene database (CoReCG) is expected to be a single point source for identification of colorectal cancer-related genes, thereby helping with the improvement of classification, diagnosis and treatment of human cancers. Database URL: lms.snu.edu.in/corecg PMID:27114494

  9. Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

    PubMed Central

    Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S.E.; Høyer, M; Apte, A.; Deasy, J.O.

    2016-01-01

    When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with 3D-CRT to either 74 Gy (N=159) or 78 Gy (N=159) @ 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3-mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and gEUD values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 Gy and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range. PMID:24936956

  10. Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

    2014-07-01

    When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness

  11. Underlying anatomy for CTV contouring and lymphatic drainage in rectal cancer radiation therapy.

    PubMed

    Arcangeli, Stefano; Valentini, Vincenzo; Nori, Stefania L; Fares, Claudia; Dinapoli, Nicola; Gambacorta, Maria Antonierrta

    2003-01-01

    Despite the low local recurrence rate that can be achieved by adequate surgery (total mesorectal excision--TME), radiation therapy was shown to play a significant role in reducing this risk. The widespread use of TME in many European Centers has introduced a new terminology and the need to identify the area at major risk for local failure using this surgical procedure. In the surgical series where extended extra-mesorectal surgery was performed, the role of lymphatic spread was evidenced, especially for low rectal cancer, through the pelvic parietal fascia and lateral pelvic spaces. The aim of this study was to better define some anatomic concepts and the main risk factors which impact on CTV contouring and field conformation in rectal cancer treatment. This information helps formulating guidelines for CTV contouring in daily radiotherapy practice, in order to define the best therapy, according to the tumor stage and location. PMID:15018321

  12. Long-term results and complications of preoperative radiation in the treatment of rectal cancer

    SciTech Connect

    Reed, W.P.; Garb, J.L.; Park, W.C.; Stark, A.J.; Chabot, J.R.; Friedmann, P.

    1988-02-01

    A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis.

  13. Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

    SciTech Connect

    Bruheim, Kjersti Svartberg, Johan; Carlsen, Erik; Dueland, Svein; Haug, Egil; Skovlund, Eva; Tveit, Kjell Magne; Guren, Marianne G.

    2008-03-01

    Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.

  14. Techniques and Outcome of Surgery for Locally Advanced and Local Recurrent Rectal Cancer.

    PubMed

    Renehan, A G

    2016-02-01

    Locally advanced primary rectal cancer is variably defined, but generally refers to T3 and T4 tumours. Radical surgery is the mainstay of treatment for these tumours but there is a high-risk for local recurrence. National Institute for Health and Care Excellence (2011) guidelines recommend that patients with these tumours be considered for preoperative chemoradiotherapy and this is the starting point for any discussion, as it is standard care. However, there are many refinements of this pathway and these are the subject of this overview. In surgical terms, there are two broad settings: (i) patients with tumours contained within the mesorectal envelope, or in the lower rectum, limited to invading the sphincter muscles (namely some T2 and most T3 tumours); and (ii) patients with tumours directly invading or adherent to pelvic organs or structures, mainly T4 tumours - here referred to as primary rectal cancer beyond total mesorectal excision (PRC-bTME). Major surgical resection using the principles of TME is the mainstay of treatment for the former. Where anal sphincter sacrifice is indicated for low rectal cancers, variations of abdominoperineal resection - referred to as tailored excision - including the extralevator abdominoperineal excision (ELAPE), are required. There is debate whether or not plastic reconstruction or mesh repair is required after these surgical procedures. To achieve cure in PRC-bTME tumours, most patients require extended multivisceral exenterative surgery, carried out within specialist multidisciplinary centres. The surgical principles governing the treatment of recurrent rectal cancer (RRC) parallel those for PRC-bTME, but typically only half of these patients are suitable for this type of major surgery. Peri-operative morbidity and mortality are considerable after surgery for PRC-bTME and RRC, but unacceptable levels of variation in clinical practice and outcome exist globally. To address this, there are now major efforts to standardise

  15. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer*

    PubMed Central

    Pellizzon, Antônio Cássio Assis

    2016-01-01

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. PMID:27403021

  16. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  17. Total sacrectomy for recurrent rectal cancer – A case report featuring technical details and potential pitfalls

    PubMed Central

    Melich, George; Weber, Michael; Stein, Barry; Minutolo, Vincenzo; Arena, Manuel; Arena, Goffredo O.

    2014-01-01

    INTRODUCTION Total sacrectomy for recurrent rectal cancer is controversial. However, recent publications suggest encouraging outcomes with high sacral resections. We present the first case report describing technical aspects, potential pitfalls and treatment of complications associated with total sacrectomy performed as a treatment of recurrent rectal cancer. PRESENTATION OF CASE A fifty-three year old man was previously treated at another institution with a low anterior resection (LAR) followed by chemo-radiation and left liver tri-segmentectomy for metastatic rectal cancer. Three years following the LAR, the patient developed a recurrence at the site of colorectal anastomosis, manifesting clinically as a contained perforation, forming a recto-cutaneous fistula through the sacrum. Abdomino-perineal resection (APR) and complete sacrectomy were performed using an anterior–posterior approach with posterior spinal instrumented fusion and pelvic fixation using iliac crest bone graft. Left sided vertical rectus abdominis muscle flap and right sided gracilis muscle flap were used for hardware coverage and to fill the pelvic defect. One year after the resection, the patient remains disease free and has regained the ability to move his lower limbs against gravity. DISCUSSION The case described in this report features some formidable challenges due to the previous surgeries for metastatic disease, and the presence of a recto-sacral cutaneous fistula. An approach with careful surgical planning including considerationof peri-operative embolization is vital for a successful outcome of the operation. A high degree of suspicion for pseudo-aneurysms formation due infection or dislodgement of metallic coils is necessary in the postoperative phase. CONCLUSION Total sacrectomy for the treatment of recurrent rectal cancer with acceptable short-term outcomes is possible.A detailed explanation to the patient of the possible complications and expectations including the concept of a

  18. Clinical predictive circulating peptides in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

    PubMed

    Crotti, Sara; Enzo, Maria Vittoria; Bedin, Chiara; Pucciarelli, Salvatore; Maretto, Isacco; Del Bianco, Paola; Traldi, Pietro; Tasciotti, Ennio; Ferrari, Mauro; Rizzolio, Flavio; Toffoli, Giuseppe; Giordano, Antonio; Nitti, Donato; Agostini, Marco

    2015-08-01

    Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45-50.4 Gy in 25-28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight <3 kDa) have been harvested from patients' plasma (n = 33) using nanoporous silica chip and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometer. Peptides fingerprint has been compared between responders and non-responders. Random Forest classification selected three peptides at m/z 1082.552, 1098.537, and 1104.538 that were able to correctly discriminate between responders (n = 16) and non-responders (n = 17) before therapy (T0) providing an overall accuracy of 86% and an area under the receiver operating characteristic (ROC) curve of 0.92. In conclusion, the nanoporous silica chip coupled to mass spectrometry method was found to be a realistic method for plasma-based peptide analysis and we provide the first list of predictive circulating biomarker peptides in rectal cancer patients underwent preoperative chemoradiotherapy. PMID:25522009

  19. Neoadjuvant Treatment Does Not Influence Perioperative Outcome in Rectal Cancer Surgery

    SciTech Connect

    Ulrich, Alexis; Weitz, Juergen Slodczyk, Matthias; Koch, Moritz; Jaeger, Dirk; Muenter, Marc; Buechler, Markus W.

    2009-09-01

    Purpose: To identify the risk factors for perioperative morbidity in patients undergoing resection of primary rectal cancer, with a specific focus on the effect of neoadjuvant therapy. Methods and Materials: This exploratory analysis of prospectively collected data included all patients who underwent anterior resection/low anterior resection or abdominoperineal resection for primary rectal cancer between October 2001 and October 2006. The study endpoints were perioperative surgical and medical morbidity. Univariate and multivariate analyses of potential risk factors were performed. Results: A total of 485 patients were included in this study; 425 patients (88%) underwent a sphincter-saving anterior resection/low anterior resection, 47 (10%) abdominoperineal resection, and 13 (2%) multivisceral resection. Neoadjuvant chemoradiotherapy was performed in 100 patients (21%), and 168 (35%) underwent neoadjuvant short-term radiotherapy (5 x 5 Gy). Patient age and operative time were independently associated with perioperative morbidity, and operative time, body mass index >27 kg/m{sup 2} (overweight), and resection type were associated with surgical morbidity. Age and a history of smoking were confirmed as independent prognostic risk factors for medical complications. Neoadjuvant therapy was not associated with a worse outcome. Conclusion: The results of this prospective study have identified several risk factors associated with an adverse perioperative outcome after rectal cancer surgery. In addition, neoadjuvant therapy was not associated with increased perioperative complications.

  20. Factors affecting sphincter-preserving resection treatment for patients with low rectal cancer

    PubMed Central

    SUN, ZHENQIANG; YU, XIANBO; WANG, HAIJIANG; MA, MING; ZHAO, ZELIANG; WANG, QISAN

    2015-01-01

    The aim of the present study was to identify the factors associated with the use of sphincter-preserving resection (SPR) surgery for the treatment of low rectal cancer. A total of 330 patients with histopathologically confirmed low rectal cancer were divided into two groups, namely the abdominoperineal resection (APR) and sphincter-preserving (SP) groups. For SPR factor analysis, the χ2 test was performed as the univariate analysis, while a logistic regression test was conducted as the multivariate analysis. Of the 330 patients, 192 cases (58.18%) received SPR surgery and 138 cases (41.82%) underwent an APR. Univariate analysis results revealed that the sphincter-preserving factor was significantly associated with age, gender, ethnicity, body mass index (BMI), total infiltrated circumference, distance of the tumor from the anal verge (DTAV), depth of invasion and tumor grade (P<0.05). However, there were no statistically significant associations with family medical history, diabetes history, venous tumor embolism, growth type, tumor length, lymphatic metastasis and level of preoperative carcinoembryonic antigen (P>0.05). Multivariate analysis indicated that the sphincter-preserving factor was strongly associated with DTAV and the depth of invasion, with significant statistical difference (P<0.05). Therefore, selecting SPR surgery for patients with low rectal cancer is dependent on age, gender, ethnicity, BMI, the total infiltrated circumference, DTAV, depth of invasion and tumor grade. In addition, DTAV and the depth of invasion are independent risk factors for the selection of SPR surgery. PMID:26622341

  1. Sphincter-preserving surgery after preoperative radiochemotherapy for T3 low rectal cancers

    PubMed Central

    BAI, XUE; LI, SHIYONG; YU, BO; SU, HONG; JIN, WEISEN; CHEN, GANG; DU, JUNFENG; ZUO, FUYI

    2012-01-01

    The aim of this study was to evaluate the feasibility and the effectiveness of preoperative radiochemotherapy followed by total mesorectal excision (TME) and sphincter-preserving procedures for T3 low rectal cancer. Patients with rectal cancer and T3 tumors located within 1–6 cm of the dentate line received preoperative radiochemotherapy. Concurrent 5-fluorouracil-based radiochemotherapy was used. Radical resection with TME and sphincter-preserving procedures were performed during the six to eight weeks following radiotherapy. Survival was analyzed using the Kaplan-Meier method. The anal function was evaluated using the Wexner score. The clinical response rate was 83.5%, overall downstaging of T classification was 75.3% and pathological complete response was 15.3%. The anastomotic fistula rate was 4.7%. A median follow-up of 30 months showed the local recurrence rate to be 4.7% and the distant metastasis rate to be 5.9%. The three-year overall survival rate was 87%. The degree of anal incontinence as measured using the Wexner score decreased over time, and the anal sphincter function in the majority of patients gradually improved. Preoperative radiochemotherapy was found to improve tumor downstaging, reduces local recurrence, increase the sphincter preservation rate, and is therefore of benefit to patients with T3 low rectal cancer. PMID:22783445

  2. JAK/STAT/SOCS-signaling pathway and colon and rectal cancer

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Kadlubar, Susan A.; Bondurant, Kristina L.; Wolff, Roger K.

    2012-01-01

    The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in immune function and cell growth. We evaluated the association between genetic variation in JAK1 (10 SNPs), JAK2 (9 SNPs), TYK2 (5 SNPs), SOCS1 (2 SNPs), SOCS2 (2 SNPs), STAT1 (16 SNPs), STAT2 (2 SNPs), STAT3 (6 SNPs), STAT4 (21 SNPs), STAT5A (2 SNPs), STAT5B (3 SNPs), STAT6 (4 SNPs) with risk of colorectal cancer. We used data from population-based case-control studies (colon cancer n=1555 cases, 1956 controls; rectal cancer n=754 cases, 959 controls). JAK2, SOCS2, STAT1, STAT3, STAT5A, STAT5B, and STAT6 were associated with colon cancer; STAT3, STAT4, STAT6, and TYK2 were associated with rectal cancer. Given the biological role of the JAK/STAT-signaling pathway and cytokines, we evaluated interaction with IFNG, TNF, and IL6; numerous statistically significant associations after adjustment for multiple comparisons were observed. The following statistically significant interactions were observed: TYK2 with aspirin/NSAID use; STAT1, STAT4, and TYK2 with estrogen status; and JAK2, STAT2, STAT4, STAT5A, STAT5B, and STAT6 with smoking status and colon cancer risk; JAK2, STAT6, and TYK2 with aspirin/NSAID use; JAK1 with estrogen status; STAT2 with cigarette smoking and rectal cancer. JAK2, SOCS1, STAT3, STAT5, and TYK2 were associated with colon cancer survival (HRR of 3.3 95% CI 2.01, 5.42 for high mutational load). JAK2, SOCS1, STAT1, STAT4, and TYK2 were associated with rectal cancer survival (HRR 2.80 95 %CI 1.63, 4.80). These data support the importance of the JAK/STAT-signaling pathway in colorectal cancer and suggest targets for intervention. PMID:22121102

  3. New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer.

    PubMed

    Kim, Nam Kyu; Hur, Hyuk

    2015-11-01

    Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment. PMID:26446626

  4. New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer

    PubMed Central

    Hur, Hyuk

    2015-01-01

    Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment. PMID:26446626

  5. Diagnostic value of dynamic contrast-enhanced magnetic resonance imaging in rectal cancer and its correlation with tumor differentiation

    PubMed Central

    SHEN, FU; LU, JIANPING; CHEN, LUGUANG; WANG, ZHEN; CHEN, YUKUN

    2016-01-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a novel imaging modality that can be used to reflect the microcirculation, although its value in diagnosing rectal cancer is unknown. The present study aimed to explore the clinical application of DCE-MRI in the preoperative diagnosis of rectal cancer, and its correlation with tumor differentiation. To achieve this, 40 pathologically confirmed patients with rectal cancer and 15 controls were scanned using DCE-MRI. The Tofts model was applied to obtain the perfusion parameters, including the plasma to extravascular volume transfer (Ktrans), the extravascular to plasma volume transfer (Kep), the extravascular fluid volume (Ve) and the initial area under the enhancement curve (iAUC). Receiver-operating characteristic (ROC) curves were plotted to determine the diagnostic value. The results demonstrated that the time-signal intensity curve of the rectal cancer lesion exhibited an outflow pattern. The Ktrans, Kep, Ve, and iAUC values were higher in the cancer patients compared with controls (P<0.05). The intraclass correlation coefficients of Ktrans, Kep, Ve and iAUC, as measured by two independent radiologists, were 0.991, 0.988, 0.972 and 0.984, respectively (all P<0.001), indicating a good consistency. The areas under the ROC curves for Ktrans and iAUC were both >0.9, resulting in a sensitivity and specificity of 100% and 93.3% for Ktrans, and of 92.5%, and 93.3% or 100%, for iAUC, respectively. In the 40 rectal cancer cases, there was a moderate correlation between Ktrans and iAUC, and pathological differentiation (0.3rectal cancer and differentiation, and therefore may provide novel insights into the preoperative diagnosis of rectal cancer. PMID:27073650

  6. Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer

    ClinicalTrials.gov

    2013-01-31

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  7. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    SciTech Connect

    Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  8. What Is the Ideal Tumor Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy?

    PubMed Central

    Kim, Soo Hee; Chang, Hee Jin; Kim, Dae Yong; Park, Ji Won; Baek, Ji Yeon; Kim, Sun Young; Park, Sung Chan; Oh, Jae Hwan; Yu, Ami; Nam, Byung-Ho

    2016-01-01

    Purpose Tumor regression grade (TRG) is predictive of therapeutic response in rectal cancer patients after chemoradiotherapy (CRT) followed by curative resection. However, various TRG systems have been suggested, with subjective categorization, resulting in interobserver variability. This study compared the prognostic validity of four different TRG systems in order to identify the most ideal TRG system. Materials and Methods This study included 933 patients who underwent preoperative CRT and curative resection. Primary tumors alone were graded according to the American Joint Committee on Cancer (AJCC), Dworak, and Ryan TRG systems, and both primary tumors and regional lymph nodes were graded according to a modified Dworak TRG system. The ability of each TRG system to predict recurrence-free survival (RFS) and overall survival (OS) was analyzed using chi-square and C statistics. Results All four TRG systems were significantly predictive of both RFS and OS (p < 0.001 each), however none was a better predictor of prognosis than ypStage. Among the four TRGs, the mDworak TRG system was a better predictor of RFS and OS than the AJCC, Dworak, and Ryan TRG systems, and both the chi-square and C statistics were higher for the former, although the differences were not statistically significant. The combination of ypStage and the modified Dworak TRG better predicted RFS and OS than ypStage alone. Conclusion The modified Dworak TRG system for evaluation of entire tumors including regional lymph nodes is a better predictor of survival than current TRG systems for evaluation of the primary tumor alone. PMID:26511803

  9. The role of targeted agents in preoperative chemoradiation for rectal cancer.

    PubMed

    Wadlow, Raymond C; Ryan, David P

    2010-08-01

    In the United States, randomized trials have established preoperative chemoradiation as the standard of care for patients with locally advanced rectal cancer. Pathologic complete response (pCR) rates occur in 10% to 16% of patients and have been shown to be correlated with both disease-free and overall survival. Therefore, recent efforts incorporating newer cytotoxic and molecularly targeted agents into chemoradiotherapy regimens have reported the pCR rate to be a surrogate marker of clinical outcomes. Substitution of oral fluoropyrimidines, including capecitabine, for infusional 5-fluorouracil reportedly generated pCR rates of up to 32% in phase 2 studies, but definitive evaluation awaits results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial. Similarly, regimens incorporating irinotecan generated pCR rates as high as 38%, but to the authors' knowledge have not been evaluated in randomized trials. In contrast, 2 large randomized trials reported that the addition of weekly oxaliplatin to fluoropyrimidine-based chemoradiation led to an increase in grade 3/4 toxicity but no difference in pCR rates. Early phase trials evaluating the anti-epidermal growth factor receptor (EGFR) antibody cetuximab in combination with chemoradiation reported modest pCR rates of 5% to 12%, and efforts have focused on identifying biomarkers of response including EGFR copy number, k-ras mutational status, and both serum and tumor-specific expression of EGFR ligands. Finally, incorporation of the anti-vascular endothelial growth factor antibody bevacizumab into chemoradiation appears to be safe and feasible, with initial studies reporting a beneficial effect on vascular normalization and correlations between circulating biomarkers of angiogenesis and pathologic response. Future efforts should include prospective studies of these agents in biomarker-defined subpopulations, as well as studies of novel agents that target angiogenesis, tumor-stromal interaction

  10. 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

  11. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer

    PubMed Central

    Park, Jun Seok; Sakai, Yoshiharu; Simon, NG Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-01-01

    Abstract Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer. An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate. The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively. Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

  12. Improved accuracy of computed tomography in local staging of rectal cancer using water enema.

    PubMed

    Lupo, L; Angelelli, G; Pannarale, O; Altomare, D; Macarini, L; Memeo, V

    1996-01-01

    A new technique in the preoperative staging computed tomography of rectal cancer using a water enema to promote full distension of the rectum was compared with standard CT in a non-randomised blind study. One hundred and twenty-one patients were enrolled. There were 57 in the water enema CT group and 64 in the standard group. The stage of the disease was assessed following strict criteria and tested against the pathological examination of the resected specimen. Water enema CT was significantly more accurate than standard CT with an accuracy of 84.2% vs. 62.5% (Kappa: 0.56 vs. 0.33: Kappa Weighted: 0.93 vs. 0.84). The diagnostic gain was mainly evident in the identification of rectal wall invasion within or beyond the muscle layer (94.7 vs. 61). The increased accuracy was 33.7% (CL95: 17-49; P < 0.001). The results indicate that water enema CT should replace CT for staging rectal cancer and may offer an alternative to endorectal ultrasound. PMID:8739828

  13. Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy

    SciTech Connect

    Pfeifer, Daniella; Gao Jingfang; Adell, Gunnar; Sun Xiaofeng . E-mail: xiasu@ibk.liu.se

    2006-07-15

    Purpose: To investigate p73 expression in normal mucosa, primary tumor, and metastasis in relation to radiotherapy (RT) response and clinicopathologic/biologic variables in rectal cancers. Methods and Materials: p73 was immunohistochemically examined on biopsies (unirradiated, n = 102), distant (from the large bowel, n = 82), and adjacent (adjacent to primary tumor, n = 89) normal mucosa samples, primary tumors (n = 131), and lymph node metastasis (n = 32) from rectal cancer patients participating in a clinical trial of preoperative RT. Seventy-four patients received surgery alone and 57 received additional RT. Results: Cytoplasmic p73 was increased in the primary tumor compared with the distant or adjacent mucosa (p {<=} 0.0001). Nuclear (p = 0.02) and cytoplasmic (p = 0.003) p73 was higher in irradiated distant mucosa samples than in unirradiated ones, and nuclear p73 tended to be increased in irradiated primary tumors compared with unirradiated ones (p = 0.06). p73 was positively related to cyclooxygenase-2 expression in irradiated tumors (p = 0.03). p73-negative tumors tended to have a lower local recurrence after RT compared with unirradiated cases (p 0.06). Conclusions: Normal epithelial cells seem more sensitive to RT than tumor cells regarding p73 expression. Patients with p73-negative rectal tumors may have a lower risk of local recurrence after RT.

  14. Low rectal cancer: Sphincter preserving techniques-selection of patients, techniques and outcomes

    PubMed Central

    Dimitriou, Nikoletta; Michail, Othon; Moris, Dimitrios; Griniatsos, John

    2015-01-01

    Low rectal cancer is traditionally treated by abdominoperineal resection. In recent years, several new techniques for the treatment of very low rectal cancer patients aiming to preserve the gastrointestinal continuity and to improve both the oncological as well as the functional outcomes, have been emerged. Literature suggest that when the intersphincteric resection is applied in T1-3 tumors located within 30-35 mm from the anal verge, is technically feasible, safe, with equal oncological outcomes compared to conventional surgery and acceptable quality of life. The Anterior Perineal PlanE for Ultra-low Anterior Resection technique, is not disrupting the sphincters, but carries a high complication rate, while the reports on the oncological and functional outcomes are limited. Transanal Endoscopic MicroSurgery (TEM) and TransAnal Minimally Invasive Surgery (TAMIS) should represent the treatment of choice for T1 rectal tumors, with specific criteria according to the NCCN guidelines and favorable pathologic features. Alternatively to the standard conventional surgery, neoadjuvant chemo-radiotherapy followed by TEM or TAMIS seems promising for tumors of a local stage T1sm2-3 or T2. Transanal Total Mesorectal Excision should be performed only when a board approved protocol is available by colorectal surgeons with extensive experience in minimally invasive and transanal endoscopic surgery. PMID:26191350

  15. Adoption of Preoperative Radiation Therapy for Rectal Cancer From 2000 to 2006: A Surveillance, Epidemiology, and End Results Patterns-of-Care Study

    SciTech Connect

    Mak, Raymond H.; McCarthy, Ellen P.; Das, Prajnan; Hong, Theodore S.; Mamon, Harvey J.

    2011-07-15

    Purpose: The German rectal study determined that preoperative radiation therapy (RT) as a component of combined-modality therapy decreased local tumor recurrence, increased sphincter preservation, and decreased treatment toxicity compared with postoperative RT for rectal cancer. We evaluated the use of preoperative RT after the presentation of the landmark German rectal study results and examined the impact of tumor and sociodemographic factors on receiving preoperative RT. Methods and Materials: In total, 20,982 patients who underwent surgical resection for T3-T4 and/or node-positive rectal adenocarcinoma diagnosed from 2000 through 2006 were identified from the Surveillance, Epidemiology, and End Results tumor registries. We analyzed trends in preoperative RT use before and after publication of the findings from the German rectal study. We also performed multivariate logistic regression to identify factors associated with receiving preoperative RT. Results: Among those treated with RT, the proportion of patients treated with preoperative RT increased from 33.3% in 2000 to 63.8% in 2006. After adjustment for age; gender; race/ethnicity; marital status; Surveillance, Epidemiology, and End Results registry; county-level education; T stage; N stage; tumor size; and tumor grade, there was a significant association between later year of diagnosis and an increase in preoperative RT use (adjusted odds ratio, 1.26/y increase; 95% confidence interval, 1.23-1.29). When we compared the years before and after publication of the German rectal study (2000-2003 vs. 2004-2006), patients were more likely to receive preoperative RT than postoperative RT in 2004-2006 (adjusted odds ratio, 2.35; 95% confidence interval, 2.13-2.59). On multivariate analysis, patients who were older, who were female, and who resided in counties with lower educational levels had significantly decreased odds of receiving preoperative RT. Conclusions: After the publication of the landmark German rectal

  16. Germline and somatic genetic predictors of pathological response in neoadjuvant settings of rectal and esophageal cancers: systematic review and meta-analysis.

    PubMed

    Salnikova, L E; Kolobkov, D S

    2016-06-01

    Oncologists have pointed out an urgent need for biomarkers that can be useful for clinical application to predict the susceptibility of patients to preoperative therapy. This review collects, evaluates and combines data on the influence of reported somatic and germline genetic variations on histological tumor regression in neoadjuvant settings of rectal and esophageal cancers. Five hundred and twenty-seven articles were identified, 204 retrieved and 61 studies included. Among 24 and 14 genetic markers reported for rectal and esophageal cancers, respectively, significant associations in meta-analyses were demonstrated for the following markers. In rectal cancer, major response was more frequent in carriers of the TYMS genotype 2 R/2 R-2 R/3 R (rs34743033), MTHFR genotype 677C/C (rs1801133), wild-type TP53 and KRAS genes. In esophageal cancer, successful therapy appeared to correlate with wild-type TP53. These results may be useful for future research directions to translate reported data into practical clinical use. PMID:26122021

  17. Treatment of rectal cancer by transanal endoscopic microsurgery: Experience with 425 patients

    PubMed Central

    Guerrieri, Mario; Gesuita, Rosaria; Ghiselli, Roberto; Lezoche, Giovanni; Budassi, Andrea; Baldarelli, Maddalena

    2014-01-01

    AIM: To describe our experience in treating rectal cancer by transanal endoscopic microsurgery (TEM), report morbidity and mortality and oncological outcome. METHODS: A total of 425 patients with rectal cancer (120 T1, 185 T2, 120 T3 lesions) were staged by digital rectal examination, rectoscopy, transanal endosonography, magnetic resonance imaging and/or computed tomography. Patients with T1-N0 lesions and favourable histological features underwent TEM immediately. Patients with preoperative stage T2-T3-N0 underwent preoperative high-dose radiotherapy; from 1997 those aged less than 70 years and in good general health also underwent preoperative chemotherapy. Patients with T2-T3-N0 lesions were restaged 30 d after radiotherapy and were then operated on 40-50 d after neoadjuvant therapy. The instrumentation designed by Buess was used for all procedures. RESULTS: There were neither perioperative mortality nor intraoperative complications. Conversion to other surgical procedures was never required. Major complications (urethral lesions, perianal or retroperitoneal phlegmon and rectovaginal fistula) occurred in six (1.4%) patients and minor complications (partial suture line dehiscence, stool incontinence and rectal haemorrhage) in 42 (9.9%). Postoperative pain was minimal. Definitive histological examination of the 425 malignant lesions showed 80 (18.8%) pT0, 153 (36%) pT1, 151 (35.5%) pT2, and 41 (9.6%) pT3 lesions. Eighteen (4.2%) patients (ten pT2 and eight pT3) had a local recurrence and 16 (3.8%) had distant metastasis. Cancer-specific survival rates at the end of follow-up were 100% for pT1 patients (253 mo), 93% for pT2 patients (255 mo) and 89% for pT3 patients (239 mo). CONCLUSION: TEM is a safe and effective procedure to treat rectal cancer in selected patients without evidence of nodal involvement. T2-T3 lesions require preoperative neoadjuvant therapy. PMID:25071352

  18. Tumor vascularity evaluated by transrectal color Doppler US in predicting therapy outcome for low-lying rectal cancer

    SciTech Connect

    Barbaro, Brunella . E-mail: a.leonemd@tiscalinet.it; Valentini, Vincenzo; Coco, Claudio; Mancini, Anna Paola; Gambacorta, Maria Antonietta; Vecchio, Fabio Maria; Bonomo, Lorenzo

    2005-12-01

    Purpose: To evaluate the impact on T downstaging of the vasculature supplying blood flow to rectal cancer evaluated by color Doppler ultrasound. Methods and Materials: Color Doppler images were graded in 29 T3-staged rectal carcinoma patients sonographically just before chemoradiation. Any arterial vessels detected in rectal masses were assigned one of two grades: vascularity was considered as grade 1 for vessels feeding the periphery and as grade 2 for vessels coursing in all rectal masses within its peripheral and central portions. The pulsatility indices (PI = peak systolic velocity - end-diastolic velocity/time-averaged maximum velocity) were calculated in the central and peripheral portions. Results: The pathologic observations showed a change in stage in 15 of the 23 patients graded 2, positive predictive value 65.2% (p = 0.047), and in one of the six rectal cancers graded 1 (negative predictive value, 83.3%). The minimal peripheral PI values in rectal cancer graded 2 were higher in nonresponding (2.2 {+-} 1.3) than in responding lesions (1.6 {+-} 0.7) p = 0.01. Conclusion: Vascularity graded 2 associated with low peripheral PI values are indicators of therapy outcome. Vascularity graded 1 and high peripheral PI values in graded 2 have negative predictive value.

  19. Use of Valtrac™-Secured Intracolonic Bypass in Laparoscopic Rectal Cancer Resection

    PubMed Central

    Ye, Feng; Chen, Dong; Wang, Danyang; Lin, Jianjiang; Zheng, Shusen

    2014-01-01

    Abstract The occurrence of anastomotic leakage (AL) remains a major concern in the early postoperative stage. Because of the relatively high morbidity and mortality of AL in patients with laparoscopic low rectal cancer who receive an anterior resection, a fecal diverting method is usually introduced. The Valtrac™-secured intracolonic bypass (VIB) was used in open rectal resection, and played a role of protecting the anastomotic site. This study was designed to assess the efficacy and safety of the VIB in protecting laparoscopic low rectal anastomosis and to compare the efficacy and complications of VIB with those of loop ileostomy (LI). Medical records of the 43 patients with rectal cancer who underwent elective laparoscopic low anterior resection and received VIB procedure or LI between May 2011 and May 2013 were retrospectively analyzed, including the patients’ demographics, clinical features, and operative data. Twenty-four patients received a VIB and 19 patients a LI procedure. Most of the demographics and clinical features of the groups, including Dukes stages, were similar. However, the median distance of the tumor edge from the anus verge in the VIB group was significantly longer (7.5 cm; inter-quartile range [IQR] 7.0–9.5 cm) than that of the L1 group (6.0 cm; IQR 6.0–7.0 cm). None of the patients developed clinical AL. The comparisons between the LI and the VIB groups were adjusted for the significant differences in the tumor level of the groups. After adjustment, the LI group experienced longer overall postoperative hospital stay (14.0 days, IQR: 12.0, 16.0 days; P < 0.001) and incurred higher costs ($6300 (IQR: $5900, $6600)) than the VIB group (7.0 days, $4800; P < 0.05). Stoma-related complications in the ileostomy group included dermatitis (n = 2), stoma bleeding (n = 1), and wound infection after closure (n = 2). No BAR-related complications occurred. The mean time to Valtrac™ ring loosening was 14.1 ± 3

  20. High Frequency of CD8 Positive Lymphocyte Infiltration Correlates with Lack of Lymph Node Involvement in Early Rectal Cancer

    PubMed Central

    Däster, Silvio; Eppenberger-Castori, Serenella; Hirt, Christian; Zlobec, Inti; Delko, Tarik; Nebiker, Christian A.; Soysal, Savas D.; Amicarella, Francesca; Iezzi, Giandomenica; Sconocchia, Giuseppe; Heberer, Michael; Lugli, Alessandro; Spagnoli, Giulio C.; Kettelhack, Christoph; Terracciano, Luigi; Oertli, Daniel; von Holzen, Urs; Tornillo, Luigi; Droeser, Raoul A.

    2014-01-01

    Aims. A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. Methods. A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2) was stained for several immunomarkers of the innate and the adaptive immune response. Patients' survival and nodal status were analyzed and correlated with infiltration of the different immune cells. Results. Of all tested markers, only CD8 (P = 0.005) and TIA-1 (P = 0.05) were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect “per se,” CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992–0.996; P = 0.009 and OR 0.988; 95% CI 0.984–0.994; P = 0.05, resp.). An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (P < 0.00001). Conclusion. Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients' nodal involvement. PMID:25609852

  1. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: a single center experience

    PubMed Central

    Choi, Euncheol; Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu

    2016-01-01

    Purpose: To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). Materials and Methods: We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. Results: The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. Conclusion: We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results. PMID:27306776

  2. Late Side Effects and Quality of Life After Radiotherapy for Rectal Cancer

    SciTech Connect

    Bruheim, Kjersti; Guren, Marianne G.; Skovlund, Eva; Hjermstad, Marianne J.; Dahl, Olav; Frykholm, Gunilla; Carlsen, Erik; Tveit, Kjell Magne

    2010-03-15

    Purpose: There is little knowledge on long-term morbidity after radiotherapy (50 Gy) and total mesorectal excision for rectal cancer. Therefore, late effects on bowel, anorectal, and urinary function, and health-related quality of life (QoL), were studied in a national cohort (n = 535). Methods and Materials: All Norwegian patients who received pre- or postoperative (chemo-)radiotherapy for rectal cancer from 1993 to 2003 were identified. Patients treated with surgery alone served as controls. Patients were without recurrence or metastases. Bowel and urinary function was scored with the LENT SOMA scale and the St. Marks Score for fecal incontinence and QoL with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Results: Median time since surgery was 4.8 years. Radiation-treated (RT+) patients (n = 199) had increased bowel frequency compared with non-radiation-treated (RT-) patients (n = 336); 19% vs. 6% had more than eight daily bowel movements (p < 0.001). In patients without stoma, a higher proportion of RT+ (n = 69) compared with RT- patients (n = 240), were incontinent for liquid stools (49% vs. 15%, p < 0.001), needed a sanitary pad (52% vs. 13%, p < 0.001), and lacked the ability to defer defecation (44% vs. 16%, p < 0.001). Daily urinary incontinence occurred more frequently after radiotherapy (9% vs. 2%, p = 0.001). Radiation-treated patients had worse social function than RT- patients, and patients with fecal or urinary incontinence had impaired scores for global quality of life and social function (p < 0.001). Conclusions: Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

  3. SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients

    SciTech Connect

    Kotti, Angeliki Holmqvist, Annica; Albertsson, Maria; Sun, Xiao-Feng

    2014-04-01

    Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  4. Combined radiation therapy, mitomycin C, and 5-fluorouracil for locally recurrent rectal carcinoma: results of a pilot study.

    PubMed

    Wong, C S; Cummings, B J; Keane, T J; Dobrowsky, W; O'Sullivan, B; Catton, C N

    1991-10-01

    Twenty-two patients underwent combined radiation therapy (XRT), mitomycin C (MMC), and 5-fluorouracil (5FU) for rectal carcinoma, locally recurrent following either abdominoperineal or anterior resections. All patients presented with symptomatic unresectable pelvic cancer. The protocol XRT doses were 45-50 Gy/20/4-6 weeks. Chemotherapy consisted of MMC 10 mg/m2 on day 1, and 5FU 15 mg/kg/day on days 1, 2, and 3 of XRT, both given by intravenous bolus injection. Only 2 of 22 patients remained NED at 5 years following treatment. All but four patients eventually experienced progression of pelvic disease. Ten of 22 patients were unable to complete the treatment protocol because of excessive acute hematological and gastrointestinal toxicity. Five patients developed neutropenic sepsis, one of whom died. Combined XRT, MMC, and 5FU as used in this study had no apparent advantage over XRT alone in terms of pelvic disease or survival, and produced significant toxicity. PMID:1938526

  5. [Mesorectal Lymph Node Metastasis Arising from Rectal Invasion by an Ovarian Cancer--A Case Report].

    PubMed

    Mizuki, Toru; Shimada, Yoshifumi; Yagi, Yutaka; Tajima, Yosuke; Nakano, Mae; Nakano, Masato; Tatsuda, Kumiko; Ishikawa, Takashi; Sakata, Jun; Kameyama, Hitoshi; Kobayashi, Takashi; Kosugi, Shin-ichi; Koyama, Yu; Wakai, Toshifumi; Enomoto, Takayuki

    2015-11-01

    A 58-year-old woman presenting with abdominal distension was diagnosed with a tumor in the right ovary. A chest-abdominal-pelvic computed tomography scan revealed multiple lung metastases, multiple liver metastases, and peritoneal dissemination. Invasion of the rectum by peritoneal dissemination of the Douglas' pouch was suspected. She was diagnosed with Stage Ⅳ right ovarian cancer and was treated with preoperative chemotherapy. After chemotherapy, debulking surgery of the abdominal cavity (total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and Hartmann's procedure) was performed. Because there was swelling observed in multiple mesorectal lymph nodes, lymph node dissection was performed based on methods used for rectal cancer surgery. Postoperative histopathological examination revealed multiple mesorectal lymph node metastases arising from ovarian cancer. We suggest that mesorectal lymph node dissection be considered a part of debulking surgery for ovarian cancers that have invaded the rectum. PMID:26805344

  6. An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer

    PubMed Central

    Agostini, Marco; Janssen, Klaus-Peter; Kim, ll-Jin; D'Angelo, Edoardo; Pizzini, Silvia; Zangrando, Andrea; Zanon, Carlo; Pastrello, Chiara; Maretto, Isacco; Digito, Maura; Bedin, Chiara; Jurisica, Igor; Rizzolio, Flavio; Giordano, Antonio; Bortoluzzi, Stefania

    2015-01-01

    Introduction Colorectal cancer is the third most common cancer in the world, a small fraction of which is represented by locally advanced rectal cancer (LARC). If not medically contraindicated, preoperative chemoradiotherapy, represent the standard of care for LARC patients. Unfortunately, patients shows a wide range of response rates in which approximately 20% has a complete pathological response, whereas in 20 to 40% the response is poor or absent. Results The following specific gene signature, able to discriminate responders' patients from non-responders, were founded: AKR1C3, CXCL11, CXCL10, IDO1, CXCL9, MMP12 and HLA-DRA. These genes are mainly involved in immune system pathways and interact with drugs traditionally used in the adjuvant treatment of rectal cancer. Discussion The present study suggests that new ideas for therapy could be found not only limited to studying genes differentially expressed between the two groups of patients but deepening the mechanisms, associated to response, in which they are involved. Methods Gene expression studies performed by: Agostini et al., Rimkus et al. and Kim et al. have been merged through a meta-analysis of the raw data. Gene expression data-sets have been processed using A-MADMAN. Common differentially expressed gene (DEG) were identified through SAM analysis. To further characterize the identified DEG we deeply investigated its biological role using an integrative computational biology approach. PMID:26359356

  7. The diagnosis and management of rectal cancer: expert discussion and recommendations derived from the 9th World Congress on Gastrointestinal Cancer, Barcelona, 2007.

    PubMed

    Van Cutsem, E; Dicato, M; Haustermans, K; Arber, N; Bosset, J-F; Cunningham, D; De Gramont, A; Diaz-Rubio, E; Ducreux, M; Goldberg, R; Glynne-Jones, R; Haller, D; Kang, Y-K; Kerr, D; Labianca, R; Minsky, B D; Moore, M; Nordlinger, B; Rougier, P; Scheithauer, W; Schmoll, H-J; Sobrero, A; Tabernero, J; Tempero, M; Van de Velde, C; Zalcberg, J

    2008-06-01

    Knowledge of the biology and management of rectal cancer continues to improve. A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is mandatory, to assure optimal diagnosis and staging, surgery, selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management. Moreover, optimal symptom management also requires a dedicated team of health care professionals. The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery. High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control. There are now randomized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting. Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy. Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer. New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority. Those involved in the care for patients with rectal cancer should be encouraged to participate in well-designed clinical trials, to increase the evidence-based knowledge and to make further progress. Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise. PMID:18539618

  8. Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome

    PubMed Central

    Haderlein, Marlen

    2016-01-01

    Background. Apoptotic rates in peripheral blood lymphocytes can predict radiation induced normal tissue toxicity. We studied whether apoptosis in lymphocytes has a prognostic value for therapy outcome. Methods. Lymphocytes of 87 rectal cancer patients were ex vivo irradiated with 2 Gy, 8 Gy, or a combination of 2 Gy ionizing radiation and Oxaliplatin. Cells were stained with Annexin V and 7-Aminoactinomycin D and apoptotic and necrotic rates were analyzed by multicolor flow cytometry. Results. After treatment, apoptotic and necrotic rates in CD8+ cells are consistently higher than in CD4+ cells, with lower corresponding necrotic rates. Apoptotic and necrotic rates of CD4+ cells and CD8+ cells correlated well within the 2 Gy, 8 Gy, and 2 Gy and Oxaliplatin arrangements (p ≤ 0.009). High apoptotic CD8+ rates after 2 Gy, 8 Gy, and 2 Gy + Oxaliplatin treatment were prognostically favorable for metastasis-free survival (p = 0.009, p = 0.038, and p = 0.009) and disease-free survival (p = 0.013, p = 0.098, and p = 0.013). Conclusions. Ex vivo CD8+ apoptotic rates are able to predict the patient outcome in regard to metastasis-free or disease-free survival. Patients with higher CD8+ apoptotic rates in the peripheral blood have a more favorable prognosis. In addition to the prediction of late-toxicity by utilization of CD4+ apoptotic rates, the therapy outcome can be predicted by CD8+ apoptotic rates. PMID:27340400

  9. Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer.

    PubMed

    Molinari, Chiara; Matteucci, Federica; Caroli, Paola; Passardi, Alessandro

    2015-12-01

    Standard treatment of patients with locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (NCRT) followed by surgery. Tumor regression after NCRT varies substantially among individuals and pathological complete response is a known prognostic factor for LARC. The identification of a predictive model for response to chemoradiotherapy would help clinicians to identify patients who would probably benefit from multimodal treatment and to perform an early assessment of individual prognosis. Carcinoembryonic antigen has proven to be a good predictor of response in several clinical trials. Other widely studied predictive models in LARC include molecular biomarkers, analyzed at various levels and by different techniques, and molecular imaging, in particular magnetic resonance imaging and positron emission tomography/computed tomography. Although none of the studied markers have been approved in clinical practice, their evaluation in larger, prospective trials and in combined predictive models could be of use to define tailored therapeutic strategies. PMID:26170142

  10. Strategies to evaluate the impact of rectal volume on prostate motion during three-dimensional conformal radiotherapy for prostate cancer*

    PubMed Central

    Poli, Ana Paula Diniz Fortuna; Dias, Rodrigo Souza; Giordani, Adelmo José; Segreto, Helena Regina Comodo; Segreto, Roberto Araujo

    2016-01-01

    Objective To evaluate the rectal volume influence on prostate motion during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Materials and Methods Fifty-one patients with prostate cancer underwent a series of three computed tomography scans including an initial planning scan and two subsequent scans during 3D-CRT. The organs of interest were outlined. The prostate contour was compared with the initial CT images considering the anterior, posterior, superior, inferior and lateral edges of the organ. Variations in the anterior limits and volume of the rectum were assessed and correlated with prostate motion in the anteroposterior direction. Results The maximum range of prostate motion was observed in the superoinferior direction, followed by the anteroposterior direction. A significant correlation was observed between prostate motion and rectal volume variation (p = 0.037). A baseline rectal volume superior to 70 cm3 had a significant influence on the prostate motion in the anteroposterior direction (p = 0.045). Conclusion The present study showed a significant interfraction motion of the prostate during 3D-CRT with greatest variations in the superoinferior and anteroposterior directions, and that a large rectal volume influences the prostate motion with a cutoff value of 70 cm3. Therefore, the treatment of patients with a rectal volume > 70 cm3 should be re-planned with appropriate rectal preparation. PMID:26929456

  11. Total mesorectal excision for mid and low rectal cancer: Laparoscopic vs robotic surgery

    PubMed Central

    Feroci, Francesco; Vannucchi, Andrea; Bianchi, Paolo Pietro; Cantafio, Stefano; Garzi, Alessia; Formisano, Giampaolo; Scatizzi, Marco

    2016-01-01

    AIM: To compare the short- and long-term outcomes of laparoscopic and robotic surgery for middle and low rectal cancer. METHODS: This is a retrospective study on a prospectively collected database containing 111 patients who underwent minimally invasive rectal resection with total mesorectal excision (TME) with curative intent between January 2008 and December 2014 (robot, n = 53; laparoscopy, n = 58). The patients all had a diagnosis of middle and low rectal adenocarcinoma with stage I-III disease. The median follow-up period was 37.4 mo. Perioperative results, morbidity a pathological data were evaluated and compared. The 3-year overall survival and disease-free survival rates were calculated and compared. RESULTS: Patients were comparable in terms of preoperative and demographic parameters. The median surgery time was 192 min for laparoscopic TME (L-TME) and 342 min for robotic TME (R-TME) (P < 0.001). There were no differences found in the rates of conversion to open surgery and morbidity. The patients who underwent laparoscopic surgery stayed in the hospital two days longer than the robotic group patients (8 d for L-TME and 6 d for R-TME, P < 0.001). The pathologic evaluation showed a higher number of harvested lymph nodes in the robotic group (18 for R-TME, 11 for L-TME, P < 0.001) and a shorter distal resection margin for laparoscopic patients (1.5 cm for L-TME, 2.5 cm for R-TME, P < 0.001). The three-year overall survival and disease-free survival rates were similar between groups. CONCLUSION: Both L-TME and R-TME achieved acceptable clinical and oncologic outcomes. The robotic technique showed some advantages in rectal surgery that should be validated by further studies. PMID:27053852

  12. Rectal cancer staging: Multidetector-row computed tomography diagnostic accuracy in assessment of mesorectal fascia invasion

    PubMed Central

    Ippolito, Davide; Drago, Silvia Girolama; Franzesi, Cammillo Talei; Fior, Davide; Sironi, Sandro

    2016-01-01

    AIM: To assess the diagnostic accuracy of multidetector-row computed tomography (MDCT) as compared with conventional magnetic resonance imaging (MRI), in identifying mesorectal fascia (MRF) invasion in rectal cancer patients. METHODS: Ninety-one patients with biopsy proven rectal adenocarcinoma referred for thoracic and abdominal CT staging were enrolled in this study. The contrast-enhanced MDCT scans were performed on a 256 row scanner (ICT, Philips) with the following acquisition parameters: tube voltage 120 KV, tube current 150-300 mAs. Imaging data were reviewed as axial and as multiplanar reconstructions (MPRs) images along the rectal tumor axis. MRI study, performed on 1.5 T with dedicated phased array multicoil, included multiplanar T2 and axial T1 sequences and diffusion weighted images (DWI). Axial and MPR CT images independently were compared to MRI and MRF involvement was determined. Diagnostic accuracy of both modalities was compared and statistically analyzed. RESULTS: According to MRI, the MRF was involved in 51 patients and not involved in 40 patients. DWI allowed to recognize the tumor as a focal mass with high signal intensity on high b-value images, compared with the signal of the normal adjacent rectal wall or with the lower tissue signal intensity background. The number of patients correctly staged by the native axial CT images was 71 out of 91 (41 with involved MRF; 30 with not involved MRF), while by using the MPR 80 patients were correctly staged (45 with involved MRF; 35 with not involved MRF). Local tumor staging suggested by MDCT agreed with those of MRI, obtaining for CT axial images sensitivity and specificity of 80.4% and 75%, positive predictive value (PPV) 80.4%, negative predictive value (NPV) 75% and accuracy 78%; while performing MPR the sensitivity and specificity increased to 88% and 87.5%, PPV was 90%, NPV 85.36% and accuracy 88%. MPR images showed higher diagnostic accuracy, in terms of MRF involvement, than native axial images

  13. Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer.

    PubMed

    Lutz, Manfred P; Zalcberg, John R; Glynne-Jones, Rob; Ruers, Theo; Ducreux, Michel; Arnold, Dirk; Aust, Daniela; Brown, Gina; Bujko, Krzysztof; Cunningham, Christopher; Evrard, Serge; Folprecht, Gunnar; Gerard, Jean-Pierre; Habr-Gama, Angelita; Haustermans, Karin; Holm, Torbjörn; Kuhlmann, Koert F; Lordick, Florian; Mentha, Gilles; Moehler, Markus; Nagtegaal, Iris D; Pigazzi, Alessio; Puciarelli, Salvatore; Roth, Arnaud; Rutten, Harm; Schmoll, Hans-Joachim; Sorbye, Halfdan; Van Cutsem, Eric; Weitz, Jürgen; Otto, Florian

    2016-08-01

    Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic

  14. Efficacy of Immunohistochemical Staining in Differentiating a Squamous Cell Carcinoma in Poorly Differentiated Rectal Cancer: Two Case Reports

    PubMed Central

    Rami, Sairafi; Han, Yoon Dae; Jang, Mi; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young

    2016-01-01

    A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient. PMID:27626026

  15. Robotic Low Ligation of the Inferior Mesenteric Artery for Rectal Cancer Using the Firefly Technique

    PubMed Central

    Bae, Sung Uk; Min, Byung Soh

    2015-01-01

    Purpose By integrating intraoperative near infrared fluorescence imaging into a robotic system, surgeons can identify the vascular anatomy in real-time with the technical advantages of robotics that is useful for meticulous lymphovascular dissection. Herein, we report our initial experience of robotic low ligation of the inferior mesenteric artery (IMA) with real-time identification of the vascular system for rectal cancer using the Firefly technique. Materials and Methods The study group included 11 patients who underwent a robotic total mesorectal excision with preservation of the left colic artery for rectal cancer using the Firefly technique between July 2013 and December 2013. Results The procedures included five low anterior resections and six ultra-low anterior resections with loop ileostomy. The median total operation time was 327 min (226-490). The low ligation time was 10 min (6-20), and the time interval between indocyanine green injection and division of the sigmoid artery was 5 min (2-8). The estimated blood loss was 200 mL (100-500). The median time to soft diet was 4 days (4-5), and the median length of stay was 7 days (5-9). Three patients developed postoperative complications; one patients developed anal stricture, one developed ileus, and one developed non-complicated intraabdominal fluid collection. The median total number of lymph nodes harvested was 17 (9-29). Conclusion Robotic low ligation of the IMA with real-time identification of the vascular system for rectal cancer using the Firefly technique is safe and feasible. This technique can allow for precise lymph node dissection along the IMA and facilitate the identification of the left colic branch of the IMA. PMID:26069127

  16. Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

    SciTech Connect

    Yoon, Frederick H.; Perera, Francisco Fisher, Barbara; Stitt, Larry

    2009-07-15

    Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.

  17. Robotic-assisted surgery versus open surgery in the treatment of rectal cancer: the current evidence.

    PubMed

    Liao, Guixiang; Li, Yan-Bing; Zhao, Zhihong; Li, Xianming; Deng, Haijun; Li, Gang

    2016-01-01

    The aim of this meta-analysis was to comprehensively compare the safety and efficacy of robotic-assisted rectal cancer surgery (RRCS) and open rectal cancer surgery (ORCS). Electronic database (PubMed, EMBASE, Web of Knowledge, and the Cochrane Library) searches were conducted for all relevant studies that compared the short-term and long-term outcomes between RRCS and ORCS. Odds ratios (ORs), mean differences, and hazard ratios were calculated. Seven studies involving 1074 patients with rectal cancer were identified for this meta-analysis. Compared with ORCS, RRCS is associated with a lower estimated blood loss (mean difference [MD]: -139.98, 95% confidence interval [CI]: -159.11 to -120.86; P < 0.00001), shorter hospital stay length (MD: -2.10, 95% CI: -3.47 to -0.73; P = 0.003), lower intraoperative transfusion requirements (OR: 0.52, 95% CI: 0.28 to 0.99, P = 0.05), shorter time to flatus passage (MD: -0.97, 95% CI = -1.06 to -0.88, P < 0.00001), and shorter time to resume a normal diet (MD: -1.71.95% CI = -3.31 to -0.12, P = 0.04). There were no significant differences in surgery-related complications, oncologic clearance, disease-free survival, and overall survival between the two groups. However, RRCS was associated with a longer operative time. RRCS is safe and effective. PMID:27228906

  18. Robotic versus conventional laparoscopic surgery for rectal cancer: systematic review and meta-analysis

    PubMed Central

    Lee, Seon Heui; Lim, Sungwon; Kim, Jin Hee

    2015-01-01

    Purpose Robotic surgery (RS) overcomes the limitations of previous conventional laparoscopic surgery (CLS). Although meta-analyses have been published recently, our study evaluated the latest comparative surgical, urologic, and sexual results for rectal cancer and compares RS with CLS in patients with rectal cancer only. Methods We searched three foreign databases (Ovid-MEDLINE, Ovid-Embase, and Cochrane Library) and five Korean databases (KoreaMed, KMbase, KISS, RISS, and KisTi) during July 2013. The Cochrane Risk of Bias and the Methodological Index for Non-Randomized were utilized to evaluate quality of study. Dichotomous variables were pooled using the risk ratio (RR), and continuous variables were pooled using the mean difference (MD). All meta-analyses were conducted with Review Manager, V. 5.3. Results Seventeen studies involving 2,224 patients were included. RS was associated with a lower rate of intraoperative conversion than that of CLS (RR, 0.28; 95% confidence interval [CI], 0.15-0.54). Time to first flatus was short (MD, -0.13; 95% CI, -0.25 to -0.01). Operating time was longer for RS than that for CLS (MD, 49.97; 95% CI, 20.43-79.52, I2 = 97%). International Prostate Symptom Score scores at 3 months better RS than CLS (MD, -2.90; 95% CI, -5.31 to -0.48, I2 = 0%). International Index of Erectile Function scores showed better improvement at 3 months (MD, -2.82; 95% CI, -4.78 to -0.87, I2 = 37%) and 6 months (MD, -2.15; 95% CI, -4.08 to -0.22, I2 = 0%). Conclusion RS appears to be an effective alternative to CLS with a lower conversion rate to open surgery, a shorter time to first flatus and better recovery in voiding and sexual function. RS could enhance postoperative recovery in patients with rectal cancer. PMID:26448918

  19. Optimal time interval between capecitabine intake and radiotherapy in preoperative chemoradiation for locally advanced rectal cancer

    SciTech Connect

    Yu, Chang Sik; Kim, Tae Won; Kim, Jong Hoon . E-mail: jhkim2@amc.seoul.kr; Choi, Won Sik; Kim, Hee Cheol; Chang, Heung Moon; Ryu, Min Hee; Jang, Se Jin; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Choi, Eun Kyung; Kim, Jin Cheon

    2007-03-15

    Purpose: Capecitabine and its metabolites reach peak plasma concentrations 1 to 2 hours after a single oral administration, and concentrations rapidly decrease thereafter. We performed a retrospective analysis to find the optimal time interval between capecitabine administration and radiotherapy for rectal cancer. Methods and Materials: The time interval between capecitabine intake and radiotherapy was measured in patients who were treated with preoperative radiotherapy and concurrent capecitabine for rectal cancer. Patients were classified into the following groups. Group A1 included patients who took capecitabine 1 hour before radiotherapy, and Group B1 included all other patients. Group B1 was then subdivided into Group A2 (patients who took capecitabine 2 hours before radiotherapy) and Group B2. Group B2 was further divided into Group A3 and Group B3 with the same method. Total mesorectal excision was performed 6 weeks after completion of chemoradiation and the pathologic response was evaluated. Results: A total of 200 patients were enrolled in this study. Pathologic examination showed that Group A1 had higher rates of complete regression of primary tumors in the rectum (23.5% vs. 9.6%, p = 0.01), good response (44.7% vs. 25.2%, p = 0.006), and lower T stages (p = 0.021) compared with Group B1; however, Groups A2 and A3 did not show any improvement compared with Groups B2 and B3. Multivariate analysis showed that increases in primary tumors in the rectum and good response were only significant when capecitabine was administered 1 hour before radiotherapy. Conclusion: In preoperative chemoradiotherapy for rectal cancer, the pathologic response could be improved by administering capecitabine 1 hour before radiotherapy.

  20. Survival implications of pretreatment pelvic CT in rectal cancer patients after neoadjuvant chemoradiotherapy and surgery

    PubMed Central

    Cui, Chunyan; Zhang, Min; Tian, Li; Jiang, Wu; Zeng, Zhifang; Li, Li

    2015-01-01

    Purpose: To determine the correlation between pretreatment computed tomography (CT) data and survival duration after neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. Materials and methods: 122 consecutive patients with advanced rectal cancer were assessed retrospectively. Pretreatment imaging and postoperative data were evaluated through Kaplan-Meier and Cox proportional hazard regression analyses. Results: Pretreatment CT identified 557 metastatic lymph nodes (mean, 4.55 per patient; median 4). Survival durations were measured during the period between the application of CT and death or the last follow-up examination. Univariate analysis showed that the following factors had a significant impact on survival: maximum tumor diameter (P = 0.019), distance from inferior tumor margin to anorectal ring (P <0.0001), number of lymph nodes involved in patients with short-axis, lymph node diameter ≥8 mm (P <0.0001) in pretreatment CT, distance from the anorectal ring (P = 0.027), ypN stage (P = 0.0008), ypM stage (P = 0.046) and number of metastatic lymph nodes (P <0.0001) in clinical assessment. Multivariate analysis showed that the following factors were significant: number of lymph nodes in patients with short-axis lymph node diameter ≥5 mm but <8 mm (P = 0.044) and in those with this diameter ≥8 mm (P = 0.028; pretreatment CT) and number of metastatic lymph nodes (assessed in histopathological examination). Conclusion: Pretreatment lymph node size and number can predict survival duration after treatment for locally advanced rectal cancer. For patients with lymph nodes >8 mm (short-axis diameter) and/or >1, such lymph nodes tend to have a poor performance for prognosis. PMID:26550194

  1. Evaluation of Tumor Response after Short-Course Radiotherapy and Delayed Surgery for Rectal Cancer

    PubMed Central

    Rega, Daniela; Pecori, Biagio; Scala, Dario; Avallone, Antonio; Pace, Ugo; Petrillo, Antonella; Aloj, Luigi; Tatangelo, Fabiana; Delrio, Paolo

    2016-01-01

    Purpose Neoadjuvant therapy is able to reduce local recurrence in rectal cancer. Immediate surgery after short course radiotherapy allows only for minimal downstaging. We investigated the effect of delayed surgery after short-course radiotherapy at different time intervals before surgery, in patients affected by rectal cancer. Methods From January 2003 to December 2013 sixty-seven patients with the following characteristics have been selected: clinical (c) stage T3N0 ≤ 12 cm from the anal verge and with circumferential resection margin > 5 mm (by magnetic resonance imaging); cT2, any N, < 5 cm from anal verge; and patients facing tumors with enlarged nodes and/or CRM+ve who resulted unfit for chemo-radiation, were also included. Patients underwent preoperative short-course radiotherapy with different interval to surgery were divided in three groups: A (within 6 weeks), B (between 6 and 8 weeks) and C (after more than 8 weeks). Hystopatolgical response to radiotherapy was measured by Mandard’s modified tumor regression grade (TRG). Results All patients completed the scheduled treatment. Sixty-six patients underwent surgery. Fifty-three of which (80.3%) received a sphincter saving procedure. Downstaging occurred in 41 cases (62.1%). The analysis of subgroups showed an increasing prevalence of TRG 1–2 prolonging the interval to surgery (group A—16.7%, group B—36.8% and 54.3% in group C; p value 0.023). Conclusions Preoperative short-course radiotherapy is able to downstage rectal cancer if surgery is delayed. A higher rate of TRG 1–2 can be obtained if interval to surgery is prolonged to more than 8 weeks. PMID:27548058

  2. Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection

    PubMed Central

    Maas, Monique; Nelemans, Patty J; Valentini, Vincenzo; Crane, Christopher H; Capirci, Carlo; Rödel, Claus; Nash, Garrett M; Kuo, Li-Jen; Glynne-Jones, Rob; García-Aguilar, Julio; Suárez, Javier; Calvo, Felipe A; Pucciarelli, Salvatore; Biondo, Sebastiano; Theodoropoulos, George; Lambregts, Doenja MJ; Beets-Tan, Regina GH; Beets, Geerard L

    2016-01-01

    Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorised into 3 groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). 1723(52%) of 3313 included patients received aCT. 898 patients had a pCR, 966 had a ypT1-2 tumour and 1302 had a ypT3-4 tumour. For 122 patients response category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. Hazard ratios for RFS with 95%CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging. PMID:25418551

  3. Robotic-assisted surgery versus open surgery in the treatment of rectal cancer: the current evidence

    PubMed Central

    Liao, Guixiang; Li, Yan-Bing; Zhao, Zhihong; Li, Xianming; Deng, Haijun; Li, Gang

    2016-01-01

    The aim of this meta-analysis was to comprehensively compare the safety and efficacy of robotic-assisted rectal cancer surgery (RRCS) and open rectal cancer surgery (ORCS). Electronic database (PubMed, EMBASE, Web of Knowledge, and the Cochrane Library) searches were conducted for all relevant studies that compared the short-term and long-term outcomes between RRCS and ORCS. Odds ratios (ORs), mean differences, and hazard ratios were calculated. Seven studies involving 1074 patients with rectal cancer were identified for this meta-analysis. Compared with ORCS, RRCS is associated with a lower estimated blood loss (mean difference [MD]: −139.98, 95% confidence interval [CI]: −159.11 to −120.86; P < 0.00001), shorter hospital stay length (MD: −2.10, 95% CI: −3.47 to −0.73; P = 0.003), lower intraoperative transfusion requirements (OR: 0.52, 95% CI: 0.28 to 0.99, P = 0.05), shorter time to flatus passage (MD: −0.97, 95% CI = −1.06 to −0.88, P < 0.00001), and shorter time to resume a normal diet (MD: −1.71.95% CI = −3.31 to −0.12, P = 0.04). There were no significant differences in surgery-related complications, oncologic clearance, disease-free survival, and overall survival between the two groups. However, RRCS was associated with a longer operative time. RRCS is safe and effective. PMID:27228906

  4. Phase I-II Trial of Cetuximab, Capecitabine, Oxaliplatin, and Radiotherapy as Preoperative Treatment in Rectal Cancer

    SciTech Connect

    Roedel, Claus Arnold, Dirk; Hipp, Matthias; Liersch, Torsten; Dellas, Kathrin; Iesalnieks, Igors; Hermann, Robert Michael; Lordick, Florian; Hohenberger, Werner; Sauer, Rolf

    2008-03-15

    Purpose: To evaluate the safety and activity of preoperative radiotherapy (RT) with concurrent cetuximab, capecitabine, and oxaliplatin in rectal cancer patients. Patients and Methods: A total of 60 patients with rectal cancer (T3-T4 or N+, M1 allowed) entered the trial at five investigator sites; the data from 58 patients were assessable. Cetuximab was given as an initial dose of 400 mg/m{sup 2} 7 days before the start of RT, and then at 250 mg/m{sup 2} once weekly during RT (50.4 Gy in 28 fractions). Capecitabine and oxaliplatin were administered according to an established schedule of oxaliplatin (50 mg/m{sup 2} on Days 1, 8, 22, and 29) and capecitabine (Days 1-14 and 22-35) at three dose levels: 1,000, 1,300, and 1,650 mg/m{sup 2}/d during the Phase I part of the study. The main endpoint of the Phase II was the pathologic complete response rate. Results: Thirteen patients were included in the Phase I part of the study, and the maximal tolerated dose was not reached. Overall, 48 patients were treated at the recommended dose of capecitabine (1,650 mg/m{sup 2}) and 45 patients (94%) underwent surgery. A pathologic complete response was observed in 4 patients (9%), and moderate (n = 12), minimal (n = 10), and no tumor regression (n = 2) was noted in 24 (53%) of 45 patients. The mean radiation dose intensity, cetuximab, capecitabine, oxaliplatin was 98%, 95%, 94%, and 94%, respectively. The incidence of Grade 3-4 diarrhea was restricted to 19%. Postoperative complications of any grade occurred in 33% of patients. Conclusions: The results of our study have shown that cetuximab can be combined safely with capecitabine and oxaliplatin plus RT. The low pathologic complete response rate achieved should stimulate additional preclinical investigations to establish the best sequence of triple combinations.

  5. Laparoscopic and Robotic Total Mesorectal Excision in the Treatment of Rectal Cancer. Brief Review and Personal Remarks

    PubMed Central

    Bianchi, Paolo Pietro; Petz, Wanda; Luca, Fabrizio; Biffi, Roberto; Spinoglio, Giuseppe; Montorsi, Marco

    2014-01-01

    The current standard treatment for rectal cancer is based on a multimodality approach with preoperative radiochemotherapy in advanced cases and complete surgical removal through total mesorectal excision (TME). The most frequent surgical approach is traditional open surgery, as laparoscopic TME requires high technical skill, a long learning curve, and is not widespread, still being confined to centers with great experience in minimally invasive techniques. Nevertheless, in several studies, the laparoscopic approach, when compared to open surgery, has shown some better short-term clinical outcomes and at least comparable oncologic results. Robotic surgery for the treatment of rectal cancer is an emerging technique, which could overcome some of the technical difficulties posed by standard laparoscopy, but evidence from the literature regarding its oncologic safety and clinical outcomes is still lacking. This brief review analyses the current status of minimally invasive surgery for rectal cancer therapy, focusing on oncologic safety and the new robotic approach. PMID:24834429

  6. Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

    PubMed Central

    You, Kai-Yun; Huang, Rong; Yu, Xin; Liu, Yi-Min; Gao, Yuan-Hong

    2016-01-01

    Abstract The long duration of 4 months of postoperative adjuvant chemotherapy is currently recommended for locally advanced rectal cancer after preoperative chemoradiation and surgery. Whether a short duration could be applied in these patients is unknown. So, the purpose of this study is to evaluate the effects on prognosis based on different durations of adjuvant chemotherapy for rectal cancer. We performed a retrospective study of 200 rectal cancer patients who were treated with preoperative chemoradiation and were pathologically graded as ypII and ypIII stages between March 2003 and May 2012. All patients were divided into 2 groups according to the median duration of adjuvant chemotherapy of 2 months. Overall survival (OS) and disease-free survival (DFS) were compared between patients with duration shorter and longer than 2 months in the whole group and subgroups of ypII and ypIII. Recurrence patterns were also analyzed in all subgroups. Multivariate analysis was performed to explore clinical factors that were significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival. In subgroup of ypII stage, the 5-year OS and DFS were similar between patients in long and short durations of adjuvant chemotherapy. For patients of ypIII stage, although no significant difference was found in OS between patients in short and long durations, DFS was showed to be higher in the group of long duration. Further analysis showed that longer duration of adjuvant chemotherapy could lead to improved control of distant metastasis and no impact on local control. Multivariable analysis indicated that long duration of adjuvant chemotherapy is significantly associated with longer distant metastasis-free survival in patients with ypIII stage, but not in those with ypII stage. A long duration of at least 2 months of postoperative adjuvant chemotherapy is necessary for patients with ypIII stage, whereas it may not be absolutely appropriate for those

  7. Posterior high sacral segmental disconnection prior to anterior en bloc exenteration for recurrent rectal cancer.

    PubMed

    Brown, K G M; Solomon, M J; Austin, K K S; Lee, P J; Stalley, P

    2016-06-01

    This article describes a novel technique for en bloc resection of locally recurrent rectal cancer that invades the high sacral bone (above S3). The involved segment of the sacrum is mobilised with osteotomes during an initial posterior approach before an anterior abdominal phase where the segment of sacral bone is delivered with the specimen. This allows en bloc resection of the involved sacrum while preserving uninvolved distal and contralateral sacral bone and nerve roots. The goal is to obtain a clear bony margin and offer a chance of cure while improving functional outcomes by maintaining pelvic stability and minimising neurological deficit. PMID:27000857

  8. The development of fulminant type 1 diabetes during chemotherapy for rectal cancer.

    PubMed

    Adachi, Junichiro; Mimura, Makiyo; Gotyo, Naoki; Watanabe, Takayuki

    2015-01-01

    A 34-year-old man with a history of rectal cancer was receiving oral chemotherapy [tegafur-uracil (UFT) with leucovorin]. He visited our hospital due to nausea and abdominal pain, and his laboratory data revealed the presence of urinary ketones, hyperglycemia and high anion gap metabolic acidosis, and HbA1c level of 6.8%. Accordingly, we diagnosed fulminant type 1 diabetes. The development of fulminant type 1 diabetes during chemotherapy for malignancy is a rare, but potentially fatal condition. Therefore, clinicians should consider diabetic ketoacidosis in the differential diagnosis when examining chemotherapy patients who present with gastrointestinal symptoms. PMID:25832949

  9. Gangrene of the penis, scrotum, and perineum, occurred after radiotherapy of rectal cancer

    PubMed Central

    Życzkowski, Marcin; Bryniarski, Piotr; Nowakowski, Krzysztof; Muskała, Bartosz; Paradysz, Andrzej

    2013-01-01

    We present a case of a 58-year-old man hospitalized because of gangrene of the penis and scrotum, after radiochemotherapy for rectal cancer. At the time of the admission the patient presented with extensive gangrene with necrosis affecting the scrotum and the penis. During the first day of hospitalization the patient was operated. Due to the progress of the disease he had to be operated again. The status of the patient, which initially was very bad, was gradually improving. He was discharged from the hospital after 59 days in a good general state with good wound healing. PMID:24707380

  10. Preservation of the vegetative pelvic nerves and local reccurence in the operative treatment of rectal cancer.

    PubMed

    Jota, G J; Karadzov, Z; Panovski, M; Vasilevski, V; Serafimoski, V

    2006-12-01

    Life quality of the patients operated from rectal cancer is a serious problem. Despite the curing as a primary objective in the treatment of the rectal cancer, special attention is paid to the life quality upon the performed operation on the subjected patients. The analyzed series consists of 29 patients with rectal cancer, operated on at the Digestive Surgery Clinic within the framework of the Clinical Centre in Skopje, in the period between 2001-2006. Our series involves patients from the T2 and T3 stage of the illness, where it possible to preserve the vegetative pelvic nerves, that are characterized by a relatively long-lasting symptomatology and relatively high percentage of lymphatic metastases. The standardization of the operative intervention resulted in an increase in the number of patients with continuous operations and preservation of the neuro-vegetative plexus without influencing the radicalism of the intervention. The application of the Stapler and Double Stapler technique brought about an increase in the number of continuous operations characterized by a termino-terminal colorectal anastomosis. On the other hand the preventive creation of LOOP ileostomies in the case of the ultra low resections resulted in a decrease in the level of dehiscence of this type as one of the most common and most difficult complications. The preservation of the pelvic neuro-vegetative plexus prolongs the operation time by 30 to 60 minutes, depending on the case and the patient. We assume that the procedure does not have a particular influence on the frequency of the complications, and at the same time it positively affects the revival of the urinal and sexual function. Taking into consideration the fact that the lymphatic dissection increases the possibility of removal of the malignant tissue and enables an adequate "staging" and on the other hand the preservation of the pelvic plexus improves the quality of life, both in terms of the sexual function and the function of

  11. Comprehensive molecular characterization of human colon and rectal cancer.

    PubMed

    2012-07-19

    To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. PMID:22810696

  12. Comprehensive Molecular Characterization of Human Colon and Rectal Cancer

    PubMed Central

    2012-01-01

    Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression. PMID:22810696

  13. Tumor Phosphatidylinositol-3-Kinase Signaling and Development of Metastatic Disease in Locally Advanced Rectal Cancer

    PubMed Central

    Ree, Anne Hansen; Kristensen, Annette Torgunrud; Saelen, Marie Grøn; de Wijn, Rik; Edvardsen, Hege; Jovanovic, Jovana; Abrahamsen, Torveig Weum; Dueland, Svein; Flatmark, Kjersti

    2012-01-01

    Background Recognizing EGFR as key orchestrator of the metastatic process in colorectal cancer, but also the substantial heterogeneity of responses to anti-EGFR therapy, we examined the pattern of composite tumor kinase activities governed by EGFR-mediated signaling that might be implicated in development of metastatic disease. Patients and Methods Point mutations in KRAS, BRAF, and PIK3CA and ERBB2 amplification were determined in primary tumors from 63 patients with locally advanced rectal cancer scheduled for radical treatment. Using peptide arrays with tyrosine kinase substrates, ex vivo phosphopeptide profiles were generated from the same baseline tumor samples and correlated to metastasis-free survival. Results Unsupervised clustering analysis of the resulting phosphorylation of 102 array substrates defined two tumor classes, both consisting of cases with and without KRAS/BRAF mutations. The smaller cluster group of patients, with tumors generating high ex vivo phosphorylation of phosphatidylinositol-3-kinase-related substrates, had a particularly aggressive disease course, with almost a half of patients developing metastatic disease within one year of follow-up. Conclusion High phosphatidylinositol-3-kinase-mediated signaling activity of the primary tumor, rather than KRAS/BRAF mutation status, was identified as a hallmark of poor metastasis-free survival in patients with locally advanced rectal cancer undergoing radical treatment of the pelvic cavity. PMID:23226389

  14. Restaging after neoadjuvant chemoradiation in rectal cancers: is histology the key in patient selection?

    PubMed Central

    Singhal, Nitin; Vallam, Karthik; Engineer, Reena; Ostwal, Vikas; Arya, Supreeta

    2016-01-01

    Background Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer. However, there is no clarity regarding the necessity for restaging scans to rule out systemic progression of disease post chemoradiation with existing literature being divided on the need for the same. Methods Data from a prospectively maintained database was retrospectively analysed. All locally advanced rectal cancers (node positive/T4/T3 with threatened or involved CRM) were included. Biopsy proof of adenocarcinoma and CT scan of abdomen and chest were mandatory. Grade of tumor and response to CTRT on restaging magnetic resonance imaging (MRI) were documented. Results Out of 119 patients subjected to CTRT, 72 underwent definitive total mesorectal excision while 13 patients progressed locoregionally on restaging MR pelvis and 15 other patients progressed systemically while the rest defaulted. Patients with poorly differentiated (PD) cancers were compared to those with well/moderately differentiated (WMD) tumors. PD tumors had a significantly higher rate of local progression (32.1% vs. 5.6% %, P=0.0011) and systemic progression (35.7% vs. 6.9%, P=0.0008) as compared to WMD tumors. Only one-third (9/28) of PD patients underwent TME while the rest progressed. Conclusions Selecting poorly differentiated tumors alone for restaging CECT abdomen and thorax will be a cost effective strategy as the rate of progression is very high. Also patients with PD tumors need to be consulted about the high probability of progression of disease. PMID:27284467

  15. Laparoscopic ovarian transposition prior to pelvic irradiation in a young female patient with advanced rectal cancer.

    PubMed

    Kihara, Kyoichi; Yamamoto, Seiichiro; Ohshiro, Taihei; Fujita, Shin

    2015-12-01

    In the report, we describe the first case of laparoscopic ovarian transposition prior to pelvic radio-chemo therapy in a young female patient with advanced rectal cancer in Japan. A 14-year-old female visited a hospital because of consistent diarrhea and melena. Colonoscopy examination showed a bulky tumor of the rectum, which was diagnosed as moderately to poorly differentiated adenocarcinoma. The diagnosis was cT3N2aM1a (due to lymph node in pelvic side wall), cStage IVA. In an attempt to improve local control and sphincter preservation, neoadjuvant concurrent radio-chemo therapy was planned. Considering that pelvic irradiation particularly in young female might cause ovarian failure, laparoscopic ovarian transposition was carried out prior to pelvic irradiation. Sequentially the patient underwent low anterior resection of the rectum and lymphadenectomy including pelvic side wall. The menstruation was maintained with delay for 6 months after adjuvant chemotherapy. There is no evidence of cancer recurrence at 3 years after the surgery.In premenopausal patients with rectal cancer undergoing pelvic irradiation, laparoscopic ovarian transposition is one of the choices to prevent ovarian failure. PMID:26943437

  16. Sacral Insufficiency Fractures After Preoperative Chemoradiation for Rectal Cancer: Incidence, Risk Factors, and Clinical Course

    SciTech Connect

    Herman, Michael P.; Kopetz, Scott; Bhosale, Priya R.; Eng, Cathy; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H.; Das, Prajnan

    2009-07-01

    Purpose: Sacral insufficiency (SI) fractures can occur as a late side effect of pelvic radiation therapy. Our goal was to determine the incidence, risk factors, and clinical course of SI fractures in patients treated with preoperative chemoradiation for rectal cancer. Materials and Methods: Between 1989 and 2004, 562 patients with non-metastatic rectal adenocarcinoma were treated with preoperative chemoradiation followed by mesorectal excision. The median radiotherapy dose was 45 Gy. The hospital records and radiology reports of these patients were reviewed to identify those with pelvic fractures. Radiology images of patients with pelvic fractures were then reviewed to identify those with SI fractures. Results: Among the 562 patients, 15 had SI fractures. The 3-year actuarial rate of SI fractures was 3.1%. The median time to SI fractures was 17 months (range, 2-34 months). The risk of SI fractures was significantly higher in women compared to men (5.8% vs. 1.6%, p = 0.014), and in whites compared with non-whites (4% vs. 0%, p = 0.037). On multivariate analysis, gender independently predicted for the risk of SI fractures (hazard ratio, 3.25; p = 0.031). Documentation about the presence or absence of pain was available for 13 patients; of these 7 (54%) had symptoms requiring pain medications. The median duration of pain was 22 months. No patient required hospitalization or invasive intervention for pain control. Conclusions: SI fractures were uncommon in patients treated with preoperative chemoradiation for rectal cancer. The risk of SI fractures was significantly higher in women. Most cases of SI fractures can be managed conservatively with pain medications.

  17. Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients With Prior Pelvic Irradiation

    SciTech Connect

    Das, Prajnan; Delclos, Marc E.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Eng, Cathy; Bedi, Manpreet; Krishnan, Sunil; Crane, Christopher H.

    2010-05-01

    Purpose: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. Methods and Materials: Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy. Results: Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of <=2 years (p = 0.001). Conclusions: Hyperfractionated, accelerated reirradiation was well tolerated, with low rates of acute toxicity and moderate rates of late toxicity. Reirradiation may help improve pelvic control in rectal cancer patients with a history of pelvic radiotherapy.

  18. Role of protective stoma in low anterior resection for rectal cancer: A meta-analysis

    PubMed Central

    Wu, Sheng-Wen; Ma, Cong-Chao; Yang, Yu

    2014-01-01

    AIM: To provide a comprehensive evaluation of the role of a protective stoma in low anterior resection (LAR) for rectal cancer. METHODS: The PubMed, EMBASE, and MEDLINE databases were searched for studies and relevant literature published between 2007 and 2014 regarding the construction of a protective stoma during LAR. A pooled risk ratio (RR) with 95% confidence intervals (CIs) was used to assess the outcomes of the studies, including the rate of postoperative anastomotic leakage and reoperations related to leakage. Funnel plots and Egger’s tests were used to evaluate the publication biases of the studies. P values < 0.05 were considered statistically significant. RESULTS: A total of 11 studies were included in the meta-analysis. In total, 5612 patients were examined, 2868 of whom had a protective stoma and 2744 of whom did not. The sample size of the studies varied from 34 to 1912 patients. All studies reported the number of patients who developed an anastomotic leakage and required a reoperation related to leakage. A random effects model was used to calculate the pooled RR with the corresponding 95%CI because obvious heterogeneity was observed among the 11 studies (I2 = 77%). The results indicated that the creation of a protective stoma during LAR significantly reduces the rate of anastomotic leakage and the number of reoperations related to leakage, with pooled RRs of 0.38 (95%CI: 0.30-0.48, P < 0.00001) and 0.37 (95%CI: 0.29-0.48, P < 0.00001), respectively. The shape of the funnel plot did not reveal any evidence of obvious asymmetry. CONCLUSION: The presence of a protective stoma effectively decreased the incidences of anastomotic leakage and reoperation and is recommended in patients undergoing low rectal anterior resections for rectal cancer. PMID:25548503

  19. Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Hamstra, Daniel A.; Stenmark, Matt H.; Ritter, Tim; Litzenberg, Dale; Jackson, William; Johnson, Skyler; Albrecht-Unger, Liesel; Donaghy, Alex; Phelps, Laura; Blas, Kevin; Halverson, Schuyler; Marsh, Robin; Olson, Karin; Feng, Felix Y.

    2013-04-01

    Purpose: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval (CI), 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.

  20. The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer: how successful have we been?

    PubMed

    Glynne-Jones, R; Dunst, J; Sebag-Montefiore, D

    2006-03-01

    The aim was to review available literature on capecitabine-based chemoradiation regimens for the preoperative treatment of patients with locally advanced rectal cancer (LARC) and determine efficacy and safety data for capecitabine in this setting. Medical literature databases (Pubmed, Medline) and abstracts/posters presented at recent scientific congresses (ASCO, ASTRO, ESTRO and ECCO) were screened and critically analysed to identify relevant data. A number of phase I/II studies have demonstrated that capecitabine is effective and well tolerated in combination with preoperative radiotherapy in patients with LARC. Phase III studies are ongoing. Continuous oral administration of capecitabine (825 mg/m(2) twice daily for 7 days/week) is an effective regimen and has similar tolerability to the less dose-intensive intermittent regimens of capecitabine given 5 days/week followed by 2 day's rest or 14 days followed by 7 day's rest as used in systemic chemotherapy for patients with colorectal or breast cancer. Capecitabine chemoradiation is associated with a relatively low rate of grade 3/4 adverse events. Capecitabine simplifies chemoradiation and provides a convenient treatment option for both patients and health care professionals. Combining capecitabine with cytotoxic agents such as oxaliplatin and irinotecan has the potential to further improve antitumour efficacy in patients receiving preoperative chemoradiation. Data from phase I/II single-agent and combination capecitabine chemoradiation studies provide a clear rationale for replacing infusional 5-FU with oral capecitabine as part of chemoradiation for patients with LARC. PMID:16500912

  1. A Phase I, Pharmacological, and Biological Study of OSI-774 in Combination With FOLFOX 4 (5-FU, Leucovorin, and Oxaliplatin) and Bevacizumab (Avastin) in Patients With Advanced Colorectal Cancer

    ClinicalTrials.gov

    2013-09-27

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; 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 IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  2. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers

    PubMed Central

    Hadaki, Maher; Harrison, Mark

    2013-01-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore—with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of ‘on target’ effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments

  3. Contact X-ray Therapy for Rectal Cancer: Experience in Centre Antoine-Lacassagne, Nice, 2002-2006

    SciTech Connect

    Gerard, Jean-Pierre Ortholan, Cecile; Benezery, Karene; Ginot, Aurelie; Hannoun-Levi, Jean-Michel; Chamorey, Emmanuel; Benchimol, Daniel; Francois, Eric

    2008-11-01

    Purpose: To report the results of using contact X-ray (CXR), which has been used in the Centre-Lacassagne since 2002 for rectal cancer. Methods and Materials: A total of 44 patients were treated between 2002 and 2006 using four distinct clinical approaches. Patients with Stage T1N0 tumors were treated with transanal local excision (TLE) and adjuvant CXR (45 Gy in three fractions) (n = 7). The 11 inoperable (or who had refused surgery) patients with Stage T2-T3 disease were treated with CXR plus external beam radiotherapy (EBRT). Those with Stage T3N0-N2 tumors were treated with preoperative CXR plus EBRT (with or without concurrent chemotherapy) followed by surgery (n = 21). Finally, the patients with Stage T2 disease were treated with CXR plus EBRT followed by TLE (n = 5). Results: The median follow-up was 25 months. In the 7 patients who underwent TLE first, no local failure was observed, and their anorectal function was good. Of the 11 inoperable patients who underwent CXR plus EBRT alone, 10 achieved local control. In the third group (preoperative CXR plus EBRT), anterior resection was performed in 16 of 21 patients. Complete sterilization of the operative specimen was seen in 4 cases (19%). No local recurrence occurred. Finally, of the 5 patients treated with CXR plus EBRT followed by TLE, a complete or near complete clinical response was observed in all. TLE with a R0 resection margin was performed in all cases. The rectum was preserved with good function in all 5 patients. Conclusion: These early results have confirmed that CXR combined with surgery (or alone with EBRT) can play a major role in the conservative and curative treatment of rectal cancer.

  4. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

    PubMed

    Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

    2013-09-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

  5. A common variant in MTHFR influences response to chemoradiotherapy and recurrence of rectal cancer

    PubMed Central

    Nikas, Jason B; Lee, Janet T; Maring, Elizabeth D; Washechek-Aletto, Jill; Felmlee-Devine, Donna; Johnson, Ruth A; Smyrk, Thomas C; Tawadros, Patrick S; Boardman, Lisa A; Steer, Clifford J

    2015-01-01

    An important determinant of the pathogenesis and prognosis of various diseases is inherited genetic variation. Single-nucleotide polymorphisms (SNPs), variations at a single base position, have been identified in both protein-coding and noncoding DNA sequences, but the vast majority of millions of those variants are far from being functionally understood. Here we show that a common variant in the gene MTHFR [rs1801133 (C>T)] not only influences response to neoadjuvant chemoradiotherapy in patients with rectal cancer, but it also influences recurrence of the disease itself. More specifically, patients with the homozygous ancestral (wild type) genotype (C/C) were 2.91 times more likely (291% increased benefit) to respond to neoadjuvant chemoradiotherapy {95% CI: [1.23, 6.89]; P=0.0150} and 3.25 times more likely (325% increased benefit) not to experience recurrence of the disease {95% CI: [1.37, 7.72]; P=0.0079} than patients with either the heterozygous (C/T) or the homozygous mutation (T/T) genotype. These results identify MTHFR as an important genetic marker and open up new, pharmacogenomic strategies in the treatment and management of rectal cancer. PMID:26693073

  6. [A Case of Locally Advanced Rectal Cancer Curatively Resected Following Chemoradiotherapy].

    PubMed

    Kawahara, Yohei; Terada, Itsuro; Terai, Shiro; Yamamoto, Seiichi; Kaji, Masahide; Maeda, Kiichi; Shimizu, Koichi

    2015-11-01

    A man in his 70s was referred to our hospital with anorexia, weight loss, and constipation. After examination by computed tomography (CT), magnetic resonance imaging (MRI), and colonoscopy, he was diagnosed as having a locally advanced rectal cancer with abscess formation. Because CT and MRI indicated that the tumor had invaded the seminal vesicle, prostate, and sacrum, we diagnosed it as an unresectable tumor. We treated the abscesses around the tumor by sigmoid colostomy with administration of antibiotics. After control of the infection, the patient received systemic chemotherapy with capecitabine/oxaliplatin (XELOX) plus bevacizumab (BV). After the 5th courses of XELOX plus BV, the primary tumor showed a tendency to shrink, but invasion to the neighboring organs was still seen. Therefore, we treated him with chemoradiotherapy (CRT) using S-1. After completion of CRT with no significant adverse effects, the tumor invasion to the neighboring organs disappeared, and we performed a low anterior resection 9 weeks later. Pathological findings revealed that the tumor had shrunk remarkably and it was resected curatively, although a few tumor cells remained in the subserosal layer of the ulcerative scar caused by the CRT. His postoperative course was uneventful, and he underwent adjuvant chemotherapy with S-1 for 3 months after discharge. To date, no disease recurrence has been detected. We report a case of locally advanced rectal cancer, which was curatively resected following chemoradiotherapy, along with a short literature review. PMID:26805354

  7. The best timing for administering systemic chemotherapy in patients with locally advanced rectal cancer

    PubMed Central

    Shimodaira, Yusuke; Harada, Kazuto; Lin, Quan

    2016-01-01

    Over the past several decades, outcomes for patients with rectal cancer have improved considerably. However, several questions have emerged as survival times have lengthened and quality of life has improved for these patients. Currently patients with locally advanced rectal cancer (LARC) are often recommended multimodality therapy with fluoropyrimidine-based chemotherapy (CT) and radiation followed by total mesorectal excision (TME), with consideration given to FOLFOX before chemoradiotherapy (CRT). Recently, Garcia-Aguilar and colleagues reported in Lancet Oncology that the addition of mFOLFOX6 administered between CRT and surgery affected the number of patients achieving pathologic complete response (pathCR), which is of great interest from the standpoint of pursuit of optimal timing of systemic CT delivery. This was a multicenter phase II study consisting of 4 sequential treatment groups of patients with LARC, and they reported that patients given higher number CT cycles between CRT and surgery achieved higher rates of pathCR than those given standard treatment. There was no association between response improvement and tumor progression, increased technical difficulty, or surgical complications. Ongoing phase III clinical trial further assessing this strategy might result in a paradigm shift. PMID:26889491

  8. Brachytherapy and Local Excision for Sphincter Preservation in T1 and T2 Rectal Cancer

    SciTech Connect

    Grimard, Laval Stern, Hartley; Spaans, Johanna N. M.Sc.

    2009-07-01

    Purpose: To report long-term results of brachytherapy after local excision (LE) in the treatment of T1 and T2 rectal cancer at risk of recurrence due to residual subclinical disease. Methods and Materials: Between 1989 and 2007, 32 patients undergoing LE and brachytherapy were followed prospectively for a mean of 6.2 years. Estimates of local recurrence (LR), disease-specific survival (DSS), and overall survival (OS) were generated. Treatment-related toxicity and the effect of known prognostic factors were determined. Results: There were 8 LR (3 T1, 5 T2), of which 5 were salvaged surgically. Median time to the 8 LR was 14 months, and the 5-year rate of local control was 76%. Although there have been 9 deaths to date, only 5 were from disease. Five-year DSS and OS rates were 85% and 78%, respectively. There were 4 cases of Grade 2-3 radionecrosis and 1 case of mild stool incontinence. The sphincter was preserved in 27 of 32 patients. Conclusion: Local excision and adjuvant brachytherapy for T1 and T2 rectal cancer is an appealing treatment alternative to immediate radical resection, particularly in the frail and elderly who are unable to undergo major surgery, as well as for patients wanting to avoid a permanent colostomy.

  9. Pathological complete response after neoadjuvant therapy for rectal cancer and the role of adjuvant therapy.

    PubMed

    Nelson, Valerie M; Benson, Al B

    2013-04-01

    Both the addition of neoadjuvant chemoradiation therapy and improvements in surgical techniques have improved local control and overall survival for locally advanced rectal cancer patients over the past few decades. The addition of adjuvant chemotherapy has likely improved outcomes as well, though the contribution has been more difficult to quantify. At present, the majority of resected locally advanced rectal cancer patients receive adjuvant chemotherapy, though there is great variability in this practice based on both patient and institution characteristics. Recently, questions have been raised regarding which sub-groups of patients benefit most from adjuvant chemotherapy. As pathologic complete response (pCR) is increasingly found to be a reasonable surrogate for long-term favorable outcomes, some have questioned the need for adjuvant therapy in this select group of patients. Multiple retrospective analyses have shown minimal to no benefit for adjuvant chemotherapy in this group. Indeed, the patients most consistently shown to benefit from adjuvant therapy both in terms of disease free survival (DFS) and overall survival (OS) are those who achieve an intermediate pathologic response to neoadjuvant treatment. Tumors that have high expression of thymidylate synthetase have also shown to benefit from adjuvant therapy. More study is needed into clinical and molecular features that predict patient benefit from adjuvant therapy. PMID:23381584

  10. [Role of neoadjuvant radiotherapy for rectal cancer : Is MRI-based selection a future model?].

    PubMed

    Kulu, Y; Hackert, T; Debus, J; Weber, M-A; Büchler, M W; Ulrich, A

    2016-07-01

    Following the introduction of total mesorectal excision (TME) in the curative treatment of rectal cancer, the role of neoadjuvant therapy has evolved. By improving the surgical technique the local recurrence rate could be reduced by TME surgery alone to below 8 %. Even if local control was further improved by additional preoperative irradiation this did not lead to a general survival benefit. Guidelines advocate that all patients in UICC stage II and III should be pretreated; however, the stage-based indications for neoadjuvant therapy have limitations. This is mainly attributable to the facts that patients with T3 tumors comprise a very heterogeneous prognostic group and preoperative lymph node diagnostics lack accuracy. In contrast, in recent years the circumferential resection margin (CRM) has become an important prognostic parameter. Patients with tumors that are very close to or infiltrate the pelvic fascia (positive CRM) have a higher rate of local recurrence and poorer survival. With high-resolution pelvic magnetic resonance imaging (MRI) examination in patients with rectal cancer, the preoperative CRM can be determined with a high sensitivity and specificity. Improved T staging and better prediction of the resection margins by pelvic MRI potentially facilitate the selection of patients for study-based treatment strategies omitting neoadjuvant radiotherapy. PMID:27339645

  11. Local Recurrence in Rectal Cancer: Anatomic Localization and Effect on Radiation Target

    SciTech Connect

    Syk, Erik Torkzad, Michael R.; Blomqvist, Lennart; Nilsson, Per J.; Glimelius, Bengt

    2008-11-01

    Purpose: To determine the sites of local recurrence after total mesorectal excision for rectal cancer in an effort to optimize the radiation target. Methods and Materials: A total of 155 patients with recurrence after abdominal resection for rectal cancer were identified from a population-based consecutive cohort of 2,315 patients who had undergone surgery by surgeons trained in the total mesorectal excision procedure. A total of 99 cross-sectional imaging studies were retrieved and re-examined by one radiologist. The clinical records were examined for the remaining patients. Results: Evidence of residual mesorectal fat was identified in 50 of the 99 patients. In 83 patients, local recurrence was identified on the imaging studies. All recurrences were within the irradiated volume if the patients had undergone preoperative radiotherapy or within the same volume if they had not. The site of recurrence was in the lower 75% of the pelvis, anatomically below the S1-S2 interspace for all patients. Only 5 of the 44 recurrences in patients with primary tumors >5 cm from the anal verge were in the lowest 20% of the pelvis. Six recurrences involved the lateral lymph nodes. Conclusion: These data suggest that a lowering of the upper limit of the clinical target volume could be introduced. The anal sphincter complex with surrounding tissue could also be excluded in patients with primary tumors >5 cm from the anal verge.

  12. A Phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer

    SciTech Connect

    Jin Jing

    2006-03-01

    Purpose: To determine the maximum tolerated dose and the dose-limiting toxicity of capecitabine with standard radiotherapy (RT) as adjuvant treatment in patients with rectal cancer. Methods and Materials: Patients with Stage II/III rectal cancer after surgery were eligible. Total RT dose was delivered as DT 50 Gy in fractions of 2.0 Gy/day for 5 weeks to the pelvic area. Capecitabine was administered concurrently with RT in escalating doses, twice daily with a 12-h interval, for two cycles of 14 days separated by a 7-day rest. Dose-limiting toxicity included Grade 3 or Grade 4 hematologic and nonhematologic toxicity. Results: Twenty-four patients were enrolled at the following dose levels: 1,000 (3 patients), 1,200 (3 patients), 1,400 (3 patients), 1,500 (3 patients), 1,600 (6 patients), and 1,700 mg/m{sup 2}/day (6 patients). Dose-limiting toxicity was observed in 1 patient at 1,600 mg/m{sup 2}/day (Grade 3 diarrhea) and in 2 patients at 1,700 mg/m{sup 2}/day (1 patient had Grade 3 and 1 Grade 4 diarrhea). Conclusion: The maximum tolerated dose (MTD) of capecitabine given concurrently with RT was 1,600 mg/m{sup 2}, daily from the 1st to the 14th day, with a 7-day rest, for two cycles.

  13. Risk factors causing structural sequelae after anastomotic leakage in mid to low rectal cancer

    PubMed Central

    Ji, Woong Bae; Kwak, Jung Myun; Kim, Jin; Um, Jun Won; Kim, Seon Hahn

    2015-01-01

    AIM: To investigate the risk factors causing structural sequelae after anastomotic leakage in patients with mid to low rectal cancer. METHODS: Prospectively collected data of consecutive subjects who had anastomotic leakage after surgical resection for rectal cancer from March 2006 to May 2013 at Korea University Anam Hospital were retrospectively analyzed. Two subgroup analyses were performed. The patients were initially divided into the sequelae (stricture, fistula, or sinus) and no sequelae groups and then divided into the permanent stoma (PS) and no PS groups. Univariate and multivariate analyses were performed to identify the risk factors of structural sequelae after anastomotic leakage. RESULTS: Structural sequelae after anastomotic leakage were identified in 29 patients (39.7%). Multivariate analysis revealed that diversion ileostomy at the first operation increases the risk of structural sequelae [odds ratio (OR) = 6.741; P = 0.017]. Fourteen patients (17.7%) had permanent stoma during the follow-up period (median, 37 mo). Multivariate analysis showed that the tumor level from the dentate line was associated with the risk of permanent stoma (OR = 0.751; P = 0.045). CONCLUSION: Diversion ileostomy at the first operation increased the risk of structural sequelae of the anastomosis, while lower tumor location was associated with the risk of permanent stoma in the management of anastomotic leakage. PMID:26019455

  14. Current status of robotic surgery for rectal cancer: A bird's eye view

    PubMed Central

    Pai, Ajit; Melich, George; Marecik, Slawomir J; Park, John J; Prasad, Leela M

    2015-01-01

    Minimally invasive surgery for rectal cancer is now widely performed via the laparoscopic approach and has been validated in randomized controlled trials to be oncologically safe with better perioperative outcomes than open surgery including shorter length of stay, earlier return of bowel function, better cosmesis, and less analgesic requirement. Laparoscopic surgery, however, has inherent limitations due to two-dimensional vision, restricted instrument motion and a very long learning curve. Robotic surgery with its superb three-dimensional magnified optics, stable retraction platform and 7 degrees of freedom of instrument movement offers significant benefits during Total Mesorectal Excision (TME) including ease of operation, markedly lower conversion rates and better quality of the specimen in addition to shorter (steeper) learning curves. This review summarizes the current evidence for the adoption of robotic TME for rectal cancer with supporting data from the literature and from the authors’ own experience. All relevant articles from PubMed using the search terms listed below and published between 2000 and 2014 including randomized trials, meta-analyses, prospective studies, and retrospective reviews with substantial numbers were included. PMID:25598596

  15. Dealing with robot-assisted surgery for rectal cancer: Current status and perspectives

    PubMed Central

    Biffi, Roberto; Luca, Fabrizio; Bianchi, Paolo Pietro; Cenciarelli, Sabina; Petz, Wanda; Monsellato, Igor; Valvo, Manuela; Cossu, Maria Laura; Ghezzi, Tiago Leal; Shmaissany, Kassem

    2016-01-01

    The laparoscopic approach for treatment of rectal cancer has been proven feasible and oncologically safe, and is able to offer better short-term outcomes than traditional open procedures, mainly in terms of reduced length of hospital stay and time to return to working activity. In spite of this, the laparoscopic technique is usually practised only in high-volume experienced centres, mainly because it requires a prolonged and demanding learning curve. It has been estimated that over 50 operations are required for an experienced colorectal surgeon to achieve proficiency with this technique. Robotic surgery enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, thus promising to overcome some of the technical difficulties associated with standard laparoscopy. It has high-definition three-dimensional vision, it translates the surgeon’s hand movements into precise movements of the instruments inside the patient, the camera is held and moved by the first surgeon, and a fourth robotic arm is available as a fixed retractor. The aim of this review is to summarise the current data on clinical and oncologic outcomes of robot-assisted surgery in rectal cancer, focusing on short- and long-term results, and providing original data from the authors’ centre. PMID:26811606

  16. Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Wolff, Roger K.

    2014-01-01

    Mitogen-activated protein kinase (MAPK) pathways regulate cellular functions including cell proliferation, differentiation, migration, and apoptosis. Associations between genes in the DUSP, ERK1/2, JNK, and p38 MAPK-signaling pathways and dietary factors associated with growth factors, inflammation, and oxidative stress and risk of colon and rectal cancer were evaluated. Data include colon cases (n=1555) and controls (n=1956) and rectal cases (n=754) and controls (n=959). Statistically significant interactions were observed for the MAPK-signaling pathways after adjustment for multiple comparisons. DUSP genes interacted with carbohydrates, mutagen index, calories, calcium, vitamin D, lycopene, dietary fats, folic acid, and selenium. MAPK1, MAPK3, MAPK1 and RAF1 within the ERK1/2 MAPK-signaling pathway interacted with dietary fats and cruciferous vegetables. Within the JNK MAPK-signaling pathway, interactions between MAP3K7 and protein, vitamin C, iron, folic acid, carbohydrates, and cruciferous vegetables; MAP3K10 and folic acid; MAP3K9 and lutein/zeaxanthin; MAPK8 and calcium; MAP3K3 and calcium and lutein; MAP3K1 and cruciferous vegetables. Interaction within the p38-signaling pathway included: MAPK14 with calories, carbohydrates saturated fat, selenium, vitamin C; MAP3K2 and carbohydrates, and folic acid. These data suggest that dietary factors involved in inflammation and oxidative stress interact with MAPK-signaling genes to alter risk of colorectal cancer. PMID:23859041

  17. Probiotics for Rectal Volume Variation During Radiation Therapy for Prostate Cancer

    SciTech Connect

    Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Lee, Juhye; Park, Dahl; Jeon, Hosang; Ha, Honggu; Kim, Taenam; Kim, Dongwon

    2013-11-15

    Purpose: To investigate the effect of the probiotic Lactobacillus acidophilus on the percentage volume change of the rectum (PVC{sub R}), a crucial factor of prostate movement. Methods and Materials: Prostate cancer patients managed with tomotherapy as a radical treatment were enrolled in the study to take a probiotic capsule containing 1.0 × 10{sup 8} colony-forming units of L acidophilus or a placebo capsule twice daily. Radiation therapy was performed at a dose of 78 Gy in 39 fractions. The PVC{sub R}, defined as the difference in rectal volume between the planning computed tomographic (CT) and daily megavoltage CT images, was analyzed. Results: Forty patients were randomized into 2 groups. The L acidophilus group showed significantly lower median rectal volume and median PVC{sub R} values than the placebo group. L acidophilus showed a significant reduction effect on the PVC{sub R} (P<.001). However, the radiation therapy fraction number did not significantly influence the PVC{sub R}. Conclusions: L acidophilus was useful in reducing the PVC{sub R}, which is the most important determining factor of prostate position, during radiation therapy for prostate cancer.

  18. Quality of life after surgery for rectal cancer: a systematic review of comparisons with the general population.

    PubMed

    Giandomenico, Francesca; Gavaruzzi, Teresa; Lotto, Lorella; Del Bianco, Paola; Barina, Andrea; Perin, Alessandro; Pucciarelli, Salvatore

    2015-01-01

    Rectal cancer treatments may impact negatively on patients' bowel and sexual functions and, in turn, on health-related quality of life. Information on the likely effects of treatment is essential in order to facilitate the care process and the adaptation of patients to their condition. Studies that report on the comparison between rectal cancer patients and the general population are a useful source of this evidence, providing elements to aid in answering questions such as 'is my life going to be the same as before?' In this article, the authors have systematically reviewed articles published in the last 6 years that report on the comparison between rectal patients' and the general population's health-related quality of life. Sixteen out of 645 articles were included. The results are summarized and critically discussed. PMID:26197061

  19. High preoperative serum globulin in rectal cancer treated with neoadjunctive chemoradiation therapy is a risk factor for poor outcome

    PubMed Central

    Li, Qingguo; Meng, Xianke; Liang, Lei; Xu, Ye; Cai, Guoxiang; Cai, Sanjun

    2015-01-01

    An elevated serum albumin (ALB) and albumin/globulin ratio (AGR) has been reported to be associated with a favorable prognosis for certain malignancies; however, little is known about the prognostic significance of globulin (GLB) in rectal cancer treated with neoadjuvant chemoradiation therapy (NCRT). The purpose of this study was to evaluate whether GLB analysis could predict the prognosis of patients received NCRT. A retrospective cohort of 293 locally advanced rectal cancer patients receiving NCRT followed by radical surgery was recruited between January 2006 and December 2012 at Fudan University Shanghai Cancer Center. Levels for preoperative GLB and ALB were obtained and used to calculate the AGR. Survival analysis was used to evaluate the predictive value of GLB. X-tile program determined 28.50, 36.20 and 1.20 as optimal cut-off value for GLB, ALB and AGR in terms of survival. Univariate and multivariate analysis revealed that low GLB levels were significantly associated with favorable rectal cancer-specific survival (RCSS) (P < 0.05). Conversely, low ALB levels were associated with a significantly worse RCSS (P = 0.010). Collectively, high preoperative GLB level was a significantly unfavorable factor for rectal cancer patients treated with NCRT. This easily obtained variable may serve as a valuable marker to predict the outcomes of such patient population. PMID:26609491

  20. Preoperative staging of rectal cancer: the MERCURY research project.

    PubMed

    Brown, G; Daniels, I R

    2005-01-01

    The development of a surgical technique that removes the tumour and all local draining nodes in an intact package, namely total mesorectal excision (TME) surgery, has provided the impetus for a more selective approach to the administration of preoperative therapy. One of the most important factors that governs the success of TME surgery is the relationship of tumour to the circumferential resection margin (CRM). Tumour involves the CRM in up to 20% of patients undergoing TME surgery, and results in both poor survival and local recurrence. It is therefore clear that the importance of the decision regarding the use of pre-operative therapy lies with the relationship of the tumour to the mesorectal fascia. In addition, a high-spatial-resolution MRI technique will identify tumours exhibiting other poor prognostic features, namely, extramural spread >5 mm, extramural venous invasion by tumour, nodal involvement, and peritoneal infiltration. The potential benefits of a selective approach using MRI-based selection criteria are evident. That is, over 50% of patients can be treated successfully with primary surgery alone without significant risk of local recurrence or systemic failure. Of the remainder, potentially dramatic improvements may be achieved through the use of intensive and targeted preoperative therapy aimed not only at reducing the size of the primary tumour and rendering potentially irresectable tumour resectable with tumour-free circumferential margins, but also at enabling patients at high risk of systemic failure to benefit from intensive combined modality therapy aimed at eliminating micrometastatic disease. PMID:15865021

  1. Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.

    PubMed

    Gómez Del Pulgar, Teresa; Cebrián, Arancha; Fernández-Aceñero, Maria Jesús; Borrero-Palacios, Aurea; Del Puerto-Nevado, Laura; Martínez-Useros, Javier; Marín-Arango, Juan Pablo; Caramés, Cristina; Vega-Bravo, Ricardo; Rodríguez-Remírez, María; Cruz-Ramos, Marlid; Manzarbeitia, Félix; García-Foncillas, Jesús

    2016-09-01

    Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio- and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre-treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease-free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence. PMID:27171907

  2. [Complete response in a case of anastomotic recurrence of rectal cancer treated with S-1 monotherapy].

    PubMed

    Kabashima, Akira; Kitagawa, Dai; Nakamura, Toshihiko; Kondo, Naoko; Teramoto, Seiichi; Saito, Genkichi; Funahashi, Tomoru; Adachi, Eisuke; Ikeda, Yoichi

    2014-11-01

    A 63-year-old woman underwent a low anterior resection for rectal cancer in 2002.A n anastomotic recurrence was diagnosed in July 2011.S he rejected the possibility of colostomy as radical surgery.Chemotherapy consisting of capecitabine+ oxaliplatin (XELOX) or folinic acid, fluorouracil, and oxaliplatin (FOLFOX6) + bevacizumab were not possible because of high costs. In view of the lower costs and the potential for ambulation, S-1 monotherapy was started. After 3 months, a reduction in the recurrent lesion was observed.After 19 months, the recurrent lesion revealed a scar, which was judged by biopsy to be Group 1.We had achieved a pathological complete response (CR).The standard treatment for recurrent colon cancer is surgical resection or multidrug chemotherapy. However, in view of a patient's quality of life (QOL), S-1 monotherapy may be considered as a potential therapy. PMID:25731306

  3. Preoperative Therapy for Lower Rectal Cancer and Modifications in Distance From Anal Sphincter

    SciTech Connect

    Gavioli, Margherita Losi, Lorena; Luppi, Gabriele; Iacchetta, Francesco; Zironi, Sandra; Bertolini, Federica; Falchi, Anna Maria; Bertoni, Filippo; Natalini, Gianni

    2007-10-01

    Purpose: To assess the frequency and magnitude of changes in lower rectal cancer resulting from preoperative therapy and its impact on sphincter-saving surgery. Preoperative therapy can increase the rate of preserving surgery by shrinking the tumor and enhancing its distance from the anal sphincter. However, reliable data concerning these modifications are not yet available in published reports. Methods and Materials: A total of 98 cases of locally advanced cancer of the lower rectum (90 Stage uT3-T4N0-N+ and 8 uT2N+M0) that had undergone preoperative therapy were studied by endorectal ultrasonography. The maximal size of the tumor and its distance from the anal sphincter were measured in millimeters before and after preoperative therapy. Surgery was performed 6-8 weeks after therapy, and the histopathologic margins were compared with the endorectal ultrasound data. Results: Of the 90 cases, 82.5% showed tumor downsizing, varying from one-third to two-thirds or more of the original tumor mass. The distance between the tumor and the anal sphincter increased in 60.2% of cases. The median increase was 0.73 cm (range, 0.2-2.5). Downsizing was not always associated with an increase in distance. Preserving surgery was performed in 60.6% of cases. It was possible in nearly 30% of patients in whom the cancer had reached the anal sphincter before the preoperative therapy. The distal margin was tumor free in these cases. Conclusion: The results of our study have shown that in very low rectal cancer, preoperative therapy causes tumor downsizing in >80% of cases and in more than one-half enhances the distance between the tumor and anal sphincter. These modifications affect the primary surgical options, facilitating or making sphincter-saving surgery possible.

  4. Survival in rectal cancer is predicted by T cell infiltration of tumour-associated lymphoid nodules

    PubMed Central

    McMullen, T P W; Lai, R; Dabbagh, L; Wallace, T M; de Gara, C J

    2010-01-01

    Lymphoid nodules are a normal component of the mucosa of the rectum, but little is known about their function and whether they contribute to the host immune response in malignancy. In rectal cancer specimens from patients with local (n = 18), regional (n = 12) and distant (n = 10) disease, we quantified T cell (CD3, CD25) and dendritic cell (CD1a, CD83) levels at the tumour margin as well as within tumour-associated lymphoid nodules. In normal tissue CD3+, but not CD25+, T cells are concentrated at high levels within lymphoid nodules, with significantly fewer cells found in surrounding normal mucosa (P = 0·001). Mature (CD83), but not immature (CD1a), dendritic cells in normal tissue are also found clustered almost exclusively within lymphoid nodules (P = < 0·0001). In rectal tumours, both CD3+ T cells (P = 0·004) and CD83+ dendritic cells (P = 0·0001) are also localized preferentially within tumour-associated lymphoid nodules. However, when comparing tumour specimens to normal rectal tissue, the average density of CD3+ T cells (P = 0·0005) and CD83+ dendritic cells (P = 0·0006) in tumour-associated lymphoid nodules was significantly less than that seen in lymphoid nodules in normal mucosa. Interestingly, regardless of where quantified, T cell and dendritic cell levels did not depend upon the stage of disease. Increased CD3+ T cell infiltration of tumour-associated lymphoid nodules predicted improved survival, independent of stage (P = 0·05). Other T cell (CD25) markers and different levels of CD1a+ or CD83+ dendritic cells did not predict survival. Tumour-associated lymphoid nodules, enriched in dendritic cells and T cells, may be an important site for antigen presentation and increased T cell infiltration may be a marker for improved survival. PMID:20408858

  5. Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

    SciTech Connect

    Rades, Dirk Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL) and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for

  6. Quality of life in rectal cancer patients after radical surgery: a survey of Chinese patients

    PubMed Central

    2014-01-01

    Background We aimed to investigate the impact of sociodemographic and clinical characteristics on health-related quality of life (HRQoL) in disease-free survivors after radical surgery for rectal cancer in a Chinese mainland population. Methods We performed a cross-sectional survey from August 2002 to February 2011 by use of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38 questionnaires of 438 patients who underwent curative surgery for rectal cancer. Patients who were followed up for a minimum of 6 months, had no relevant major comorbidities and whose disease had not recurred were asked to complete both questionnaires. The impact of sociodemographic and clinical characteristics on HRQoL were compared by univariate and multivariate regression analyses. Results In total, 285 patients responded to the survey (response rate, 65.1%). Psychological-related HRQoL variables such as emotional function (P = 0.021) and future perspectives (P = 0.044) were poorer for younger patients than for older patients; and physiological-related HRQoL was reflected by physical function (P = 0.039), which was poorer for older patients than for younger patients. In terms of physiologic function and symptoms concerning HRQoL, such as pain (P = 0.002) and insomnia (P = 0.018), females had lower values than males. Low education and unemployment were associated with a worse HRQoL. HRQoL was worse for patients with stomas compared to those without, especially in psychosocial areas such as role function (P = 0.025), social function (P <0.001) and body image (P = 0.004). Financial HRQoL was worse for younger patients and patients with stoma. Conclusions HRQoL aspects and degrees to which they were impaired after curative surgery for rectal cancer were different when compared by many sociodemographic and clinical factors in Chinese mainland patients. PMID:24886668

  7. Multivariate Analysis of Risk Factors Associated With the Nonreversal Ileostomy Following Sphincter-Preserving Surgery for Rectal Cancer

    PubMed Central

    Kim, Young Ah; Lee, Gil Jae; Park, Sung Won; Lee, Won-Suk

    2015-01-01

    Purpose A loop ileostomy is used to protect an anastomosis after anal sphincter-preserving surgery, especially in patients with low rectal cancer, but little information is available concerning risk factors associated with a nonreversal ileostomy. The purpose of this study was to identify risk factors of ileostomy nonreversibility after a sphincter-saving resection for rectal cancer. Methods Six hundred seventy-nine (679) patients with rectal cancer who underwent sphincter-preserving surgery between January 2004 and December 2011 were evaluated retrospectively. Of the 679, 135 (19.9%) underwent a defunctioning loop ileostomy of temporary intent, and these patients were divided into two groups, that is, a reversal group (RG, 112 patients) and a nonreversal group (NRG, 23 patients) according to the reversibility of the ileostomy. Results In 23 of the 135 rectal cancer patients (17.0%) that underwent a diverting ileostomy, stoma reversal was not possible for the following reasons; stage IV rectal cancer (11, 47.8%), poor tone of the anal sphincter (4, 17.4%), local recurrence (2, 8.7%), anastomotic leakage (1, 4.3%), radiation proctitis (1, 4.3%), and patient refusal (4, 17.4%). The independent risk factors of the nonreversal group were anastomotic leakage or fistula, stage IV cancer, local recurrence, and comorbidity. Conclusion Postoperative complications such as anastomotic leakage or fistula, advanced primary disease (stage IV), local recurrence and comorbidity were identified as risk factors of a nonreversal ileostomy. These factors should be considered when drafting prudential guidelines for ileostomy closure. PMID:26161377

  8. Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis for Peutz-Jeghers syndrome with synchronous rectal cancer.

    PubMed

    Zhong, Min-Er; Niu, Bei-Zhan; Ji, Wu-Yang; Wu, Bin

    2016-06-14

    We report on a patient diagnosed with Peutz-Jeghers syndrome (PJS) with synchronous rectal cancer who was treated with laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). PJS is an autosomal dominant syndrome characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and increased risks of gastrointestinal and nongastrointestinal cancer. This report presents a patient with a 20-year history of intermittent bloody stool, mucocutaneous pigmentation and a family history of PJS, which together led to a diagnosis of PJS. Moreover, colonoscopy and biopsy revealed the presence of multiple serried giant pedunculated polyps and rectal adenocarcinoma. Currently, few options exist for the therapeutic management of PJS with synchronous rectal cancer. For this case, we adopted an unconventional surgical strategy and ultimately performed laparoscopic restorative proctocolectomy with IPAA. This procedure is widely considered to be the first-line treatment option for patients with ulcerative colitis or familial adenomatous polyposis. However, there are no previous reports of treating PJS patients with laparoscopic IPAA. Since the operation, the patient has experienced no further episodes of gastrointestinal bleeding and has demonstrated satisfactory bowel control. Laparoscopic restorative proctocolectomy with IPAA may be a safe and effective treatment for patients with PJS with synchronous rectal cancer. PMID:27298573

  9. Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis for Peutz-Jeghers syndrome with synchronous rectal cancer

    PubMed Central

    Zhong, Min-Er; Niu, Bei-Zhan; Ji, Wu-Yang; Wu, Bin

    2016-01-01

    We report on a patient diagnosed with Peutz-Jeghers syndrome (PJS) with synchronous rectal cancer who was treated with laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). PJS is an autosomal dominant syndrome characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and increased risks of gastrointestinal and nongastrointestinal cancer. This report presents a patient with a 20-year history of intermittent bloody stool, mucocutaneous pigmentation and a family history of PJS, which together led to a diagnosis of PJS. Moreover, colonoscopy and biopsy revealed the presence of multiple serried giant pedunculated polyps and rectal adenocarcinoma. Currently, few options exist for the therapeutic management of PJS with synchronous rectal cancer. For this case, we adopted an unconventional surgical strategy and ultimately performed laparoscopic restorative proctocolectomy with IPAA. This procedure is widely considered to be the first-line treatment option for patients with ulcerative colitis or familial adenomatous polyposis. However, there are no previous reports of treating PJS patients with laparoscopic IPAA. Since the operation, the patient has experienced no further episodes of gastrointestinal bleeding and has demonstrated satisfactory bowel control. Laparoscopic restorative proctocolectomy with IPAA may be a safe and effective treatment for patients with PJS with synchronous rectal cancer. PMID:27298573

  10. Risk Factors of Permanent Stomas in Patients with Rectal Cancer after Low Anterior Resection with Temporary Stomas

    PubMed Central

    Lee, Chul Min; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Chun, Ho-Kyung

    2015-01-01

    Purpose The aim of this study was to identify risk factors influencing permanent stomas after low anterior resection with temporary stomas for rectal cancer. Materials and Methods A total of 2528 consecutive rectal cancer patients who had undergone low anterior resection were retrospectively reviewed. Risk factors for permanent stomas were evaluated among these patients. Results Among 2528 cases of rectal cancer, a total of 231 patients had a temporary diverting stoma. Among these cases, 217 (93.9%) received a stoma reversal. The median period between primary surgery and stoma reversal was 7.5 months. The temporary and permanent stoma groups consisted of 203 and 28 patients, respectively. Multivariate analysis showed that independent risk factors for permanent stomas were anastomotic-related complications (p=0.001) and local recurrence (p=0.001). The 5-year overall survival for the temporary and permanent stoma groups were 87.0% and 70.5%, respectively (p<0.001). Conclusion Rectal cancer patients who have temporary stomas after low anterior resection with local recurrence and anastomotic-related complications may be at increased risk for permanent stoma. PMID:25683994

  11. Adjuvant chemotherapy for ypT0N0M0 rectal cancer following chemoradiotherapy and total mesorectal excision.

    PubMed

    Kainthla, Radhika; Huerta, Sergio

    2016-10-01

    The management of adenocarcinoma of the rectum is a dynamic field in oncology. The multidisciplinary approach to the management of this disease continues to evolve in each segment of its trimodality treatment. New scheduling regimens and radiosensitizing agents continue to emerge. Although total mesorectal excision continues to be the operation of choice for rectal cancers, what is done before and after surgery continues to evolve to maximize an ideal oncologic outcome with minimal morbidity. The achievement of a pathological complete response [pCR (i.e. ypT0N0)] in a fraction of patients undergoing neoadjuvant chemoradiation poses an interesting management dilemma. The cohort of patients who can achieve a pCR have superior oncologic outcomes compared to nonresponders. The present review addresses the need for adjuvant therapy in patients with a pCR. We discuss the evolution of the role of adjuvant therapy in patients with rectal cancer and the studies addressing the elimination of this strategy in all patients with rectal cancer with a goal of determining the current evidence that might result in the omission of adjuvant therapy for patients with ypT0N0 rectal cancer after chemoradiation and total mesorectal excision. PMID:27387144

  12. Grading-System-Dependent Volume Effects for Late Radiation-Induced Rectal Toxicity After Curative Radiotherapy for Prostate Cancer

    SciTech Connect

    Laan, Hans Paul van der

    2008-03-15

    Purpose: To assess the association between the dose distributions in the rectum and late Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer (RTOG/EORTC), Late Effects of Normal Tissue SOMA, and Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 graded rectal toxicity among patients with prostate cancer treated with RT. Methods and Materials: Included in the study were 124 patients who received three-dimensional conformal RT for prostate cancer to a total dose of 70 Gy in 2-Gy fractions. All patients completed questionnaires regarding rectum complaints before RT and during long-term follow-up. Late rectum Grade 2 or worse toxicity, according to RTOG/EORTC, LENT SOMA, and CTCAE v3.0 criteria, was analyzed in relation to rectal dose and volume parameters. Results: Dose-volume thresholds (V40 {>=}65%, V50 {>=}55%, V65 {>=}45%, V70 {>=}20%, and a rectum volume {<=}140 cm{sup 3}), significantly discriminated patients with late Grade 0-1 and Grade 2 or worse rectal toxicity, particularly using the LENT SOMA and CTCAE v3.0 systems. The rectum volume receiving {>=}70 Gy (V70) was most predictive for late Grade 2 or worse rectal toxicity with each of the grading systems. The associations were strongest, however, with use of the LENT SOMA system. Conclusions: Volume effects for late radiation-induced rectal toxicity are present, but their clinical significance depends on the grading system used. This should be taken into account in the interpretation of studies reporting on radiation-induced rectal toxicity.

  13. Anastomotic leakage in rectal cancer surgery: The role of blood perfusion

    PubMed Central

    Rutegård, Martin; Rutegård, Jörgen

    2015-01-01

    Anastomotic leakage after anterior resection for rectal cancer remains a common and often devastating complication. Preoperative risk factors for anastomotic leakage have been studied extensively and are used for patient selection, especially whether to perform a diverting stoma or not. From the current literature, data suggest that perfusion in the rectal stump rather than in the colonic limb may be more important for the integrity of the colorectal anastomosis. Moreover, available research suggests that the mid and upper rectum is considerably more vascularized than the lower part, in which the posterior compartment seems most vulnerable. These data fit neatly with the observation that anastomotic leaks are far more frequent in patients undergoing total compared to partial mesorectal excision, and also that most leaks occur dorsally. Clinical judgment has been shown to ineffectively assess anastomotic viability, while promising methods to measure blood perfusion are evolving. Much interest has recently been turned to near-infrared light technology, enhanced with fluorescent agents, which enables intraoperative perfusion assessment. Preliminary data are promising, but large-scale controlled trials are lacking. With maturation of such technology, perfusion measurements may in the future inform the surgeon whether anastomoses are at risk. In high colorectal anastomoses, anastomotic revision might be feasible, while a diverting stoma could be fashioned selectively instead of routinely for low anastomoses. PMID:26649151

  14. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    PubMed Central

    Acosta, Oscar; Drean, Gael; Ospina, Juan David; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; De Crevoisier, Renaud

    2013-01-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80Gy to the prostate by IMRT. Within the patients presenting bleeding, a significant dose excess (6Gy on average, p<0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step. PMID:23528429

  15. Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul

    2016-01-01

    Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer. PMID:27306773

  16. Is Preoperative Chemoradiotherapy Beneficial for Sphincter Preservation in Low-Lying Rectal Cancer Patients?

    PubMed Central

    Park, In Ja; Yu, Chang Sik; Lim, Seok-Byung; Lee, Jong Lyul; Kim, Chan Wook; Yoon, Yong Sik; Park, Seong Ho; Kim, Jin Cheon

    2016-01-01

    Abstract The present study explored the benefit of preoperative chemoradiotherapy (PCRT) for sphincter preservation in locally advanced low-lying rectal cancer patients who underwent stapled anastomosis, especially in those with deep and narrow pelvises determined by magnetic resonance imaging. Patients with locally advanced low-lying rectal cancer (≤5 cm from the anal verge) who underwent stapled anastomosis were included. Patients were categorized into two groups (PCRT+ vs. PCRT–) according to PCRT application. Patients in the PCRT+ group were matched to those in the PCRT– group according to potential confounding factors (age, gender, clinical stage, and body mass index) for sphincter preservation. Sphincter preservation, permanent stoma, and anastomosis-related complications were compared between the groups. Pelvic magnetic resonance imaging was used to measure 12 dimensions representing pelvic cavity depth and width with which deep and narrow pelvis was defined. The impact of PCRT on sphincter preservation and permanent stoma in pelvic dimensions defined as deep and narrow pelvis was evaluated, and factors associated with sphincter preservation and permanent stoma were analyzed. One hundred sixty-six patients were one-to-one matched between the PCRT+ and PCRT− groups. Overall, sphincter-saving surgery was performed in 66.3% and the rates were not different between the 2 groups. Anastomotic complications and permanent stoma occurred nonsignificantly more frequently in the PCRT+ group. PCRT was not associated with higher rate of sphincter preservation in all pelvic dimensions defined as deep and narrow pelvis, while PCRT was related to higher rate of permanent stoma in shorter transverse diameter and interspinous distance. On logistic regression analysis, PCRT was not shown to influence both sphincter preservation and permanent stoma, while longer transverse diameter and interspinous distance were associated with lower rate of permanent stoma. PCRT had

  17. Adjuvant versus neoadjuvant chemoradiotherapy in distal rectal cancer: Comparison of two decades in a single center

    PubMed Central

    Zengel, Baha; Uslu, Adam; Adıbelli, Zehra; Yetiş, Halit; Cengiz, Fevzi; Aykas, Ahmet; Şimşek, Cenk; Akpınar, Göksever; Eliyatkın, Nuket; Duran, Ali

    2015-01-01

    Objective: Standard surgery alone was not able to decrease local recurrence (LR) rate below 20% in rectal cancer treatment. Thus, many centers administered neoadjuvant radiotherapy (preopRTx) with or without concomitant chemotherapy for the prevention of LR. In this study, the results of 164 consecutive patients with mid- and distal rectal cancer who received surgery and adjuvant chemoradiotherapy (Group A) or neoadjuvant chemoradiotherapy (Group NA) followed by surgery are presented. Material and Methods: The staging system used in this study is that of the American Joint Committee on Cancer (AJCC), also known as the TNM system. Eligible patients were required to have radiologically assessed stage 1 (only T2N0M0) to stage 3C (T4bN1-2M0) tumor with pathologically confirmed R0 resection. The surgical method was total mesorectal excision (TME). Radiotherapy was applied with daily 180 cGy fractions for 28 consecutive days. Chemo-therapy comprised 5-fluorouracil (450 mg/m2/d) and leucovorin (20 mg/m2/d) bolus at days 1–5 and 29–33. Results: Nine patients (13%) in Group NA achieved pathologic complete response (pCR). In Group NA and Group A, locoregional recurrence (LRR) rates were 6.7% and 30.8%, (p<0.001), the mean LR-free survival was 190.0±7.3 months and 148.0±11.7 months (p=0.002) and the mean overall survival (OS) was 119.2±15.3 months and 103.0±9.4 months (p=0.23), respectively. A significant difference with regard to LR has been obtained with a statistical power of 0.92. Secondary outcome measures (DFS and OS) have not been met. Conclusion: Neoadjuvant chemoradiotherapy with TME is an efficient treatment protocol, particularly for the treatment of magnetic resonance imaging-staged 2A to 3C patients with two or three distal rectal adenocarcinomas. Given that a considerable proportion of patients with cT2N0M0 would develop pCR, this method of treatment can be considered for further studies. PMID:26668530

  18. Laparoscopic resection of lower rectal cancer with telescopic anastomosis without abdominal incisions

    PubMed Central

    Li, Shi-Yong; Chen, Gang; Du, Jun-Feng; Chen, Guang; Wei, Xiao-Jun; Cui, Wei; Zuo, Fu-Yi; Yu, Bo; Dong, Xing; Ji, Xi-Qing; Yuan, Qiang

    2015-01-01

    AIM: To assess laparoscopic radical resection of lower rectal cancer with telescopic anastomosis through transanal resection without abdominal incisions. METHODS: From March 2010 to June 2014, 30 patients (14 men and 16 women, aged 36-78 years, mean age 59.8 years) underwent laparoscopic radical resection of lower rectal cancer with telescopic anastomosis through anus-preserving transanal resection. The tumors were 5-7 cm away from the anal margin in 24 cases, and 4 cm in six cases. In preoperative assessment, there were 21 cases of T1N0M0 and nine of T2N0M0. Through the middle approach, the sigmoid mesentery was freed at the root with an ultrasonic scalpel and the roots of the inferior mesenteric artery and vein were dissected, clamped and cut. Following the total mesorectal excision principle, the rectum was separated until the anorectal ring reached 3-5 cm from the distal end of the tumor. For perineal surgery, a ring incision was made 2 cm above the dentate line, and sharp dissection was performed submucosally towards the superior direction, until the plane of the levator ani muscle, to transect the rectum. The rectum and distal sigmoid colon were removed together from the anus, followed by a telescopic anastomosis between the full thickness of the proximal colon and the mucosa and submucosal tissue of the rectum. RESULTS: For the present cohort of 30 cases, the mean operative time was 178 min, with an average of 13 positive lymph nodes detected. One case of postoperative anastomotic leak was observed, requiring temporary colostomy, which was closed and recovered 3 mo later. The postoperative pathology showed T1-T2N0M0 in 19 cases and T2N1M0 in 11 cases. Twelve months after surgery, 94.4% patients achieved anal function Kirwan grade 1, indicating that their anal function returned to normal. The patients were followed up for 1-36 mo, with an average of 23 mo. There was no local recurrence, and 17 patients survived for > 3 years (with a survival rate of 100

  19. Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: A longitudinal prospective study

    SciTech Connect

    Allal, Abdelkarim S. . E-mail: abdelkarim.allal@hcuge.ch; Gervaz, Pascal; Gertsch, Philippe; Bernier, Jacques; Roth, Arnaud D.; Morel, Philippe; Bieri, Sabine

    2005-03-15

    Purpose: To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer. Methods and materials: We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses. Results: Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas. Conclusion: One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our

  20. Anatomical basis and clinical research of pelvic autonomic nerve preservation with laparoscopic radical resection for rectal cancer.

    PubMed

    Liu, Yan; Lu, Xiao-ming; Tao, Kai-xiong; Ma, Jian-hua; Cai, Kai-lin; Wang, Lin-fang; Niu, Yan-feng; Wang, Guo-bin

    2016-04-01

    The clinical effect of laparoscopic rectal cancer curative excision with pelvic autonomic nerve preservation (PANP) was investigated. This study evaluated the frequency of urinary and sexual dysfunction of 149 male patients with middle and low rectal cancer who underwent laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP) from March 2011 to March 2013. Eighty-four patients were subjected to laparoscopic surgery, and 65 to open surgery respectively. The patients were followed up for 12 months, interviewed, and administered a standardized questionnaire about postoperative functional outcomes and quality of life. In the laparoscopic group, 13 patients (18.37%) presented transitory postoperative urinary dysfunction, and were medically treated. So did 12 patients (21.82%) in open group. Sexual desire was maintained by 52.86%, un-ability to engage in intercourse by 47.15%, and un-ability to achieve orgasm and ejaculation by 34.29% of the patients in the laparoscopic group. Sexual desire was maintained by 56.36%, un-ability to engage in intercourse by 43.63%, and un-ability to achieve orgasm and ejaculation by 33.73% of the patients in the open group. No significant differences in urinary and sexual dysfunction between the laparoscopic and open rectal resection groups were observed (P>0.05). It was concluded that laparoscopic rectal cancer radical excision with PANP did not aggravate or improve sexual and urinary dysfunction. PMID:27072964

  1. Endoscopic submucosal dissection versus local excision for early rectal cancer: a systematic review and meta-analysis.

    PubMed

    Wang, S; Gao, S; Yang, W; Guo, S; Li, Y

    2016-01-01

    Endoscopic submucosal dissection (ESD) and local excision (LE) are minimally invasive procedures that can be used to treat early rectal cancer. There are no current guidelines or consensus on the optimal treatment strategy for these lesions. A systematic review was conducted to compare the efficacy and safety of ESD and LE. A meta-analysis was conducted following all aspects of the Cochrane Handbook for systematic reviews and preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. To perform the statistical analysis, the odds ratio (OR) was used for categorical variables and the weighted mean difference (WMD) for continuous variables. Four studies, involving a total of 307 patients, were identified. The length of hospital stay was longer in the group of patients undergoing LE [weighted mean difference (WMD) -1.94; 95% CI -2.85 to -1.02; p < 0.0001]. The combined results of the individual studies showed no significant differences as regards en-bloc resection rate (OR 0.82; 95% CI 0.25-2.70; p = 0.74), R0 resection rate (OR 1.53; 95% CI 0.62-3.73; p = 0.35), overall complication rate (OR 0.67; 95% CI 0.26-1.69; p = 0.40), and tumor size (WMD 0.57; 95% CI -3.64 to 4.78; p = 0.79) between ESD and LE. When adopting the fixed effect model which takes into account the study size, ESD was associated with a lower recurrence rate than LE (OR 0.15; 95% CI 0.03-0.87; p = 0.03), while with the random-effect model the difference was not significant (OR 0.18; 95% CI 0.02-2.04; p = 0.17). Over the last decade improvements in technology have improved the technical feasibility of rectal ESD. In specialized centers with highly experienced endoscopists, ESD can provide high-quality en-bloc excision of rectal neoplasms equivalent to traditional local excision. PMID:26519288

  2. Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

    SciTech Connect

    Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko

    2014-07-01

    Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

  3. Late Patient-Reported Toxicity After Preoperative Radiotherapy or Chemoradiotherapy in Nonresectable Rectal Cancer: Results From a Randomized Phase III Study

    SciTech Connect

    Braendengen, Morten; Tveit, Kjell Magne; Bruheim, Kjersti; Cvancarova, Milada; Berglund, Ake; Glimelius, Bengt

    2011-11-15

    Purpose: Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT. Methods and Materials: Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy Multiplication-Sign 25 {+-} 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function -vaginal changes questionnaire (SVQ). Results: Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life. Conclusions: Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.

  4. Selecting Patients With Locally Advanced Rectal Cancer for Neoadjuvant Treatment Strategies

    PubMed Central

    Dewdney, Alice; Cunningham, David

    2013-01-01

    Rectal cancer remains a significant problem worldwide. Outcomes vary significantly according to the stage of disease and prognostic factors, including the distance of the tumor from the circumferential resection margin. Accurate staging, including high-resolution magnetic resonance imaging, allows stratification of patients into low-, moderate-, and high-risk disease; this information can be used to inform multidisciplinary team decisions regarding the role of neoadjuvant therapy. Both neoadjuvant short-course radiotherapy and long-course chemoradiation reduce the risk of local recurrence compared with surgery alone, but they have little impact on survival. Although there remains a need to reduce overtreatment of those patients at moderate risk, evaluation of intensified regimens for those with high-risk disease is still required to reduce distant failure rates and improve survival in these patients with an otherwise poor prognosis. PMID:23821325

  5. Patient-reported outcomes after neoadjuvant therapy for rectal cancer: a systematic review.

    PubMed

    Gavaruzzi, Teresa; Lotto, Lorella; Giandomenico, Francesca; Perin, Alessandro; Pucciarelli, Salvatore

    2014-08-01

    Neoadjuvant therapy followed by total mesorectal excision is standard of care for locally advanced rectal cancer. However, this approach has been previously shown to be associated with high rate of morbidity and it may have a negative effect on patients' reported outcomes (PROs). In order to summarize findings on the effect of the neoadjuvant approach on PROs, we systematically reviewed articles published in the last five years. Thirty-five articles met the inclusion criteria. Ten articles compared the effect of surgery with and without neoadjuvant therapy, six articles compared different neoadjuvant therapies, ten articles reported on patients who were all treated with neoadjuvant therapy, and nine articles examined the effect of neoadjuvant therapy in the analyses. The results are summarized by function investigated and critically commented. PMID:24745308

  6. [A Case of Unresectable Rectal Cancer Associated with Hemorrhage of the Primary Tumor after Chemotherapy].

    PubMed

    Yamada, Moyuru; Takahashi, Hidekazu; Murata, Masaru; Tanaka, Nobuo; Asai, Kensuke; Saso, Kazuhiro; Yagi, Tomoko; Katsuyama, Shinsuke; Sawami, Hirokazu; Takayama, Osamu; Baba, Masashi; Yamamoto, Masayuki; Hiratsuka, Masahiro

    2015-11-01

    A 47-year-old man visited our hospital with complaints of abdominal pain and hematuria.He was diagnosed with unresectable rectal cancer invading the urinary bladder with multiple liver metastases. Systemic chemotherapy with mFOLFOX6 and panitumumab was started soon after sigmoid colostomy. Three months later, both the primary tumor and the liver metastases had partially responded. Another 2 months later, he complained of terrible abdominal pain. CT images revealed a huge primary tumor and hemorrhage in the sigmoid mesocolon occupying the pelvic cavity. A salvage operation was performed and the primary tumor was palliatively resected. Soon after the operation, a local recurrence appeared and grew rapidly. He died 8 months after diagnosis. Rapid growth of the primary tumor seemed a limiting factor for the prognosis. PMID:26805129

  7. Acute Toxicity of Radiochemotherapy in Rectal Cancer Patients: A Risk Particularly for Carriers of the TGFB1 Pro25 variant

    SciTech Connect

    Schirmer, Markus Anton; Mergler, Caroline Patricia Nadine; Rave-Fraenk, Margret; Herrmann, Markus Karl; Hennies, Steffen; Gaedcke, Jochen; Conradi, Lena-Christin; Jo, Peter; Beissbarth, Tim; Hess, Clemens Friedrich; Becker, Heinz; Ghadimi, Michael; Brockmoeller, Juergen; Christiansen, Hans; Wolff, Hendrik Andreas

    2012-05-01

    Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions. Methods and Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade {>=}2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped. Results: In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT. Conclusion: The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques.

  8. Cost-effectiveness of adjuvant chemotherapy with uracil–tegafur for curatively resected stage III rectal cancer

    PubMed Central

    Hisashige, A; Yoshida, S; Kodaira, S

    2008-01-01

    Recently, the National Surgical Adjuvant Study of Colorectal Cancer in Japan, a randomised controlled trial of oral uracil–tegafur (UFT) adjuvant therapy for stage III rectal cancer, showed remarkable survival gains, compared with surgery alone. To evaluate value for money of adjuvant UFT therapy, cost-effective analysis was carried out. Cost-effectiveness analysis of adjuvant UFT therapy was carried out from a payer's perspective, compared with surgery alone. Overall survival and relapse-free survival were estimated by Kaplan–Meier method, up to 5.6 years from randomisation. Costs were estimated from trial data during observation. Quality-adjusted life-years (QALYs) were calculated using utility score from literature. Beyond observation period, they were simulated by the Boag model combined with the competing risk model. For 5.6-year observation, 10-year follow-up and over lifetime, adjuvant UFT therapy gained 0.50, 0.96 and 2.28 QALYs, and reduced costs by $2457, $1771 and $1843 per person compared with surgery alone, respectively (3% discount rate for both effect and costs). Cost-effectiveness acceptability and net monetary benefit analyses showed the robustness of these results. Economic evaluation of adjuvant UFT therapy showed that this therapy is cost saving and can be considered as a cost-effective treatment universally accepted for wide use in Japan. PMID:18797469

  9. Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer.

    PubMed

    Roh, Kangsan; Yeo, Seung-Gu; Yoo, Byong Chul; Kim, Kyung-Hee; Kim, Sun Young; Kim, Min-Jeong

    2016-09-01

    Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response to CRT would be valuable for individualizing treatment for LARC patients. The current study used metabolomics-based approaches to identify molecular markers that predict the response to CRT. Seventy-six patients with LARC who received pelvic radiotherapy and concurrent chemotherapy using tegafur-uracil and leucovorin were enrolled. Radical surgery was performed 6-8 weeks after the completion of CRT. The postsurgical pathological CRT response was evaluated using the ypStage or tumor regression grade. Profiling patterns of low-mass ions (LMIs) in the pretreatment sera were obtained from all patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Our previously developed two-step algorithms, which showed a powerful diagnostic capability during colorectal cancer screening, were then used to screen for meaningful LMIs with discriminatory power. One combination consisting of seven LMIs was identified, whose discriminatory score separated a good CRT response (ypStage 0-1) from a poor CRT response (ypStage 3-4) successfully. However, each individual LMI alone showed insignificant discriminatory power. This finding suggests that analysis of the LMIs in pretreatment serum could serve as a predictive marker of the CRT response in patients with LARC. PMID:27272410

  10. Association Between the Cytogenetic Profile of Tumor Cells and Response to Preoperative Radiochemotherapy in Locally Advanced Rectal Cancer

    PubMed Central

    González-González, María; Garcia, Jacinto; Alcazar, José A.; Gutiérrez, María L.; Gónzalez, Luis M.; Bengoechea, Oscar; Abad, María M.; Santos-Briz, Angel; Blanco, Oscar; Martín, Manuela; Rodríguez, Ana; Fuentes, Manuel; Muñoz-Bellvis, Luis; Orfao, Alberto; Sayagues, Jose M.

    2014-01-01

    Abstract Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence in situ hybridization (51 different probes) and response to neoadjuvant radiochemotherapy, evaluated by Dworak criteria in 45 rectal cancer tumors before (n = 45) and after (n = 31) treatment. Losses of chromosomes 1p (44%), 8p (53%), 17p (47%), and 18q (38%) and gains of 1q (49%) and 13q (75%) as well as amplification of 8q (38%) and 20q (47%) chromosomal regions were those specific alterations found at higher frequencies. Significant association (P < 0.05) was found between alteration of 1p, 1q, 11p, 12p, and 17p chromosomal regions and degree of response to neoadjuvant therapy. A clear association was observed between cytogenetic profile of the ancestral tumor cell clone and response to radiochemotherapy; cases presenting with del(17p) showed a poor response to neoadjuvant treatment (P = 0.03), whereas presence of del(1p) was more frequently observed in responder patients (P = 0.0002). Moreover, a significantly higher number of copies of chromosomes 8q (P = 0.004), 13q (P = 0.003), and 20q (P = 0.002) were found after therapy versus paired pretreatment rectal cancer samples. Our results point out the existence of an association between tumor cytogenetics and response to neoadjuvant therapy in locally advanced rectal cancer. Further studies in larger series of patients are necessary to confirm our results. PMID:25474426

  11. Association between the cytogenetic profile of tumor cells and response to preoperative radiochemotherapy in locally advanced rectal cancer.

    PubMed

    González-González, María; Garcia, Jacinto; Alcazar, José A; Gutiérrez, María L; Gónzalez, Luis M; Bengoechea, Oscar; Abad, María M; Santos-Briz, Angel; Blanco, Oscar; Martín, Manuela; Rodríguez, Ana; Fuentes, Manuel; Muñoz-Bellvis, Luis; Orfao, Alberto; Sayagues, Jose M

    2014-11-01

    Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence in situ hybridization (51 different probes) and response to neoadjuvant radiochemotherapy, evaluated by Dworak criteria in 45 rectal cancer tumors before (n = 45) and after (n = 31) treatment. Losses of chromosomes 1p (44%), 8p (53%), 17p (47%), and 18q (38%) and gains of 1q (49%) and 13q (75%) as well as amplification of 8q (38%) and 20q (47%) chromosomal regions were those specific alterations found at higher frequencies. Significant association (P < 0.05) was found between alteration of 1p, 1q, 11p, 12p, and 17p chromosomal regions and degree of response to neoadjuvant therapy. A clear association was observed between cytogenetic profile of the ancestral tumor cell clone and response to radiochemotherapy; cases presenting with del(17p) showed a poor response to neoadjuvant treatment (P = 0.03), whereas presence of del(1p) was more frequently observed in responder patients (P = 0.0002). Moreover, a significantly higher number of copies of chromosomes 8q (P = 0.004), 13q (P = 0.003), and 20q (P = 0.002) were found after therapy versus paired pretreatment rectal cancer samples. Our results point out the existence of an association between tumor cytogenetics and response to neoadjuvant therapy in locally advanced rectal cancer. Further studies in larger series of patients are necessary to confirm our results. PMID:25474426

  12. Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

    SciTech Connect

    Crane, Christopher H.; Eng, Cathy; Feig, Barry W.; Das, Prajnan; Skibber, John M.; Chang, George J.; Wolff, Robert A.; Krishnan, Sunil; Hamilton, Stanley; Janjan, Nora A.; Maru, Dipen M.; Ellis, Lee M.; Rodriguez-Bigas, Miguel A.

    2010-03-01

    Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m{sup 2} orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.

  13. Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer

    SciTech Connect

    Kim, Dae Yong; Jung, Kyung Hae . E-mail: khjung@ncc.re.kr; Kim, Tae Hyun; Kim, Duck-Woo; Chang, Hee Jin; Jeong, Jun Yong; Kim, Young Hoon; Son, Seok-Hyun; Yun, Tak; Hong, Chang Won; Sohn, Dae Kyung; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-02-01

    Purpose: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. Results: Radiologic examination showed that tumor volume decreased by 68.2% {+-} 20.5% in the FL group and 68.3% {+-} 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). Conclusion: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

  14. Risk of Hypogonadism From Scatter Radiation During Pelvic Radiation in Male Patients With Rectal Cancer

    SciTech Connect

    Yau, Ivan; Vuong, Te Garant, Aurelie; Ducruet, Thierry; Doran, Patrick; Faria, Sergio; Liberman, Sender; Richard, Carole; Letellier, Francois; Charlebois, Patrick; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2009-08-01

    Purpose: Recent studies have reported fluctuations in sex hormones during pelvic irradiation. The objective of this study was to observe the effects of radiation on hormonal profiles for two treatment modalities: conventional external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDRBT) given neoadjuvantly for patients with rectal cancer. Methods and Materials: Routine serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were collected from 119 consecutive male patients receiving either EBRT, using 45.0-50.4 Gy in 25-28 fractions with concurrent 5-fluorouracil chemotherapy or HDRBT using 26 Gy in 4 fractions. Results: Thirty patients with initially abnormal profiles were excluded. Profiles included in this study were collected from 51 patients treated with EBRT and 38 patients treated with HDRBT, all of whom had normal hormonal profiles before treatment. Mean follow-up times were 17 months for the entire patient cohort-14 and 20 months, respectively-for the EBRT and HDRBT arms. Dosimetry results revealed a mean cumulative testicular dose of 1.24 Gy received in EBRT patients compared with 0.27 Gy in the HDRBT group. After treatment, FSH and LH were elevated in all patients but were more pronounced in the EBRT group. The testosterone-to-LH ratio was significantly lower (p = 0.0036) in EBRT patients for tumors in the lower third of the rectum. The 2-year hypogonadism rate observed was 2.6% for HDRBT compared with 17.6% for EBRT (p = 0.09) for tumors in the lower two thirds of the rectum. Conclusion: HDRBT allows better hormonal sparing than EBRT during neoadjuvant treatment of patients with rectal cancer.

  15. Biological Image-Guided Radiotherapy in Rectal Cancer: Challenges and Pitfalls

    SciTech Connect

    Roels, Sarah; Slagmolen, Pieter; Lee, John A.; Loeckx, Dirk; Maes, Frederik; Stroobants, Sigrid; Ectors, Nadine; Penninckx, Freddy; Haustermans, Karin

    2009-11-01

    Purpose: To investigate the feasibility of integrating multiple imaging modalities for image-guided radiotherapy in rectal cancer. Patients and Methods: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) were performed before, during, and after preoperative chemoradiotherapy (CRT) in patients with resectable rectal cancer. The FDG-PET signals were segmented with an adaptive threshold-based and a gradient-based method. Magnetic resonance tumor volumes (TVs) were manually delineated. A nonrigid registration algorithm was applied to register the images, and mismatch analyses were carried out between MR and FDG-PET TVs and between TVs over time. Tumor volumes delineated on the images after CRT were compared with the pathologic TV. Results: Forty-five FDG-PET/CT and 45 MR images were analyzed from 15 patients. The mean MRI and FDG-PET TVs showed a tendency to shrink during and after CRT. In general, MRI showed larger TVs than FDG-PET. There was an approximately 50% mismatch between the FDG-PET TV and the MRI TV at baseline and during CRT. Sixty-one percent of the FDG-PET TV and 76% of the MRI TV obtained after 10 fractions of CRT remained inside the corresponding baseline TV. On MRI, residual tumor was still suspected in all 6 patients with a pathologic complete response, whereas FDG-PET showed a metabolic complete response in 3 of them. The FDG-PET TVs delineated with the gradient-based method matched closest with pathologic findings. Conclusions: Integration of MRI and FDG-PET into radiotherapy seems feasible. Gradient-based segmentation is recommended for FDG-PET. Spatial variance between MRI and FDG-PET TVs should be taken into account for target definition.

  16. Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

    SciTech Connect

    Peeters, Stephanie T.H.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl; Heemsbergen, Wilma D.; Putten, Wim L.J. van; Slot, Annerie; Dielwart, Michel F.H.; Koper, Peter C.M.

    2006-03-15

    Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.

  17. Prediction of Response to Preoperative Chemoradiotherapy in Rectal Cancer by Multiplex Kinase Activity Profiling

    SciTech Connect

    Folkvord, Sigurd; Flatmark, Kjersti; Dueland, Svein

    2010-10-01

    Purpose: Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC). Methods and Materials: Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatment as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set. Results: In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance. Conclusions: Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.

  18. Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

    SciTech Connect

    Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher; Christie, Alana; Lotan, Yair; Pistenmaa, David; Kavanagh, Brian D.; Nanda, Akash; Kueplian, Patrick; Brindle, Jeffrey; Cooley, Susan; Perkins, Alida; Raben, David; Xie, Xian-Jin; Timmerman, Robert D.

    2014-07-01

    Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.

  19. Health-related quality of life after laparoscopic and open surgery for rectal cancer in a randomized trial

    PubMed Central

    Andersson, J; Angenete, E; Gellerstedt, M; Angerås, U; Jess, P; Rosenberg, J; Fürst, A; Bonjer, J; Haglind, E

    2013-01-01

    Background Previous studies comparing laparoscopic and open surgical techniques have reported improved health-related quality of life (HRQL). This analysis compared HRQL 12 months after laparoscopic versus open surgery for rectal cancer in a subset of a randomized trial. Methods The setting was a multicentre randomized trial (COLOR II) comparing laparoscopic and open surgery for rectal cancer. Involvement in the HRQL study of COLOR II was optional. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38, and EuroQol – 5D (EQ-5D™) before surgery, and 4 weeks, 6, 12 and 24 months after operation. Analysis was done according to the manual for each instrument. Results Of 617 patients in hospitals participating in the HRQL study of COLOR II, 385 were included. The HRQL deteriorated to moderate/severe degrees after surgery, gradually returning to preoperative values over time. Changes in EORTC QLQ-C30 and QLQ-CR38, and EQ-5D™ were not significantly different between the groups regarding global health score or any of the dimensions or symptoms at 4 weeks, 6 or 12 months after surgery. Conclusion In contrast to previous studies in patients with colonic cancer, HRQL after rectal cancer surgery was not affected by surgical approach. Registration number: NCT0029779 (http://www.clinicaltrials.gov). PMID:23640671

  20. Phase II Study of Weekly Intravenous Oxaliplatin Combined With Oral Daily Capecitabine and Radiotherapy With Biologic Correlates in Neoadjuvant Treatment of Rectal Adenocarcinoma

    SciTech Connect

    Fakih, Marwan G. BullardDunn, Kelli; Yang, Gary Y.; Pendyala, Lakshmi; Toth, Karoly; Andrews, Chris; Rustum, Youcef M.; Ross, Mary Ellen; LeVea, Charles; Puthillath, Ajithkumar; Park, Young-Mee; Rajput, Ashwani

    2008-11-01

    Purpose: To evaluate the efficacy of a combination of capecitabine, oxaliplatin, and radiotherapy (RT) in the neoadjuvant treatment of Stage II and III rectal cancers. Methods: Capecitabine was given at 725 mg/m{sup 2} orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given intravenously at 50 mg/m{sup 2} once weekly five times starting the first day of RT. The radiation dose was 50.4 Gy in 28 fractions (1.8 Gy/fraction), five fractions weekly. Endorectal tumor biopsies were obtained before treatment and on the third day of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and apoptosis. Results: A total of 25 patients were enrolled in this study; 6 patients (24%) had a complete pathologic response. T-downstaging occurred in 52% of patients, and N-downstaging occurred in 53%. Grade 3 diarrhea was the most common Grade 3-4 toxicity, occurring in 20% of patients. Only 2 patients experienced disease recurrence, with a median of 20 months of follow-up. Thymidylate synthase, thymidine phosphorylase, ERCC1, and apoptosis did not vary significantly between the pretreatment and Day 3 tumor biopsies, nor did they predict for T-downstaging or a complete pathologic response. Conclusion: Capecitabine at 725 mg/m{sup 2} orally twice daily, oxaliplatin 50 mg/m{sup 2}/wk, and RT at 50.4 Gy is an effective neoadjuvant combination for Stage II and III rectal cancer and results in a greater rate of complete pathologic responses than historically shown in fluoropyrimidine plus RT controls.

  1. Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome

    PubMed Central

    Davis, Sidney; Mohebbi, Mohammadreza; Sugamaran, Bhuvana; Porter, Ian W.; Bell, Stephen; Warrier, Satish K.; Wale, Roger

    2016-01-01

    Background Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS]. Methods A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy. Results 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4–9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non-responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders. Conclusions The majority

  2. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Acosta, Oscar; Drean, Gael; Ospina, Juan D.; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (⩾Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

  3. Caveolin-1 as a Prognostic Marker for Local Control After Preoperative Chemoradiation Therapy in Rectal Cancer

    SciTech Connect

    Roedel, Franz Capalbo, Gianni; Roedel, Claus; Weiss, Christian

    2009-03-01

    Purpose: Caveolin-1 is a protein marker for caveolae organelles and has an essential impact on cellular signal transduction pathways (e.g., receptor tyrosine kinases, adhesion molecules, and G-protein-coupled receptors). In the present study, we investigated the expression of caveolin-1 in patients with rectal adenocarcinoma and correlated its expression pattern with the risk for disease recurrences after preoperative chemoradiation therapy (CRT) and surgical resection. Methods and Materials: Caveolin-1 mRNA and protein expression were evaluated by Affymetrix microarray analysis (n = 20) and immunohistochemistry (n = 44) on pretreatment biopsy samples of patients with locally advanced adenocarcinoma of the rectum, and were correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure and overall survival. Results: A significantly decreased median caveolin-1 intracellular mRNA level was observed in tumor biopsy samples as compared with noncancerous mucosa. Individual mRNA levels and immunohistologic staining, however, revealed an overexpression in 7 of 20 patients (35%) and 17 of 44 patients (38.6%), respectively. Based on immunohistochemical evaluation, local control rates at 5 years for patients with tumors showing low caveolin-1 expression were significantly better than for patients with high caveolin-1-expressing carcinoma cells (p = 0.05; 92%, 95% confidence interval [95% CI] = 82-102% vs. 72%, 95% CI = 49-84%). A low caveolin-1 protein expression was also significantly related to an increased overall survival rate (p = 0.05; 45%, 95% CI 16-60% vs. 82%, 95% CI = 67-97%). Conclusion: Caveolin-1 may provide a novel prognostic marker for local control and survival after preoperative CRT and surgical resection in rectal cancer.

  4. Comparison Between Perfusion Computed Tomography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Rectal Cancer

    SciTech Connect

    Kierkels, Roel G.J.; Backes, Walter H.; Janssen, Marco H.M.; Buijsen, Jeroen; Beets-Tan, Regina G.H.; Lambin, Philippe; Lammering, Guido; Oellers, Michel C.; Aerts, Hugo J.W.L.

    2010-06-01

    Purpose: To compare pretreatment scans with perfusion computed tomography (pCT) vs. dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rectal tumors. Methods and Materials: Nineteen patients diagnosed with rectal cancer were included in this prospective study. All patients underwent both pCT and DCE-MRI. Imaging was performed on a dedicated 40-slice CT-positron emission tomography system and a 3-T MRI system. Dynamic contrast enhancement was measured in tumor tissue and the external iliac artery. Tumor perfusion was quantified in terms of pharmacokinetic parameters: transfer constant K{sup trans}, fractional extravascular-extracellular space v{sub e}, and fractional plasma volume v{sub p}. Pharmacokinetic parameter values and their heterogeneity (by 80% quantile value) were compared between pCT and DCE-MRI. Results: Tumor K{sup trans} values correlated significantly for the voxel-by-voxel-derived median (Kendall's tau correlation, tau = 0.81, p < 0.001) and 80% quantile (tau = 0.54, p = 0.04), as well as for the averaged uptake (tau = 0.58, p = 0.03). However, no significant correlations were found for v{sub e} and v{sub p} derived from the voxel-by-voxel-derived median and 80% quantile and derived from the averaged uptake curves. Conclusions: This study demonstrated for the first time that pCT provides K{sup trans} values comparable to those of DCE-MRI. However, no correlation was found for the v{sub e} and v{sub p} parameters between CT and MRI. Computed tomography can serve as an alternative modality to MRI for the in vivo evaluation of tumor angiogenesis in terms of the transfer constant K{sup trans}.

  5. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy.

    PubMed

    Acosta, Oscar; Drean, Gael; Ospina, Juan D; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-21

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step. PMID:23528429

  6. Initial Staging of Locally Advanced Rectal Cancer and Regional Lymph Nodes

    PubMed Central

    Cerny, Milena; Dunet, Vincent; Prior, John Olivier; Hahnloser, Dieter; Wagner, Anna Dorothea; Meuli, Reto Antoine; Schmidt, Sabine

    2016-01-01

    Purpose The aim of the study was to compare diffusion-weighted MRI (DW-MRI) parameters with 18F-FDG PET/CT in primary locally advanced rectal cancer (LARC). Methods From October 2012 to September 2014, 24 patients with histologically confirmed and untreated LARC (T3–T4) prospectively underwent a pelvic 1.5-T DW-MRI (b = 0 s/mm2, b = 600 s/mm2) and a whole-body 18F-FDG PET/CT, before neoadjuvant therapy. The 2 examinations were performed on the same day. Two readers measured 18F-FDG SUVmax and SUVmean of the rectal tumor and of the pathological regional lymph nodes on PET/CT and compared these with minimum and mean values of the ADC (ADCmin and ADCmean) on maps generated from DW-MRI. The diagnostic performance of ADC values in identifying pathological lymph nodes was also assessed. Results Regarding tumors (n = 24), we found a significant negative correlation between SUVmean and corresponding ADCmean values (ρ = −0.61, P = 0.0017) and between ADCmin and SUVmax (ρ = −0.66, P = 0.0005). Regarding the lymph nodes (n = 63), there was a significant negative correlation between ADCmean and SUVmean values (ρ = −0.38, P = 0.0021), but not between ADCmin and SUVmax values (ρ = −0.11, P = 0.41). Neither ADCmean nor ADCmin values helped distinguish pathological from benign lymph nodes (AUC of 0.24 [confidence interval, 0.10–0.38] and 0.41 [confidence interval, 0.22–0.60], respectively). Conclusions The correlations between ADCmean and SUVmean suggest an association between tumor cellularity and metabolic activity in untreated LARC and in regional lymph nodes. However, compared with 18F-FDG PET/CT, ADC values are not reliable for identifying pathological lymph nodes. PMID:26828149

  7. Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial

    PubMed Central

    Elwanis, Mostafa Abd; Maximous, Doaa W; Elsayed, Mohamed Ibrahim; Mikhail, Nabiel NH

    2009-01-01

    Introduction Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery. Aim To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine. Patients and methods This trial included 43 patients with low lying (4–7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4–6 weeks by total mesorectal excision technique. Results Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3–23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5–85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5–62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3–23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8–17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3–23.1) respectively. Conclusion In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate. PMID:19508705

  8. Analysis of autonomic nerve preservation and pouch reconstruction influencing fragmentation of defecation after sphincter-preserving surgery for rectal cancer.

    PubMed

    Katsumata, K; Sumi, T; Enomoto, M; Mori, Y; Aoki, T

    2010-01-01

    Our questionnaire survey on defecation disorders after rectal cancer surgery revealed that 66.7% of postoperative patients were most annoyed with fragmentation of defecation. Therefore, we performed a change-over-time analysis on the relationship of fragmentation and factors including location of rectal cancer, surgical technique, anastomosis method, pouch reconstruction, extent of lymph node dissection, and degree of pelvic and colonic nerve preservation surrounding the superior mesenteric artery. The fragmentation decreased over time at the postoperative time points of 6 months, 2 and 5 years. A statistical analysis of factors influencing fragmentation revealed that location of cancer, reconstruction technique, anastomosis method and degree of pelvic nerve preservation were significant factors for the entire patient population and that colonic nerve preservation was a significant factor 5 years after surgery. Analysis of patients with lower rectal cancer only showed that in addition to surgical technique and anastomosis method, pouch reconstruction was effective and autonomic nerve preservation was effective 5 years after surgery. As a result, when the anastomotic site was closer to the anus, the frequency of fragmentation increased; we concluded that pouch reconstruction was an effective surgical technique and colonic nerve preservation was effective in the longer term. PMID:21051900

  9. Preoperative radiotherapy for rectal cancer: a comparative study of quality control adherence at two cancer hospitals in Spain and Poland

    PubMed Central

    Fundowicz, Magdalena; Macia, Miguel; Marin, Susanna; Bogusz-Czerniewicz, Marta; Konstanty, Ewelina; Modolel, Ignaci; Malicki, Julian; Guedea, Ferran

    2014-01-01

    Background We performed a clinical audit of preoperative rectal cancer treatment at two European radiotherapy centres (Poland and Spain). The aim was to independently verify adherence to a selection of indicators of treatment quality and to identify any notable inter-institutional differences. Methods A total of 162 patients, in Catalan Institute of Oncology (ICO) 68 and in Greater Poland Cancer Centre (GPCC) 94, diagnosed with locally advanced rectal cancer and treated with preoperative radiotherapy or radio-chemotherapy were included in retrospective study. A total of 7 quality control measures were evaluated: waiting time, multidisciplinary treatment approach, portal verification, in vivo dosimetry, informed consent, guidelines for diagnostics and therapy, and patient monitoring during treatment. Results Several differences were observed. Waiting time from pathomorphological diagnosis to initial consultation was 31 (ICO) vs. 8 (GPCC) days. Waiting time from the first visit to the beginning of the treatment was twice as long at the ICO. At the ICO, 82% of patient experienced treatment interruptions. The protocol for portal verification was the same at both institutions. In vivo dosimetry is not used for this treatment localization at the ICO. The ICO utilizes locally-developed guidelines for diagnostics and therapy, while the GPCC is currently developing its own guidelines. Conclusions An independent external clinical audit is an excellent approach to identifying and resolving deficiencies in quality control procedures. We identified several procedures amenable to improvement. Both institutions have since implemented changes to improve quality standards. We believe that all radiotherapy centres should perform a comprehensive clinical audit to identify and rectify deficiencies. PMID:24991212

  10. [A Case of Unresectable Rectal Cancer with Multiple Liver Metastases Treated Effectively with 22 Courses of XELOX Therapy].

    PubMed

    Tanaka, Masanao; Shibano, Nariyuki

    2016-05-01

    The patient was a 64-year-old man who underwent medical examination for anorexia and hematochezia. An abdominal computed tomography (CT) scan showed a large advanced rectal cancer with multiple metastases to the liver. We judged a radical operation to be impossible and performed a sigmoid colostomy for unresectable rectal cancer with multiple liver metastases. Postoperatively, we started XELOX therapy and confirmed the patient had a complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) after completion of the 5th course. In addition, the multiple liver metastases reduced remarkably in size and were judged as having a partial response (PR). To date, the patient has completed 22 courses and these good effects continue. PMID:27210099

  11. Timing of Therapies in the Multidisciplinary Treatment of Locally Advanced Rectal Cancer: Available Evidence and Implications for Routine Practice.

    PubMed

    Sclafani, Francesco; Chau, Ian

    2016-07-01

    A multimodality disciplinary approach is paramount for the management of locally advanced rectal cancer. Over the last decade, (chemo)radiotherapy followed by surgery plus or minus adjuvant chemotherapy has represented the mainstay of treatment for this disease. Nevertheless, robust evidence suggesting the optimal timing and sequence of therapies in this setting has been overall limited. A number of questions are still unsolved including the length of the interval between neoadjuvant radiotherapy and surgery or the timing of systemic chemotherapy. Interestingly, emerging data support the contention that altering sequence or timing or both of the components of this multimodality approach may provide an opportunity to implement treatment strategies that far better address the risk and expectations of individual patients. In this article, we review the available evidence on timing of therapies in the multidisciplinary treatment of locally advanced rectal cancer and discuss the potential implications for routine practice that may derive from a change of the currently accepted treatment paradigm. PMID:27238468

  12. Effect of particle beam radiotherapy on locally recurrent rectal cancer: Three case reports

    PubMed Central

    MOKUTANI, YUKAKO; YAMAMOTO, HIROFUMI; UEMURA, MAMORU; HARAGUCHI, NAOTSUGU; TAKAHASHI, HIDEKAZU; NISHIMURA, JUNICHI; HATA, TAISHI; TAKEMASA, ICHIRO; MIZUSHIMA, TSUNEKAZU; DOKI, YUICHIRO; MORI, MASAKI

    2015-01-01

    Surgical resection is the most effective therapy for locally recurrent rectal cancer (LRRC); however, it often necessitates invasive procedures that may lead to major complications. Particle beam radiotherapy (RT), including carbon ion RT (C-ion RT) and proton beam RT, is a promising new modality that exhibits considerable efficacy against various types of human cancer. C-ion RT reportedly offers a therapeutic alternative for LRRC. In the present study, we describe three cases of LRRC treated by particle beam RT. In all the cases, LRRC was diagnosed by computed tomography, magnetic resonance imaging and positron emission tomography imaging. No serious adverse effects were observed during RT. One patient experienced re-recurrence of LRRC, but survived for 6 years following particle beam RT; the second patient remains recurrence-free after a 2-year follow-up; and the third patient has developed recurrence at different sites in the pelvis but, to date, has survived for 4 years following particle beam RT. Therefore, LRRC was controlled by particle beam RT in two of the three cases, suggesting that particle beam RT is a safe alternative treatment for patients with LRRC. PMID:26171176

  13. [A Case of Rectal Stenosis For Gastric Cancer Recurrence Effectively Treated with a Colonic Stent].

    PubMed

    Kimura, Yutaka; Ebihara, Ken; Kato, Fumitaka; Makari, Yoichi; Mikami, Johta; Kawase, Tomono; Hamakawa, Takuya; Tsukamoto, Yuki; Fujimori, Masaki; Gobaru, Aya; Mitsudo, Daichi; Yabuta, Takamasa; Nakata, Ken; Tsujie, Masaki; Kitamura, Shinji; Ohzato, Hiroki

    2015-11-01

    A man in his 70s underwent distal gastrectomy and D1 dissection with Roux-en-Y reconstruction in March 2009 for advanced gastric cancer with peritoneal metastasis. He was diagnosed with signet-ring cell carcinoma, Stage Ⅳ(T4a, N3a, H0, P1, CY1, M1) and R2. Seventeen cycles of S-1 plus CDDP were administered from April 2009 to December 2010 and 19 cycles of S-1 monotherapy were administered from January 2011 to March 2014. He developed peritoneal recurrence with serum tumor marker elevation in May 2014. Stenosis of the common bile duct, hydronephrosis, and rectal stenosis in Ra-Rs was observed in June 2014. A bile duct stent and a double J catheter was inserted. A colonic stent (NitiTM, 22 mm×6 cm) was also inserted. He could eat after the surgery and was discharged from the hospital. We suggest that a colonic stent is an effective treatment for colon stenosis due to peritoneal metastasis from gastric cancer. PMID:26805139

  14. [Long-Term Successful Management of Recurrent Rectal Cancer in the Predialysis State with FOLFIRI Chemotherapy].

    PubMed

    Koike, Naoto; Takeuchi, Toshiaki; Fujii, Takayuki; Ohshima, Yuji; Arita, Seiji; Isaka, Naohide; Shinozaki, Eiji

    2015-11-01

    A 71-year-old man with predialysis terminal renal insufficiency experienced peritoneal dissemination 1.5 years after low anterior resection for advanced rectal cancer. He received FOLFIRI therapy (70% dose); he achieved partial response (PR) under computed tomography and stable disease (SD) was maintained over a long term. Although Grade 3 myelosuppression was occasionally noted, he was treated with FOLFIRI for 2 years without other severe complications and without requiring the initiation of hemodialysis. After the initiation of hemodialysis, FOLFIRI treatment was continued for 1 year until progressive disease (PD). He received mFOLFOX6 as second-line therapy for 6 months, followed by LV-5-FU and a molecular targeting agent. These treatments prolonged his survival for 1 year and 8 months. FOLFIRI can be administered as an effective first-line therapy even for patients with predialysis terminal renal impairment without major renal damage. FOLFOX and molecular targeting agents should be made available and prolonged survival can be expected for advanced colorectal cancer patients with terminal renal disease after the initiation of hemodialysis. PMID:26602405

  15. Histological differences between preoperative chemoradiotherapy and chemotherapy for rectal cancer: a clinicopathological study.

    PubMed

    Sakuyama, Naoki; Kojima, Motohiro; Kawano, Shingo; Akimoto, Tetsuo; Saito, Norio; Ito, Masaaki; Ochiai, Atsushi

    2016-05-01

    Pathological studies on the different histological effects between neoadjuvant chemotherapy (NAC) and preoperative chemoradiation therapy (preoperative CRT) have not been performed. The purpose of this study is to elucidate the histological differences in tissue received from NAC and preoperative CRT for rectal cancer to evaluate whether a pathological assessment method used after CRT can be applied for NAC. One hundred and thirty-eight patients were enrolled in this study; 88 patients underwent their operations after preoperative CRT or NAC, and 50 patients underwent surgery only. Residual tumor area was measured using morphometry software and we compared the stromal component of myofibroblasts, immune cells, and vasculature to elucidate the difference of therapeutic effect between them. The grade of reduction after preoperative CRT was more prominent than that seen in NAC. Also, ypT downstaging was more prominent in preoperative CRT than in NAC, and ypN downstaging was more frequent in NAC than in preoperative CRT. Preoperative CRT showed more marked myofibroblasts and fewer immune cells than did NAC, which indicates different effects on the cancer microenvironment. Our histological results suggest different effects between NAC and preoperative CRT on tumor tissue. The best assessment method available for a variable therapeutic protocol should be further investigated. PMID:27112135

  16. The evaluation of a rectal cancer decision aid and the factors influencing its implementation in clinical practice

    PubMed Central

    2014-01-01

    Background Colorectal cancer is common in North America. Two surgical options exist for rectal cancer patients: low anterior resection with re-establishment of bowel continuity, and abdominoperineal resection with a permanent stoma. A rectal cancer decision aid was developed using the International Patient Decision Aid Standards to facilitate patients being more actively involved in making this decision with the surgeon. The overall aim of this study is to evaluate this decision aid and explore barriers and facilitators to implementing in clinical practice. Methods First, a pre- and post- study will be guided by the Ottawa Decision Support Framework. Eligible patients from a colorectal cancer center include: 1) adult patients diagnosed with rectal cancer, 2) tumour at a maximum of 10 cm from anal verge, and 3) surgeon screened candidates eligible to consider both low anterior resection and abdominoperineal resection. Patients will be given a paper-version and online link to the decision aid to review at home. Using validated tools, the primary outcomes will be decisional conflict and knowledge of surgical options. Secondary outcomes will be patient’s preference, values associated with options, readiness for decision-making, acceptability of the decision aid, and feasibility of its implementation in clinical practice. Proposed analysis includes paired t-test, Wilcoxon, and descriptive statistics. Second, a survey will be conducted to identify the barriers and facilitators of using the decision aid in clinical practice. Eligible participants include Canadian surgeons working with rectal cancer patients. Surgeons will be given a pre-notification, questionnaire, and three reminders. The survey package will include the patient decision aid and a facilitators and barriers survey previously validated among physicians and nurses. Principal component analysis will be performed to determine common themes, and logistic regression will be used to identify variables

  17. Anaesthetic management of laparoscopic surgery for rectal cancer in patients of dilated cardiomyopathy with poor ejection fraction: a case report

    PubMed Central

    Wu, Yao-Hua; Hu, Liang; Xia, Jin; Hao, Quan-Shui; Feng, Li; Xiang, Hong-Bing

    2015-01-01

    A patient with dilated cardiomyopathy with poor ejection fraction posted for laparoscopic surgery for rectal cancer which was successfully performed under general anesthesia with endotracheal intubation and mechanical ventilation was reported. Our observations strongly indicate that detailed preoperative assessment, watchful intraoperative monitoring, and skillful optimization of fluid status and hemodynamic play important role in the high risk patient under general anesthesia with endotracheal intubation and mechanical ventilation. PMID:26309623

  18. GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer

    PubMed Central

    Lee, Hee Yeon; Jung, Ji-Han; Cho, Hyun-Min; Kim, Sung Hwan; Lee, Kang-Moon; Kim, Hyung-Jin; Lee, Jong Hoon; Shim, Byoung Yong

    2015-01-01

    Purpose We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. Materials and Methods All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m2/day) and leucovorin (20 mg/m2/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Results High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045). Conclusion GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT. PMID:25687871

  19. Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy

    PubMed Central

    Song, Yong-xi; Sun, Jing-xu; Chen, Xiao-wan; Zhao, Jun-hua; Ma, Bin; Wang, Jun; Wang, Zhen-ning

    2016-01-01

    Background Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. Methods We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992–2009. We enrolled patients with yp stages I–III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan–Meier survival analysis with propensity score-matching and Cox proportional hazards models. Results Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged < 73 years and ypN+ category, and but did not translate into survival benefits in patients aged ≥ 73 years and ypN+ category. No significant interactions were observed among ypN− patients, and oxaliplatin did not significantly improve OS, regardless of age. Conclusions In patients with rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN− patients. PMID:26910371

  20. Radiation-Induced Thymidine Phosphorylase Upregulation in Rectal Cancer Is Mediated by Tumor-Associated Macrophages by Monocyte Chemoattractant Protein-1 From Cancer Cells

    SciTech Connect

    Kim, Tae-Dong; Li Ge; Song, Kyoung-Sub; Kim, Jin-Man; Kim, Jun-Sang; Kim, Jong-Seok; Yun, Eun-Jin; Park, Jong-Il; Park, Hae-Duck; Hwang, Byung-Doo; Lim, Kyu Yoon, Wan-Hee

    2009-03-01

    Purpose: The mechanisms of thymidine phosphorylase (TP) regulation induced by radiation therapy (XRT) in various tumors are poorly understood. We investigated the effect and mechanisms of preoperative XRT on TP expression in rectal cancer tissues. Methods and Materials: TP expression and CD68 and monocyte chemoattractant protein-1 (MCP-1) levels in rectal cancer tissues and cancer cell lines were evaluated before and after XRT in Western blotting, immunohistochemistry, enzyme-linked immunoassay, and reverse transcription-polymerase chain reaction studies. Isolated peripheral blood monocytes were used in the study of chemotaxis under the influence of MCP-1 released by irradiated colon cancer cells. Results: Expression of TP was significantly elevated by 9 Gy of XRT in most rectal cancer tissues but not by higher doses of XRT. In keeping with the close correlation of the increase in both TP expression and the number of tumor-associated macrophages (TAMs), anti-TP immunoreactivity was found in the CD68-positive TAMs and not the neoplastic cells. Expression of MCP-1 was increased in most cases after XRT, and this increase was strongly correlated with TP expression. However, this increase in MCP-1 expression occurred in tumor cells and not stromal cells. The XRT upregulated MCP-1 mRNA and also triggered the release of MCP-1 protein from cultured colon cancer cells. The supernatant of irradiated colon cancer cells showed strong chemotactic activity for monocyte migration, but this activity was completely abolished by neutralizing antibody. Conclusions: Use of XRT induces MCP-1 expression in cancer cells, which causes circulating monocytes to be recruited into TAMs, which then upregulate TP expression in rectal cancer tissues.

  1. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy

    SciTech Connect

    Kim, Jun-Sang . E-mail: k423j@cnu.ac.kr; Kim, Jin-Man; Li, Shengjin; Yoon, Wan-Hee; Song, Kyu-Sang; Kim, Ki-Hwan; Yeo, Seung-Gu; Nam, Ji Sook; Cho, Moon-June

    2006-09-01

    Purpose: To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods and Materials: A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level. Results: Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p 0.012 vs. odds ratio, 3.235; p < 0.001, respectively). Conclusion: A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.

  2. Distal intramural spread of rectal cancer after preoperative radiotherapy: The results of a multicenter randomized clinical study

    SciTech Connect

    Chmielik, Ewa; Bujko, Krzysztof . E-mail: bujko@coi.waw.pl; Nasierowska-Guttmejer, Anna; Nowacki, Marek P.; Kepka, Lucyna; Sopylo, Rafal; Wojnar, Andrzej; Majewski, Przemyslaw; Sygut, Jacek; Karmolinski, Andrzej; Huzarski, Tomasz; Wandzel, Piotr

    2006-05-01

    Purpose: To evaluate the extent of distal intramural spread (DIS) after preoperative radiotherapy for rectal cancer. Methods and Materials: A total of 316 patients with T{sub 3-4} primary resectable rectal cancer were randomized to receive either preoperative 5x5 Gy radiation with immediate surgery or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) with delayed surgery. The slides of the 106 patients who received short-course radiation and of the 86 who received chemoradiation were available for central microscopic evaluation of DIS. Results: The length of DIS did not differ significantly (p = 0.64) between the short-course group and the chemoradiation group and was 0 in 47% vs. 49%; 1 to 5 mm in 41% vs. 42%; 6 to 10 mm in 8% vs. 9%, and greater than 10 mm in 4% vs. 0, respectively. Among the 11 clinically complete responders, DIS was found 1 to 5 mm from the microscopically detected ulceration of the mucosa in 5 patients. The discontinuous DIS was more frequent in the chemoradiation group as compared with the short-course group (i.e., 57% vs. 16% of cases, p < 0.001). Conclusions: Approximately 1 out of 10 advanced rectal cancers after preoperative radiotherapy or radiochemotherapy was characterized by DIS of over 5 mm. No significant difference was seen in the length of DIS between the 2 groups.

  3. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    SciTech Connect

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-12-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  4. An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis

    PubMed Central

    EMPUKU, SHINICHIRO; NAKAJIMA, KENTARO; AKAGI, TOMONORI; KANEKO, KUNIHIKO; HIJIYA, NAOKI; ETOH, TSUYOSHI; SHIRAISHI, NORIO; MORIYAMA, MASATSUGU; INOMATA, MASAFUMI

    2016-01-01

    Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves the postoperative local control rate, but also induces downstaging. However, it has not been established how to individually select patients who receive effective preoperative CRT. The aim of this study was to identify a predictor of response to preoperative CRT for locally advanced rectal cancer. This study is additional to our multicenter phase II study evaluating the safety and efficacy of preoperative CRT using oral fluorouracil (UMIN ID: 03396). From April, 2009 to August, 2011, 26 biopsy specimens obtained prior to CRT were analyzed by cyclopedic microarray analysis. Response to CRT was evaluated according to a histological grading system using surgically resected specimens. To decide on the number of genes for dividing into responder and non-responder groups, we statistically analyzed the data using a dimension reduction method, a principle component analysis. Of the 26 cases, 11 were responders and 15 non-responders. No significant difference was found in clinical background data between the two groups. We determined that the optimal number of genes for the prediction of response was 80 of 40,000 and the functions of these genes were analyzed. When comparing non-responders with responders, genes expressed at a high level functioned in alternative splicing, whereas those expressed at a low level functioned in the septin complex. Thus, an 80-gene expression set that predicts response to preoperative CRT for locally advanced rectal cancer was identified using a novel statistical method. PMID:27123272

  5. [A Case of Stage Ⅳ Rectal Cancer with No Evidence of Disease after Neoadjuvant Chemotherapy and Surgery].

    PubMed

    Yamaguchi, Kazuya; Watanabe, Ichiro; Sasaki, Megumi; Shibasaki, Yukari; Miyazaki, Koji; Aoyagi, Haruhiko; Higuchi, Katsuyoshi; Koseki, Keita; Kitago, Kuniaki; Nishi, Naoto; Nihei, Zenro; Ito, Masashi

    2015-11-01

    A 46-year-old man presented with hematochezia in October 2012. A circumferential type 2 rectal cancer was detected with colonoscopy. Contrast-enhanced CT showed multiple liver and lung metastases. Chemotherapy was administered after the diagnosis of cStage Ⅳ rectal cancer. After 1 course of XELOX plus Bmab, the treatment was changed to XELOX plus Cmab for 21 courses. An infusion reaction occurred during the 21st course. Because a complete response of the liver metastases and a reduction in size of the primary tumor had been achieved, we performed a low anterior resection in April 2014. The final pathological diagnosis was type 2, 10×25 mm, tub1, pMP, int, INF b, pN1 (251). There was no evidence of disease (NED) after the surgery. We are closely following up this patient with no postoperative chemotherapy, and as of July 2015, there is no sign of recurrence. We describe a case of a Stage Ⅳ rectal cancer that was resected with radical surgery after neoadjuvant chemotherapy. We also include a brief review of the literature. PMID:26805126

  6. Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

    PubMed Central

    Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

    2016-01-01

    AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

  7. Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients

    PubMed Central

    Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

    2016-01-01

    Abstract The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors. Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann–Whitney U test and the Mantel–Cox log-rank sum test. A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P < 0.001). Advanced T-stage (P < 0.001), lymph node invasion (P = 0.001) and incomplete mesorectum (P = 0.007) were encountered significantly more often in patients with positive CRM status. Logistic regression analysis revealed that APR (P < 0.001) and open resection (P = 0.046) were independent predictors of positive CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively). This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates. PMID:26844498

  8. [A patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy who responded completely to S-1 therapy followed by open gastrectomy].

    PubMed

    Ohashi, Ichiro; Arai, Isao; Tamura, Chieko; Inoue, Shigeharu; Wakasa, Kenichi

    2012-11-01

    We report a rare case of a patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy, who responded completely to S-1 therapy followed by open gastrectomy. A 72-year-old man with a chief complaint of occult blood in the feces was referred to our hospital and was diagnosed with rectal cancer by colonoscopy. In addition, we found concomitant gastric cancer by gastrointestinal fiberscopy. Abdominal plain computed tomography showed no liver metastasis. In August 2010, we performed laparoscopic resection of the rectal cancer. However, at the time of discharge, abdominal enhanced computed tomography showed multiple liver metastases. Then, we administered 4 courses of S-1 therapy. In December 2010, abdominal enhanced computed tomography showed no liver metastasis. In March 2011, because no other lesion without residual gastric cancer was detected, the patient underwent gastrectomy followed by S-1 therapy. As of January 2012, the patient is alive and disease free. S-1 therapy with laparoscopic resection for rectal cancer and gastrectomy may help prolong the survival of patients with multiple liver metastases of gastric and rectal cancers. PMID:23268031

  9. [Prevention of intraoperative incidental injuries during sphincter-preserving surgery for rectal cancer and management of postoperative complication].

    PubMed

    Han, Fanghai; Li, Hongming

    2016-06-01

    Prevention of intraoperative incidental injuries during radical operation for rectal cancer and management of postoperative complication are associated with successful operation and prognosis of patients. This paper discusses how to prevent such intraoperative incidental injuries and how to manage postoperative complication. (1) Accurate clinical evaluation should be performed before operation and reasonable treatment decision should be made, including determination of the distance from transection to lower margin of the tumor, T and M staging evaluated by MRI, fascia invasion of mesorectum, metastasis of lateral lymph nodes, metastatic station of mesentery lymph node, association between levator ani muscle and anal sphincter, course and length of sigmoid observed by Barium enema, length assessment of pull-through bowel. Meanwhile individual factors of patients and tumors must be realized accurately. (2) Injury of pelvic visceral fascia should be avoided during operation. Negative low and circumference cutting edge must be ensured. Blood supply and adequate length of pull-down bowel must be also ensured. Urinary system injury, pelvic bleeding and intestinal damage should be avoided. Team cooperation and anesthesia procedure should be emphasized. Capacity of handling accident events should be cultivated for the team. (3) intraoperative incidental injuries during operation by instruments should be avoided, such as poor clarity of camera due to spray and smog, ineffective instruments resulted from repeated usage. (4) As to the prevention and management of postoperative complication of rectal cancer operation, prophylactic stoma should be regularly performed for rectal cancer patients undergoing anterior resection, while drainage tube placement does not decrease the morbidities of anastomosis and other complications. After sphincter-preserving surgery for rectal cancer, attentions must be paid to the occurrence of anastomotic bleeding, pelvic bleeding, anastomotic

  10. SU-D-BRA-04: Fractal Dimension Analysis of Edge-Detected Rectal Cancer CTs for Outcome Prediction

    SciTech Connect

    Zhong, H; Wang, J; Hu, W; Shen, L; Wan, J; Zhou, Z; Zhang, Z

    2015-06-15

    Purpose: To extract the fractal dimension features from edge-detected rectal cancer CTs, and to examine the predictability of fractal dimensions to outcomes of primary rectal cancer patients. Methods: Ninety-seven rectal cancer patients treated with neo-adjuvant chemoradiation were enrolled in this study. CT images were obtained before chemoradiotherapy. The primary lesions of the rectal cancer were delineated by experienced radiation oncologists. These images were extracted and filtered by six different Laplacian of Gaussian (LoG) filters with different filter values (0.5–3.0: from fine to coarse) to achieve primary lesions in different anatomical scales. Edges of the original images were found at zero-crossings of the filtered images. Three different fractal dimensions (box-counting dimension, Minkowski dimension, mass dimension) were calculated upon the image slice with the largest cross-section of the primary lesion. The significance of these fractal dimensions in survival, recurrence and metastasis were examined by Student’s t-test. Results: For a follow-up time of two years, 18 of 97 patients had experienced recurrence, 24 had metastasis, and 18 were dead. Minkowski dimensions under large filter values (2.0, 2.5, 3.0) were significantly larger (p=0.014, 0.006, 0.015) in patients with recurrence than those without. For metastasis, only box-counting dimensions under a single filter value (2.5) showed differences (p=0.016) between patients with and without. For overall survival, box-counting dimensions (filter values = 0.5, 1.0, 1.5), Minkowski dimensions (filter values = 0.5, 1.5, 2.0, 2,5) and mass dimensions (filter values = 1.5, 2.0) were all significant (p<0.05). Conclusion: It is feasible to extract shape information by edge detection and fractal dimensions analysis in neo-adjuvant rectal cancer patients. This information can be used to prognosis prediction.

  11. Increasing late stage colorectal cancer and rectal cancer mortality demonstrates the need for screening: a population based study in Ireland, 1994-2010

    PubMed Central

    2014-01-01

    Background This paper describes trends in colorectal cancer incidence, survival and mortality from 1994 to 2010 in Ireland prior to the introduction of population-based screening. Methods We examined incidence (National Cancer Registry Ireland (NCRI) and mortality (Central Statistics Office) from 1994 to 2010. Age standardised rates (ASR) for incidence and mortality have been calculated, weighted by the European standard population. Annual percentage change was calculated in addition to testing for linear trends in treatment and case fraction of early and late stage disease. Relative survival was calculated considering deaths from all causes. Results The colorectal cancer ASR was 63.7 per 100,000 in males and 38.7 per 100,000 in females in 2010. There was little change in the ASR over time in either sex, or when colon and rectal cancers were considered separately; however the number of incident cancers increased significantly during 1994-2010 (1752 to 2298). The case fractions of late stage (III/IV) colon and rectal cancers rose significantly over time. One and 5 year relative survival improved for both sexes between the periods 1994-2008. Colorectal cancer mortality ASRs decreased annually from 1994-2009 by 1.8% (95% CI -2.2, -1.4). Rectal cancer mortality ASRs rose annually by 2.4% (95% CI 1.1, 3.6) and 2.8% (95% CI 1.2, 4.4) in males and females respectively. Conclusions Increases in late-stage disease and rectal cancer mortality demonstrate an urgent need for colorectal cancer screening. However, the narrow age range at which screening is initially being rolled-out in Ireland means that the full potential for reductions in late-stage cancers and incidence and mortality are unlikely to be achieved. While it is possible that the observed increase in rectal cancer mortality may be partly an artefact of cause of death misclassification, it could also be explained by variations in treatment and adherence to best practice guidelines; further investigation is

  12. Clinical Parameters Predicting Pathologic Tumor Response After Preoperative Chemoradiotherapy for Rectal Cancer

    SciTech Connect

    Yoon, Sang Min; Kim, Dae Yong Kim, Tae Hyun; Jung, Kyung Hae; Chang, Hee Jin; Koom, Woong Sub; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-11-15

    Purpose: To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer. Methods and Materials: The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Results: Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004). Conclusions: The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.

  13. [A Case Report of a Pathological Complete Response of Rectal Cancer to Preoperative Chemoradiotherapy with Tegafur].

    PubMed

    Morikawa, Tatsuya; Teraishi, Fuminori; Shima, Yasuo; Iwata, Jun

    2016-03-01

    We report the case of a patient with advanced rectal cancer who achieved a pathological complete response to preoperative chemoradiotherapy (CRT). A 65-year-old man was diagnosed as having a two-thirds circumferential well-to moderately differentiated tumor (Rb-P, type 2). To control local recurrence, we treated the patient with CRT. Radiotherapy was administered in fractions of 2 Gy/day (total, 40 Gy). Concurrently, S-1 was administered orally at a fixed daily dose of 80 mg/m2 for 20 days. Withdrawal and/or dose reduction of S-1 was not necessary in spite of Grade 1 or 2 toxic effects, including diarrhea and periproctitis, occurring on day 7. Laparoscopic abdominoperineal resection was performed 6 weeks after the final dose of chemotherapy was administered. The histopathological regression grade was Grade 3. No recurrence was detected on enhanced CT more than 5 years after surgery. This case suggests that the regimen was both effective and tolerated, and that preoperative chemoradiotherapy may be effective for tumor suppression to prevent local recurrence. PMID:27067861

  14. [A Case of Locally Advanced Rectal Cancer Successfully Treated by Conversion Surgery after Multidisciplinary Treatment].

    PubMed

    Shimizu, Yosuke; Yamashita, Shinya; Tominaga, Harumi; Kimura, Yuri; Odagiri, Kazuki; Kurokawa, Tomoaki; Yamaguchi, Megumi; Takahashi, Gen; Sawada, Genta; Jeongho, Moon; Inoue, Masasi; Irei, Toshimitsu; Nakahira, Sin; Hatanaka, Nobutaka

    2015-10-01

    A 70-year-old woman who complained of abdominal pain and a prolapsed tumor from the anus was diagnosed with an intestinal obstruction resulting from anal canal cancer. Computed tomography (CT) and magnetic resonance imaging revealed a huge tumor (11×5×12 cm) invading the vagina and levator ani muscle. Enlarged inguinal lymph nodes on both sides indicated metastasis. The clinical stage was T4b (vagina, levator ani muscle, and pudenda) N0H0M1a (LYM), stage IV (Japanese Classification of Colorectal Carcinoma: 8th edition). As curative resection was not possible, a transvers colostomy was performed to relieve the intestinal obstruction. This was followed by chemoradiotherapy (45 Gy/1.8 Gy×25; TS-1, 80 mg/body for 2 weeks and a 1-week interval, for 2 courses) and up to 10 courses of Bev+mFOLFOX6 continuously. After this regimen, there was a remarkable reduction in tumor size. Positron emission tomography-CT revealed no FDG uptake in the primary rectal site or inguinal lymph nodes, but a maximum standardized uptake value (SUVmax) of 6.3 was detected in the vagina. Six weeks after chemotherapy, the patient underwent a pelvic exenteration including resection of the vagina, bladder, and pudenda. The pathological stage was yp T4b (vagina) N0H0M0, stageⅡ. Curative resection was performed, and the patient had a Grade 2 pathological response after chemoradiotherapy. PMID:26489576

  15. Predictive Response Value of Pre- and Postchemoradiotherapy Variables in Rectal Cancer: An Analysis of Histological Data

    PubMed Central

    Santos, Marisa D.; Silva, Cristina; Rocha, Anabela; Nogueira, Carlos; Matos, Eduarda; Lopes, Carlos

    2016-01-01

    Background. Neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery in locally advanced rectal cancer (LARC) improves pelvic disease control. Survival improvement is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. Potential predictive factors for Mandard response are analyzed. Materials and Methods. 167 patients with LARC were treated with nCRT and curative surgery. Tumor biopsies and surgical specimens were reviewed and analyzed regarding mitotic count, necrosis, desmoplastic reaction, and inflammatory infiltration grade. Surgical specimens were classified according to Mandard TRG. The patients were divided as “good responders” (Mandard TRG1-2) and “bad responders” (Mandard TRG3-5). According to results from our previous data, good responders have better prognosis than bad responders. We examined predictive factors for Mandard response and performed statistical analysis. Results. In univariate analysis, distance from anal verge and ten other postoperative variables related with nCRT tumor response had predictive value for Mandard response. In multivariable analysis only mitotic count, necrosis, and differentiation grade in surgical specimen had predictive value. Conclusions. There is a lack of clinical and pathological preoperative variables able to predict Mandard response. Only postoperative pathological parameters related with nCRT response have predictive value. PMID:26885438

  16. [Rectal mucosa metastasis in recurrent prostate cancer : (68)Ga-PSMA-PET/CT allows targeted salvage radiotherapy].

    PubMed

    Düwel, C; Blümel, C; Westenfelder, K; Wagner-Thiessen, E; Becker, A; Gschwend, J E; Eiber, M; Maurer, T

    2016-08-01

    This article presents for the first time a case of rectal mucosa metastasis of recurrent prostate cancer that was diagnosed with (68)Ga-PSMA PET/CT. After histological confirmation, the patient was treated with salvage radiotherapy. This case report underlines the specificity and efficacy of PSMA-based PET imaging. In case of biochemical relapse, it can be used even at low PSA levels to detect prostate cancer metastases that might also be in atypical locations. Thus, (68)Ga-PSMA PET/CT may allow new options for salvage therapy. PMID:27385310

  17. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer: An International Multi-Institutional Study.

    PubMed

    Park, Jun Seok; Sakai, Yoshiharu; Simon, Ng Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-05-01

    Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer.An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate.The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively.Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

  18. Gefitinib and Combination Chemotherapy in Treating Patients With Advanced or Recurrent Colorectal Cancer

    ClinicalTrials.gov

    2013-01-15

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  19. Prospective Randomized Study Comparing Robotic-Assisted Surgery with Traditional Laparotomy for Rectal Cancer-Indian Study.

    PubMed

    Somashekhar, S P; Ashwin, K R; Rajashekhar, Jaka; Zaveri, Shabber

    2015-12-01

    Rectal cancer is one of the common cancers in India. Surgical management is the mainstay of initial treatment for majority of patients. Minimally invasive surgery has gained acceptance for the surgical treatment of rectal cancer because, compared with laparotomy, it is associated with fewer complications, shorter hospitalization, and faster recovery. The aim of this study is to evaluate the safety, feasibility, technique, and outcomes (postoperative, oncological, and functional) of robotic-assisted rectal surgery in comparison with open surgery in the Indian population. A prospective randomized study was undertaken from August 2011 to December 2012. Fifty patients who presented with rectal carcinoma were randomized to either robotic arm (RA) or open arm (OA) group. Both groups were matched for clinical stage and operation type. Technique and feasibility of robotic-assisted surgery in terms of operating time, estimated blood loss, margins status, total number of lymph nodes retrieved, hospital stay, conversion to open procedure, complications, and functional outcomes were analyzed. The mean operative time was significantly longer in the RA than in the OA group (310 vs 246 min, P < 0.001) but was significantly reduced in the latter part of the robotic-assisted patients compared with the initial patients. The mean estimated blood loss was significantly less in the RA compared with the OA group (165.14 vs 406.04 ml, P < 0.001). None of the patients had margin positivity. The mean distal resection margin was significantly longer in the RA than in the OA group (3.6 vs 2.4 cm, P < 0.001). A total of 100 % of patients in the RA group had complete mesorectal excision while two patients in the OA group had incomplete mesorectal excision. The average number of retrieved lymph nodes was adequate for accurate staging. The number of lymph nodes removed by robotic method is slightly higher than the open method (16.88 vs 15.20) but with no statistical significance

  20. Clinical significance of enlarged lateral pelvic lymph nodes before and after preoperative chemoradiotherapy for rectal cancer

    PubMed Central

    INOUE, YASUHIRO; SAIGUSA, SUSUMU; HIRO, JUNICHIRO; TOIYAMA, YUJI; ARAKI, TOSHIMITSU; TANAKA, KOJI; MOHRI, YAUSHIKO; KUSUNOKI, MASATO

    2016-01-01

    Preoperative chemoradiotherapy (CRT) with total mesorectal excision (TME) is the widely accepted treatment for rectal cancer (RC) in Western countries. However, there remains controversy as to whether preoperative CRT is useful in tumors that extend beyond the mesorectum, including metastasis to the lateral pelvic lymph nodes (LPLN). The aim of this study was to assess the prognostic significance of LPLN enlargement in patients with RC who receive preoperative CRT followed by TME without LPLN dissection. We evaluated the prognostic effect of radiographic LPLN enlargement before and after CRT, as well as the patients' clinicopathological and genetic profiles. Of the 104 patients investigated, pretreatment imaging identified 19 (18%) as LPLN-positive (>7 mm in diameter). Of these 19 patients, 7 (37%) exhibited LPLN downsizing to <7 mm following CRT. The median follow-up period was 52 months. The 5-year cancer-specific survival (CSS) or relapse-free survival (RFS) did not differ significantly between patients who did and those who did not have positive LPLN on pretreatment imaging. However, LPLN that remained positive after CRT were significantly associated with poorer 5-year CSS (73 vs. 84%, respectively; P=0.0052) and RFS (32 vs. 78%, respectively; P=0.0264). None of the patients whose LPLN were downsized to <7 mm following CRT developed recurrence; however, those with positive LPLN after CRT had a 55% higher recurrence rate, characterized by delayed local recurrence, a pattern that may be affected by certain chemokines. In conclusion, changes in initially positive LPLN (>7 mm) may predict the prognosis of patients with RC who receive preoperative CRT-TME. LPLN positivity after CRT was associated with shorter CSS and RFS. Strategies to improve patient survival may include selective LPLN dissection or more aggressive multimodality therapy. PMID:27313860

  1. Prostate cancer multi-feature analysis using trans-rectal ultrasound images.

    PubMed

    Mohamed, S S; Salama, M M A; Kamel, M; El-Saadany, E F; Rizkalla, K; Chin, J

    2005-08-01

    This note focuses on extracting and analysing prostate texture features from trans-rectal ultrasound (TRUS) images for tissue characterization. One of the principal contributions of this investigation is the use of the information of the images' frequency domain features and spatial domain features to attain a more accurate diagnosis. Each image is divided into regions of interest (ROIs) by the Gabor multi-resolution analysis, a crucial stage, in which segmentation is achieved according to the frequency response of the image pixels. The pixels with a similar response to the same filter are grouped to form one ROI. Next, from each ROI two different statistical feature sets are constructed; the first set includes four grey level dependence matrix (GLDM) features and the second set consists of five grey level difference vector (GLDV) features. These constructed feature sets are then ranked by the mutual information feature selection (MIFS) algorithm. Here, the features that provide the maximum mutual information of each feature and class (cancerous and non-cancerous) and the minimum mutual information of the selected features are chosen, yielding a reduced feature subset. The two constructed feature sets, GLDM and GLDV, as well as the reduced feature subset, are examined in terms of three different classifiers: the condensed k-nearest neighbour (CNN), the decision tree (DT) and the support vector machine (SVM). The accuracy classification results range from 87.5% to 93.75%, where the performance of the SVM and that of the DT are significantly better than the performance of the CNN. PMID:16030375

  2. NOTE: Prostate cancer multi-feature analysis using trans-rectal ultrasound images

    NASA Astrophysics Data System (ADS)

    Mohamed, S. S.; Salama, M. M. A.; Kamel, M.; El-Saadany, E. F.; Rizkalla, K.; Chin, J.

    2005-08-01

    This note focuses on extracting and analysing prostate texture features from trans-rectal ultrasound (TRUS) images for tissue characterization. One of the principal contributions of this investigation is the use of the information of the images' frequency domain features and spatial domain features to attain a more accurate diagnosis. Each image is divided into regions of interest (ROIs) by the Gabor multi-resolution analysis, a crucial stage, in which segmentation is achieved according to the frequency response of the image pixels. The pixels with a similar response to the same filter are grouped to form one ROI. Next, from each ROI two different statistical feature sets are constructed; the first set includes four grey level dependence matrix (GLDM) features and the second set consists of five grey level difference vector (GLDV) features. These constructed feature sets are then ranked by the mutual information feature selection (MIFS) algorithm. Here, the features that provide the maximum mutual information of each feature and class (cancerous and non-cancerous) and the minimum mutual information of the selected features are chosen, yeilding a reduced feature subset. The two constructed feature sets, GLDM and GLDV, as well as the reduced feature subset, are examined in terms of three different classifiers: the condensed k-nearest neighbour (CNN), the decision tree (DT) and the support vector machine (SVM). The accuracy classification results range from 87.5% to 93.75%, where the performance of the SVM and that of the DT are significantly better than the performance of the CNN.

  3. Collection of Biospecimen & Clinical Information in Patients w/ Gastrointestinal Cancers

    ClinicalTrials.gov

    2012-05-24

    Gastrointestinal Neoplasms; Gynecologic Cancers; Gynecologic Cancers Cervical Cancer; Gastric (Stomach) Cancer; Gastro-Esophageal(GE) Junction Cancer; Gastrointenstinal Stromal Tumor (GIST); Colon/Rectal Cancer; Colon/Rectal Cancer Colon Cancer; Colon/Rectal Cancer Rectal Cancer; Colon/Rectal Cancer Anal Cancer; Anal Cancer; Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Pancreatic Cancer

  4. Morphine Rectal

    MedlinePlus

    Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate ( ... Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use ...

  5. Extended Intervals after Neoadjuvant Therapy in Locally Advanced Rectal Cancer: The Key to Improved Tumor Response and Potential Organ Preservation

    PubMed Central

    Probst, Christian P; Becerra, Adan Z; Aquina, Christopher T; Tejani, Mohamedtaki A; Wexner, Steven D; Garcia-Aguilar, Julio; Remzi, Feza H; Dietz, David W; Monson, John RT; Fleming, Fergal J

    2016-01-01

    Background Many rectal cancer patients experience tumor downstaging and some are found to achieve a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Previous data suggest that there is an association between the time interval from nCRT completion to surgery and tumor response rates, including pCR. However, these studies have been primarily from single institutions with small sample sizes. The aim of this study was to examine the relationship between a longer interval after nCRT and pCR in a nationally representative cohort of rectal cancer patients. Study Design Clinical stage II–III rectal cancer patients undergoing nCRT with a documented surgical resection were selected from the 2006 – 2011 National Cancer Data Base. Multivariable logistic regression analysis was used to assess the association between nCRT-surgery interval time (<6 weeks, 6–8 weeks, >8 weeks) and the odds of pCR. The relationship between nCRT-surgery interval, surgical morbidity, and tumor downstaging was also examined. Results Overall, 17,255 patients met the inclusion criteria. A nCRT-surgery interval time >8 weeks was associated with higher odds of pCR (OR=1.12, 95%CI=1.01–1.25) and tumor downstaging (OR=1.11, 95%CI =1.02–1.25). The longer time delay was also associated with lower odds of 30-day readmission (OR=0.82, 95%CI: 0.70–0.92). Conclusions A nCRT-surgery interval time >8 weeks results in increased odds of pCR with no evidence of associated increased surgical complications compared to 6–8 weeks. This data supports the implementation of a lengthened interval after nCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation (non-operative management). PMID:26206642

  6. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

  7. Indication of pre-surgical radiochemotherapy enhances psychosocial morbidity among patients with resectable locally advanced rectal cancer.

    PubMed

    Bencova, V; Krajcovicova, I; Svec, J

    2016-01-01

    Patients with cancer experience stress-determined psychosocial comorbidities and behavioural alterations. Patients expectation to be cured by the first line surgery and their emotional status can be negatively influenced by the decision to include neoadjuvant long-course radiotherapy prior to surgical intervention. From the patient's perspective such treatment algorithmindicates incurability of the disease. The aim of this study was to analyse the extent and dynamics of stress and related psychosocial disturbances among patients with resectable rectal cancer to whom the neoadjuvant radiochemotherapy before surgery has been indicated.Three standardised assessment tools evaluating psychosocial morbidity of rectal cancer patients have been implemented: The EORTC QLQ C30-3, the EORTC QLQ CR29 module and the HADS questionnaires previously tested for internal consistency were answered by patients before and after long-course radiotherapy and after surgery and the scores of clinical and psychosocial values were evaluated by means of the EORTC and HADS manuals. The most profound psychosocial distress was experienced by patients after the decision to apply neoadjuvant radiotherapy and concomitant chemotherapy before surgical intervention. The involvement of pre-surgical radiotherapy into the treatment algorithm increased emotional disturbances (anxiety, feelings of hopelessness) and negatively influenced patient's treatment adherence and positive expectations from the healing process. The negative psychosocial consequences appeared to be more enhanced in female patients. Despite provided information about advances of neoadjuvant radiotherapy onto success of surgical intervention, the emotional and cognitive disorders improved only slightly. The results clearly indicate that addressed communication and targeted psychosocial support has to find place before pre-surgical radiochemotherapy and as a standard part through the trajectory of the entire multimodal rectal cancer

  8. A Specific miRNA Signature Correlates With Complete Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

    SciTech Connect

    Della Vittoria Scarpati, Giuseppina; Falcetta, Francesca; Carlomagno, Chiara; Ubezio, Paolo; Marchini, Sergio; De Stefano, Alfonso; Singh, Vijay Kumar; D'Incalci, Maurizio; De Placido, Sabino; Pepe, Stefano

    2012-07-15

    Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific 'signature' correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909 Asterisk-Operator , miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.

  9. Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review

    PubMed Central

    Fornaro, Lorenzo; Caparello, Chiara; Vivaldi, Caterina; Rotella, Virginia; Musettini, Gianna; Falcone, Alfredo; Baldini, Editta; Masi, Gianluca

    2014-01-01

    Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently available neoadjuvant protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or short-course RT, together with improved surgical techniques, have largely reduced the risk of local relapse, with limited impact on distant recurrence. Available results of phase III trials with additional cytotoxic agents combined with standard CT-RT are disappointing, as no significant reduction in the risk of recurrence has been demonstrated. In order to improve the control of micrometastatic disease, integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach. In particular, the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models, and thus may represent a suitable companion in the neoadjuvant treatment of LARC. Preliminary results of phase I-II clinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection: treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules. PMID:24876730

  10. Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model

    NASA Astrophysics Data System (ADS)

    Tomatis, S.; Rancati, T.; Fiorino, C.; Vavassori, V.; Fellin, G.; Cagna, E.; Mauro, F. A.; Girelli, G.; Monti, A.; Baccolini, M.; Naldi, G.; Bianchi, C.; Menegotti, L.; Pasquino, M.; Stasi, M.; Valdagni, R.

    2012-03-01

    The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with

  11. [Combination therapy of hypopharyngeal cancer].

    PubMed

    Miyahara, H

    1987-06-01

    Between 1978 and 1983, ninety-three patients with cancer of the hypopharynx were treated. They were evaluated as to sex, age, primary site, TNM classification, stage, habits of smoking and drinking, past history of irradiation, treatment modality and end results. Eighty-seven percent of the patients visited us at as late a stage as advanced stage III or IV, and were treated mainly by combined therapy involving irradiation and pharyngolaryngoesophagectomy. The 3-year and 5-year survival rates were 38.6% and 33.3%, respectively. After December 1983, 14 new patients with advanced disease including three with coervical esophageal cancer were treated with neo-adjuvant combination chemotherapy which included cisplatin, peplomycin, methotrexate, and bleomycin over two courses of therapy. The response rate (CR + PR) was high, being 82% for the primary tumor and 78% for the metastatic node. Histopathological effects of neo-adjuvant chemotherapy were studied in the resected specimens. The evaluation was based on the Ohboshi-Shimosato classification. The histological effects did not agree with the clinical effects. Grade II b change was evaluated mostly in CR cases and grade II a change was seen in PR cases. It thus seems that neo-adjuvant chemotherapy prior to surgery and/or radiation including cisplatin and other agents is very useful as a multidisciplinary treatment for cancer of the hypopharynx. PMID:3592715

  12. Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: Use of dose-volume constraints to achieve rectal isotoxicity

    SciTech Connect

    Vargas, Carlos; Yan Di; Kestin, Larry L.; Krauss, Daniel; Lockman, David M.; Brabbins, Donald S.; Martinez, Alvaro A. . E-mail: amartinez@beaumont.edu

    2005-09-01

    Purpose: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started. Methods and Materials: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage {<=} T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years. Results: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No

  13. ACR Appropriateness Criteria® Local Excision in Early Stage Rectal Cancer.

    PubMed

    Russo, Suzanne; Blackstock, A William; Herman, Joseph M; Abdel-Wahab, May; Azad, Nilofer; Das, Prajnan; Goodman, Karyn A; Hong, Theodore S; Jabbour, Salma K; Jones, William E; Konski, Andre A; Koong, Albert C; Kumar, Rachit; Rodriguez-Bigas, Miguel; Small, William; Thomas, Charles R; Suh, W Warren

    2015-10-01

    Low anterior resection or abdominoperineal resection are considered standard treatments for early rectal cancer but may be associated with morbidity in selected patients who are candidates for early distal lesions amenable to local excision (LE). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel recognizes the importance of accurate staging to identify patients who may be candidates for a LE approach. Patients who may be candidates for LE alone include those with small, low-lying T1 tumors, without adverse pathologic features. Several surgical approaches can be utilized for LE however none include lymph node evaluation. Adjuvant radiation±chemotherapy may be warranted depending on the risk of nodal metastases. Patients with high-risk T1 tumors, T2 tumors not amenable to radical surgery may also benefit from adjuvant treatment; however, patients with positive margins or T3 lesions should be offered abdominoperineal resection or low anterior resection. Neoadjuvant radiation±chemotherapy followed by LE in higher risk patients results in excellent local control, but it is not clear if this approach reduces recurrence rates over surgery alone. PMID:26371522

  14. SU-E-J-270: Study of PET Response to HDR Brachytherapy of Rectal Cancer

    SciTech Connect

    Hobbs, R; Le, Y; Armour, E; Efron, J; Azad, N; Wahl, R; Gearhart, S; Herman, J

    2014-06-01

    Purpose: Dose-response studies in radiation therapy are typically using single response values for tumors across ensembles of tumors. Using the high dose rate (HDR) treatment plan dose grid and pre- and post-therapy FDG-PET images, we look for correlations between voxelized dose and FDG uptake response in individual tumors. Methods: Fifteen patients were treated for localized rectal cancer using 192Ir HDR brachytherapy in conjunction with surgery. FDG-PET images were acquired before HDR therapy and 6–8 weeks after treatment (prior to surgery). Treatment planning was done on a commercial workstation and the dose grid was calculated. The two PETs and the treatment dose grid were registered to each other using non-rigid registration. The difference in PET SUV values before and after HDR was plotted versus absorbed radiation dose for each voxel. The voxels were then separated into bins for every 400 cGy of absorbed dose and the bin average values plotted similarly. Results: Individual voxel doses did not correlate with PET response; however, when group into tumor subregions corresponding to dose bins, eighty percent of the patients showed a significant positive correlation (R2 > 0) between PET uptake difference in the targeted region and the absorbed dose. Conclusion: By considering larger ensembles of voxels, such as organ average absorbed dose or the dose bins considered here, valuable information may be obtained. The dose-response correlations as measured by FDG-PET difference potentially underlines the importance of FDG-PET as a measure of response, as well as the value of voxelized information.

  15. Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

    SciTech Connect

    Zampino, Maria Giulia Magni, Elena; Leonardi, Maria Cristina; Petazzi, Elena; Santoro, Luigi; Luca, Fabrizio; Chiappa, Antonio; Petralia, Giuseppe; Trovato, Cristina; Fazio, Nicola; Orecchia, Roberto; Nole, Franco; Braud, Filippo de

    2009-10-01

    Purpose: To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). Methods and Materials: From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m{sup 2}, orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m{sup 2}, orally, twice daily, 14 days on 7 days off) up until 2 weeks before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. Results: Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors {<=}6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). Conclusions: Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.

  16. Utility of Rectoscopy in the Assessment of Response to Neoadjuvant Treatment for Locally Advanced Rectal Cancer

    PubMed Central

    Lopez-Lopez, Victor; Abrisqueta, Jesús; Lujan, Juán; Hernández, Quiteria; Ono, Akiko; Parrilla, Pascual

    2016-01-01

    Background/Aims: The management of locally advanced rectal cancer has changed substantially over the last few decades with neoadjuvant chemoradiotherapy. The aim of the present study is to compare the results between neoadjuvant post-treatment rectoscopy and the anatomopathological findings of the surgical specimen. Patients and Methods: We conducted a prospective study of 67 patients with locally advanced adenocarcinoma of the rectum (stages II and III). Two groups were established: One with complete clinical response (cCR) and one without (non-cCR), based on the findings at rectoscopy. Assessment of tumor regression grade in the surgical specimen was determined using Mandard's tumor regression scale. Results: Seventeen patients showed a cCR. Thirty-five biopsies were negative and 32 were positive for mailgnancy. All the cCR patients had a negative biopsy (P < 0.0001). All 32 positive biopsies revealed the presence of adenocarcinoma, and of the 35 negative biopsies, 18 had no malignancy and 17 were diagnosed with adenocarcinoma (P < 0.0001). Sixteen of the 17 cCR patients showed a complete pathological response and one patient showed the presence of adenocarcinoma. Of the 50 non-cCR patients 48 revealed the presence of adenocarcinoma and two had absence of malignancy. According to the Mandard classification, 16 of the 17 cCR patients were grade I and 1 grade II; 2 non-cCR patients were grade I, 7 grade II, 13 grade III, 19 grade IV, and 9 grade V. Conclusions: Endoscopic and histological findings could be determinants in the assessment of response to neoadjuvant treatment. PMID:26997222

  17. Preoperative Helical Tomotherapy and Megavoltage Computed Tomography for Rectal Cancer: Impact on the Irradiated Volume of Small Bowel

    SciTech Connect

    Engels, Benedikt; De Ridder, Mark Tournel, Koen; Sermeus, Alexandra; De Coninck, Peter; Verellen, Dirk; Storme, Guy A.

    2009-08-01

    Purpose: Preoperative (chemo)radiotherapy is considered to be standard of care in locally advanced rectal cancer, but is associated with significant small-bowel toxicity. The aim of this study was to explore to what extent helical tomotherapy and daily megavolt (MV) CT imaging may reduce the irradiated volume of small bowel. Methods and Materials: A 3D-conformal radiotherapy (3D-CRT) plan with CTV-PTV margins adjusted for laser-skin marks (15, 15, and 10 mm for X, Y, and Z directions, respectively) was compared with helical tomotherapy (IMRT) using the same CTV-PTV margins, and to helical tomotherapy with margins adapted to daily MV-CT imaging (IMRT/IGRT; 8, 11, 7, and 10 mm for X, Y{sub ant}, Y{sub post} and Z resp.) for 11 consecutive patients. The planning goals were to prescribe 43.7 Gy to 95% of the PTV, while minimizing the volume of small bowel receiving more than 15 Gy (V{sub 15} {sub SB}). Results: The mean PTV was reduced from 1857.4 {+-} 256.6 cc to 1462.0 {+-} 222.3 cc, when the CTV-PTV margins were adapted from laser-skin marks to daily MV-CT imaging (p < 0.01). The V{sub 15} {sub SB} decreased from 160.7 {+-} 102.9 cc to 110.9 {+-} 74.0 cc with IMRT and to 81.4 {+-} 53.9 cc with IMRT/IGRT (p < 0.01). The normal tissue complication probability (NTCP) for developing Grade 2+ diarrhea was reduced from 39.5% to 26.5% with IMRT and to 18.0% with IMRT/IGRT (p < 0.01). Conclusion: The combination of helical tomotherapy and daily MV-CT imaging significantly decreases the irradiated volume of small bowel and its NTCP.

  18. Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

    SciTech Connect

    Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong; Kim, Jong Hoon; Yoon, Sang Nam; Lim, Seok-Byung; Yu, Chang Sik; Kim, Mi-Jung; Jang, Se-Jin; Lee, Jung Shin; Kim, Jin Cheon; Kim, Tae Won

    2011-03-01

    Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{sup 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.

  19. Significant Shrinkage of Multifocal Liver Metastases and Long-Term Survival in a Patient With Rectal Cancer, After Trans-Arterial Chemoembolization (TACE): A Case Report.

    PubMed

    Suciu, Bogdan Andrei; Gurzu, Simona; Marginean, Lucian; Milutin, Doina; Halmaciu, Ioana; Jung, Ioan; Branzaniuc, Klara; Molnar, Calin

    2015-10-01

    In this paper, we present the successful therapeutic approach of unresectable liver metastases in a patient with rectal cancer.A 63-year-old male underwent endoscopic polypectomy followed by rectosigmoid resection for an adenocarcinoma of the rectum diagnosed in pT2N0 stage. The angio-computed tomography (CT) revealed four metastatic hepatic nodules ranging from 12 to 130 mm in diameter. After one cure of trans-arterial chemoembolization (TACE) with lipiodol and 5-fluorouracil, combined with FOLFOX4 + capecitabine systemic chemotherapy, the diameter of all hepatic nodules decreased to half size, at 6 months after TACE. Further curative surgical hepatic metastasectomy was done and complete pathologic response was obtained. The patient is free of recurrences and metastases after 26 months of follow-up.This representative case shows that an efficient trans-disciplinary approach could lead to successful therapeutic management even in patients with advanced-staged colorectal carcinomas. PMID:26496332

  20. Relationships Between Rectal Wall Dose-Volume Constraints and Radiobiologic Indices of Toxicity for Patients With Prostate Cancer

    SciTech Connect

    Marzi, Simona . E-mail: marzi@ifo.it; Arcangeli, Giorgio; Saracino, Bianca; Petrongari, Maria G.; Bruzzaniti, Vicente; Iaccarino, Giuseppe; Landoni, Valeria; Soriani, Antonella; Benassi, Marcello

    2007-05-01

    Purpose: The purpose of this article was to investigate how exceeding specified rectal wall dose-volume constraints impacts on the risk of late rectal bleeding by using radiobiologic calculations. Methods and Materials: Dose-volume histograms (DVH) of the rectal wall of 250 patients with prostate cancer were analyzed. All patients were treated by three-dimensional conformal radiation therapy, receiving mean target doses of 80 Gy. To study the main features of the patient population, the average and the standard deviation of the distribution of DVHs were generated. The mean dose , generalized equivalent uniform dose formulation (gEUD), modified equivalent uniform dose formulation (mEUD){sub 0}, and normal tissue complication probability (NTCP) distributions were also produced. The DVHs set was then binned into eight classes on the basis of the exceeding or the fulfilling of three dose-volume constraints: V{sub 40} = 60%, V{sub 50} = 50%, and V{sub 70} = 25%. Comparisons were made between them by , gEUD, mEUD{sub 0}, and NTCP. Results: The radiobiologic calculations suggest that late rectal toxicity is mostly influenced by V{sub 70}. The gEUD and mEUD{sub 0} are risk factors of toxicity always concordant with NTCP, inside each DVH class. The mean dose, although a reliable index, may be misleading in critical situations. Conclusions: Both in three-dimensional conformal radiation therapy and particularly in intensity-modulated radiation therapy, it should be known what the relative importance of each specified dose-volume constraint is for each organ at risk. This requires a greater awareness of radiobiologic properties of tissues and radiobiologic indices may help to gradually become aware of this issue.

  1. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy

    PubMed Central

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Abstract Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process. We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients. We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152–19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123–17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069–15.966, and P = 0.04. Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

  2. A predictive nomogram improved diagnostic accuracy and interobserver agreement of perirectal lymph nodes metastases in rectal cancer

    PubMed Central

    Ding, Ying; Tu, Shanshan; Liu, Yi; Qian, Youcun; Xu, Linghui; Tong, Tong; Cai, Sanjun; Peng, Junjie

    2016-01-01

    Objective To develop a predictive nomogram to improve the diagnostic accuracy and interobserver agreement of pre-therapeutic lymph nodes metastases in patients with rectal cancer. Materials and Methods An institutional database of 411 patients with rectal cancer was used to develop a nomogram to predict perirectal lymph nodes metastases. Patients' clinicopathological and MRI-assessed imaging variables were included in the multivariate logistic regression analysis. The model was externally validated and the performance was assessed by area under curve (AUC) of the receiver operator characteristics (ROC) curves. The interobserver agreement was measured between two independent radiologists. Results The diagnostic accuracy of the conventional MRI-assessed cN stage was 68%; 14.2% of the patients were over-staged and 17.8% of the patients were under-staged. A total of 35.1% of the patients had disagreed diagnosis for the cN stage between the two radiologists, with a kappa value of 0.295. A nomogram for predicting pathological lymph nodes metastases was successfully developed, with an AUC of 0.78 on the training data and 0.71 on the validation data. The predictors included in the nomogram were MRI cT stage, CRM involvement, preoperative CEA, tumor grade and lymph node size category. This nomogram yielded improved prediction in cN stage than the conventional MRI-based assessment. Conclusions By incorporating clinicopathological and MRI imaging features, we established a nomogram that improved the diagnostic accuracy and remarkably minimized the interobserver disagreement in predicting lymph nodes metastases in rectal cancers. PMID:26910373

  3. Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

    SciTech Connect

    DeVries, Alexander Friedrich; Piringer, Gudrun; Kremser, Christian; Judmaier, Werner; Saely, Christoph Hubert; Lukas, Peter; Öfner, Dietmar

    2014-12-01

    Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

  4. Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

    SciTech Connect

    Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

    2010-09-01

    Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% {+-} 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p <.05). When the TVRR was categorized into three groups (<60%, 60-80%, and >80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of {>=}60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

  5. Prognostic and Predictive Value of Baseline and Posttreatment Molecular Marker Expression in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy

    SciTech Connect

    Bertolini, Federica . E-mail: bertolini.federica@policlinico.mo.it; Bengala, Carmelo; Losi, Luisa; Pagano, Maria; Iachetta, Francesco; Dealis, Cristina; Jovic, Gordana; Depenni, Roberta; Zironi, Sandra; Falchi, Anna Maria; Luppi, Gabriele; Conte, Pier Franco

    2007-08-01

    Purpose: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. Methods and Materials: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. Results: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. Conclusions: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer.

  6. Treatment outcome of localized prostate cancer by 70 Gy hypofractionated intensity-modulated radiotherapy with a customized rectal balloon

    PubMed Central

    Kim, Hyunjung; Kim, Jun Won; Hong, Sung Joon; Rha, Koon Ho; Lee, Chang-Geol; Yang, Seung Choul; Choi, Young Deuk; Suh, Chang-Ok

    2014-01-01

    Purpose We aimed to analyze the treatment outcome and long-term toxicity of 70 Gy hypofractionated intensity-modulated radiotherapy (IMRT) for localized prostate cancer using a customized rectal balloon. Materials and Methods We reviewed medical records of 86 prostate cancer patients who received curative radiotherapy between January 2004 and December 2011 at our institution. Patients were designated as low (12.8%), intermediate (20.9%), or high risk (66.3%). Thirty patients received a total dose of 70 Gy in 28 fractions over 5 weeks via IMRT (the Hypo-IMRT group); 56 received 70.2 Gy in 39 fractions over 7 weeks via 3-dimensional conformal radiotherapy (the CF-3DRT group, which served as a reference for comparison). A customized rectal balloon was placed in Hypo-IMRT group throughout the entire radiotherapy course. Androgen deprivation therapy was administered to 47 patients (Hypo-IMRT group, 17; CF-3DRT group, 30). Late genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated according to the Radiation Therapy Oncology Group criteria. Results The median follow-up period was 74.4 months (range, 18.8 to 125.9 months). The 5-year actuarial biochemical relapse-free survival rates for low-, intermediate-, and high-risk patients were 100%, 100%, and 88.5%, respectively, for the Hypo-IMRT group and 80%, 77.8%, and 63.6%, respectively, for the CF-3DRT group (p < 0.046). No patient presented with acute or late GU toxicity ≥grade 3. Late grade 3 GI toxicity occurred in 2 patients (3.6%) in the CF-3DRT group and 1 patient (3.3%) in the Hypo-IMRT group. Conclusion Hypo-IMRT with a customized rectal balloon resulted in excellent biochemical control rates with minimal toxicity in localized prostate cancer patients. PMID:25324991

  7. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy.

    PubMed

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-11-01

    Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152-19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123-17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069-15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

  8. Treating patients with advanced rectal cancer and lateral pelvic lymph nodes with preoperative chemoradiotherapy based on pretreatment imaging

    PubMed Central

    Otowa, Yasunori; Yamashita, Kimihiro; Kanemitsu, Kiyonori; Sumi, Yasuo; Yamamoto, Masashi; Kanaji, Shingo; Imanishi, Tatsuya; Nakamura, Tetsu; Suzuki, Satoshi; Tanaka, Kenichi; Kakeji, Yoshihiro

    2015-01-01

    Preoperative chemoradiotherapy (CRT) and lateral pelvic lymph node (LPLN) dissection (LPLD) based on pretreatment imaging are performed to improve oncological outcomes at our institution. However, the advantage of LPLD following preoperative CRT in advanced rectal cancer remains unclear. The objective of the present study was to assess the validity of this approach. Thirty-two patients with advanced rectal cancer were included in the study. All patients were treated with preoperative CRT and curative operation. Of these, 16 patients who were treated between August 2005 and June 2008 underwent LPLD on both sides (LPLD group). Sixteen patients who were treated between July 2008 and January 2013 underwent LPLD only on the side with suspected LPLN metastasis determined by pretreatment imaging; in cases without LPLN metastasis, only total mesorectal excision was performed (limited-LPLD group). The overall survival and relapse-free survival between the LPLD and the limited-LPLD groups were compared. Preoperative CRT was able to lower clinical lymph node status in 50% of the cases. In addition, pathological lymph node status did not exceed the pretreatment clinical lymph node status stage in the LPLD group. There were no differences in the overall survival and relapse-free survival between the two groups (P=0.729 and P=0.874, respectively). We conclude that multi-imaging studies have a very low risk of overlooking pathologically positive LPLN metastases. Therefore, limited LPLD is a feasible strategy for patients with advanced rectal cancer and suspicious LPLN metastases based on pretreatment imaging. PMID:26604786

  9. GTI-2040, Oxaliplatin, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer or Other Solid Tumors

    ClinicalTrials.gov

    2013-03-26

    Recurrent Colon Cancer; Recurrent 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; Unspecified Adult Solid Tumor, Protocol Specific

  10. Laparoscopic total pelvic exenteration using transanal minimal invasive surgery technique with en bloc bilateral lymph node dissection for advanced rectal cancer.

    PubMed

    Hayashi, Kengo; Kotake, Masanori; Kakiuchi, Daiki; Yamada, Sho; Hada, Masahiro; Kato, Yosuke; Hiranuma, Chikashi; Oyama, Kaeko; Hara, Takuo

    2016-12-01

    A 59-year-old man presenting with fecal occult blood visited our hospital. He was diagnosed with advanced lower rectal cancer, which was contiguous with the prostate and the left seminal vesicle. There were no metastatic lesions with lymph nodes or other organs. We performed laparoscopic total pelvic exenteration (LTPE) using transanal minimal invasive surgery technique with bilateral en bloc lateral lymph node dissection for advanced primary rectal cancer after neoadjuvant chemoradiotherapy. The total operative time was 760 min, and the estimated blood loss was 200 ml. LTPE is not well established technically, but it has many advantages including good visibility of the surgical field, less blood loss, and smaller wounds. A laparoscopic approach may be an appropriate choice for treating locally advanced lower rectal cancer, which requires TPE. PMID:27460130

  11. Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2015-05-15

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  12. Oncologic Safety of Local Excision Compared With Total Mesorectal Excision for ypT0-T1 Rectal Cancer

    PubMed Central

    Jung, Sung Min; Yu, Chang Sik; Park, In Ja; Kim, Tae Won; Kim, Jong Hoon; Yoon, Yong Sik; Lim, Seok-Byung; Kim, Jin Cheon

    2016-01-01

    Abstract Good oncologic outcomes, demonstrated by a complete pathologic response after preoperative chemoradiotherapy (PCRT), have led to local excision (LE) in selected patients with rectal cancer. We evaluated the oncologic safety of LE compared with total mesorectal excision (TME) in patients with ypT0-T1 rectal cancer. A retrospective review of 304 patients who underwent PCRT, followed by LE or TME, for ypT0-T1 rectal cancer was performed. Propensity scores were computed and used to match groups (LE:TME = 1:1), and analysis of disease-free survival (DFS) and overall survival (OS) was made by comparing patients who underwent LE or TME. Prognostic factors of relapse were analyzed for all patients. Tumor categories were ypT0 in 25 (61.9%) cases, ypTis in 6 (14.3%) cases, and ypT1 in 11 (26.2%) cases for the LE group, and ypT0 in 28 (66.7%) cases, ypTis in 4 (9.5%) cases, and ypT1 in 10 (23.8%) cases for the matched TME patients. There was no significant difference between the matched LE and TME groups in relapse (4.8% and 7.14%, respectively; P = 0.646), 5-year DFS (95.2% vs 91.6%; P = 0.33) and 5-year OS (96.6% vs 88.0%; P = 0.238). In the multivariate Cox regression analysis, tumor distance from the anal verge (hazard ratio [HR] = 0.78; 95% confidence interval (CI) = 0.616–0.992) and the tumor grade (HR = 4.29; 95% CI = 1.430–12.886) were significantly associated with the recurrence risk. LE results in oncologic outcomes that are comparable to those achieved by TME in selected patients with ypT0-T1 rectal cancer after PCRT. PMID:27196490

  13. MRI Risk Stratification for Tumor Relapse in Rectal Cancer Achieving Pathological Complete Remission after Neoadjuvant Chemoradiation Therapy and Curative Resection

    PubMed Central

    Kim, Honsoul; Myoung, Sungmin; Koom, Woong Sub; Kim, Nam Kyu; Kim, Myeong-Jin; Ahn, Joong Bae; Hur, Hyuk; Lim, Joon Seok

    2016-01-01

    Purpose Rectal cancer patients achieving pCR are known to have an excellent prognosis, yet no widely accepted consensus on risk stratification and post-operative management (e.g., adjuvant therapy) has been established. This study aimed to identify magnetic resonance imaging (MRI) high-risk factors for tumor relapse in pathological complete remission (pCR) achieved by rectal cancer patients who have undergone neoadjuvant concurrent chemoradiation therapy (CRT) and curative resection. Materials and Methods We analyzed 88 (male/female = 55/33, median age, 59.5 years [range 34–78]) pCR-proven rectal cancer patients who had undergone pre-CRT MRI, CRT, post-CRT MRI and curative surgery between July 2005 and December 2012. Patients were observed for post-operative tumor relapse. We analyzed the pre/post-CRT MRIs for parameters including mrT stage, mesorectal fascia (mrMRF) status, tumor volume, tumor regression grade (mrTRG), nodal status (mrN), and extramural vessel invasion (mrEMVI). We performed univariate analysis and Kaplan-Meier survival analysis. Results Post-operative tumor relapse occurred in seven patients (8.0%, n = 7/88) between 5.7 and 50.7 (median 16.8) months. No significant relevance was observed between tumor volume, volume reduction rate, mrTRG, mrT, or mrN status. Meanwhile, positive mrMRF (Ppre-CRT = 0.018, Ppre/post-CRT = 0.006) and mrEMVI (Ppre-CRT = 0.026, Ppre-/post-CRT = 0.008) were associated with higher incidence of post-operative tumor relapse. Kaplan-Meier survival analysis revealed a higher risk of tumor relapse in patients with positive mrMRF (Ppre-CRT = 0.029, Ppre-/post-CRT = 0.009) or mrEMVI (Ppre-CRT = 0.024, Ppre-/post-CRT = 0.003). Conclusion Positive mrMRF and mrEMVI status was associated with a higher risk of post-operative tumor relapse of pCR achieved by rectal cancer patients, and therefore, can be applied for risk stratification and to individualize treatment plans. PMID:26730717

  14. [A case of surgical approach to the recurrence of the para-aortic lymph nodes after resection of rectal cancer].

    PubMed

    Fukunaga, Hiroki; Ota, Hirofumi; Fujie, Yujirou; Shimizu, Kaori; Ogino, Takayuki; Toyoda, Yasuhiro; Yoshioka, Akiko; Yoshioka, Setsuko; Hojou, Shigeyuki; Endo, Wakio; Kakutani, Aki; Maeura, Yoshiichi

    2009-11-01

    A 63-year-old female diagnosed as rectal cancer underwent low anterior resection and received adjuvant chemotherapy (folinate/tegafur/uracil therapy). After 6 months, lymph node metastasis was confirmed by an elevation of the tumor marker (CEA) and a FDG-PET image. After administration of 37 courses of mFOLFOX6 therapy, surgical excision was performed to the lymph node recurrence, because it was difficult to continue mFOLFOX6 therapy with grade 3 neuropathy. After 8 months from the last operation, no lymph node metastasis was appeared in the para-aortic area. PMID:20037371

  15. Preoperative Treatment of Locally Advanced Rectal Cancer: Assets and Drawbacks of Short Course and Long Course in Clinical Practice.

    PubMed

    Ngan, Samuel Y

    2016-07-01

    Preoperative short-course radiotherapy and preoperative long-course chemoradiotherapy are the standards of care for high-risk rectal cancer in different parts of the world. Both treatments are effective in local control and carry a low morbidity. The advantage of short course is its simplicity, whereas long course has the advantage of downsizing tumors thus increasing the chance of sphincter preservation. Although 2 randomized trials comparing short course and long course have been performed, the better form of preoperative treatment remains a subject of discussion. This article reviews the evidence supporting each approach, and it discusses their relative merits and future directions. PMID:27238469

  16. [Spontaneous Rupture of the Thoracic Aorta after Surgery of Rectal Cancer in an Elderly Patient;Report of a Case].

    PubMed

    Tokumo, Masaki; Okada, Koichiro; Kunisue, Hironori; Teruta, Shoma; Kakishita, Tomokazu; Naito, Minoru

    2016-03-01

    We reported a case of a 90-year-old man who underwent abdominoperineal resection of the rectum for advanced rectal cancer. On the 16th postoperative day, he suddenly lost consciousness during an exchange of the colostomy pouches. His heart arrested in a moment, and cardiopulmonary resuscitation was immediately performed, but in vain. The autopsy imaging revealed collapse of the heart and the thoracic aorta, as well as profuse blood-like effusion in the left pleural cavity. We considered that hemorrhagic shock due to spontaneous rupture of the thoracic aorta was the cause of his death. PMID:27075292

  17. High Ligation of Inferior Mesenteric Artery in Left Colonic and Rectal Cancers: Lymph Node Yield and Survival Benefit.

    PubMed

    Charan, Ishwar; Kapoor, Akhil; Singhal, Mukesh Kumar; Jagawat, Namrata; Bhavsar, Deepak; Jain, Vikas; Kumar, Vanita; Kumar, Harvindra Singh

    2015-12-01

    During surgery for colorectal cancer, the inferior mesenteric artery (IMA) may be ligated either directly at the origin of the IMA from the aorta (high ligation) or at a point just below the origin of the left colic artery (low ligation). Sixty patients of left colonic and rectal cancer undergoing elective curative surgery in 2007 and 2008 were selected for this observational study. The resected lymph nodes were grouped into three levels: along the bowel wall (D1), along IMA below left colic (D2), and along the IMA and its root (D3). Statistical analysis was performed with SPSS version 20.0. D2 level was involved pathologically in 20 (33.3 %) and D3 in six out of 44 (13.6 %) patients. The median nodal yield with high and low ligation were 33 and 25, respectively (p = 0.048). Median overall survival for high ligation was 62 months versus 42 months for low ligation (p = 0.190). High ligation of the IMA for rectal and left colonic cancers can improve lymph node yield, thus facilitating accurate tumor staging and thus better disease prognostication, but the survival benefit is not significant. PMID:27011519

  18. SB-715992 in Treating Patients With Advanced or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2015-02-13

    Recurrent Colon Cancer; Recurrent 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

  19. Apparent Diffusion Coefficient Predicts Pathology Complete Response of Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy

    PubMed Central

    Chen, Yuan-Gui; Chen, Ming-Qiu; Guo, Yu-Yan; Li, Si-Cong; Wu, Jun-Xin; Xu, Ben-Hua

    2016-01-01

    Objective To evaluate the predictive value of the apparent diffusion coefficient (ADC) for pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer. Methods A total of 265 patients with rectal adenocarcinoma, whole Diffusion-Weighted MRI (DWI-MRI) images, clinically stage II to III (cT3-4 and/or cN+) and treated with NCRT followed by TME were screened. Fifty patients with pCR and another 50 patients without pCR with similar clinical charcacters and treatment regimens were selected for statistical analysis. All the patients’ pre-CRT and post-CRT average ADC values were calculated from the coefficient maps created by DWI-MRI and recorded independently. The difference in the ADC values between the pCR and non-pCR was analyzed by the Mann-Whitney U test. The cut-off ADC value of the receiver operating characteristic (ROC) curve with pCR was then established. Results The mean pre- and post-ADC values in all patients, and in pCR patients and non-pCR patients were 0.879±0.06 and 1.383±0.11, 0.859±0.04 and 1.440±0.10, 0.899±0.07 and 1.325±0.09 (×10-3mm2/s), respectively. The difference between the pre- and post-ADC values in all patients, pCR patients, and non-pCR patients were considered to be statistically significant. The pre-ADC value was significantly lower in the pCR patients than in the non-pCR patients (p = 0.003), whereas the post-ADC values were significantly higher in the pCR patients than in the non-pCR patients. The percentage increase of the ADC value (ΔADC%) in the pCR and non-pCR patients were 68% and 48% respectively (p<0.001). The ROC curves of the cut-off value of the pre-CRT patient ADC value was 0.866×10-3mm2/s. The AUC, sensitivity, specificity, PPV, NPV, and accuracy of diagnosing pCR were 0.670 (95% CI 0.563–0.777), 0.600, 0.640, 60%, 60%, and 60%, respectively. The cut-off value of ΔADC% was 58%. The corresponding AUC, sensitivity, specificity, PPV, NPV, and accuracy of diagnosing p

  20. Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Chen, Ronald C.; Mamon, Harvey J.; Ancukiewicz, Marek; Killoran, Joseph H.; Crowley, Elizabeth M.; Blaszkowsky, Lawrence S.; Wo, Jennifer Y.; Ryan, David P.; Hong, Theodore S.

    2012-07-15

    Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associations between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.

  1. Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor

    PubMed Central

    Jönsson, Mats; Ekstrand, Anna; Edekling, Thomas; Eberhard, Jakob; Grabau, Dorthe; Borg, David; Nilbert, Mef

    2009-01-01

    Background KRAS mutations represent key alterations in colorectal cancer development and lead to constitutive EGFR signaling. Since EGFR inhibition represents a therapeutic strategy in advanced colorectal cancer, KRAS mutation analysis has quickly been introduced as a treatment-predictive test. Methods We used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 (39%) tumors. Results KRAS mutations were significantly more often found in rectal cancer (21/38, 55%) than in colon cancer (32/98, 33%) (P = 0.02). This finding was explained by marked differences mutation rates in female patients who showed mutations in 33% of the colon cancers and in 67% of the rectal cancers (P = 0.01). Concurrent KRAS mutations were identified in three tumors; two colorectal cancers harbored Gly12Asp/Gly13Asp and Gly12Cys/Gly13Asp and a third tumor carried Gly12Cys/Gly12Asp in an adenomatous component and additionally acquired Gly12Val in the invasive component. Conclusion The demonstration of a particularly high KRAS mutation frequency among female rectal cancer patients suggests that this subset is the least likely to respond to anti-EGFR therapies, whereas the observation of concurrent KRAS mutations imply that repeated KRAS targeting may occur during tumor progression in a subset of colorectal cancers. PMID:19832985

  2. [A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report].

    PubMed

    Udagawa, Masaru; Tominaga, Ben; Kobayashi, Daisuke; Ishikawa, Yuuya; Watanabe, Shuuichi; Adikrisna, Rama; Okamoto, Hiroyuki; Yabata, Eiichi

    2015-11-01

    We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases. PMID:26805112

  3. Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer

    PubMed Central

    Blaszkowsky, L. S.; Ryan, D. P.; Szymonifka, J.; Borger, D. R.; Zhu, A. X.; Clark, J. W.; Kwak, E. L.; Mamon, H. J.; Allen, J. N.; Vasudev, E.; Shellito, P. C.; Cusack, J. C.; Berger, D. L.; Hong, T. S.

    2014-01-01

    Background To determine the maximal tolerated dose of erlotinib when added to 5-fluorouracil (5-FU) chemoradiation and bevacizumab and safety and efficacy of this combination in patients with locally advanced rectal cancer. Patients and methods Patients with Magnetic resonance imaging (MRI) or ultrasound defined T3 or T4 adenocarcinoma of the rectum and without evidence of metastatic disease were enrolled. Patients received infusional 5-FU 225 mg/M2/day continuously, along with bevacizumab 5 mg/kg days 14, 1, 15 and 29. Standard radiotherapy was administered to 50.4 Gy in 28 fractions. Erlotinib started at a dose of 50 mg orally daily and advanced by 50 mg increments in the subsequent cohort. Open total mesorectal excision was carried out 6–9 weeks following the completion of chemoradiation. Results Thirty-two patients received one of three dose levels of erlotinib. Erlotinib dose level of 100 mg was determined to be the maximally tolerated dose. Thirty-one patients underwent resection of the primary tumor, one refused resection. Twenty-seven patients completed study therapy, all of whom underwent resection. At least one grade 3–4 toxicity occurred in 46.9% of patients. Grade 3–4 diarrhea occurred in 18.8%. The pathologic complete response (pCR) for all patients completing study therapy was 33%. With a median follow-up of 2.9 years, there are no documented local recurrences. Disease-free survival at 3 years is 75.5% (confidence interval: 55.1–87.6%). Conclusions Erlotinib added to infusional 5-FU, bevacizumab and radiation in patients with locally advanced rectal cancer is relatively well tolerated and associated with an encouraging pCR. Clinicaltrials.gov NCT00307736. PMID:24356623

  4. Phase I Trial of Neoadjuvant Preoperative Chemotherapy With S-1 and Irinotecan Plus Radiation in Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Sato, Takeo; Kokuba, Yukihito; Koizumi, Wasaburo; Hayakawa, Kazushige; Okayasu, Isao; Watanabe, Masahiko

    2007-12-01

    Purpose: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with preoperative chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. Patients and Methods: We gave preoperative radiotherapy (total dose, 45 Gy) to 23 patients with locally advanced (T3/T4) rectal cancer. Concurrently, S-1 was given orally at a fixed dose of 80 mg/m{sup 2}/day on Days 1-5, 8-12, 22-26, and 29-33, and irinotecan was given as a 90-min continuous i.v. infusion on Days 1, 8, 22, and 29. The dose of irinotecan was initially 40 mg/m{sup 2}/day and gr