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Sample records for rectal cancer combined

  1. Combined-modality therapy for rectal cancer using irinotecan.

    PubMed

    Minsky, Bruce D

    2002-05-01

    Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease. Irinotecan (CPT-11, Camptosar)-based regimens have improved survival in patients with metastatic disease and are being actively investigated in combination with pelvic radiation therapy for patients with rectal cancer.

  2. Combined modality therapy for rectal cancer.

    PubMed

    Minsky, Bruce D; Röedel, Claus; Valentini, Vincenzo

    2010-01-01

    The standard adjuvant treatment for cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These include the role of short course radiation, whether postoperative adjuvant chemotherapy necessary for all patients and whether the type of surgery after chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.

  3. 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

  4. Oxaliplatin-based combined-modality therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2003-08-01

    There are two conventional treatments for clinically resectable rectal cancer. The first is surgery, and, if the tumor is T3 and/or N1-2, this is followed by postoperative combined-modality therapy. The second, for patients with ultrasound T3 or clinical T4 disease, is preoperative combined-modality therapy followed by surgery and postoperative chemotherapy. In this review, the results of these approaches as well as novel combined-modality approaches using oxaliplatin-based regimens will be presented.

  5. The use of capecitabine in the combined-modality therapy for rectal cancer.

    PubMed

    Liauw, Stanley L; Minsky, Bruce D

    2008-03-01

    Locally advanced rectal adenocarcinoma is treated by combined-modality therapy, which consists of surgery, chemotherapy, and radiation therapy. A series of randomized trials established a preferred treatment sequence of preoperative radiation therapy and 5-fluorouracil(5-FU)-based chemotherapy, total mesorectal excision, and adjuvant 5-FU-based chemotherapy for patients with stage II/III disease. Capecitabine is an oral prodrug of 5-FU that has potential advantages compared with intravenous 5-FU, including ease of administration and potentially increased therapeutic effect. Capecitabine is converted by a 3-step enzymatic process; the last step involves the enzyme thymidine phosphorylase, which is overexpressed in tumor tissues and is stimulated by concurrent radiation therapy. Over the past 5 years, several phase I/II trials of capecitabine-based therapy were reported. This review discusses the evolution of combined-modality therapy for rectal cancer with specific attention given to the use of capecitabine in conjunction with radiation therapy.

  6. Combined-modality therapy of rectal cancer with oxaliplatin-based regimens.

    PubMed

    Minsky, Bruce D

    2004-06-01

    There are 2 conventional treatments for clinically resectable rectal cancer. First is surgery and, if the tumor is stage T3 and/or N1/2, this is followed by postoperative combined modality therapy. The second is preoperative combined modality therapy followed by surgery and postoperative combined modality therapy if the tumor is stage uT3/4 and/or node-positive. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of these new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting are in progress and suggest higher complete response rates. There is considerable interest in integrating oxaliplatin into preoperative combined modality therapy regimens for rectal cancer. Based on results from phase I/II trials, the recommended regimen for patients who receive oxaliplatin-based combined modality therapy is continuous infusion 5-fluorouracil or capecitabine with pelvic radiation.

  7. Combined-modality therapy of rectal cancer with irinotecan-based regimens.

    PubMed

    Minsky, Bruce D

    2004-12-01

    There are two conventional treatments for clinically resectable rectal cancer. The first is surgery followed by postoperative combined-modality therapy if the tumor is T3 and/or N1/2. The second, if the tumor is ultrasound T3 or clinical T4, is preoperative combined-modality therapy followed by surgery and postoperative chemotherapy. There are a number of new chemotherapeutic agents that have been developed for the treatment of colorectal cancer. Phase I/II trials are examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting. There is considerable interest in integrating irinotecan (Camptosar) into preoperative combined-modality therapy regimens for rectal cancer. Based on these trials, the recommended regimen for patients who receive irinotecan-based combined-modality therapy is continuous infusion fluorouracil (5-FU), irinotecan, and pelvic radiation. New trials examining preoperative combined-modality therapy regimens substituting capecitabine (Xeloda) for continuous infusion 5-FU are in progress.

  8. 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

  9. 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

  10. 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.

  11. Combined laparoscopic and transanal total mesorectal excision for rectal cancer: Initial experience and early results

    PubMed Central

    Thomsen, Morten Holt; Ovesen, Henrik; Eriksen, Jens Ravn

    2017-01-01

    INTRODUCTION: Incomplete specimens resulting in residual mesorectum in the patient and an increased risk of local recurrence remains a problem. We have introduced transanal-total mesorectal excision (Ta-TME) in our department to potentially overcome this problem due to more direct access to the lower pelvis in patients undergoing TME for rectal cancer and this article presents our initial experience with the new procedure. MATERIALS AND METHODS: Patients with a T1-T3 mid or low rectal cancer eligible for TME or intersphincteric abdominoperineal excision were selected for a combined transanal and transabdominal laparoscopic resection. The primary aim of the study was to evaluate the feasibility and efficacy of the method with a special focus on the quality of the specimen. RESULTS: During a 9-month period, 11 patients were operated with this technique. All procedures resulted in complete or nearly complete specimen. We did, however, find the procedure technically demanding and experienced several complications with three anastomotic leaks (all with preserved intestinal continuity) and a urethral lesion. CONCLUSION: Ta-TME is feasible and might be the answer to obtaining good quality specimens and overcome some of the technical difficulties that can be encountered in the obese narrow male pelvis. The procedure however is technically demanding. PMID:28281474

  12. 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.

  13. Phase I Study of Neoadjuvant Radiotherapy With 5-Fluorouracil for Rectal Cancer

    ClinicalTrials.gov

    2017-03-02

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Rectal Adenocarcinoma; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  14. Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: a phase I study.

    PubMed

    François, Eric; Ychou, Marc; Ducreux, Michel; Bertheault-Cvitkovic, Frédérique; Giovannini, Marc; Conroy, Thierry; Lemanski, Claire; Thomas, Olivier; Magnin, Valérie

    2005-12-01

    The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

  15. 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.

  16. 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.

  17. Rectal imaging and cancer.

    PubMed

    Vining, D J

    1998-09-01

    Rectal imaging has evolved substantially during the past 25 years and now offers surgeons exquisite anatomic detail and physiologic information. Dynamic cystoproctography, helical computed tomography, endoscopic ultrasonography, endorectal magnetic resonance imaging, and immunoscintigraphy have become standards for the diagnosis of rectal disease, staging of neoplasia, and survey of therapeutic results. The indications, limitations, and relative costs of current imaging methods are reviewed, and advances in imaging technology that promise future benefits to colorectal surgeons are introduced.

  18. ACR Appropriateness Criteria on Resectable Rectal Cancer

    SciTech Connect

    Suh, W. Warren; Konski, Andre A.; Mohiuddin, Mohammed; Poggi, Matthew M.; Regine, William F.; Cosman, Bard C.; Saltz, Leonard; Johnstone, Peter A.S.

    2008-04-01

    The American College of Radiology (ACR) Appropriateness Criteria on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology-Rectal/Anal Cancer, based on a literature review completed in 2007.

  19. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  20. Combined preoperative neoadjuvant radiotherapy and chemotherapy for anal and rectal cancer

    SciTech Connect

    Smith, D.E.; Muff, N.S.; Shetabi, H.

    1986-05-01

    Neoadjuvant therapy combining 5-fluorouracil, mitomycin C, and moderate-dose radiotherapy was given preoperatively to 29 patients with adenocarcinoma of the rectum, 3 patients with squamous cell cancer, and 1 patient with basaloid carcinoma of the anus. Significant downstaging, and even eradication, of these lesions was realized in a high percentage of cases. Population-based data for the period of 1979 to 1984 which encompasses the time of our study indicate the survival of those treated by the neoadjuvant therapy was superior to that of patients treated by surgery alone or by surgery followed by radiotherapy. In general, patients with the poorest clinical presentation had been referred for this therapy.

  1. 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

  2. [Surgical treatment of rectal cancer].

    PubMed

    Vergara-Fernández, O; Salinas-Aragón, L E; Camacho-Mauries, D; Medina-Franco, H

    2010-01-01

    Rectal affection accounts for 30% of colorectal cancer. The standard of treatment is surgical resection, which often is curative. For superior and middle-rectal involvement, low anterior resection (LAR) is the preferred procedure. For tumors involving the lower portion of the rectum, abdominoperineal resection (APR) or LAR are the options of treatment, depending on sphincter involvement. The main surgical objective is to achieve a R0 resection with an appropriated total mesorrectal excision, greater number of lymph nodes and negative distal and radial margins. These surgical parameters have been used as quality indicators and have prognostic implications in terms of overall and disease-free survival. Total mesorectal excision with preservation of hypogastric nerves has shown a reduction in rates of sexual and bladder dysfunction as well as lower local recurrence. At specialized centers such procedures are performed by minimal invasive surgery; however the number of meta-analysis is scarce.

  3. Stages of Rectal Cancer

    MedlinePlus

    ... a monoclonal antibody or angiogenesis inhibitor ). Chemotherapy to control the growth of the tumor . Radiation therapy, chemotherapy, or a combination of both, as palliative therapy to relieve symptoms and improve the quality of life . Placement of a stent to help ...

  4. 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

  5. Fournier gangrene: rare complication of rectal cancer.

    PubMed

    Ossibi, Pierlesky Elion; Souiki, Tarik; Ibn Majdoub, Karim; 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.

  6. Puborectal sling interposition combined with seton drainage for pouch-vaginal fistula after rectal cancer surgery with colonic J pouch-anal reconstruction: report of a case.

    PubMed

    Kawamoto, Aya; Inoue, Yasuhiro; Okigami, Masato; Okugawa, Yoshinaga; Hiro, Junichiro; Toiyama, Yuji; Tanaka, Koji; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

    2014-01-01

    The management of postoperative rectovaginal fistula (RVF) after rectal cancer surgery is difficult and requires reconstruction of the anastomotic site and fistula. Though various surgical procedures have been reported for the repair of RVFs, the results of surgical repair are often unsatisfactory, and failure of the initial repair leads to difficulty in the later operations. Furthermore, it has been reported that cases associated with local infection result in low success rates. We report a case of an 80-year-old woman with a recurrent colonic J pouch-vaginal fistula after anoabdominal rectal resection with partial internal sphincteric resection, who achieved a good outcome following a repair using a puborectal sling interposition combined with seton drainage. It may be a useful option for RVF management in repair of such pouch-vaginal fistula after coloanal anastomosis with intersphincteric resection.

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

    ClinicalTrials.gov

    2016-11-23

    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

  8. Future of therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2013-06-01

    Since 2004, the standard of care for patients with cT3 and/or N+ rectal cancer has been preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. A number of advances have occurred and are defining the future of rectal cancer therapy. Among these are short course radiation, the impact of postoperative adjuvant chemotherapy, selective radiation and selective surgery, and new chemoradiation regimens with novel agents. This review will examine these developments and assess their impact on the future therapy of rectal cancer.

  9. 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.

  10. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  11. 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

  12. Novel radiation techniques for rectal cancer

    PubMed Central

    2014-01-01

    The concepts for management of rectal cancer have changed drastically over the past few years. Through national bowel cancer screening programmes in the Western countries and the increasing use of endoscopic procedures as diagnostic tool, there is increase in detection of rectal cancer in early stages. There is increase in ageing population worldwide but more so in Western countries. In addition, there is realisation of harm from extirpative surgical procedures which are directed towards managing advanced rectal cancer in the past. Increase in cost of health care burden has also led the investigators to seek alternative treatment options which are effective, safe and cost effective. There are several modern radiation techniques which fits this bill and we need to be aware of newer novel radiation techniques to fulfil this gap. PMID:24982769

  13. [A Case of Advanced Rectal Cancer in Which Combined Prostate Removal and ISR Using the da Vinci Surgical System with Preoperative Chemotherapy Allowed Curative Resection].

    PubMed

    Kawakita, Hideaki; Katsumata, Kenji; Kasahara, Kenta; Kuwabara, Hiroshi; Shigoka, Masatoshi; Matsudo, Takaaki; Enomoto, Masanobu; Ishizaki, Tetsuo; Hisada, Masayuki; Kasuya, Kazuhiko; Tsuchida, Akihiko

    2016-11-01

    A 53-year-old male presented with a chief complaint of dyschezia.Lower gastrointestinal endoscopy confirmed the presence of a type II tumor in the lower part of the rectum, and a biopsy detected a well-differentiated adenocarcinoma.As invasion of the prostate and levator muscle of the anus was suspected on diagnostic imaging, surgery was performed after preoperative chemotherapy.With no clear postoperative complications, the patient was discharged 26 days after surgery. After 24 months, the number of urination ranged from 1 to 6, with a Wexner score of 6 and a mild desire to urinate in the absence of incontinence.At present, the patient is alive without recurrence.When combined with chemotherapy, robotassisted surgery allows the curative resection of extensive rectal cancer involving the suspected invasion of other organs.In this respect, it is likely to be a useful method to conserve anal and bladder function.

  14. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwangzoo

    2016-01-01

    Purpose To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary. PMID:27592514

  15. Transanal Approach to Rectal Polyps and Cancer

    PubMed Central

    Rai, Vinay; Mishra, Nitin

    2016-01-01

    A transanal approach to rectal polyp and cancer excision is often an appropriate alternative to conventional rectal resection, and has a lower associated morbidity. There has been a steady evolution in the techniques of transanal surgery over the past 30 years. It started with traditional transanal excision and was revolutionized by introduction of transanal endoscopic microsurgery in early 1980s. Introduction of transanal minimally invasive surgery made it more accessible to surgeons around the world. Now robotic platforms are being tried in certain institutions. Concerns have been raised about recurrence rates of cancers with transanal approach and success of subsequent salvage operations. PMID:26929754

  16. Combination of three-gene immunohistochemical panel and magnetic resonance imaging-detected extramural vascular invasion to assess prognosis in non-advanced rectal cancer patients

    PubMed Central

    Li, Xiao-Fu; Jiang, Zheng; Gao, Ying; Li, Chun-Xiang; Shen, Bao-Zhong

    2016-01-01

    AIM To identify a small, clinically applicable immunohistochemistry (IHC) panel that could be combined with magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) for assessment of prognosis concerning the non-advanced rectal cancer patients prior to operation. METHODS About 329 patients with pathologically confirmed rectal carcinoma (RC) were screened in this research, all of whom had been examined via an MRI and were treatment-naïve from July 2011 to July 2014. The candidate proteins that were reported to be altered by RC were examined in tissues by IHC. All chosen samples were adopted from the fundamental cores of histopathologically confirmed carcinomas during the initial surgeries. RESULTS Of the three proteins that were tested, c-MYC, PCNA and TIMP1 were detected with relatively significant expression in tumors, 35.9%, 23.7% and 58.7% respectively. The expression of the three proteins were closely connected with prognosis (P = 0.032, 0.003, 0.021). The patients could be classified into different outcome groups according to an IHC panel (P < 0.01) via these three proteins. Taking into consideration known survival covariates, especially EMVI, the IHC panel served as an independent prognostic factor. The EMVI combined with the IHC panel could categorize patients into different prognostic groups with distinction (P < 0.01). CONCLUSION These studies argue that this three-protein panel of c-MYC, PCNA, coupled with TIMP1 combined with MRI-detected EMVI could offer extra prognostic details for preoperative treatment of RC. PMID:27784970

  17. Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

    ClinicalTrials.gov

    2013-02-26

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer; Stage IVA Rectal Cancer; Stage IVB Rectal Cancer

  18. Multidisciplinary management of resectable rectal cancer. New developments and controversies.

    PubMed

    Minsky, Bruce D; Guillem, Jose G

    2008-11-15

    Until 2004, initial surgery and, in cases of pT3 and/or node-positive disease, postoperative chemoradiotherapy (radiation plus concurrent chemotherapy) was the conventional approach for patients with clinical T3 and/or node-positive rectal cancer. The German CAO/ARO/AIO 94 trial confirmed that, compared with preoperative chemoradiotherapy, postoperative chemoradiotherapy is associated with significantly higher local failure and toxicity rates as well as a decrease in the incidence of sphincter preservation. These data resulted in a change from postoperative to preoperative chemoradiotherapy. This shift to preoperative therapy has prompted a series of new questions regarding the multidisciplinary management of rectal cancer, including: What is the ideal neoadjuvant approach (short-course vs. combined-modality therapy)? Is postoperative adjuvant chemotherapy necessary for all patients following preoperative chemoradiotherapy? Do patients with node-negative rectal cancer require pelvic radiation? What is the ideal combined-modality regimen? Does an increase in response rate translate into improved local control and survival? And lastly, what is the benefit of novel radiation sensitization and delivery techniques? This review will address these and other questions surrounding the multidisciplinary management of rectal cancer.

  19. Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer.

    PubMed

    Chung, Heeteak; Polf, Jerimy; Badiyan, Shahed; Biagioli, Matthew; Fernandez, Daniel; Latifi, Kujtim; Wilder, Richard; Mehta, Minesh; Chuong, Michael

    2017-01-01

    The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields. Dose volume histograms (DVH) were generated for the prostate, rectum, bladder, and right and left femoral heads. The normal tissue complication probability (NTCP) for ≥grade 2 rectal toxicity was calculated using the Lyman-Kutcher-Burman model and compared between patients with and without the rectal spacer. A significantly lower mean rectal DVH was achieved in patients with rectal spacer compared to those without. For LAT plans, the mean rectal V70 with and without rectal spacer was 4.19 and 13.5%, respectively. For LAO/RAO plans, the mean rectal V70 with and without rectal spacer was 5.07 and 13.5%, respectively. No significant differences were found in any rectal dosimetric parameters between the LAT and the LAO/RAO plans generated with the rectal spacers. We found that ≥ 9 mm space resulted in a significant decrease in NTCP modeled for ≥grade 2 rectal toxicity. Rectal spacers can significantly decrease modeled rectal dose and predicted ≥grade 2 rectal toxicity in prostate cancer patients treated in silico with PBS. A minimum of 9 mm separation between the prostate and anterior rectal wall yields the largest benefit.

  20. [A case of pathological complete response to lt. Lateral lymph node metastasis from lower rectal cancer by S-1 combined neoadjuvant chemoradiotherapy].

    PubMed

    Kimura, Shunichi; Ohnuma, Shinobu; Karasawa, Hideaki; Aoki, Takeshi; Kudoh, Katsuyoshi; Watanabe, Kazuhiro; Tanaka, Naoki; Nagao, Munenori; Abe, Tomoya; Musha, Hiroaki; Morikawa, Takanori; Motoi, Fuyuhiko; Katayose, Yu; Naitoh, Takeshi; Unno, Michiaki

    2014-11-01

    A 54-year-old man presented with an enlarged left (lt) lateral lymph node (LLN), which was detected by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET-CT). Endoscopic examination of the colon revealed the presence of a type 1 tumor, 20mm in diameter, in the lower rectum; the tumor was diagnosed as a well-differentiated adenocarcinoma (tub1). The patient received combined neoadjuvant chemoradiotherapy (nCRT)with S- 1 for treatment of the rectal cancer and LLN metastasis (MP, T2N3M0, Stage IIIb). S-1 was administered orally at a dose of 120 mg/day on days 1-14, and 22-35; a total dose of 45 Gy was delivered (1.8 Gy/day, for 25 days). Upon nCRT, there was a remarkable reduction in the tumor size, the primary tumor receded, and the LLN decreased from 16 mm to 8 mm in diameter. The maximum standardized uptake value (SUVmax) also decreased from 3.8 to 1.9 on PET-CT. Six weeks after nCRT, ultralow anterior resection and bilateral lymph node dissections were performed. Histopathological examination showed a partial presence of cancer cells in the scarred primary tumor; however, no viable cancer cells were observed in the lt. LLN.

  1. Neoadjuvant Treatment in Rectal Cancer: Actual Status

    PubMed Central

    Garajová, Ingrid; Di Girolamo, Stefania; de Rosa, Francesco; Corbelli, Jody; Agostini, Valentina; Biasco, Guido; Brandi, Giovanni

    2011-01-01

    Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas. PMID:22295206

  2. [Peri-operative treatments for rectal cancer].

    PubMed

    Gérard, Jean-Pierre; Doyen, Jerome; Bénézery, Karen; Borens, Bruno; Hannoun-Levi, Jean-Michel; François, Éric

    2015-06-01

    Depending on its location or stage, rectal cancer may differ significantly. Before any treatment decision a careful work up is mandatory relying mainly on endoscopy and imaging (MRI). Surgery according to the TME principle is the cornerstone of treatment. Most of the time surgery is associated with external beam radiotherapy often combined with concurrent chemotherapy (capecitabine) according to the neoadjuvant regimen CAP 50 (5 weeks long). It is sometimes possible to escalate safely the dose of irradiation using contact X-ray brachytherapy 50 Kv or Iridium 192 interstitial brachytherapy. Adjuvant chemotherapy may be given in case of pejorative pathological findings but its benefit is not yet proven in contrast with colon cancer. Local recurrences are becoming unusual as is permanent APE surgery with permanent stoma. To reduce the risk of distant metastasis clinical trials are testing first line chemotherapy in T3-4 lesions. For early stage (T2-"small" T3) clinical trials try to achieve organ preservation. Intensification of CAP 50 either with more chemotherapy or radiation dose escalation using contact X-ray aim at achieving a clinical complete response followed by local excision or close surveillance.

  3. [Rectal stenosis due to Schnitzler metastasis following surgery for gastric cancer--a case successfully treated with TS-1 and CDDP combination chemotherapy].

    PubMed

    Niinobu, Takahiro; Nakagawa, Sumiko; Itani, Yutaka; Nishikawa, Yasuaki; Amano, Masahiro; Higaki, Naozumi; Hayashida, Hiroto; Sakon, Masato

    2005-10-01

    The patient, a 40-year-old woman, underwent total gastrectomy and excision of the pancreatic tail, spleen and gallbladder for gastric cancer in September 2000. The lesion was judged to be P1, SE, H0, N2 and Stage IV and the patient was managed on a regular schedule as an outpatient. In September 2004, she passed blood-stained feces and rectal palpation detected a hard nodule at the anterior rectal wall. A fiber optic examination of the sigmoid colon detected an ulcerous lesion with a hemorrhage at the anterior rectal wall. A biopsy revealed the lesion to be Group V poorly differentiated adenocarcinoma. Starting in October 2004, 100 mg/day of TS-1 was administered for 3 weeks; intravenous drip infusion of 100 mg/body of CDDP was conducted in the second week for a period of 24 hours. After 3 courses of this regimen, a fiber optic examination of the colon conducted in February 2005 no longer detected the rectal tumor, leaving only a cicatrix. Upon a CT examination, the para-aortic lymph nodes that had been enlarged were notably reduced in size and an improvement was eminent in the hypertrophic rectal wall. The patient no longer experienced constipation or melena. Her clinical course is being observed while an oral administration of 100 mg/day of TS-1 continues.

  4. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-12-13

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  5. Evidence and research in rectal cancer.

    PubMed

    Valentini, Vincenzo; Beets-Tan, Regina; Borras, Josep M; Krivokapić, Zoran; Leer, Jan Willem; Påhlman, Lars; Rödel, Claus; Schmoll, Hans Joachim; Scott, Nigel; Velde, Cornelius Van de; Verfaillie, Christine

    2008-06-01

    The main evidences of epidemiology, diagnostic imaging, pathology, surgery, radiotherapy, chemotherapy and follow-up are reviewed to optimize the routine treatment of rectal cancer according to a multidisciplinary approach. This paper reports on the knowledge shared between different specialists involved in the design and management of the multidisciplinary ESTRO Teaching Course on Rectal Cancer. The scenario of ongoing research is also addressed. In this time of changing treatments, it clearly appears that a common standard for large heterogeneous patient groups have to be substituted by more individualised therapies based on clinical-pathological features and very soon on molecular and genetic markers. Only trained multidisciplinary teams can face this new challenge and tailor the treatments according to the best scientific evidence for each patient.

  6. Transanal local excision of rectal cancer.

    PubMed

    Read, D R; Sokil, S; Ruiz-Salas, G

    1995-01-01

    Twenty-five patients with invasive rectal cancer treated by transanal excision between 1978-1989 are presented. Two patients had poorly differentiated tumours and were converted to abdominoperineal resection and one patient had extensive liver metastases documented preoperatively. The remaining twenty-two, mean age 64 years, fulfilled the criteria for local treatment. Eighty-two percent of tumours were T1 or T2 stage. There was no operative mortality. Six complications in five patients occurred, none requiring surgical intervention. Five patients died of unrelated causes without evidence of recurrence at 4, 4, 14, 26 and 58 months. The length of follow-up for the surviving group (17 patients) was 16 to 115 months (mean 63 months). Two patients developed local recurrence at 32 and 60 months. Transanal excision can be curative for selected rectal cancers.

  7. Neo-adjuvant radiotherapy in rectal cancer

    PubMed Central

    Glimelius, Bengt

    2013-01-01

    In rectal cancer treatment, attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence. Several large randomized trials have also shown that combinations of surgery, radiotherapy and chemotherapy have markedly reduced the risk of a loco-regional recurrence, but this has not yet had any major influence on overall survival. The best results have been achieved when the radiotherapy has been given preoperatively. Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance, i.e., when a total mesorectal excision has been performed. The relative reduction is then 50%-70%. The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance, as practised in some Asian countries. Many details about how the radiotherapy is performed are still open for discussion, and practice varies between countries. A highly fractionated radiation schedule (5 Gy × 5), proven efficacious in many trials, has gained much popularity in some countries, whereas a conventionally fractionated regimen (1.8-2.0 Gy × 25-28), often combined with chemotherapy, is used in other countries. The additional therapy adds morbidity to the morbidity that surgery causes, and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals) is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, there is a great need to develop predictors of response, so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging. PMID:24379566

  8. 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

  9. 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.

  10. Locally advanced rectal cancer: the importance of a multidisciplinary approach.

    PubMed

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-12-14

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

  11. Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients

    PubMed Central

    Biffi, Roberto; Marsiglia, Hugo; Fossa, Barbara Jereczek; Leonardi, Maria Cristina; Cante, Domenico; Lazzari, Roberta; Chiappa, Antonio; Cenciarelli, Sabine; Andreoni, Bruno; Zampino, Maria Giulia; Orecchia, Roberto

    2007-01-01

    Background although preoperative RT (Radiation Therapy) is becoming the preferred approach for combined treatment of locally advanced rectal adenocarcinoma, no regimen can be now considered as a standard. Since the toxicity of preoperative RT isn't yet completely known, and the advantages of preoperative RT could be counterbalanced by increased postoperative morbidity and mortality, a monocentre series of preoperative bifractionated accelerated RT was retrospectively reviewed to clarify toxicity and outcomes after a prolonged follow up. Methods patients were screened following these eligibility criteria: histology-proven adenocarcinoma of the rectum; distal tumour extent at 12 cm or less from the anal verge; clinical stage T3–4/anyN, or anyT/N1–2; ECOG Performance Status 0–2. A total dose of 41.6 Gy (26 twice daily fractions of 1.6 Gy) was delivered. Surgery was carried out 17 ± 2 days after RT completion, adopting the total mesorectal excision technique. Results 24 men and 23 women were enrolled; median age was 55 years (r.: 39–77). Twenty-eight patients were stage II and 19 stage III. 9 patients suffered from a recurrent tumour. 2 patients experienced a severe grade 4 gastrointestinal toxicity (a colo-vaginal fistula and an intestinal obstruction, both successfully treated). Operative mortality was nil; postoperative early complications occurred in 13 cases; mean length of hospital stay was 15 days. After a mean follow up of 44 months (r.: 18–84) 8 patients had deceased for recurrent disease, 15 were alive with a disease progression (2 pelvic recurrences and 13 pure distant deposits) and 24 were alive, without disease. The 5-year actuarial overall survival was 74.2%, the disease-free survival 62.9% and the regional control rate 84.7%. Long-term complications included 1 case of radiation enteritis requiring surgery, 2 cases of anastomotic stricture and 3 cases of bladder incontinence. Conclusion bifractionated accelerated RT administered in the

  12. Rectal and colon cancer: Not just a different anatomic site.

    PubMed

    Tamas, K; Walenkamp, A M E; de Vries, E G E; van Vugt, M A T M; Beets-Tan, R G; van Etten, B; de Groot, D J A; Hospers, G A P

    2015-09-01

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs.

  13. Treatment Option Overview (Rectal Cancer)

    MedlinePlus

    ... a monoclonal antibody or angiogenesis inhibitor ). Chemotherapy to control the growth of the tumor . Radiation therapy, chemotherapy, or a combination of both, as palliative therapy to relieve symptoms and improve the quality of life . Placement of a stent to help ...

  14. General Information about Rectal Cancer

    MedlinePlus

    ... a monoclonal antibody or angiogenesis inhibitor ). Chemotherapy to control the growth of the tumor . Radiation therapy, chemotherapy, or a combination of both, as palliative therapy to relieve symptoms and improve the quality of life . Placement of a stent to help ...

  15. 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

  16. 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.

  17. Abdominosacral resection for locally recurring rectal cancer

    PubMed Central

    Belli, Filiberto; Gronchi, Alessandro; Corbellini, Carlo; Milione, Massimo; Leo, Ermanno

    2016-01-01

    AIM To investigate feasibility and outcome of abdominal-sacral resection for treatment of locally recurrent rectal adenocarcinoma. METHODS A population of patients who underwent an abdominal-sacral resection for posterior recurrent adenocarcinoma of the rectum at the National Cancer Institute of Milano, between 2005 and 2013, is considered. Retrospectively collected data includes patient characteristics, treatment and pathology details regarding the primary and the recurrent rectal tumor surgical resection. A clinical and instrumental follow-up was performed. Surgical and oncological outcome were investigated. Furthermore an analytical review of literature was conducted in order to compare our case series with other reported experiences. RESULTS At the time of abdomino-sacral resection, the mean age of patients was 55 (range, 38-64). The median operating time was 380 min (range, 270-480). Sacral resection was performed at S2/S3 level in 3 patients, S3/S4 in 3 patients and S4/S5 in 4 patients. The median operating time was 380 ± 58 min. Mean intraoperative blood loss was 1750 mL (range, 200-680). The median hospital stay was 22 d. Overall morbidity was 80%, mainly type II complication according to the Clavien-Dindo classification. Microscopically negative margins (R0) is obtained in all patients. Overall 5-year survival after first surgical procedure is 60%, with a median survival from the first surgery of 88 ± 56 mo. The most common site of re-recurrence was intrapelvic. CONCLUSION Sacral resection represents a feasible approach to posterior rectal cancer recurrence without evidence of distant spreading. An accurate staging is essential for planning the best therapy. PMID:28070232

  18. Focusing the management of rectal cancer

    PubMed Central

    Dbeis, Rachel; Smart, Neil J.

    2016-01-01

    Rectal cancer treatment has undergone major changes over the last 15 years with a focus on individualized care based around MRI assessment of the relationship of the tumour to the mesorectal fascia, improved surgical techniques and targeted use of pre-operative oncological therapies in patients with locally advanced disease. The recognition that some tumours responded completely to pre-operative chemoradiotherapy, and the selective use of a non-operative policy has led to a quest to further identify those patients and their tumour in whom this approach could be used, irrespective of MRI stage. With no clear patient factors identified, the tumour and its gene expression has become a target for research to identify individual single-nucleotide polymorphisms, which may indicate a response to specific treatment, or not. To date some agents have been identified and trialed, such as cetuximab, with individual tumours being assessed for response allowing directed treatment. The reviewed paper by Sebio and colleagues report a study that links polymorphisms in the DNA repair gene XRCC1 with response to neoadjuvant 5-Fluorouracil treatment in rectal cancer patients. However, genetic heterogeneity alone may not explain the variations of drug response and environmental factors may lead to epigenetic effects and therefore alter responses. Therefore whilst this study demonstrates the impact of different single nucleotide polymorphisms (SNPs), it is only one step forward, but perhaps a step in the right direction. PMID:28149883

  19. Rectal prolapse as initial clinical manifestation of colon cancer.

    PubMed

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  20. 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

  1. 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.

  2. Fournier gangrene: first manifestation of occult rectal cancer.

    PubMed

    Ruiz-Tovar, J; Córdoba, L; Devesa, J M

    2011-01-01

    Fournier gangrene is a necrotizing fasciitis of the genital and perineal region. Diverse factors predispose to Fournier gangrene, such as diabetes mellitus, ethylism, liver dysfunction, haematological disorders, obesity or recent regional instrumentation. Rectal tumours can also predispose to Fournier gangrene; most of the reported cases are perforated or unresectable colorectal tumours, but some cases of anorectal cancer diagnosed after recovery from Fournier gangrene have also been reported. In these cases, the presence of a rectal tumour at the time of, or prior to, diagnosis of Fournier gangrene could not be ruled out. We present three cases of rectal cancer whose first manifestation was as Fournier gangrene.

  3. 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

  4. 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

  5. The accuracy of endorectal ultrasonography in rectal cancer staging

    PubMed Central

    COTE, ADRIAN; GRAUR, FLORIN; LEBOVICI, ANDREI; MOIS, EMIL; AL HAJJAR, NADIM; MARE, CODRUTA; BADEA, RADU; IANCU, CORNEL

    2015-01-01

    Background and aims The incidence of rectal cancer in the European Union is about 35% of the total colorectal cancer incidence. Staging rectal cancer is important for planning treatment. It is essential for the management of rectal cancer to have adequate preoperative imaging, because accurate staging can influence the therapeutic strategy, type of resection, and candidacy for neoadjuvant therapy. The aim of this work is to evaluate the accuracy of endorectal ultrasound (ERUS) in rectal cancer staging. Methods A retrospective study was performed to assess the accuracy of ERUS by analyzing patients discharged from Regional Institute of Gastroenterology and Hepatology (IRGH) Cluj-Napoca, Romania, diagnosed with rectal cancer between 01 January 2011 and 31 December 2013. Patients who were preoperatively staged by other imaging methods and those who had ERUS performed in another service were excluded from the analysis. As inclusion criteria remained ERUS performed for patients with rectal cancer in IRGH Cluj-Napoca where they were also operated. We analyzed preoperative T stage obtained by ERUS and it was compared with the histopathology findings. Results The number of patients discharged with a diagnosis of rectal cancer were 200 (operated – 157) in 2011, 193 (operated – 151) in 2012, and 198 (operated – 142) in 2013. We analyzed a total of 51 cases diagnosed with rectal cancer who performed ERUS in IRGH Cluj-Napoca. The results according to the T stage obtained by ERUS and histopathology test were: Under-stage T2= 25.0%, T3=7.9% of cases; Over-stage T2=25.0%, T3=31.6% and T4=60.0% of cases. Less than 20% of patients underwent preoperative radio-chemotherapy. Conclusions ERUS is a method of staging rectal cancer which is human dependent. ERUS is less accurate for T staging of stenotic tumours, but the accuracy may still be within acceptable limits. Surgeons use ERUS to adopt a treatment protocol, knowing the risk of under-staging and over-staging of this method

  6. Unique considerations in the patient with rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-08-01

    In the past two decades, substantial progress has been made in the adjuvant management of colorectal cancer. Chemotherapy has improved overall survival in patients with node-positive (N+) disease. In contrast with colon cancer, which has a low incidence of local recurrence, patients with rectal cancer have a higher incidence requiring the addition of pelvic radiation therapy (chemoradiation). Patients with rectal cancer have a number of unique management considerations: for example, the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? This review will address these and other controversies specific to patients with rectal cancer.

  7. [Quality standards in rectal cancer surgery].

    PubMed

    Pera, M; Pascual, M

    2005-01-01

    The results of surgery for rectal cancer have classically been measured through indicators such as morbidity, mortality, and length of hospital stay. In the last few years other parameters have been included that evaluate healthcare quality such as the functional results of the surgical technique employed and quality of life. Total resection of the mesorectum, performed by experienced surgeons, is the surgical technique of choice. Currently, the sphincter can be preserved in 70% of patients. Anastomotic dehiscence after anterior resection of the rectum is the most serious complication and the most important risk factor is the height of the anastomosis. The overall dehiscence rate should be less than 15% and operative mortality should be between 2% and 3%. The colonic reservoir improves functional outcome and consequently it is the procedure of choice to reconstruct transit after low anterior resection. Local recurrence should be less than 10% and 5-year survival should be between 70% and 80%. In general, quality of life is better after anterior resection of the rectum than after abdominoperineal amputation, despite the functional deterioration presented by some patients.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Novel combination combining J-Vac and VAC sponge for draining a rectal wound.

    PubMed

    Durai, R; Ng, P C H

    2010-01-01

    Active drains, which work by negative pressure, require a closed space for retaining the vacuum. Here the authors describe their novel technique of combining a J-Vac drain and the sponge of a vacuum assisted closure dressing pack to drain a rectal wound. This modification may be useful for rectal wounds and anastomotic leaks.

  14. Results of radical surgery for rectal cancer.

    PubMed

    Heald, R J; Karanjia, N D

    1992-01-01

    This paper examines the hypothesis that a reduction in the distal mural margin during anterior resection for sphincter conservation in rectal cancer excision is safe, provided total mesorectal excision is undertaken with wash-out of the clamped rectum. One hundred ninety-two patients underwent anterior resection and 21 (less than 10%) patients underwent abdomino-perineal excision (APE) by one surgeon (RJH). Anterior resections were classified as "curative" (79%) and "non-curative" (21%); in the "curative" sub-group less than 4% of patients developed local recurrence. The series was retrospectively analyzed for the effect of mural margins on local recurrence with 152 patients undergoing "curative" anterior resections and 40 patients undergoing "non-curative" resections. In the 152 specimens from curative resections, 110 had a resection margin greater than 1 cm and 42 had a resection margin less than 1 cm. Four patients developed local recurrence in the greater than 1 cm margin group (95% confidence interval: 0.8%-7.8%) and no patients developed local recurrence in the less than or equal to 1 cm margin group (95% confidence interval: 0%-5.9%). In each patient with local recurrence a cause for failure was apparent. There was no statistically significant difference in local recurrence rate between the less than or equal to 1 cm margin group and the greater than 1 cm margin group. A reduction in resection margin therefore did not compromise survival after anterior resection. The significance of lateral resection margins is discussed. The role of deep radiotherapy and cytotoxics are considered.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. 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

  16. Reproducibility with repeat CT in radiomics study for rectal cancer

    PubMed Central

    Hu, Panpan; Wang, Jiazhou; Zhong, Haoyu; Zhou, Zhen; Shen, Lijun; Hu, Weigang; Zhang, Zhen

    2016-01-01

    Purpose To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. Results Volume normalized features are much more reproducible than unnormalized features. The average value of all slices is the most reproducible feature type in rectal cancer. Different filters have little effect for the reproducibility of radiomics features. For the average type features, 496 out of 775 features showed high reproducibility (ICC ≥ 0.8), 225 out of 775 features showed medium reproducibility (0.8 > ICC ≥ 0.5) and 54 out of 775 features showed low reproducibility (ICC < 0.5). Methods 40 rectal cancer patients with stage II were enrolled in this study, each of whom underwent two CT scans within average 8.7 days. 775 radiomics features were defined in this study. For each features, five different values (value from the largest slice, maximum value, minimum value, average value of all slices and value from superposed intermediate matrix) were extracted. Meanwhile a LOG filter with different parameters was applied to these images to find stable filter value. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) of two CT scans were calculated to assess the reproducibility, based on original features and volume normalized features. Conclusions Features are recommended to be normalized to volume in radiomics analysis. The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and prognosis prediction. PMID:27669756

  17. Total mesorectal excision and management of rectal cancer.

    PubMed

    Pinsk, Ilia; Phang, P Terry

    2007-10-01

    Treatment of rectal cancer over the last two decades has evolved with changes in techniques of surgery and radiation based on national and international trials. Preoperative adjuvant radiation is now preferred over postoperative adjuvant radiation, and total mesorectal excision with preservation of pelvic nerves is the gold standard for surgical treatment of rectal cancer. Preservation of the anal sphincter without compromising oncological outcome is an additional benefit for patients with carcinoma in the distal rectum. Further progress in imaging and a multidisciplinary team approach will facilitate individualization of treatment strategy with more focus on quality of life.

  18. Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy

    SciTech Connect

    Shiraishi, Yutaka; Hanada, Takashi; Ohashi, Toshio; Yorozu, Atsunori; Toya, Kazuhito; Saito, Shiro; Shigematsu, Naoyuki

    2013-09-01

    Purpose: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after {sup 125}I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. Methods and Materials: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose–volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUD{sub sum}) was determined by a summation of the brachytherapy and external-beam radiation therapy components. Results: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUD{sub sum} increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUD{sub sum} (P=.000) as risk factors for grade 2+ rectal bleeding. Conclusions: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.

  19. Metachronous penile metastasis from rectal cancer after total pelvic exenteration.

    PubMed

    Kimura, Yuta; Shida, Dai; Nasu, Keiichi; Matsunaga, Hiroki; Warabi, Masahiro; Inoue, Satoru

    2012-10-14

    Despite its abundant vascularization and extensive circulatory communication with neighboring organs, metastases to the penis are a rare event. A 57-year-old male, who had undergone total pelvic exenteration for rectal cancer sixteen months earlier, demonstrated an abnormal uptake within his penis by positron emission tomography/computed tomography. A single elastic nodule of the middle penis shaft was noted deep within Bucks fascia. No other obvious recurrent site was noted except the penile lesion. Total penectomy was performed as a curative resection based on a diagnosis of isolated penile metastasis from rectal cancer. A histopathological examination revealed an increase of well differentiated adenocarcinoma in the corpus spongiosum consistent with his primary rectal tumor. The immunohistochemistry of the tumor cells demonstrated positive staining for cytokeratin 20 and negative staining for cytokeratin 7, which strongly supported a diagnosis of penile metastasis from the rectum. The patient is alive more than two years without any recurrence.

  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.

  1. Effect of misclassified underlying cause of death on survival estimates of colon and rectal cancer.

    PubMed

    Yin, Daixin; Morris, Cyllene R; Bates, Janet H; German, Robert R

    2011-07-20

    Inaccurate coding of patients' Underlying Cause of Death (UCOD) has constrained cause-specific survival estimates for colon and rectal cancers. Using California data from the Accuracy of Cancer Mortality study, we compared the cancer site data from the California Cancer Registry (CCR) with UCODs reported on death certificates and reclassified the UCODs based on cancer registry data when they disagreed. We then calculated 1-, 3-, 5-, and 10-year cause-specific survival for colon and rectal cancers separately, before and after the reclassification. Records from 26 312 colon and 10 687 rectal cancer patients were examined. UCOD records disagreed with CCR records for 700 (6%) of 11 404 colon cancer deaths and with 1958 (39%) of 5011 rectal cancer deaths, and 82% of the misclassified rectal cancer deaths were coded as colon cancer deaths in the UCOD. Reclassification decreased cause-specific survival for both colon and rectal cancers, but the impact was more pronounced for rectal cancer (eg, 5-year cause-specific survival of colon cancer decreased by 2.8% and of rectal cancer decreased by 20.0% relative to previous estimates; absolute rates changed from 65.4% to 63.6%, and 81.2% to 64.9%, respectively, after reclassification). Interchangeable use of the terms colon cancer and colorectal cancer is likely to be one of the reasons for UCOD misclassification. Educational measures could improve the accuracy of UCOD for colon and rectal cancer deaths.

  2. Rectal cancer with synchronous liver metastases: Do we have a clear direction?

    PubMed

    Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J; Poston, G J; Påhlman, L

    2015-12-01

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms.

  3. The curative management of synchronous rectal and prostate cancer

    PubMed Central

    Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

    2016-01-01

    Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity

  4. 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).

  5. Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

    PubMed

    Catalona, William J; Richie, Jerome P; Ahmann, Frederick R; Hudson, M'Liss A; Scardino, Peter T; Flanigan, Robert C; DeKernion, Jean B; Ratliff, Timothy L; Kavoussi, Louis R; Dalkin, Bruce L; Waters, W Bedford; MacFarlane, Michael T; Southwick, Paula C

    2017-02-01

    To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 μg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 μg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 μg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.

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

    ClinicalTrials.gov

    2017-01-24

    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. Bladder and rectal complications following radiotherapy for cervix cancer

    SciTech Connect

    Stryker, J.A.; Bartholomew, M.; Velkley, D.E.; Cunningham, D.E.; Mortel, R.; Craycraft, G.; Shafer, J.

    1988-01-01

    One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad.

  8. Clinically relevant study end points in rectal cancer.

    PubMed

    Fernandez-Martos, Carlos; Guerrero, Angel; Minsky, Bruce

    2012-01-01

    In rectal cancer currently there are no clearly validated early end points which can serve as surrogates for long-term clinical outcome such as local control and survival. However, the use of a variety of response rates (i.e. pathological complete response, downsizing the primary tumor, tumor regression grade (TRG), radiological response) as endpoints in early (phase II) clinical trials is common since objective response to therapy is an early indication of activity. Disease-free survival (DFS) has been proposed as the most appropriate end point in adjuvant trials and is one of the most frequently used in newer rectal cancer trials. Due to the devastating nature of local recurrence in locally advanced rectal cancer, local control (which is itself a subset of the overall DFS endpoint) is still considered an important endpoint. Recently, circumferential resection margin (CRM) has been proposed as novel early end point because the CRM status can account for effects on DFS and overall survival after chemoradiation, radiation (RT), or surgery alone. Consensus is needed to define the most appropriate end points in both early and phase III trials in locally advanced cancer.

  9. 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

  10. GLUT-1 expression and response to chemoradiotherapy in rectal cancer.

    PubMed

    Brophy, Sarah; Sheehan, Katherine M; McNamara, Deborah A; Deasy, Joseph; Bouchier-Hayes, David J; Kay, Elaine W

    2009-12-15

    Preoperative chemoradiotherapy is used in locally advanced rectal cancer to reduce local recurrence and improve operability, however a proportion of tumors do not undergo significant regression. Identification of predictive markers of response to chemoradiotherapy would improve patient selection and may allow response modification by targeting of specific pathways. The aim of this study was to determine whether expression of glucose transporter-1 (GLUT-1) and p53 in pretreatment rectal cancer biopsies was predictive of tumor response to chemoradiotherapy. Immunohistochemical staining for GLUT-1 and p53 was performed on 69 pretreatment biopsies and compared to tumor response in the resected specimen as determined by the tumor regression grade (TRG) scoring system. GLUT-1 expression was significantly associated with reduced response to chemoradiotherapy and increasing GLUT expression correlated with poorer response (p=0.02). GLUT-1 negative tumors had a 70% probability of good response (TRG3/4) compared to a 31% probability of good response in GLUT-1 positive tumors. GLUT-1 may be a useful predictive marker of response to chemoradiotherapy in rectal cancer.

  11. [Causes of local recurrence after curative surgery for rectal cancer].

    PubMed

    Hôhn, József; Varga, László; Baradnay, Gellért; Simonka, Zsolt; Géczi, Tibor; Nagy, Ferenc; Molnár, Tamás; Maráz, Anikó; Kahán, Zsuzsa; Balogh, Adám

    2003-01-01

    The rate of local recurrence (LR) has been 20-40% after resective surgery for rectal cancer by the traditional - Miles or Dixon - operative technics. The authors performed curative resection in 358 patients with rectal cancer in a 10 year period (01.01.1990 - 31.12.2000) in the Surgical Department of Szeged University. Since 01.01.1996 the authors changed this type of surgery for the Heald technics (total mesorectal excision - TME - with sharp dissection, using the UltraCision device) for the surgical treatment of middle or lower third rectal cancer. To compare the results of the two procedures, the authors analysed their material in two periods: Period I: 01.01.1991 - 31.12.1992: 62 patients operated on with the traditional operative technics; LR 15% within 2 years after surgery. Period II: 01.01.1997 - 31.12.1998: 78 patients operated on with the Heald technics (TME with sharp dissection); LR 6.4% within 2 years after surgery. Based on their results, the authors found that the modern operative technics by Heald, used in the second period of the study, was a relevant factor decreasing LR from 15% to 6.4%, while the gender, age of the patients, ratio of the abdominoperineal extirpation versus anterior resection (APRE/AR) and the free margin of more than 3 cm proved to be irrelevant.

  12. Comparison of laparoscopic vs. open surgery for rectal cancer

    PubMed Central

    Ding, Zihai; Wang, Zheng; Huang, Shijie; Zhong, Shizhen; Lin, Jianhua

    2017-01-01

    This study was conducted to evaluate the safety of laparoscopic radical resection for rectal cancer. A total of 64 cases of rectal cancer patients undergoing radical surgery between January, 1998 and March, 2010 were collected. The patients were divided into the laparoscopic rectal surgery group (LS group, n=31) and the open surgery group (OS group, n=33). Operation time, postoperative recovery, complications and tumor-free survival rate were compared between the two groups. The inclusion criteria were as follows: Standard Karnofsky score >70 prior to surgery, definitive pathological diagnosis and complete clinical data. The exclusion criteria were concomitant tumors affecting survival. With the Dixon operation, the LS group had a longer operation time compared with the OS group (271.2±56.2 vs. 216.0±62.7 min, respectively; P=0.036), and an earlier time of oral intake (3.0±0.9 vs. 4.7±1.0 days, respectively; P=0.000). There were no significant differences between the LS and OS groups in terms of intraoperative blood loss, number of lymph nodes retrieved, duration of postoperative hyperthermia and hospitalization time (P>0.05). With the Miles operation, there were no obvious differences between the LS and OS groups regarding operation time, intraoperative blood loss, number of lymph nodes retrieved, time of oral intake, duration of postoperative hyperthermia and hospitalization time (P>0.05). Furthermore, there were no significant differences between the LS and OS groups with the Dixon or Miles operation in terms of 3-year tumor-free survival rate (P>0.05). Thus, laparoscopic surgery appears to be a safe and feasible option for the treatment of rectal cancer. PMID:28357087

  13. Clinical application of multimodality imaging in radiotherapy treatment planning for rectal cancer.

    PubMed

    Wang, Yan Yang; Zhe, Hong

    2013-12-11

    Radiotherapy plays an important role in the treatment of rectal cancer. Three-dimensional conformal radiotherapy and intensity-modulated radiotherapy are mainstay techniques of radiotherapy for rectal cancer. However, the success of these techniques is heavily reliant on accurate target delineation and treatment planning. Computed tomography simulation is a cornerstone of rectal cancer radiotherapy, but there are limitations, such as poor soft-tissue contrast between pelvic structures and partial volume effects. Magnetic resonance imaging and positron emission tomography (PET) can overcome these limitations and provide additional information for rectal cancer treatment planning. PET can also reduce the interobserver variation in the definition of rectal tumor volume. However, there is a long way to go before these image modalities are routinely used in the clinical setting. This review summarizes the most promising studies on clinical applications of multimodality imaging in target delineation and treatment planning for rectal cancer radiotherapy.

  14. ¹H NMR-based metabolic profiling of human rectal cancer tissue

    PubMed Central

    2013-01-01

    Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Clinical impact of HLA class I expression in rectal cancer

    PubMed Central

    Speetjens, Frank M.; de Bruin, Elza C.; Morreau, Hans; Zeestraten, Eliane C. M.; Putter, Hein; van Krieken, J. Han; van Buren, Maaike M.; van Velzen, Monique; Dekker-Ensink, N. Geeske; van de Velde, Cornelis J. H.

    2007-01-01

    Purpose To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. Experimental design Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). Results Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with ≤50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. Conclusions Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient’s prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed. PMID:17874100

  20. Systematic review of prognostic importance of extramural venous invasion in rectal cancer

    PubMed Central

    Chand, Manish; Siddiqui, Muhammed RS; Swift, Ian; Brown, Gina

    2016-01-01

    AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer. METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and PubMed until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out. RESULTS: Fourteen studies reported the prevalence of extramural venous invasion (EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26 (0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395 (0.29, 0.51)]. CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future. PMID:26819536

  1. [Different strategies between Japan and other countries for the diagnosis and treatment of rectal cancer].

    PubMed

    Watanabe, Toshiaki

    2008-11-01

    In the treatment of rectal cancer, various attempts have been made to reduce the local recurrence rate. In Japan, lateral node dissection (LND) has been widely performed as a standard procedure for lower rectal cancers. Studies since the 1980s have shown that LND reduces the local recurrence rate and improves the survival rate. However, significant sexual or urinary dysfunction has been reported due to impairment of autonomic nerves by LND. To overcome these problems, autonomic nerve-preserving LND has been introduced. At present, autonomic nerve-preserving LND is the standard procedure for the treatment of lower rectal cancers in Japan. On the other hand, radiotherapy combined with total mesorectal excision is the standard procedure in other countries. Survival data also differ between Japan and elsewhere. In Japanese series, the postoperative survival rate is higher than those in other countries. This may be due to differences in the method of lymph node examination, surgical technique, etc. However, this is a very important issue in determining the postoperative adjuvant chemotherapy. In Japan, these differences need to be taken into account in determining the postoperative adjuvant chemotherapy regimen.

  2. 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

  3. Treatment Options by Stage (Rectal Cancer)

    MedlinePlus

    ... a monoclonal antibody or angiogenesis inhibitor ). Chemotherapy to control the growth of the tumor . Radiation therapy, chemotherapy, or a combination of both, as palliative therapy to relieve symptoms and improve the quality of life . Placement of a stent to help ...

  4. Necrotizing Fasciitis of the Thigh Secondary to Radiation Colitis in a Rectal Cancer Patient

    PubMed Central

    Park, So Hyun; Choi, Jung Ran; Song, Ji Young; Kang, Kyu Keun; Yoo, Woong Sun; Han, Sung Wan

    2012-01-01

    Necrotizing fasciitis usually occurs after dermal injury or through hematogenous spread. To date, few cases have been reported as necrotizing fasciitis of the thigh secondary to rectal perforation in rectal cancer patients. A 66-year-old male complained of pelvic and thigh pain and subsequently developed necrotizing fasciitis in his right thigh. Four years earlier, he had undergone a low anterior resection and radiotherapy due to of rectal cancer. An ulcerative lesion had been observed around the anastomosis site during the colonoscopy that had been performed two months earlier. Pelvic computed tomography and sigmoidoscopy showed rectal perforation and presacral abscess extending to buttock and the right posterior thigh fascia. Thus, the necrotizing fasciitis was believed to have occurred because of ulcer perforation, one of the complications of chronic radiation colitis, at the anastomosis site. When a rectal-cancer patient complains of pelvic and thigh pain, the possibility of a rectal perforation should be considered. PMID:23346513

  5. Robotic-Laparoscopic Rectal Cancer Excision Versus Traditional Laparoscopy

    PubMed Central

    Tam, Michael S.; Abbass, Mohammad

    2014-01-01

    Background and Objectives: Robotic surgery has been advocated for the radical excision of rectal cancer. Most data supporting its use have been reported from European and Asian centers, with a paucity of data from the United States documenting clear advantages of the robotic technique. This study compares the short-term outcome of robotic versus laparoscopic surgery. Methods: Consecutive patients who underwent laparoscopic (group 1) or robotic (group 2) rectal cancer excision at a single institution over a 2-year period were retrospectively reviewed. The main outcome measures were operative time, blood loss, conversion rates, number of lymph nodes, margin positivity, length of hospital stay, complications, and readmission rates. Results: Forty-two patients were analyzed. The median operative time was shorter in group 1 than that in group 2 (240 minutes vs 260 minutes, P = .04). No difference was noted in blood loss, transfusion rates, intraoperative complications, or conversion rates. There was no difference in circumferential or distal margin positivity. The median length of stay was shorter in group 1 (5 days vs 6 days, P = .05). The 90-day complication rate was similar in both groups (33% vs 43%, P = .75), but there was a trend toward more anastomotic leaks in group 1 (14% vs 0%, P = .23). Similarly, a non–statistically significant trend toward a higher readmission rate was noted in group 1 (24% vs 5%, P = .18). Conclusion: Robotic rectal cancer excision yielded a longer operative time and hospital length of stay, although immediate oncologic results were comparable. The need for randomized data is critical to determine whether the added resource utilization in robotic surgery is justifiable. PMID:25392653

  6. Patient factors may predict anastomotic complications after rectal cancer surgery

    PubMed Central

    Hayden, Dana M.; Mora Pinzon, Maria C.; Francescatti, Amanda B.; Saclarides, Theodore J.

    2014-01-01

    Purpose Anastomotic complications following rectal cancer surgery occur with varying frequency. Preoperative radiation, BMI, and low anastomoses have been implicated as predictors in previous studies, but their definitive role is still under review. The objective of our study was to identify patient and operative factors that may be predictive of anastomotic complications. Methods A retrospective review was performed on patients who had sphincter-preservation surgery performed for rectal cancer at a tertiary medical center between 2005 and 2011. Results 123 patients were included in this study, mean age was 59 (26–86), 58% were male. There were 33 complications in 32 patients (27%). Stenosis was the most frequent complication (24 of 33). 11 patients required mechanical dilatation, and 4 had operative revision of the anastomosis. Leak or pelvic abscess were present in 9 patients (7.3%); 4 were explored, 2 were drained and 3 were managed conservatively. 4 patients had permanent colostomy created due to anastomotic complications. Laparoscopy approach, BMI, age, smoking and tumor distance from anal verge were not significantly associated with anastomotic complications. After a multivariate analysis chemoradiation was significantly associated with overall anastomotic complications (Wall = 0.35, p = 0.05), and hemoglobin levels were associated with anastomotic leak (Wald = 4.09, p = 0.04). Conclusion Our study identifies preoperative anemia as possible risk factor for anastomotic leak and neoadjuvant chemoradiation may lead to increased risk of complications overall. Further prospective studies will help to elucidate these findings as well as identify amenable factors that may decrease risk of anastomotic complications after rectal cancer surgery. PMID:25685338

  7. [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.

  8. Radiation plus chemotherapy as adjuvant therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-04-01

    The most common neo-adjuvant therapy for rectal cancer is chemotherapy and concurrent radiation therapy. In general, it is delivered pre-operatively for patients with clinical evidence of T(3-4) disease or post-operatively in patients who have undergone surgery and have T(3) and/or N(1-2) disease. This chapter reviews the rationale and results for neo-adjuvant therapy, the selection process for pre-operative versus post-operative treatment, and new approaches and controversies.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. MRE11 and ATM Expression Levels Predict Rectal Cancer Survival and Their Association with Radiotherapy Response

    PubMed Central

    Revoltar, Maxine; Lim, Stephanie H.; Tut, Thein-Ga; Abubakar, Askar; Henderson, Chris J.; Chua, Wei; Ng, Weng; Lee, Mark; De Souza, Paul; Morgan, Matthew; Lee, C. Soon; Shin, Joo-Shik

    2016-01-01

    Background Aberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer. Methods MRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann–Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis. Results A high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (P = 0.035) and overall survival (OS) (P = 0.003) in the whole cohort, and with DFS (P = 0.028) and OS (P = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115–4.256, P = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222–3.899, P = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone. Conclusions The MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival. PMID:27930716

  14. Defining the distal margin of rectal cancer for surgical planning

    PubMed Central

    Kato, Takashi; Tanaka, Jun-Ichi

    2017-01-01

    Accurate measurement of the distal rectal tumor margin is essential in selecting the appropriate surgical procedure. However, there is no standard measurement method. The National Cancer Institute consensus group recommends use of the anal verge (AV) as a landmark, and the European Society of Gastrointestinal and Abdominal Radiology recommends use of the anorectal ring (ARR). In addition, whether measurements should be made on double contrast barium enema (BE) radiographs or magnetic resonance (MR) images remains controversial. We measured the distal tumor margin on both BE and MR images obtained preoperatively from 52 patients who underwent sphincter-saving resection for rectal cancer. The distances from the distal end of the tumor to the AV and the ARR were measured on both types of images, and the variability was investigated by Bland-Altman analysis. The mean distance from the tumor to the AV was 8.9 cm on the BE radiographs and 7.7 cm on the MR images (P=0.013). The mean distances to the ARR were 6.8 and 5.6 cm, respectively (P=0.070). Significant proportional bias was shown as the measured distances increased, the difference between the BE- and magnetic resonance imaging (MRI)-based measurements increased. Use of one or the other landmark did not affect selection of the appropriate surgical procedure. We conclude that an approximate 1-cm underestimation should be taken into account when MRI-based measurement of the distal rectal tumor margin is used to choose between sphincter-saving resection and abdominoperineal resection. PMID:28280625

  15. Robotic Surgery for Colon and Rectal Cancer.

    PubMed

    Park, Eun Jung; Baik, Seung Hyuk

    2016-01-01

    Robotic surgery, used generally for colorectal cancer, has the advantages of a three-dimensional surgical view, steadiness, and seven degrees of robotic arms. However, there are disadvantages, such as a decreased sense of touch, extra time needed to dock the robotic cart, and high cost. Robotic surgery is performed using various techniques, with or without laparoscopic surgery. Because the results of this approach are reported to be similar to or less favorable than those of laparoscopic surgery, the learning curve for robotic colorectal surgery remains controversial. However, according to short- and long-term oncologic outcomes, robotic colorectal surgery is feasible and safe compared with conventional surgery. Advanced technologies in robotic surgery have resulted in favorable intraoperative and perioperative clinical outcomes as well as functional outcomes. As the technical advances in robotic surgery improve surgical performance as well as outcomes, it increasingly is being regarded as a treatment option for colorectal surgery. However, a multicenter, randomized clinical trial is needed to validate this approach.

  16. [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.

  17. Laparoscopic-assisted one-stage resection of rectal cancer with synchronous liver metastasis utilizing a pfannenstiel incision.

    PubMed

    Aljiffry, Murad; Alrajraji, Mawaddah; Al-Sabah, Salman; Hassanain, Mazen

    2014-01-01

    Laparoscopic approaches have been increasingly used in selected patients with either colorectal or liver cancer. However, simultaneous resection of colorectal carcinoma with synchronous liver metastases is still a subject of debate. The present case describes combined laparoscopic rectal and liver resections for a patient with primary rectal cancer and a synchronous liver metastasis utilizing a Pfannenstiel incision for specimen extraction. The operative time was 370 min and estimated blood loss was 400 mL. Postoperatively, the patient required parenteral analgesia for 48 h, resumed normal diet on day 3 and was discharged on day 7 after the operation. A laparoscopic approach utilizing a Pfannenstiel extraction incision may present an advantageous and attractive option for simultaneous laparoscopic rectal and liver resection in selected patients with the aim of improving short-term outcomes.

  18. Presacral venous bleeding during mobilization in rectal cancer

    PubMed Central

    Casal Núñez, Jose Enrique; Vigorita, Vincenzo; Ruano Poblador, Alejandro; Gay Fernández, Ana María; Toscano Novella, Maria Ángeles; Cáceres Alvarado, Nieves; Pérez Dominguez, Lucinda

    2017-01-01

    AIM To analyze the anatomy of sacral venous plexus flow, the causes of injuries and the methods for controlling presacral hemorrhage during surgery for rectal cancer. METHODS A review of the databases MEDLINE® and Embase™ was conducted, and relevant scientific articles published between January 1960 and June 2016 were examined. The anatomy of the sacrum and its venous plexus, as well as the factors that influence bleeding, the causes of this complication, and its surgical management were defined. RESULTS This is a review of 58 published articles on presacral venous plexus injury during the mobilization of the rectum and on techniques used to treat presacral venous bleeding. Due to the lack of cases published in the literature, there is no consensus on which is the best technique to use if there is presacral bleeding during mobilization in surgery for rectal cancer. This review may provide a tool to help surgeons make decisions regarding how to resolve this serious complication. CONCLUSION A series of alternative treatments are described; however, a conventional systematic review in which optimal treatment is identified could not be performed because few cases were analyzed in most publications. PMID:28321171

  19. Locally advanced rectal cancer: time for precision therapeutics.

    PubMed

    Weiser, Martin R; Zhang, Zhen; Schrag, Deborah

    2015-01-01

    The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence.

  20. Current debate in the oncologic management of rectal cancer

    PubMed Central

    Millard, Trish; Kunk, Paul R; Ramsdale, Erika; Rahma, Osama E

    2016-01-01

    Despite the considerable amount of research in the field, the management of locally advanced rectal cancer remains a subject to debate. To date, effective treatment centers on surgical resection with the standard approach of total mesorectal resection. Radiation therapy and chemotherapy have been incorporated in order to decrease local and systemic recurrence. While it is accepted that a multimodality treatment regimen is indicated, there remains significant debate for how best to accomplish this in regards to order, dosing, and choice of agents. Preoperative radiation is the standard of care, yet remains debated with the option for chemoradiation, short course radiation, and even ongoing studies looking at the possibility of leaving radiation out altogether. Chemotherapy was traditionally incorporated in the adjuvant setting, but recent reports suggest the possibility of improved efficacy and tolerance when given upfront. In this review, the major studies in the management of locally advanced rectal cancer will be discussed. In addition, future directions will be considered such as the role of immunotherapy and ongoing trials looking at timing of chemotherapy, inclusion of radiation, and non-operative management. PMID:27795811

  1. 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

  2. Current debate in the oncologic management of rectal cancer.

    PubMed

    Millard, Trish; Kunk, Paul R; Ramsdale, Erika; Rahma, Osama E

    2016-10-15

    Despite the considerable amount of research in the field, the management of locally advanced rectal cancer remains a subject to debate. To date, effective treatment centers on surgical resection with the standard approach of total mesorectal resection. Radiation therapy and chemotherapy have been incorporated in order to decrease local and systemic recurrence. While it is accepted that a multimodality treatment regimen is indicated, there remains significant debate for how best to accomplish this in regards to order, dosing, and choice of agents. Preoperative radiation is the standard of care, yet remains debated with the option for chemoradiation, short course radiation, and even ongoing studies looking at the possibility of leaving radiation out altogether. Chemotherapy was traditionally incorporated in the adjuvant setting, but recent reports suggest the possibility of improved efficacy and tolerance when given upfront. In this review, the major studies in the management of locally advanced rectal cancer will be discussed. In addition, future directions will be considered such as the role of immunotherapy and ongoing trials looking at timing of chemotherapy, inclusion of radiation, and non-operative management.

  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. Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

    PubMed Central

    Mihmanlı, Mehmet; Kabul Gürbulak, Esin; Akgün, İsmail Ethem; Celayir, Mustafa Fevzi; Yazıcı, Pınar; Tunçel, Deniz; Bek, Tuba Tülin; Öz, Ayhan; Ömeroğlu, Sinan

    2016-01-01

    AIM To investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer. METHODS We evaluated 87 patients with locally advanced mid- or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at Şişli Hamidiye Etfal Training and Research Hospital, Istanbul between January 2009 and January 2014. Patients were divided into two groups according to the interval before surgery: < 8 wk (group I) and ≥ 8 wk (group II). Data related to patients, cancer characteristics and pathological examination were collected and analyzed. RESULTS When the distribution of timing between group I (n = 45) and group II (n = 42) was viewed, comparison of interval periods (median ± SD) of groups showed a significant difference of as 5 ± 1.28 wk in group I and 10.1 ± 2.2 wk in group II (P < 0.001). The median follow-up period for all patients was 34.5 (9.9-81) mo. group II had significantly higher rates of pathological complete response (pCR) than group I had (19% vs 8.9%, P = 0.002). Rate of tumor regression grade (TRG) poor response was 44.4% in group I and 9.5% in group II (P < 0.002). A poor pathological response was associated with worse disease-free survival (P = 0.009). The interval time did not show any association with local recurrence (P = 0.79). CONCLUSION Delaying the neoadjuvant CRT-surgery interval may provide nodal down-staging, improve pCR rate, and decrease the rate of TRG poor response. PMID:27672428

  6. Update and Debate Issues in Surgical Treatment of Middle and Low Rectal Cancer

    PubMed Central

    Kim, Min Sung; AL-Asari, Sami F.

    2012-01-01

    Based on a review of the literature, this paper provides an update on surgical treatment of middle and low rectal cancer and discusses issues of debate surrounding that treatment. The main goal of the surgical treatment of rectal cancer is radical resection of the tumor and surrounding lymphatic tissue. Local excision of early rectal cancer can be another treatment option, in which the patient can avoid possible complications related to radical surgery. Neoadjuvant chemoradiation therapy (CRT) has been recommended for patients with cT3-4N0 or any T N+ rectal cancer because CRT shows better local control and less toxicity than adjuvant CRT. However, recent clinical trials showed promising results for local excision after neoadjuvant CRT in selected patients with low rectal cancer. In addition, the "wait and see" concept is another modality that has been reported for the management of tumors that show complete clinical remission after neoadjuvant CRT. Although radical surgery for middle and low rectal cancer is the cornerstone therapy, an ultralow anterior resection with or without intersphincteric resection (ISR) has become an alternative standard surgical method for selected patients. Many studies have reported on the oncological safety of the ISR, but few of them have addressed the issue the functional outcome. Furthermore, an abdominoperineal resection (APR) has problems with high rates of tumor perforations and positive circumferential resection margins, and those factors have contributed to its having a high rate of local recurrence and a poor survival rate for rectal cancer compared with sphincter-saving procedures. Recently, great efforts have been made to reduce these problems, and the total levator excision or the extended APR concept has emerged. Surgical management for low rectal cancer should aim to radically excise the tumor and to preserve as much of the sphincter function as possible by using multidisciplinary approaches. However, further prospective

  7. Have the changes in treatment of rectal cancer made a significant difference to our patients?

    PubMed

    Benson, Al B; Guillem, José G; Minsky, Bruce D

    2011-12-01

    The treatment for patients with locally advanced, resectable rectal cancer has evolved over the years. Various combinations and sequences of chemotherapy, radiation therapy, and total mesorectal excision (TME)-based surgery are the mainstay of current therapy. Preoperative combined chemoradiation, followed by surgery, is now the preferred treatment strategy, with the majority of patients receiving either infusion fluorouracil (5-FU) or capecitabine (Xeloda) with radiation. Clinical trials with oxaliplatin (Eloxatin)-based neoadjuvant chemoradiation have not shown improvement in the pathologic complete response rate (pCR) compared with 5-FU; however, final data addressing local recurrence rates and disease-free survival are pending.The use of adjuvant chemotherapy following preoperative chemoradiation and surgery has not been optimally defined. Some studies have shown that patients who obtained significant pathologic downstaging after chemoradiation and surgery have improved survival with the use of adjuvant chemotherapy. Since FOLFOX (folinic acid, 5-FU, and oxaliplatin) is the preferred adjuvant chemotherapy regimen for stage III colon cancer based on randomized clinical trial results, FOLFOX is also recommended for rectal cancer patients as an adjuvant therapy approach.

  8. Prognostic significance of survivin in rectal cancer patients treated with surgery and postoperative concurrent chemo-radiation therapy

    PubMed Central

    Il Yu, Jeong; Lee, Hyebin; Park, Hee Chul; Choi, Doo Ho; Choi, Yoon-La; Do, In-Gu; Kim, Hee Cheol; Lee, Woo Yong; Yun, Seong Hyeon; Cho, Yong Beom; Huh, Jung Wook; Park, Yoon Ah; Park, Young Suk; Park, Joon Oh; Kim, Seung Tae; Park, Won

    2016-01-01

    Background & Aims This study is designed to investigate the expression of survivin and p53 in human rectal cancer tissues and analyze associations between expression and clinical outcomes in terms of disease recurrence and survival duration. Results During follow-up (median 119.0, range 6.6 to 161.3 months), tumor recurrence was detected in 50 patients (43.1%), and local recurrence developed as a first failure site in 13 patients (11.2%). Positive immunostaining of nuclear and cytoplasmic survivin was observed in about one quarter of patients, and about half of all patients had positive staining for p53. Both survivin and p53 were significant prognostic factors of disease-free survival in the univariate analyses, but only survivin remained a significant prognostic factor in the multivariate analysis. Methods We performed a retrospective study with 116 locally advanced rectal cancer patients who underwent total mesorectal excision (TME) followed by postoperative concurrent chemo-radiation therapy (CCRT). Immunohistochemical staining was conducted using antibodies for survivin or p53, and their expression was analyzed using an individual score that combined the percentage of positive cells and staining intensity. Conclusions Overexpression of nuclear and cytoplasmic survivin in locally advanced rectal cancer patients was associated with a higher recurrence rate in rectal cancer patients treated with TME followed by postoperative CCRT. PMID:27391438

  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. Chemoradiation for rectal cancer: rationale, approaches, and controversies.

    PubMed

    Minsky, Bruce D

    2010-10-01

    The standard adjuvant treatment of cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These controversies include the role of short course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation, as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.

  11. 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

  12. Restaging locally advanced rectal cancer by different imaging modalities after preoperative chemoradiation: a comparative study

    PubMed Central

    2013-01-01

    Background To compare the accuracy of different imaging modalities, alone and in combination in predicting findings at surgery after preoperative chemoradiation for locally advanced rectal cancer. Methods Following chemoradiation, tumors were reclassified on the basis of findings on pelvic computed tomography (CT) (94 patients), endorectal ultrasonography (EUS) (138 patients) alone or by both CT and EUS (80 patients). The ability of the imaging modalities, to predict the pathologic T status, N status, and TNM stage at surgery was evaluated and compared. Results Mean age of the patients was 64.5 years (range 28–88 years); 55% were male. CT and EUS combined had a positive predictive value of 20% for pathologic pT1 stage, 29% for pT1, 29% for pT2, and 58% for pT3. Predictive values for the operative TNM stage were 50% for stage I, 45% for stage II, and 31% for stage III. These values did not exceed those for each modality alone. Conclusion The performance of preoperative CT and EUS in predicting the T and TNM stage of rectal cancer at surgery is poor. Neither modality alone nor the two combined is sufficiently accurate to serve as the basis for decisions regarding treatment modification. PMID:24286200

  13. Preoperative Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Musio, Daniela; Izzo, Luciano; Pugliese, Federico; Izzo, Paolo; Bolognese, Antonio

    2013-01-01

    Purpose. To evaluate the treatment tolerance and clinical outcomes in patients aged 70 and older with locally advanced rectal carcinoma treated with multimodality approach. Methods and Materials. We retrospectively analysed 20 consecutive elderly patients, with histologically proven rectal adenocarcinoma, staged T3-4, and/or node-positive tumour, who received chemoradiotherapy and proceeded to surgical approach. Performance status score and adult comorbidity evaluation-27 score were calculated, and their influence on treatment tolerance and clinical outcomes was analysed. Results. All patients completed programmed chemoradiotherapy treatment. Gastrointestinal toxicity was the most common acute side effects: proctitis in 70% of patients and diarrhoea in 55%, classified as Grade 3 in 3 patients only. Radiation dermatitis was reported in 7 patients (35%) and it was graded G3 in one patient. There was no haematological toxicity. Eighteen patients out of 20 underwent surgery. Sphincter preservation was assured in 13 patients. Comorbidity index was related to higher severe acute toxicity (P = 0.015) but no influenced treatment outcomes. Conclusion. Treatment tolerance with combined modality is good in elderly patients. Due to age, no dose reduction for radiation therapy and chemotherapy should be considered. PMID:24392453

  14. 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

  15. 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

  16. Clinical value of MRI-detected extramural venous invasion in rectal cancer.

    PubMed

    Tripathi, Pratik; Rao, Sheng Xiang; Zeng, Meng Su

    2017-01-01

    Extramural venous invasion (EMVI) is associated with a poor prognosis and a poor overall survival rate in rectal cancer. It can independently predict local and distant tumor recurrences. Preoperative EMVI detection in rectal cancer is useful for determining the treatment strategy. EMVI status is beneficial for the post-treatment evaluation and analysis of rectal cancer. Magnetic resonance imaging (MRI) is a non-invasive diagnostic modality with no radiation effects. High-resolution MRI can detect EMVI with high accuracy. In addition, MRI results are equal to or even better than pathological results in the detection of medium to large EMVI in rectal cancer. MRI-detected EMVI (mrEMVI) can be used as a potential biomarker that facilitates treatment methods. This review highlights the importance of MRI before and after rectal cancer treatment. In addition, we analyze the prognostic correlation between mrEMVI and circulating tumor cells (CTC) in rectal cancer. This article may help shed light on the significance of mrEMVI.

  17. A case of metastatic carcinoma of anal fistula caused by implantation from rectal cancer.

    PubMed

    Takahashi, Rina; Ichikawa, Ryosuke; Ito, Singo; Mizukoshi, Kosuke; Ishiyama, Shun; Sgimoto, Kiichi; Kojima, Yutaka; Goto, Michitoshi; Tomiki, Yuichi; Yao, Takashi; Sakamoto, Kazuhiro

    2015-12-01

    This case involved an 80-year-old man who was seen for melena. Further testing revealed a tubular adenocarcinoma 50 mm in size in the rectum. In addition, an anal fistula was noted behind the anus along with induration. A biopsy of tissue from the external (secondary) opening of the fistula also revealed adenocarcinoma. Nodules suspected of being metastases were noted in both lung fields. The patient was diagnosed with rectal cancer, a cancer arising from an anal fistula, and a metastatic pulmonary tumor, and neoadjuvant chemotherapy was begun. A laparoscopic abdominoperineal resection was performed 34 days after 6 cycles of mFOLFOX-6 therapy. Based on pathology, the rectal cancer was diagnosed as moderately differentiated adenocarcinoma, and this adenocarcinoma had lymph node metastasis (yp T3N2aM1b). There was no communication between the rectal lesion and the anal fistula, and a moderately differentiated tubular adenocarcinoma resembling the rectal lesion was noted in the anal fistula. Immunohistochemical staining indicated that both the rectal lesion and anal fistula were cytokeratin 7 (CK7) (-) and cytokeratin 20 (CK20) (+), and the patient's condition was diagnosed as implantation of rectal cancer in an anal fistula.In instances where an anal fistula develops in colon cancer, cancer implantation in that fistula must also be taken into account, and further testing should be performed prior to surgery.

  18. Differences in carcinoembryonic antigen levels between colon and rectal cancer.

    PubMed

    Ding, Yunlong; Xuan, Weibo; Chen, Chunlin; Chen, Zhe; Yang, Ziyi; Zuo, Yunfei; Ren, Shuangyi

    2014-07-01

    The aim of the present study was to investigate the levels of the serum tumor biomarker carcinoembryonic antigen (CEA) in patients with carcinoma of the colon and rectum in different clinical stages. Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer worldwide and previous studies have reported rapidly updated therapeutic regimes. While the majority of studies focus on CRC as a single entity, certain studies distinguish colon cancer (CC) from rectal cancer (RC), as there is a hypothesis stating that CC and RC are two naturally different entities. CEA is reported to be an important tumor-associated antigen overexpressed in CRC, which is routinely detected as a significant indicator of CRC. Our study aimed to identify potential differences in the expression of CEA between CC and RC, which may, to some degree, reflect the natural differences between the two. We investigated 240 CRC cases between July, 2010 and December, 2012 from The First and Second Affiliated Hospitals of Dalian Medical University, including 117 CC and 123 RC patients with tumors classified by Duke's staging as A-D. The serum CEA level was measured preoperatively by radioimmunoassays as a routinely used auxiliary indicator. The expression of CEA differed between CC and RC, with the former exhibiting variation among the four stages, whereas no variation was observed in RC. In addition, there were differences between CC and RC regarding the CEA level in stage C and D. Furthermore, the CEA level in stage C of CC was significantly lower compared to that in any other stage. In conclusion, the intrinsic distribution of the CEA level between CC and RC suggests that CC and RC may be two naturally different entities; the significantly low CEA level in stage C of CC indicates that stage C may be crucial in the evolution of CC.

  19. Variation in the CYP19A1 gene and risk of colon and rectal cancer.

    PubMed

    Slattery, Martha L; Lundgreen, Abbie; Herrick, Jennifer S; Kadlubar, Susan; Caan, Bette J; Potter, John D; Wolff, Roger K

    2011-07-01

    CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case-control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16-1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50-0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26-2.37). We observed statistically significant interactions between genetic variation in NFκB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism.

  20. Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice.

    PubMed

    Netter, Jeanne; Douard, Richard; Durdux, Catherine; Landi, Bruno; Berger, Anne; Taieb, Julien

    2016-11-01

    More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the 'gold standard' for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer remain justified in future to achieve a high level of proof in keeping with evidence-based medical standards.

  1. Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer

    SciTech Connect

    Baeten, Coen . E-mail: C.Baeten@surgery.azm.nl; Castermans, Karolien; Lammering, Guido; Hillen, Femke; Wouters, Bradly G.; Hillen, Harry; Griffioen, Arjan W.; Baeten, Cornelius G.M.I.

    2006-11-15

    Background: We and others have shown that angiogenesis and leukocyte infiltration are important prognostic factors in rectal cancer. However, little is known about its possible changes in response to radiotherapy (RTX), which is frequently given to rectal tumors as a neoadjuvant treatment to improve the prognosis. We therefore investigated the biologic effects of RTX on these parameters using fresh-frozen biopsy samples of tumor and normal mucosa tissue before and after RTX. Methods: Biopsy samples were taken from a total of 34 patients before and after either a short course or long course of RTX combined with chemotherapy. The following parameters were analyzed by immunohistochemistry, flow cytometry, or quantitative real-time polymerase chain reaction: Microvessel density, leukocyte infiltration, proliferating epithelial and tumor cells, proliferating endothelial cells, adhesion molecule expression on endothelial cells, and the angiogenic mRNA profile. Results: The tumor biopsy samples taken after RTX treatment demonstrated a significant decrease in microvessel density and the number of proliferating tumor cells and proliferating endothelial cells (p < 0.001). In contrast, the leukocyte infiltration, the levels of basic fibroblast growth factor in carcinoma tissue, and the adhesion molecule expression on endothelial cells in normal as well as carcinoma tissue increased significantly (p < 0.05). Conclusion: Our data show that together with an overall decrease in tumor cell and endothelial cell proliferation, RTX results in an increase in the expression of adhesion molecules that stimulate leukocyte infiltration. This suggests the possibility that, in addition to its direct cytotoxic effect, radiation may also stimulate an immunologic tumor response that could contribute to the documented improvement in local tumor control and distal failure rate of rectal cancers.

  2. 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

  3. New perspectives in treatment decision for integrated management of rectal cancer: multimodal research for multimodal treatments

    PubMed Central

    VALENTINI, V.; CELLINI, F.

    2014-01-01

    Rectal cancer management improved results in the last thirty-five applying new integrated treatment options. Preoperative radiochemotherapy or radiotherapy alone joined to the modern surgery gaining significant improvement of outcomes. Nevertheless, a definitive conclusion about superiority of one on the other in term of survival and toxicity is still lacking, and further improvement is in general required and seems obtainable. The need for a wide sharing of the accumulated knowledge is represented by the consensus conferences that over the years summarizes the state of the art for the management of rectal cancer. One of the most promising opportunities comes from the attempt of characterization of the tumor heterogeneity. An always-increasing number of new parameters come from different sources including genomic, imaging, pathological features and many others. The need of new informatics technologies able to handle and continuously incorporate new inputs derived from the evidences is also imperative. The combined use of large shared databases and “learning models” could allow generating and rapidly testing new hypotheses, providing further survival improvement in the next years. PMID:24979100

  4. Does gadolinium-based contrast material improve diagnostic accuracy of local invasion in rectal cancer MRI? A multireader study.

    PubMed

    Gollub, Marc J; Lakhman, Yulia; McGinty, Katrina; Weiser, Martin R; Sohn, Michael; Zheng, Junting; Shia, Jinru

    2015-02-01

    OBJECTIVE. The purpose of this study was to compare reader accuracy and agreement on rectal MRI with and without gadolinium administration in the detection of T4 rectal cancer. MATERIALS AND METHODS. In this study, two radiologists and one fellow independently interpreted all posttreatment MRI studies for patients with locally advanced or recurrent rectal cancer using unenhanced images alone or combined with contrast-enhanced images, with a minimum interval of 4 weeks. Readers evaluated involvement of surrounding structures on a 5-point scale and were blinded to pathology and disease stage. Sensitivity, specificity, negative predictive value, positive predictive value, and AUC were calculated and kappa statistics were used to describe interreader agreement. RESULTS. Seventy-two patients (38 men and 34 women) with a mean age of 61 years (range, 32-86 years) were evaluated. Fifteen patients had 32 organs invaded. Global AUCs without and with gadolinium administration were 0.79 and 0.77, 0.91 and 0.86, and 0.83 and 0.78 for readers 1, 2, and 3, respectively. AUCs before and after gadolinium administration were similar. Kappa values before and after gadolinium administration for pairs of readers ranged from 0.5 to 0.7. CONCLUSION. On the basis of pathology as a reference standard, the use of gadolinium during rectal MRI did not significantly improve radiologists' agreement or ability to detect T4 disease.

  5. 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

  6. 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.

  7. Optimal follow-up to curative colon and rectal cancer surgery: how and for how long?

    PubMed

    Asgeirsson, Theodor; Zhang, Sen; Senagore, Anthony J

    2010-10-01

    In 2009, the projected incidence for colon and rectal cancers in the United States was 106,100 and 40,870, respectively, and approximately 75% of these patients were treated with curative intent. Surveillance or follow-up after colon and rectal cancer resection serves multiple purposes; however, the primary argument supporting the validity of surveillance is the detection of metachronous and recurrent cancers amenable to curative treatment. The surveillance may provide some comfort for cancer survivors who can be informed that they have no evidence of disease.

  8. Nitrates in drinking water and risk of death from rectal cancer in Taiwan.

    PubMed

    Kuo, Hsin-Wei; Wu, Trong-Neng; Yang, Chun-Yuh

    2007-10-01

    The relationship between nitrate levels in drinking water and rectal cancer development has been inconclusive. A matched case-control and nitrate ecology study was used to investigate the association between mortality attributed to rectal cancer and drinking-water nitrate exposure in Taiwan. All deaths due to rectal cancer of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for rectal cancer death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.22 (0.98-1.52) and 1.36 (1.08-1.70), respectively. The findings of this study warrant further investigation of the role of nitrates in drinking water in the etiology of rectal cancer in Taiwan.

  9. Age and cellular context influence rectal prolapse formation in mice with caecal wall colorectal cancer xenografts

    PubMed Central

    Tommelein, Joke; Gremonprez, Félix; Verset, Laurine; De Vlieghere, Elly; Wagemans, Glenn; Gespach, Christian; Boterberg, Tom; Demetter, Pieter; Ceelen, Wim; Bracke, Marc; De Wever, Olivier

    2016-01-01

    In patients with rectal prolapse is the prevalence of colorectal cancer increased, suggesting that a colorectal tumor may induce rectal prolapse. Establishment of tumor xenografts in immunodeficient mice after orthotopic inoculations of human colorectal cancer cells into the caecal wall is a widely used approach for the study of human colorectal cancer progression and preclinical evaluation of therapeutics. Remarkably, 70% of young mice carrying a COLO320DM caecal tumor showed symptoms of intussusception of the large bowel associated with intestinal lumen obstruction and rectal prolapse. The quantity of the COLO320DM bioluminescent signal of the first three weeks post-inoculation predicts prolapse in young mice. Rectal prolapse was not observed in adult mice carrying a COLO320DM caecal tumor or young mice carrying a HT29 caecal tumor. In contrast to HT29 tumors, which showed local invasion and metastasis, COLO320DM tumors demonstrated a non-invasive tumor with pushing borders without presence of metastasis. In conclusion, rectal prolapse can be linked to a non-invasive, space-occupying COLO320DM tumor in the gastrointestinal tract of young immunodeficient mice. These data reveal a model that can clarify the association of patients showing rectal prolapse with colorectal cancer. PMID:27689329

  10. 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

  11. The functional outcomes of coloanal and low colorectal anastomoses with reservoirs after low rectal cancer resections.

    PubMed

    Rubin, François; Douard, Richard; Wind, Philippe

    2014-12-01

    Nearly half of patients undergoing low anterior rectal cancer resection have a functional sequelae after straight coloanal or low colorectal anastomoses (SA), including low anterior rectal resection syndrome, which combines stool fragmentation, urge incontinence, and incontinence. SA are responsible for anastomotic leakage rates of 0 to 29.2 per cent. Adding a colonic reservoir improves the functional results while reducing anastomotic complications. These colonic reservoir techniques include the colonic J pouch (CJP), transverse coloplasty (TC), and side-to-end anastomosis (STEA) procedures. The aim of this literature review was to compare the functional outcomes of these three techniques from a high level of evidence. CJP with a 4- to 6-cm reservoir is a good surgical option because it reduces functional impairments during the first year, and probably up to 5 years, but is not always feasible. TC appears to perform as well as CJP, is achievable in over 95 per cent of patients, but still with some doubts about a higher anastomotic leakage rate and worse functional outcomes. STEA appears equivalent to CJP in terms of morbidity and even better functional outcomes. STEA, with a terminal side segment size of 3 cm, is feasible in the majority of nonobese patients, combines good functional results, has low anastomotic leakage rates, and is easy to complete.

  12. [Combination chemotherapy composed of mFOLFOX 6, FOLFIRI 2 and surgery and radiation therapy for locoregional recurrences and multiple lung metastases from rectal cancer--a case report].

    PubMed

    Kubo, Hidefumi; Kitahara, Masahiro; Kanekiyo, Shinsuke; Tada, Kosuke; Katayama, Setsu

    2008-07-01

    A 61-year-old man underwent amputation of the rectum for advanced lower rectal cancer in April 2005. UFT-E granules were administered orally daily at 400 mg/body/day following surgery. He developed perineal pain and perineal discharges following an increase the CEA level in April 2006. PET revealed a tumor in the perineum and multiple lung metastases. Chemotherapy with mFOLFOX 6 for 8 courses and FOLFIRI 2 for 4 courses were administered since July in 2006. Although CT revealed a the reduction in multiple lung metastases, CEA was increased to over a maximum 109, high fever continued and the pinealtumor was enlarged in December 2006. The patient underwent resection of the perinealmass, but he developed perinealsevere pain and perinealdischarge. So radiotherapy of the pelvic region was given at a total dose of 40 Gy(given 2 Gy each fragment)followed by administration of FOLFIRI 2 for 12 courses. After chemoradiotherapy, the CEA level was remarkably decreased. PET could not detect any mass in lung fields and revealed a little accumulation in the pelvic region. Chemotherapy with FOLFIRI 2 is administered monthly now, and the CEA level has been within the normal range since July of 2007. The pineal pain and pineal discharge disappeared, so the quality of life has improved dramatically.

  13. 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.

  14. Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer

    PubMed Central

    Zhang, Jinning; Zhou, Yuhui; Dang, Shuwei; Chen, Hongsheng; Wu, Qiong; Liu, Ming

    2016-01-01

    DNA methylation was regarded as the promising biomarker for rectal cancer diagnosis. However, the optimal methylation biomarkers with ideal diagnostic performance for rectal cancer are still limited. To identify new molecular markers for rectal cancer, we mapped DNA methylation and transcriptomic profiles in the six rectal cancer and paired normal samples. Further analysis revealed the hypermethylated probes in cancer prone to be located in gene promoter. Meanwhile, transcriptome analysis presented 773 low-expressed and 1,161 over-expressed genes in rectal cancer. Correction analysis identified a panel of 36 genes with an inverse correlation between methylation and gene expression levels, including 10 known colorectal cancer related genes. From the other 26 novel marker genes, GFRA1 and GSTM2 were selected for further analysis on the basis of their biological functions. Further experiment analysis confirmed their methylation and expression status in a larger number (44) of rectal cancer samples, and ROC curves showed higher AUC than SEPT9, which has been used as a biomarker in rectal cancer. Our data suggests that aberrant DNA methylation of contiguous CpG sites in methylation array may be potential diagnostic markers of rectal cancer. PMID:27566576

  15. Discrimination of rectal cancer through human serum using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Yang, Tianyue; Li, Siqi; Zhang, Su; Jin, Lili

    2015-05-01

    In this paper, surface-enhanced Raman spectroscopy (SERS) was used to detect the changes in blood serum components that accompany rectal cancer. The differences in serum SERS data between rectal cancer patients and healthy controls were examined. Postoperative rectal cancer patients also participated in the comparison to monitor the effects of cancer treatments. The results show that there are significant variations at certain wavenumbers which indicates alteration of corresponding biological substances. Principal component analysis (PCA) and parameters of intensity ratios were used on the original SERS spectra for the extraction of featured variables. These featured variables then underwent linear discriminant analysis (LDA) and classification and regression tree (CART) for the discrimination analysis. Accuracies of 93.5 and 92.4 % were obtained for PCA-LDA and parameter-CART, respectively.

  16. Rectal Cancer With Disseminated Carcinomatosis of the Bone Marrow: Report of a Case

    PubMed Central

    Nakashima, Yuichiro; Takeishi, Kazuki; Guntani, Atsushi; Tsujita, Eiji; Yoshinaga, Keiji; Matsuyama, Ayumi; Hamatake, Motoharu; Maeda, Takashi; Tsutsui, Shinichi; Matsuda, Hiroyuki; Fujihara, Megumu; Ishida, Teruyoshi

    2014-01-01

    We report a rare case of disseminated carcinomatosis of the bone marrow from rectal cancer with disseminated intravascular coagulation (DIC). A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. Histologic examination showed disseminated carcinomatosis of the bone marrow. The DIC was considered to be caused by disseminated carcinomatosis of the bone marrow from rectal cancer, and we immediately started treatment with anti-DIC therapy and anticancer chemotherapy with the modified FOLFOX6 regimen (mFOLFOX6). After some response to therapy, the patient's general condition deteriorated, and he died 128 days after admission. This is the first English report showing disseminated carcinomatosis of the bone marrow from colorectal cancer treated with mFOLFOX6. PMID:25216414

  17. Extralevator abdominoperineal excision versus conventional surgery for low rectal cancer: a single surgeon experience

    PubMed Central

    Neşşar, Gürel; Demirbağ, Ali Eba; Celep, Bahadır; Elbir, Orhan Hayri; Kayaalp, Cüneyt

    2016-01-01

    Objective Extralevator abdominoperineal excision (ELAPE) reduces the risk of positive circumferential resection margin (CRM) and of intraoperative perforation (IOP), both of which are associated with high local recurrence rates and poor survival outcomes for rectal cancer. The aim of this study was to compare the results of ELAPE with conventional abdominoperineal excision (APE) for low rectal cancer. Material and Methods A total of 25 consecutive patients underwent ELAPE for low rectal cancer between November 2008 and September 2011. Fifty-six patients treated by conventional APE prior to 2008 were selected from our rectal cancer database for comparison as a historical cohort. Results The mean follow-up was 44.7 months in the ELAPE group, and 70.6 months in the APE group. Patients undergoing ELAPE had a lower CRM positivity and IOP rate than APE (12% vs. 20%, p=0,531; 4% vs. 8,9%, p=0,826; respectively). The ELAPE group was associated with higher perineal wound complications than the APE group (16.0% vs. 1.8%, p=0.030). Local recurrence rates for patients in both groups did not differ significantly (4.0% vs. 3.6%, p=1.0). Conclusion The results of this study suggest that ELAPE technique was associated with less CRM involvement and reduced rates of IOP but markedly higher rates of postoperative perineal complications occurred as compared to conventional surgery. ELAPE must be reserved for advanced low rectal cancers. PMID:28149119

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

    PubMed

    Akiyoshi, Takashi

    2016-01-14

    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.

  19. 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

    2014-06-06

    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.

  20. The development of metachronous prostate cancer and chronic myeloid leukemia in a patient with metastatic rectal cancer.

    PubMed

    Oztop, I; Yaren, A; Demirpence, M; Alacacioglu, I; Tuna, B; Piskin, O; Yilmaz, U

    2008-01-01

    We report herein an unusual case of metachronous triple cancers (rectum, prostate and Philadelphia(+) [Ph(+)] chronic myeloid leukemia [CML]). A metastatic rectal cancer was diagnosed in a 76-year-old male patient, who was treated with transanal tumor resection and chemotherapy. Thirty months from the initial rectal cancer diagnosis, prostate cancer was diagnosed and the patient was administered maximal androgen blockade and received palliative radiotherapy to the lumbar spine because of painful bone metastases. Thirty months after the diagnosis of rectal cancer and 12 months after the diagnosis of prostate cancer the patient developed Ph(+) CML and imatinib treatment was started. After one-year period in remission, CML evolved into accelerated phase and the patient died of intracranial hemorrhage.

  1. A rare presentation of breast cancer: near obstructing rectal mass and gastric outlet obstruction

    PubMed Central

    Martin, Rachel; Mathews, Winn; Scarcliff, Steven

    2016-01-01

    Breast cancer metastasizes to the gastrointestinal (GI) tract are exceedingly rare. The low incidence and vague presentation of GI metastasizes often cause delay in diagnosis and treatment. Here, we present a case of metastatic breast cancer causing gastric outlet obstruction and rectal obstruction. PMID:27672104

  2. 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

  3. ACR Appropriateness Criteria®—Recurrent Rectal Cancer

    PubMed Central

    Suh, W. Warren; Herman, Joseph M.; Blackstock, A. William; Hong, Theodore S.; Poggi, Matthew M.; Rodriguez-Bigas, Miguel; Small, William; Thomas, Charles R.; Zook, Jennifer

    2012-01-01

    ABSTRACT The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions. These Criteria are reviewed every 2 years by a multidisciplinary expert panel. The development and review of these guidelines includes 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. Local recurrence of rectal cancer can result in devastating symptoms for patients, including intractable pain and discharge. Prior treatment can limit subsequent treatment options. Preoperative 5-FU based chemoradiotherapy is the treatment of choice for patients with a local recurrence who did not receive adjuvant therapy after initial resection or who might have received chemotherapy alone. Chemoradiotherapy followed by evaluation for surgery is the preferred treatment for patients who have undergone previous radiotherapy after surgery. The inclusion of surgery has resulted in the best outcomes in a majority of studies. Palliative chemoradiotherapy is appropriate for patients who have received previous radiotherapy whose recurrent disease is considered inoperable. Radiotherapy can be delivered on a standard or hyperfractionated treatment schedule. Newer systemic treatments have improved response rates and given physicians more options for treating patients in this difficult situation. The use of induction chemotherapy prior to radiotherapy is an evolving treatment option. Specialized treatment modalities should be used at institutions with experience in these techniques and preferably in patients enrolled in clinical trials. PMID:22574231

  4. 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.

  5. Rectal bleeding after radiation therapy for endometrial cancer

    PubMed Central

    Mitra, Devarati; Nout, Remi; Catalano, Paul J.; Creutzberg, Carien; Cimbak, Nicole; Lee, Larissa; Viswanathan, Akila

    2015-01-01

    Background & Purpose The goals of this study were to determine the rate and risk factors of rectal bleeding (RB) after external beam radiotherapy and vaginal brachytherapy (EBRT+VB), and to compare this data to previously unreported RB rates from PORTEC-2 patients receiving EBRT or VB alone. Materials & Methods Retrospective chart review identified 212 endometrial cancer patients receiving adjuvant EBRT+VB between 2006–2013. Patient-reported RB data were also obtained from PORTEC-2 patients randomized to EBRT (n=166) or VB (n=182). The two populations were compared using an RB Scale of symptom severity. Results After a median 35 months, 17.9% of EBRT+VB patients (n=38) experienced any RB with 1.9% (n=4) having bleeding requiring intervention. Age ≤70 years was the only predictor of RB (OR 2.8; 95% CI 1.1–8.7; p=0.027). Rates of patient-reported RB after EBRT were similar with 15.0% (n=25) having any RB and 0.6% (n=1) having “very much” bleeding. On regression analysis, any EBRT (either EBRT alone or EBRT+VB) increased the risk of RB compared to those who received VB alone (OR 3.0; p=0.0028; 95% CI 1.4–6.7). The rates of more severe RB were low and did not significantly differ between treatments. Conclusions Significant RB is rare after radiation. The addition of VB to EBRT does not significantly alter bleeding rates. PMID:26003340

  6. Low thrombospondin 2 expression is predictive of low tumor regression after neoadjuvant chemoradiotherapy in rectal cancer

    PubMed Central

    Lin, Cheng-Yi; Lin, Ching-Yih; Chang, I-Wei; Sheu, Ming-Jen; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Lee, Ying-En; He, Hong-Lin

    2015-01-01

    Background: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin-binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. Methods: The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancer patients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. Results: Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). Conclusion: Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer. PMID:26807188

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

    PubMed

    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.

  8. 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

  9. Cyclin D1 Gene G870A Polymorphism Predicts Response to Neoadjuvant Radiotherapy and Prognosis in Rectal Cancer

    SciTech Connect

    Ho-Pun-Cheung, Alexandre; Assenat, Eric; Thezenas, Simon; Bibeau, Frederic; Rouanet, Philippe; Azria, David; Cellier, Dominic; Grenier, Jean; Ychou, Marc; Senesse, Pierre; Lopez-Crapez, Evelyne . E-mail: ecrapez@valdorel.fnclcc.fr

    2007-07-15

    Purpose: To investigate whether CCND1 genetic variations associated with a constitutive nuclear protein may influence either the pathologic response to preoperative RT or the prognosis in a series of rectal cancer patients. Methods and Materials: Seventy rectal cancer patients treated by neoadjuvant radiotherapy were included in the study. CCND1 exon 5 mutations were screened, and the G870A polymorphism was assessed for correlation with clinical variables, tumor response, and patient outcome. Results: No exon 5 mutation was found. Concerning the G870A polymorphism, the A/A variant was significantly associated with radiosensitivity (p = 0.022). Moreover, patients harboring the A allele were correlated with a lower risk of local failure (p = 0.017). Also, combination of the G870A polymorphism with the post-therapeutic lymph node status allowed the elaboration of a prognostic index, which accurately distinguished subgroups of patients with predictable recurrence-free (p = 0.003) and overall (p = 0.044) survival. Conclusions: Although CCND1 exon 5 mutations are rare in rectal cancer, G870A polymorphism is a frequent variation that may predict radiosensitivity and prognosis.

  10. 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.

  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. EURECCA consensus conference highlights about colon & rectal cancer multidisciplinary management: the radiology experts review.

    PubMed

    Tudyka, V; Blomqvist, L; Beets-Tan, R G H; Boelens, P G; Valentini, V; van de Velde, C J; Dieguez, A; Brown, G

    2014-04-01

    Some interesting shifts have taken place in the diagnostic approach for detection of colorectal lesions over the past decade. This article accompanies the recent EURECCA consensus group reccomendations for optimal management of colon and rectal cancers. In summary, imaging has a crucial role to play in the diagnosis, staging assessment and follow up of patients with colon and rectal cancer. Recent advances include the use of CT colonography instead of Barium Enema in the diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern mutlidetector CT scanning techniques have also shown improvements in prognostic stratification of patients with colonic cancer and clinical trials are underway testing the selective use of neoadjuvant therapy for imaging identified high risk colon cancers. In rectal cancer, high resolution MRI with a voxel size less or equal to 3 × 1 × 1 mm3 on T2-weighted images has a proven ability to accurately stage patients with rectal cancer. Moreover, preoperative identification of prognostic features allows stratification of patients into different prognostic groups based on assessment of depth of extramural spread, relationship of the tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI). These poor prognostic features predict an increased risk of local recurrence and/or metastatic disease and should form the basis for preoperative local staging and multidisciplinary preoperative discussion of patient treatment options.

  13. Associations between red meat and risks for colon and rectal cancer depend on the type of red meat consumed.

    PubMed

    Egeberg, Rikke; Olsen, Anja; Christensen, Jane; Halkjær, Jytte; Jakobsen, Marianne Uhre; Overvad, Kim; Tjønneland, Anne

    2013-04-01

    Cancer prevention guidelines recommend limiting intake of red meat and avoiding processed meat; however, few studies have been conducted on the effects of specific red meat subtypes on colon cancer or rectal cancer risk. The study aim was to evaluate associations between intake of red meat and its subtypes, processed meat, fish, and poultry and risk for colon cancer or rectal cancer in the Danish Diet, Cancer and Health cohort study. We also evaluated whether fish or poultry should replace red meat intake to prevent colon cancer or rectal cancer. During follow-up (13.4 y), 644 cases of colon cancer and 345 cases of rectal cancer occurred among 53,988 participants. Cox proportional hazards models were used to compute incidence rate ratio (IRRs) and 95% CIs. No associations were found between intake of red meat, processed meat, fish, or poultry and risk for colon cancer or rectal cancer. The risk associated with specific red meat subtypes depended on the animal of origin and cancer subsite; thus, the risk for colon cancer was significantly elevated for higher intake of lamb [IRR(per 5g/d) = 1.07 (95% CI: 1.02-1.13)], whereas the risk for rectal cancer was elevated for higher intake of pork [IRR(per 25g/d) = 1.18 (95% CI: 1.02-1.36)]. Substitution of fish for red meat was associated with a significantly lower risk for colon cancer [IRR(per 25g/d) = 0.89 (95% CI: 0.80-0.99)] but not rectal cancer. Substitution of poultry for red meat did not reduce either risk. This study suggests that the risks for colon cancer and potentially for rectal cancer differ according to the specific red meat subtype consumed.

  14. 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.

  15. Critical analysis of the literature investigating urogenital function preservation following robotic rectal cancer surgery

    PubMed Central

    Panteleimonitis, Sofoklis; Ahmed, Jamil; Harper, Mick; Parvaiz, Amjad

    2016-01-01

    AIM To analyses the current literature regarding the urogenital functional outcomes of patients receiving robotic rectal cancer surgery. METHODS A comprehensive literature search of electronic databases was performed in October 2015. The following search terms were applied: “rectal cancer” or “colorectal cancer” and robot* or “da Vinci” and sexual or urolog* or urinary or erect* or ejaculat* or impot* or incontinence. All original studies examining the urological and/or sexual outcomes of male and/or female patients receiving robotic rectal cancer surgery were included. Reference lists of all retrieved articles were manually searched for further relevant articles. Abstracts were independently searched by two authors. RESULTS Fifteen original studies fulfilled the inclusion criteria. A total of 1338 patients were included; 818 received robotic, 498 laparoscopic and 22 open rectal cancer surgery. Only 726 (54%) patients had their urogenital function assessed via means of validated functional questionnaires. From the included studies, three found that robotic rectal cancer surgery leads to quicker recovery of male urological function and five of male sexual function as compared to laparoscopic surgery. It is unclear whether robotic surgery offers favourable urogenital outcomes in the long run for males. In female patients only two studies assessed urological and three sexual function independently to that of males. In these studies there was no difference identified between patients receiving robotic and laparoscopic rectal cancer surgery. However, in females the presented evidence was very limited making it impossible to draw any substantial conclusions. CONCLUSION There seems to be a trend towards earlier recovery of male urogenital function following robotic surgery. To evaluate this further, larger well designed studies are required. PMID:27933136

  16. Pathological Assessment of Rectal Cancer after Neoadjuvant Chemoradiotherapy: Distribution of Residual Cancer Cells and Accuracy of Biopsy

    PubMed Central

    Xiao, Lin; Yu, Xin; Deng, Wenjing; Feng, Huixia; Chang, Hui; Xiao, Weiwei; Zhang, Huizhong; Xi, Shaoyan; Liu, Mengzhong; Zhu, Yujia; Gao, Yuanhong

    2016-01-01

    We investigated the distribution of residual cancer cells (RCCs) within different layers of the bowel wall in surgical specimens and the value of biopsies of primary rectal lesion after preoperative volumetric modulated arc therapy (VMAT) with concurrent chemotherapy in patients with rectal cancer. Between April 2011 and April 2013, 178 patients with rectal cancer who received preoperative VMAT, concurrent chemotherapy, and surgery were evaluated; 79 of the patients received a biopsy of the primary lesion after chemoradiotherapy and prior to surgery. The distribution of RCCs in the surgical specimens and the sensitivity and specificity of the biopsy of primary rectal lesions for pathological response were evaluated. Fifty-two patients had a complete pathological response in the bowel wall. Of the 120 patients with ypT2-4, the rate of detection of RCCs in the mucosa, submucosa, and muscularis propria was 20%, 36.7%, 69.2%, respectively. The sensitivity and specificity of biopsies of primary rectal lesions was 12.9% and 94.1%, respectively. After chemoradiotherapy, the RCCs were primarily located in the deeper layers of the bowel wall, and the biopsy results for primary rectal lesions were unreliable due to poor sensitivity. PMID:27721486

  17. Clinical Trial of Oral Nelfinavir Before and During Radiation Therapy for Advanced Rectal Cancer

    PubMed Central

    Hill, Esme J.; Roberts, Corran; Franklin, Jamie M.; Enescu, Monica; West, Nicholas; MacGregor, Thomas P.; Chu, Kwun-Ye; Boyle, Lucy; Blesing, Claire; Wang, Lai-Mun; Mukherjee, Somnath; Anderson, Ewan M.; Brown, Gina; Dutton, Susan; Love, Sharon B.; Schnabel, Julia A.; Quirke, Phil; Muschel, Ruth; McKenna, William G.; Partridge, Michael; Sharma, Ricky A.

    2016-01-01

    Purpose Nelfinavir, a PI3-kinase pathway inhibitor, is a radiosensitizer which increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach. Patients and Methods Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1250 mg bd) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Perfusion CT (p-CT) and DCE-MRI scans were performed pre-treatment, after 7 days of nelfinavir and prior to last fraction of RT. Biopsies taken pre-treatment and 7 days after the last fraction of RT were analysed for tumor cell density (TCD). Results There were 3 drug-related grade 3 adverse events: diarrhea, rash, lymphopenia. On DCE-MRI, there was a mean 42% increase in median Ktrans, and a corresponding median 30% increase in mean blood flow on p-CT during RT in combination with nelfinavir. Median TCD decreased from 24.3% at baseline to 9.2% in biopsies taken 7 days after RT (P=0.01). Overall, 5/9 evaluable patients exhibited good tumor regression on MRI assessed by Tumor Regression Grade (mrTRG). Conclusions This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy. It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors. The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation, including measurement of tumor blood flow. PMID:26861457

  18. 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.

  19. A long and distant journey: a case of rectal cancer with metastasis to the orbit.

    PubMed

    Pearlman, Michelle; Kwong, Wilson T

    2015-01-01

    We present the case of a 33-year-old man with acute onset of eye pain and diplopia as the presenting symptoms of rectal cancer with orbital metastasis. Colorectal cancer with orbital metastasis is exceedingly rare with only 7 cases worldwide despite the prevalence of colorectal cancer. The rarity of this presentation may be related to the long path through multiple vascular beds that tumor emboli from the rectum must travel in order to reach the orbit.

  20. Examining the Quality of Rectal Cancer Operative Reports in Teaching Institutions: Is There an Opportunity for Resident Education?

    PubMed

    Parrish, Aaron B; Sanaiha, Yas; Petrie, Beverley A; Russell, Marcia M; Chen, Formosa

    2016-10-01

    The American Society of Colon and Rectal Surgeons rectal cancer checklist describes a set of best practices for rectal cancer surgery. The objective of this study was to assess the quality of operative reports for rectal cancer surgery based on the intraoperative American Society of Colon and Rectal Surgeons checklist items. Patients undergoing rectal cancer surgery at two public teaching hospitals from 2009 to 2015 were included. A total of 12 intraoperative checklist items were assessed. One hundred and fifty-eight operative reports were reviewed. Overall adherence to checklist items was 55 per cent, and was significantly higher in attending versus resident dictated reports (67% vs 51%, P < 0.01). Senior residents had significantly higher adherence to checklist items than junior residents (55% vs 44%, P < 0.01). However, overall adherence to rectal cancer checklist items was low. This represents an opportunity to improve the quality of operative documentation in rectal cancer surgery, which could also impact the technical quality of the operation itself.

  1. 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.

  2. 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.

  3. 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

  4. Clinical significance of radiation-induced CD133 expression in residual rectal cancer cells after chemoradiotherapy.

    PubMed

    Kawamoto, Aya; Tanaka, Koji; Saigusa, Susumu; Toiyama, Yuji; Morimoto, Yuhki; Fujikawa, Hiroyuki; Iwata, Takashi; Matsushita, Kohei; Yokoe, Takeshi; Yasuda, Hiromi; Inoue, Yasuhiro; Miki, Chikao; Kusunoki, Masato

    2012-03-01

    CD133 and CD44 have been considered as markers for colorectal cancer stem cells (CSCs). The association of CD133 and CD44 expression with radiation has not been fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients using real-time RT-PCR and compared to clinicopathological variables and clinical outcome. Their protein levels were examined in the radiation-treated HT29 human colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44 was significantly lower in post-CRT specimens (P<0.01). CD133 was associated with distant recurrence after CRT followed by surgery (P<0.05). Patients with elevated CD133 in residual cancer cells showed poor disease-free survival (P<0.05). No significant association between post-CRT CD44 and clinical outcome was found. The in vitro study showed that CD133 protein was increased in a radiation dose-dependent manner, despite of the decreased number of clonogenic radiation-surviving cells. CD44 protein was decreased after irradiation. CD133, but not CD44, was increased in radiation-resistant surviving colon cancer cells. Post-CRT CD133 in residual cancer cells may predict metachronous distant recurrence and poor survival of rectal cancer patients after CRT.

  5. Quantitative analysis of rectal cancer by spectral domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Zhang, Q. Q.; Wu, X. J.; Tang, T.; Zhu, S. W.; Yao, Q.; Gao, Bruce Z.; Yuan, X. C.

    2012-08-01

    To quantify OCT images of rectal tissue for clinic diagnosis, the scattering coefficient of the tissue is extracted by curve fitting the OCT signals to a confocal single model. A total of 1000 measurements (half and half of normal and malignant tissues) were obtained from 16 recta. The normal rectal tissue has a larger scattering coefficient ranging from 1.09 to 5.41 mm-1 with a mean value of 2.29 mm-1 (std:±0.32), while the malignant group shows lower scattering property and the values ranging from 0.25 to 2.69 mm-1 with a mean value of 1.41 mm-1 (std:±0.18). The peri-cancer of recta has also been investigated to distinguish the difference between normal and malignant rectal tissue. The results demonstrate that the quantitative analysis of the rectal tissue can be used as a promising diagnostic criterion of early rectal cancer, which has great value for clinical medical applications.

  6. Essential Items for Structured Reporting of Rectal Cancer MRI: 2016 Consensus Recommendation from the Korean Society of Abdominal Radiology.

    PubMed

    2017-01-01

    High-resolution rectal MRI plays a crucial role in evaluating rectal cancer by providing multiple prognostic findings and imaging features that guide proper patient management. Quality reporting is critical for accurate effective communication of the information among multiple disciplines, for which a systematic structured approach is beneficial. Existing guides on reporting of rectal MRI are divergent on some issues, largely reflecting the differences in overall management of rectal cancer patients between the United States and Europe. The Korean Society of Abdominal Radiology (KSAR) study group for rectal cancer has developed an expert consensus recommendation regarding essential items for structured reporting of rectal cancer MRI using a modified Delphi method. This recommendation aims at presenting an up-to-date, evidence-based, practical, structured reporting template that can be readily adopted in daily clinical practice. In addition, a thorough explanation of the clinical and scientific rationale underlying the reporting items and their formats is provided. This KSAR recommendation may serve as a useful tool to help achieve more standardized optimal care for rectal cancer patients using rectal MRI.

  7. Essential Items for Structured Reporting of Rectal Cancer MRI: 2016 Consensus Recommendation from the Korean Society of Abdominal Radiology

    PubMed Central

    2017-01-01

    High-resolution rectal MRI plays a crucial role in evaluating rectal cancer by providing multiple prognostic findings and imaging features that guide proper patient management. Quality reporting is critical for accurate effective communication of the information among multiple disciplines, for which a systematic structured approach is beneficial. Existing guides on reporting of rectal MRI are divergent on some issues, largely reflecting the differences in overall management of rectal cancer patients between the United States and Europe. The Korean Society of Abdominal Radiology (KSAR) study group for rectal cancer has developed an expert consensus recommendation regarding essential items for structured reporting of rectal cancer MRI using a modified Delphi method. This recommendation aims at presenting an up-to-date, evidence-based, practical, structured reporting template that can be readily adopted in daily clinical practice. In addition, a thorough explanation of the clinical and scientific rationale underlying the reporting items and their formats is provided. This KSAR recommendation may serve as a useful tool to help achieve more standardized optimal care for rectal cancer patients using rectal MRI. PMID:28096724

  8. 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.

  9. 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

  10. 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.

  11. Evidence of improving survival of patients with rectal cancer in France: a population based study

    PubMed Central

    Finn-Faivre, C; Maurel, J; Benhamiche, A; Herbert, C; Mitry, E; Launoy, G; Faivre, J

    1999-01-01

    BACKGROUND—Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. 
AIMS—To determine trends in management and prognosis of rectal cancer in two French regions. 
SUBJECTS—1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. 
METHODS—Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. 
RESULTS—Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17.7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period). 
CONCLUSIONS—Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival. 

 Keywords: rectal cancer; treatment; stage at diagnosis; survival; time trends; cancer registries PMID:10026324

  12. High Rate of Positive Circumferential Resection Margins Following Rectal Cancer Surgery: A Call to Action

    PubMed Central

    Rickles, Aaron S.; Dietz, David W.; Chang, George J.; Wexner, Steven D.; Berho, Mariana E.; Remzi, Feza H.; Greene, Frederick L.; Fleshman, James W.; Abbas, Maher A.; Peters, Walter; Noyes, Katia; Monson, John R.T.; Fleming, Fergal J.

    2017-01-01

    Objective To identify predictors of positive circumferential resection margin following rectal cancer resection in the United States. Background Positive circumferential resection margin is associated with a high rate of local recurrence and poor morbidity and mortality for rectal cancer patients. Prior study has shown poor compliance with national rectal cancer guidelines, but whether this finding is reflected in patient outcomes has yet to be shown. Methods Patients who underwent resection for stage I-III rectal cancer were identified from the 2010-2011 National Cancer Database. The primary outcome was a positive circumferential resection margin. The relationship between patient, hospital, tumor, and treatment-related characteristics was analyzed using bivariate and multivariate analysis. Findings A positive circumferential resection margin was noted in 2,859 (17.2%) of the 16,619 patients included. Facility location, clinical T and N stage, histologic type, tumor size, tumor grade, lymphovascular invasion, perineural invasion, type of operation, and operative approach were significant predictors of positive circumferential resection margin on multivariable analysis. Total proctectomy had nearly a 30% increased risk of positive margin compared to partial proctectomy (OR 1.293, 95%CI 1.185-1.411) and a laparoscopic approach had nearly 22% less risk of a positive circumferential resection margin compared to an open approach (OR 0.882, 95%CI 0.790-0.985). Interpretation Despite advances in surgical technique and multimodality therapy, rates of positive circumferential resection margin remain high in the United States. Several tumor and treatment characteristics were identified as independent risk factors, and advances in rectal cancer care are necessary to approach the outcomes seen in other countries. PMID:26473651

  13. Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

    PubMed Central

    Dayde, Delphine; Tanaka, Ichidai; Jain, Rekha; Tai, Mei Chee; Taguchi, Ayumu

    2017-01-01

    The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer. PMID:28272347

  14. A watch-and-wait approach to the management of rectal cancer.

    PubMed

    Das, Prajnan; Minsky, Bruce D

    2013-10-01

    There has been increasing interest in whether a watch-and-wait strategy can be pursued instead of routine surgery in selected rectal cancer patients who have a clinical complete response (cCR) after chemoradiation. The watch-and-wait approach could potentially reduce treatment-related toxicity in selected rectal cancer patients. A large study from Brazil and a prospective trial from the Netherlands appear to support this approach, although multiple other studies have raised concerns about the high rate of local recurrence with this strategy. This article reviews current evidence in support of a watch-and-wait approach to rectal cancer management, and discusses the challenges and limitations of this approach. Among these are the facts that current methods of assessing tumor response have limited accuracy, and that a cCR does not necessarily imply pathologic complete response. Careful patient selection and systematic methods of response assessment and follow-up will be critical to the success of nonoperative approaches. Based on the available evidence, ideally a watch-and-wait approach for patients with rectal cancer should be pursued within the context of a prospective clinical trial.

  15. Adjuvant radiotherapy for the treatment of stage IV rectal cancer after curative resection

    PubMed Central

    Kim, Min Jung; Kim, Sang Jin; Park, Sung-Chan; Kim, Dae Yong; Park, Ji Won; Ryoo, Seung-Bum; Jeong, Seung-Yong; Park, Kyu Joo; Oh, Heung Kwon; Kim, Duck-Woo; Kang, Sung-Bum; Joo, Jung Nam; Oh, Jae Hwan

    2016-01-01

    Abstract The role of pelvic radiotherapy (RT) in stage IV rectal cancer with total mesorectal excision (TME) has not been defined. We evaluated the impact of RT on oncologic outcomes among patients with stage IV rectal cancer who underwent TME and performed a meta-analysis of published studies. The records of stage IV rectal cancer patients who underwent TME between August 2001 and December 2011 were reviewed. Patients who received pelvic RT (RT group) and those who did not (non-RT group) were matched using a propensity score. Oncologic outcomes were compared between the groups. A systematic literature search and meta-analysis was conducted. One hundred seventy-six patients were matched with propensity score matching, resulting in 39 patients in each group. The local recurrence-free survival (LRFS) of the RT group was significantly higher than that of the non-RT group (2-year LRFS: 100% vs 83.6%, respectively, P = 0.038). The overall survival, disease-free survival, and systemic recurrence were not significantly different between the groups. In the meta-analysis, the RT group had a reduced risk for loco-regional recurrence than the non-RT group (RR: 0.48, 95% confidence interval: 0.29–0.79). Pelvic RT might have benefits for loco-regional control in patients with stage IV rectal cancer who undergo TME. PMID:27893653

  16. Sphincter-saving surgeries for rectal cancer: A single center study from Kashmir

    PubMed Central

    Mir, Shabeer Ahmed; Chowdri, Nisar A.; Parray, Fazl Q.; Mir, Parvez Ahmed; Bashir, Yasir; Nafae, Muntakhab

    2013-01-01

    Summary and Background Data: The goals in the treatment of rectal cancer are cure, local control, and preservation of sphincter, bladder and sexual function. Surgical resection using sharp mesorectal dissection is important for achieving these goals. Objectives: The current treatment of choice for carcinoma rectum is sphincter saving procedures, which have practically replaced the previously done abdominoperineal resection. We performed a study in our institute to evaluate the surgical outcome and complications of rectal cancer. Materials and Methods: This prospectivestudy included 117 patients, treated for primary rectal cancer by low anterior resection (LAR) from May 2007 to December 2010. All patients underwent standard total mesorectal excision (TME) followed by restoration of continuity. Results: The peri-operative mortality rate was 2.5% (3/117). Post-operative complications occurred in 32% of the patients. After a median follow up of 42 months, local recurrences developed in 6 (5%) patients and distant metastasis in 5 (4.2%). The survival rate was 93%. Conclusion: The concept of total mesorectal excision (TME), advances in stapling technology and neoadjuvant therapy have made it possible to preserve the anal sphincter in most of the patients. Rectal cancer needs to be managed especially in a specialized unit for better results. PMID:24455643

  17. Rectal cancer mortality and total hardness levels in Taiwan's drinking water.

    PubMed

    Yang, C Y; Tsai, S S; Lai, T C; Hung, C F; Chiu, H F

    1999-05-01

    The possible association between the risk of rectal cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible rectal cancer deaths (986 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (986 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair matched to the cases by sex, year of birth, and year of death. The results show a significant negative relationship between drinking water hardness and rectal cancer mortality. Odds ratio and 95% confidence intervals were 1.24 (1.01-1. 55) and 1.38 (1.10-1.73), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. Trend analyses showed an increasing odds ratio for rectal cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health.

  18. Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer.

    PubMed

    Dayde, Delphine; Tanaka, Ichidai; Jain, Rekha; Tai, Mei Chee; Taguchi, Ayumu

    2017-03-07

    The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

  19. Chromosomal copy number changes of locally advanced rectal cancers treated with preoperative chemoradiotherapy

    PubMed Central

    Grade, Marian; Gaedcke, Jochen; Wangsa, Danny; Varma, Sudhir; Beckmann, Jaje; Liersch, Torsten; Hess, Clemens; Becker, Heinz; Difilippantonio, Michael J.; Ried, Thomas; Ghadimi, B. Michael

    2009-01-01

    Introduction Standard treatment of rectal cancer patients comprises preoperative chemoradiotherapy followed by radical surgery. However, clinicians are faced with the problem that response rates vary from one individual to another. Predictive biomarkers would therefore be helpful. Materials and Methods In order to identify genomic imbalances that might assist in stratifying tumors into responsive or non-responsive, we used metaphase comparative genomic hybridization to prospectively analyze pre-therapeutic biopsies from 42 patients with locally advanced rectal cancers. These patients were subsequently treated with 5-FU based preoperative chemoradiotherapy. Results Based on downsizing of the T-category, 21 rectal cancers were later classified as responsive, while 21 were non-responsive. Comparing these two groups, we could show that gains of chromosomal regions 7q32-q36 and 7q11-q31, and amplifications of 20q11-q13 were significantly associated with responsiveness to preoperative chemoradiotherapy (P<0.05). However, the probability to detect these copy number changes by chance is high (P=0.21). Conclusion Our primary results suggest that pre-therapeutic evaluation of chromosomal copy number changes may be of value for response prediction of rectal cancers to preoperative chemoradiotherapy. This will require validation in a larger cohort of patients. PMID:19602460

  20. [Evaluation of Intra-abdominal fat distribution using X-ray CT data for detection of rectal cancer].

    PubMed

    Ogura, Toshihiro; Takatsu, Kazuaki; Negishi, Ryoichi; Koizumi, Kouichi; Satou, Masanori; Yanai, Kazuya; Sasaki, Isamu; Fukuda, Kazuya; Nagashima, Hiroyuki; Kouno, Atsushi; Shimomura, Younosuke

    2005-06-20

    To develop a novel method of detecting rectal cancer, we assessed relationships between intra-abdominal fat distribution and rectal cancer in Japanese patients. Subjects comprised 38 patients with rectal cancer apparent on CT-colonography and 110 other cases. The intra-abdominal fat area was determined by calculating pixel distribution with attenuation values from -140 HU to -40 HU. The area of intra-abdominal fat was measured on axial images using an interslice gap of 10 mm. Profile curves of intra-abdominal fat were in the plane direction from diaphragm to anus. Of note is the fact that Ogura's peak, a secondary small peak around the rectal cancer, was apparent on the profile of intra-abdominal fat, with 73.7% of rectal cancers displaying Ogura's peak. In comparison, only 19.1% of other cases displayed Ogura's peak on this profile. The relationship between fat and rectal cancer is difficult to explain. However, making good use of these results showing intra-abdominal fat distribution, a computer-aided diagnosis (CAD) system for detecting rectal cancer according to the presence of Ogura's peak has potential as a method of mass screening. As only 148 cases were investigated in the present study, the accumulation of additional data is needed. More detailed studies with larger patient populations are warranted.

  1. Challenge or opportunity: outcomes of laparoscopic resection for rectal cancer in patients with high operative risk.

    PubMed

    Lu, Ai-Guo; Zhao, Xue-wei; Mao, Zhi-hai; Han, Ding-pei; Zhao, Jing-kun; Wang, Puxiongzhi; Zhang, Zhuo; Zong, Ya-ping; Thasler, Wolfgang; Feng, Hao

    2014-11-01

    This study investigated the impact of laparoscopic rectal cancer resection for patients with high operative risk, which was defined as American Society of Anesthesiology (ASA) grades III and IV. This study was conducted at a single center on patients undergoing rectal resection from 2006 to 2010. After screening by ASA grade III or IV, 248 patients who met the inclusion criteria were identified, involving 104 open and 144 laparoscopic rectal resections. The distribution of the Charlson Comorbidity Index was similar between the two groups. Compared with open rectal resection, laparoscopic resection had a significantly lower total complication rate (P<.0001), lower pain rate (P=.0002), and lower blood loss (P<.0001). It is notable that the two groups of patients had no significant difference in cardiac and pulmonary complication rates. Thus, these data showed that the laparoscopic group for rectal cancer could provide short-term outcomes similar to those of their open resection counterparts with high operative risk. The 5-year actuarial survival rates were 0.8361 and 0.8119 in the laparoscopic and open groups for stage I/II (difference not significant), as was the 5-year overall survival rate in stage III/IV (P=.0548). In patients with preoperative cardiovascular or pulmonary disease, the 5-year survival curves were significantly different (P=.0165 and P=.0210), respectively. The cost per patient did not differ between the two procedures. The results of this analysis demonstrate the potential advantages of laparoscopic rectal cancer resection for high-risk patients, although a randomized controlled trial should be conducted to confirm the findings of the present study.

  2. Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization.

    PubMed

    Damania, Dhwanil; Roy, Hemant K; Subramanian, Hariharan; Weinberg, David S; Rex, Douglas K; Goldberg, Michael J; Muldoon, Joseph; Cherkezyan, Lusik; Zhu, Yuanjia; Bianchi, Laura K; Shah, Dhiren; Pradhan, Prabhakar; Borkar, Monica; Lynch, Henry; Backman, Vadim

    2012-06-01

    Developing a minimally invasive and cost-effective prescreening strategy for colon cancer is critical because of the impossibility of conducting colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (L(d)) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with nondiminutive/nonadvanced adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 patients with cancer. We found that the L(d) obtained from rectal colonocytes was well correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured L(d) is an accurate marker of field carcinogenesis. This approach provides a potential prescreening strategy for risk stratification before colonoscopy.

  3. Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization

    PubMed Central

    Damania, Dhwanil; Roy, Hemant K.; Subramanian, Hariharan; Weinberg, David S.; Rex, Douglas K.; Goldberg, Michael J.; Muldoon, Joseph; Cherkezyan, Lusik; Zhu, Yuanjia; Bianchi, Laura K.; Shah, Dhiren; Pradhan, Prabhakar; Borkar, Monica; Lynch, Henry; Backman, Vadim

    2013-01-01

    Developing a minimally invasive and cost effective pre-screening strategy for colon cancer is critical, because of the impossibility of performing colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial-wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (Ld) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with non-advanced-non-diminutive adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 cancer patients. We found that the Ld obtained from rectal colonocytes was well-correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured Ld is an accurate marker of field carcinogenesis. This approach provides a potential pre-screening strategy for risk stratification before colonoscopy. PMID:22491589

  4. Robotic surgery for rectal cancer: current immediate clinical and oncological outcomes.

    PubMed

    Araujo, Sergio Eduardo Alonso; Seid, Victor Edmond; Klajner, Sidney

    2014-10-21

    Laparoscopic rectal surgery continues to be a challenging operation associated to a steep learning curve. Robotic surgical systems have dramatically changed minimally invasive surgery. Three-dimensional, magnified and stable view, articulated instruments, and reduction of physiologic tremors leading to superior dexterity and ergonomics. Therefore, robotic platforms could potentially address limitations of laparoscopic rectal surgery. It was aimed at reviewing current literature on short-term clinical and oncological (pathological) outcomes after robotic rectal cancer surgery in comparison with laparoscopic surgery. A systematic review was performed for the period 2002 to 2014. A total of 1776 patients with rectal cancer underwent minimally invasive robotic treatment in 32 studies. After robotic and laparoscopic approach to oncologic rectal surgery, respectively, mean operating time varied from 192-385 min, and from 158-297 min; mean estimated blood loss was between 33 and 283 mL, and between 127 and 300 mL; mean length of stay varied from 4-10 d; and from 6-15 d. Conversion after robotic rectal surgery varied from 0% to 9.4%, and from 0 to 22% after laparoscopy. There was no difference between robotic (0%-41.3%) and laparoscopic (5.5%-29.3%) surgery regarding morbidity and anastomotic complications (respectively, 0%-13.5%, and 0%-11.1%). Regarding immediate oncologic outcomes, respectively among robotic and laparoscopic cases, positive circumferential margins varied from 0% to 7.5%, and from 0% to 8.8%; the mean number of retrieved lymph nodes was between 10 and 20, and between 11 and 21; and the mean distal resection margin was from 0.8 to 4.7 cm, and from 1.9 to 4.5 cm. Robotic rectal cancer surgery is being undertaken by experienced surgeons. However, the quality of the assembled evidence does not support definite conclusions about most studies variables. Robotic rectal cancer surgery is associated to increased costs and operating time. It also seems to be

  5. [Downstaging after neoadjuvant therapy for rectal cancer modifies the planned original surgery].

    PubMed

    Scutari, F; Tramutola, G; Morlino, A; Rossi, M T; Manzione, L; Rosati, G; Sopranzi, A

    2008-01-01

    Cancer of the rectum has been for more years burdened with a heavy rate of local relapse about 30%. The introduction of total meso-rectum excision has reduced the rate of up to 5-8%. Later more studies proved how the preoperative radiotherapy was able to reduce the rate of local relapse. The Authors introduce studies about downstaging after neoadjuvant chemoradiotherapy for rectal cancer and discuss about their own series from 2005 to 2007.

  6. A Penetrating Stab Wound of the Perianal Area Causing a Combined Rectal and Bladder Injury: One Case Report

    PubMed Central

    Tazi, Mohammed Fadl; Khallouk, Abdelhak; Ahallal, Youness; Riyach, Omar; El Ammari, Jalal Eddine; El Fassi, Mohammed Jamal; Farih, Moulay Hassan

    2012-01-01

    Although the management of either isolated rectal or bladder injury is no more controversial, their combined effect and their optimal management has been seldom reported in the English literature. From a case report of a 45-year-old male who was found to have a combined bladder and rectal injury secondary to a stab wound of the perianal area, the authors develop a diagnostic and therapeutic algorithm for the management of this uncommon trauma. PMID:22844630

  7. 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.

  8. A Successfully Resected Case of Recurrent Lung and Liver Metastases of Rectal Cancer Treated with XELIRI + Bevacizumab Therapy.

    PubMed

    Aisu, Naoya; Yoshida, Yoichiro; Ishii, Fuminori; Miyake, Toru; Tanimura, Shu; Wada, Yoshito; Yamauchi, Yasushi; Hoshino, Seiichiro; Noritomi, Tomoaki; Yamashita, Yuichi

    2013-01-01

    It has been reported that many colorectal cancer (CRC) patients with synchronous or metachronous liver metastases underwent surgery subsequent to neoadjuvant combination chemotherapy with folinic acid, fluorouracil, and oxaliplatin (FOLFOX), folinic acid, fluorouracil, and irinotecan (FOLFIRI), or capecitabine and oxaliplatin (XELOX). However, there are very few reports of the use of capecitabine and irinotecan (XELIRI). We herein report a successfully resected case of recurrent lung and liver metastases of rectal cancer treated with combination chemotherapy with XELIRI + bevacizumab (BV) therapy. A 63-year-old male developed recurrence of a solitary nodule in the right lower lobe of the lung and multiple liver metastases after low anterior resection for rectal cancer 1 year previously. Partial resection of the right lower lobe of the lung was performed and treatment with XELIRI + BV was initiated. A computed tomography scan revealed a reduction in tumor size without any new lesions after four cycles of XELIRI + BV therapy. Partial hepatectomy of S1, S5, and S7 was safely performed. The patient is now undergoing adjuvant chemotherapy and has been free from recurrence for 18 months following surgery. There are only few studies with relatively low patient numbers reporting on the outcome after resection of both pulmonary and hepatic metastases of CRC. We therefore report a patient who underwent sequential resection of pulmonary and hepatic metastases with XELIRI + BV therapy.

  9. 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

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

    PubMed

    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.

  11. 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.

  12. Age distribution, polyps and rectal cancer in the Egyptian population-based cancer registry

    PubMed Central

    Veruttipong, Darlene; Soliman, Amr S; Gilbert, Samuel F; Blachley, Taylor S; Hablas, Ahmed; Ramadan, Mohamed; Rozek, Laura S; Seifeldin, Ibrahim A

    2012-01-01

    AIM: To describe the clinical and epidemiologic profiles of the disease and to compare the findings with those generated from the previous hospital-based studies. METHODS: The Gharbiah cancer registry is the only population-based cancer registry in Egypt since 1998. We analyzed the data of all colorectal cancer patients included in the registry for the period of 1999-2007. All medical records of the 1364 patients diagnosed in Gharbiah during the study period were retrieved and the following information abstracted: age, residence, diagnosis date, grade, stage, topology, clinical characteristics, and histology variables. Egyptian census data for 1996 and 2006 were used to provide the general population’s statistics on age, sex, residence and other related demographic factors. In addition to age- and sex-specific incidence rate analyses, we analyze the data to explore the incidence distribution by rural-urban differences among the 8 districts of the province. We also compared the incidence rates of Gharbiah to the rates of the Surveillance Epidemiology and End Results (SEER) data of the United States. RESULTS: Over the 9 year-period, 1364 colorectal cancer cases were included. The disease incidence under age 40 years was relatively high (1.3/105) while the incidence in the age groups 40 and over was very low (12.0/105, 19.4/105 and 21.2/105 in the age groups 40-59 years, 60-69 years and > 70 years, respectively). The vast majority of tumors (97.2%) had no polyps and 37.2% of the patients presented with primary lesions in the rectum. Colorectal cancer was more common in patients from urban (55%) than rural (45%) areas. Regional differences in colon and rectal cancer incidence in the 8 districts of the study province may reflect different etiologic patterns in this population. The registry data of Egypt shows a slightly higher incidence of colorectal cancer than the United States in subjects under age 40 years. The results also shows significantly lower incidence of

  13. 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.

  14. Do Older Americans Undergo Stoma Reversal Following Low Anterior Resection for Rectal Cancer?

    PubMed Central

    Dodgion, Christopher M.; Neville, Bridget A.; Lipsitz, Stuart R.; Hu, Yue-Yung; Schrag, Deborah; Breen, Elizabeth; Greenberg, Caprice C.

    2013-01-01

    Objective For low-lying rectal cancers, proximal diversion can reduce anastomotic leak after sphincter preserving surgery; however, evidence suggests that such temporary diversions are often not reversed. We aimed to evaluate non-reversal and delayed stoma reversal in elderly patients undergoing low anterior resection (LAR). Design SEER-Medicare linked analysis from 1991-2007. Settings and Participants 1,179 primary stage I-III rectal cancer patients over age 66 who underwent LAR with synchronous diverting stoma. Main Outcome Measures 1) Stoma creation and reversal rates. 2) Time to reversal. 3) Characteristics associated with reversal and shorter time to reversal. Results Within 18 months of LAR, 51% (603/1179) of patients underwent stoma reversal. Stoma reversal was associated with age < 80 years (p<0.0001), male gender (p=0.018), less comorbidities (p=0.017), higher income [quartile 4 vs. 1, (p=0.002)], early tumor stage [1 vs. 3; (p<0.001)], neoadjuvant radiation (p<0.0001), rectal tumor location [vs. rectosigmoid, (p=0.001)], more recent diagnosis (p=0.021), and shorter length of stay on LAR admission (p=0.021). Median time to reversal was 126 days (IQR: 79-249). Longer time to reversal was associated with older age (p=0.031), presence of comorbidities (p=0.014), more advanced tumor stage (p=0.007), positive lymph nodes (p=0.009), receipt of adjuvant radiation therapy (p=0.008), more recent diagnosis (p=0.004) and longer LOS on LAR admission (p <0.0001). Conclusions Half of elderly rectal cancer patients who undergo LAR with temporary stoma have not undergone stoma reversal by 18 months. Identifiable risk factors predict both non-reversal and longer time to reversal. These results help inform pre-operative discussions and promote realistic expectations for elderly rectal cancer patients. PMID:23298948

  15. Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy

    SciTech Connect

    Wallin, Asa R.; Svanvik, Joar; Adell, Gunnar; Sun Xiaofeng . E-mail: xiasu@ibk.liu.se

    2006-06-01

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients. Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT. Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes' stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01). Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. Protocol for a multicentre randomised feasibility trial evaluating early Surgery Alone In LOw Rectal cancer (SAILOR)

    PubMed Central

    Thorne, Kymberley; Hutchings, Hayley; Islam, Saiful; Holland, Gail; Hatcher, Olivia; Gwynne, Sarah; Jenkins, Ian; Coyne, Peter; Duff, Michael; Feldman, Melanie; Winter, Des C; Gollins, Simon; Quirke, Phil; West, Nick; Brown, Gina; Fitzsimmons, Deborah; Brown, Alan; Beynon, John

    2016-01-01

    Introduction There are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence. Advances in MRI-guided prediction of resection margin status and improvements in abdominoperineal excision of the rectum (APER) technique supports a reassessment of the contribution of preoperative RT. A more selective approach to RT may be appropriate given the associated toxicity. Methods and analysis This trial will explore the feasibility of a definitive trial evaluating the omission of RT in resectable low rectal cancer requiring APER. It will test the feasibility of randomising patients to (1) standard care (neoadjuvant long course RT±chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy over 5 weeks as current standard, with restaging and surgery after 8–12 weeks. Recruitment will be for 24 months with a minimum 12-month follow-up. Objectives Objectives include testing the ability to recruit, consent and retain patients, to quantify the number of patients eligible for a definitive trial and to test feasibility of outcomes measures. These include locoregional recurrence rates, distance to circumferential resection margin, toxicity and surgical complications including perineal wound healing, quality of life and economic analysis. The quality of MRI staging, RT delivery and surgical specimen quality will be closely monitored. Ethics and dissemination The trial is approved by the Regional Ethics Committee and Health Research Authority (HRA) or equivalent. Written informed consent will be obtained. Serious adverse events will be reported to Swansea Trials Unit (STU), the ethics committee and trial sites. Trial results will be submitted for peer review

  3. The Impact of Ileostomy-Related Complications on the Multidisciplinary Treatment of Rectal Cancer

    PubMed Central

    Phatak, Uma R.; Kao, Lillian S.; You, Y. Nancy; Rodriguez-Bigas, Miguel A.; Skibber, John M.; Feig, Barry W.; Nguyen, Sa; Chang, George J.

    2014-01-01

    Background Radical resection is the primary treatment for rectal cancer. When anastomosis is possible, a temporary ileostomy is used to decrease morbidity from a poorly healed anastomosis. However, ileostomies are associated with complications, dehydration, and need for a second operation. Our purpose was to evaluate the impact of ileostomy related complications on the treatment of rectal cancer. Methods A retrospective cohort study of patients who underwent sphincter preserving surgery between January 2005 and December 2010 at a tertiary cancer center. The primary outcome was the overall rate of ileostomy related complications. Secondary outcomes included complications related to ileostomy status, ileostomy closure, anastomotic complications at primary resection, rate of stoma closure, and completion of adjuvant chemotherapy. Statistical analyses were performed with STATA 12. Results A total of 294 patients were analyzed, 32% (n=95) were women. Two hundred seventy-one (92%) received neoadjuvant chemoradiation. The median tumor distance from the anal verge was 7 centimeters (interquartile range 5-10). Two hundred eighty-one (96%) underwent stoma closure at a median 7 months (interquartile range 5.4 – 8.3). The most common complication related to readmission was dehydration (n=32, 11%). Readmission within 60 days of primary resection was associated with delay in initiating adjuvant chemotherapy (OR 3.01, 95% CI 1.42-6.38, p=0.004). Conclusion Diverting ileostomies created during surgical treatment of rectal cancers are associated with morbidity; however this is balanced against the risk of anastomosis-related morbidity at rectal resection. Given the potential benefit of fecal diversion, patient-oriented interventions to improve ostomy management, particularly during adjuvant chemotherapy, can be expected to yield marked benefits. PMID:24085329

  4. 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.

  5. 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

  6. Renaissance of contact x-ray therapy for treating rectal cancer.

    PubMed

    Gérard, Jean-Pierre; Myint, Arthur Sun; Croce, Olivier; Lindegaard, Jacob; Jensen, Anie; Myerson, Robert; Hannoun-Lévi, Jean-Michel; Marcie, Serge

    2011-07-01

    Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation therapy technique to achieve local control and rectal preservation for early rectal adenocarcinoma. Despite these results, CXRT has not been used due to the shortage of the no longer manufactured Philips RT 50™ unit. Recently, a new CXRT machine (Papillon 50™) became available on the market. This machine delivers a beam of 50 kV with a dose rate close to 15 Gy/min and has a percentage depth dose of 50% at 6-7 mm. The applicator size varies from 2-3 cm in diameter. Due to the original design of the main tube, treatment delivery is quick and more comfortable for the patients. An online viewing system incorporated in the tube allows a good visualization of the tumor with improved accuracy of radiation delivery. An international collaborative trial (Contact Endoscopic Microsurgery [CONTEM]) was set up to accrue approximately 300 cases of rectal adenocarcinoma staged T1, T2 or early T3 tumors in the UK, France, Denmark and Sweden. This trial should confirm the role of CXRT in curative treatment with organ preservation for early rectal cancers.

  7. Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery Matter?

    PubMed Central

    Panagiotopoulou, Ioanna G.; Parashar, Deepak; Qasem, Eyas; Mezher-Sikafi, Rasha; Parmar, Jitesh; Wells, Alan D.; Bajwa, Farrukh M.; Menon, Madhav; Jephcott, Catherine R.

    2015-01-01

    The objective of this paper was to evaluate whether delaying surgery following long-course chemoradiotherapy for rectal cancer correlates with pathologic complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in the UK for the management of locally advanced rectal cancer. Optimal timing of surgery following CRT is still not clearly defined. All patients with a diagnosis of rectal cancer who had undergone long-course CRT prior to surgery between January 2008 and December 2011 were included. Statistical analysis was performed using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in the selected period. Twenty-seven percent (16/59) of patients showed a complete histopathologic response and 59.3% (35/59) of patients had tumor down-staging from radiologically-assessed node positive to histologically-proven node negative disease. There was no statistically significant delay to surgery after completion of CRT in the 16 patients with complete response (CR) compared with the rest of the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70–87.5) and IR group median: 72 days (IQR: 57–83), P = 0.470]. Although no statistically significant predictors of either complete response or tumor nodal status down-staging were identified in logistic regression analyses, a trend toward complete response was seen with longer delay to surgery following completion of long-course CRT. PMID:26414816

  8. Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery Matter?

    PubMed

    Panagiotopoulou, Ioanna G; Parashar, Deepak; Qasem, Eyas; Mezher-Sikafi, Rasha; Parmar, Jitesh; Wells, Alan D; Bajwa, Farrukh M; Menon, Madhav; Jephcott, Catherine R

    2015-06-01

    The objective of this paper was to evaluate whether delaying surgery following long-course chemoradiotherapy for rectal cancer correlates with pathologic complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in the UK for the management of locally advanced rectal cancer. Optimal timing of surgery following CRT is still not clearly defined. All patients with a diagnosis of rectal cancer who had undergone long-course CRT prior to surgery between January 2008 and December 2011 were included. Statistical analysis was performed using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in the selected period. Twenty-seven percent (16/59) of patients showed a complete histopathologic response and 59.3% (35/59) of patients had tumor down-staging from radiologically-assessed node positive to histologically-proven node negative disease. There was no statistically significant delay to surgery after completion of CRT in the 16 patients with complete response (CR) compared with the rest of the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70-87.5) and IR group median: 72 days (IQR: 57-83), P = 0.470]. Although no statistically significant predictors of either complete response or tumor nodal status down-staging were identified in logistic regression analyses, a trend toward complete response was seen with longer delay to surgery following completion of long-course CRT.

  9. 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.

  10. Tegafur-uracil (UFT) plus folinic acid in advanced rectal cancer.

    PubMed

    Sanchiz, F; Milla, A

    1994-12-01

    We previously reported positive results to Tegafur-Uracil (UFT) chemotherapy in a group of patients with advanced rectal cancer. We have continued the study and now report the effectiveness of UFT plus folinic acid (FA) in 52 patients with advanced rectal cancer. The therapeutic schedule was UFT, 600 mg/m2/day x 14 days p.o. + FA, 90 mg/m2/day x 14 days p.o. Fifty-two out of a total of 56 patients were evaluated for response and toxicity. A higher incidence of positive responses in patients without previous chemotherapy was appreciated. Twenty-one of the 52 evaluated patients showed a partial response (PR). Responses were strongly correlated with previous chemotherapy (14/20; 70% PR of cases without previous chemotherapy vs 7/32; 22% of cases with previous chemotherapy). All responding patients came forward with a median time to progression of 8.2 months (19.6 months for patients without previous chemotherapy vs 7.7 months for patients with previous chemotherapy, P < 0.01). We concluded that the UFT plus FA could be a treatment of choice for patients with advanced rectal cancer.

  11. The intentional oblique transection double stapling technique in anterior resection for rectal cancer.

    PubMed

    Kuramoto, Masafumi; Ikeshima, Satoshi; Yamamoto, Kenichiro; Morita, Keisuke; Uchihara, Tomoyuki; Itouyama, Rumi; Yoshimatsu, Shinichi; Shimada, Shinya; Baba, Hideo

    2017-04-01

    The double stapling technique (DST) is an intestinal reconstruction technique that has been widely adopted in anterior resection (AR) for rectal cancer. However, anastomotic leakage (AL) after the operation remains a major concern for colorectal surgeons. The sharp-angled corner of the remnant rectum that is often created by the ordinary DST can be a risk factor for AL. We have developed a new method of performing intentional oblique transection DST (IOT-DST). Using this technique, the anal side of the rectum is intentionally obliquely transected with linear staplers, and the area of the sharp-angled edge is totally punched out with a circular stapler. Between September 2015 and March 2016, we used the IOT-DST technique in the treatment of 15 consecutive rectal cancer patients and experienced no anastomosis-related complications, including leakage and stenosis. IOT-DST is easy to use and less stressful to perform than other techniques. IOT-DST has the potential to become the standard technique for AR in rectal cancer surgery.

  12. 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.

  13. Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

    PubMed Central

    Avoranta, Suvi Tuulia; Korkeila, Eija Annika; Syrjänen, Kari Juhani; Pyrhönen, Seppo Olavi; Sundström, Jari Toivo Tapio

    2012-01-01

    AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer. METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed. RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as “front-positive” and in 41% as “front-negative”. The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the “front-positive” tumors. CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease. PMID:22969228

  14. Preoperative chemoradiotherapy followed by local excision in clinical T2N0 rectal cancer

    PubMed Central

    Shin, Young Seob; Yoon, Yong sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Tae Won; Chang, Heung Moon; Park, Jin-hong; Ahn, Seung Do; Lee, Sang-Wook; Choi, Eun Kyung; Kim, Jin Cheon; Kim, Jong Hoon

    2016-01-01

    Purpose To investigate whether preoperative chemoradiotherapy (PCRT) followed by local excision (LE) is feasible approach in clinical T2N0 rectal cancer patients. Materials and Methods Patients who received PCRT and LE because of clinical T2 rectal cancer within 7 cm from anal verge between January 2006 and June 2014 were retrospectively analyzed. LE was performed in case of a good clinical response after PCRT. Patients’ characteristics, treatment record, tumor recurrence, and treatment-related complications were reviewed at a median follow-up of 49 months. Results All patients received transanal excision or transanal minimally invasive surgery. Of 34 patients, 19 patients (55.9%) presented pathologic complete response (pCR). The 3-year local recurrence-free survival and disease free-survival were 100.0% and 97.1%, respectively. There was no recurrence among the patients with pCR. Except for 1 case of grade 4 enterovesical fistula, all other late complications were mild and self-limiting. Conclusion PCRT followed by an LE might be feasible as an alternative to total mesorectal excision in good responders with clinical T2N0 distal rectal cancer. PMID:27730804

  15. Neoadjuvant therapy of rectal cancer using oral tegaful-uracil (UFT) plus concomitant radiotherapy--a case report.

    PubMed

    Yamaguchi, Yoshiyuki; Ohshita, Akiko; Hironaka, Katsuji; Emi, Manabu; Kawabuchi, Yoshiharu; Sakatani, Akio; Arihiro, Koji

    2005-09-01

    A 59-year-old male patient with rectal cancer 2 cm in diameter (T2) at the peritoneal reflection with suspicious left lateral node metastasis was treated with 400 mg of preoperative oral uracil and tegaful (UFT) for 5 weeks, 5 days a week in combination with concomitant radiotherapy of 45 Gy per 25 fractions for 5 weeks. After resting for another 5 weeks, colon fiberscopy, barium enema, and computed tomography revealed a trace of the primary tumor and a 40% shrinkage of the lateral metastasis. The serum CEA level decreased to the normal range during treatment. The adverse effects were nausea, bloody stool and elevation of transaminase, all at grade 1. Low anterior resection with a left hemi-lateral lymphadenectomy was performed through a suprapubic, one hand-size incision without laparoscopy. The preoperative treatment did not affect any operative procedures, and no postoperative complications occurred. The surgical specimen showed that the rectal tumor had been remarkably shrunk by the preoperative treatment, to the level of a superficial type tumor. Histological analysis indicated moderately differentiated adenocarcinoma cells that were present at only 2 mm in diameter in the mucosal layer, 6 mm in the submucosal layer, and 1 mm or less in the muscular layer with scar formation. No metastasis was detected in the 16 lymph nodes dissected, but an organizing tumor thrombus, which had preoperatively been diagnosed as lateral node metastasis, was detected. These results suggest that preoperative oral UFT plus concomitant radiotherapy may be a feasible, tolerable and effective treatment for patients with rectal cancer.

  16. 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

  17. 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

  18. Risk factors of late rectal bleeding after carbon ion therapy for prostate cancer

    SciTech Connect

    Ishikawa, Hitoshi; Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Kamada, Tadashi; Hirasawa, Naoki; Yanagi, Takeshi; Mizoe, Jun-Etsu; Akakura, Koichiro; Suzuki, Hiroyoshi; Shimazaki, Jun; Tsujii, Hirohiko

    2006-11-15

    Purpose: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. Methods and Materials: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. Results: Although no Grade 3-4 late morbidities of the rectum were observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose-volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 {+-} 5.6% with toxicity; 11.4 {+-} 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50 (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI toxicity. Conclusions: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.

  19. Timing Is Everything: What Is the Optimal Duration After Chemoradiation for Surgery for Rectal Cancer?

    PubMed

    Goodman, Karyn A

    2016-09-06

    The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 47-year-old woman was referred for management of a newly diagnosed rectal cancer. She presented with a 2-month history of rectal bleeding and change in bowel habits. She underwent a colonoscopy that demonstrated a 5-cm fungating, friable, and partially obstructing mass in the distal rectum, approximately 5 cm from the anal verge. The tumor was palpable on digital rectal examination on the anterior wall of rectum. The biopsy demonstrated a moderately differentiated invasive adenocarcinoma, microsatellite stable. A staging work-up, including a computed tomography scan of the chest, abdomen, and pelvis, demonstrated rectal wall thickening in the midrectum and small lymph nodes in the left perirectal fat. There was a nonspecific 3-mm right lower lobe pulmonary nodule. Rectal magnetic resonance imaging demonstrated a 3-cm mass arising from mid-distal rectum with minimal extension beyond muscularis propria into the mesorectal fat, but without invasion of mesorectal fascia (Fig 1). There were at least three small mesorectal lymph nodes present; the largest rounded node measured up to 5 mm, and no additional pelvic lymphadenopathy was identified. Her carcinoembryonic antigen was 1.1, and all other laboratory studies were within normal limits. She was seen in the Colorectal Multidisciplinary Conference for a discussion of her treatment options.

  20. 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

  1. Participation in Activities Associated With Quality of Life for Long-Term Survivors of Rectal Cancer

    PubMed Central

    McMullen, Carmit; Liu, Liyan; Bulkley, Joanna E; Hornbrook, Mark C; Wendel, Christopher; Grant, Marcia; Altschuler, Andrea; Temple, Larissa KF; Krouse, Robert S; Herrinton, Lisa

    2017-01-01

    Context: Cancer patients’ participation in social, recreational, and civic activities is strongly associated with quality of life (QOL), but these activities are not well integrated into cancer survivorship research or interventions. Objective: Test the hypothesis that for long-term (≥ 5 years) survivors of rectal cancer, clinical factors (type of surgery and bowel function) are associated with long-term participation in activities and that participation in activities is associated with long-term QOL. Design: Observational study with longitudinal and cross-sectional components. Main Outcome Measures: Participation in activities and QOL. Tumor registry records were used to identify patients and obtain clinical data; surveys assessed participation and QOL. Using general linear models, we analyzed participation in activities in relation to type of surgery and bowel function after adjustment for potential confounders. We analyzed overall QOL relative to participation in activities after adjustment. Results: A total of 567 rectal cancer survivors completed a mailed questionnaire. Overall response rate was 61%. The type of operation (p < 0.0001), receipt of radiation therapy (p = 0.002), and bowel function (p < 0.0001) were associated with participation in activities. Participation in activities was the strongest predictor of QOL (p < 0.0001), explaining 20% of the variance (R2) in QOL, with all other variables together accounting for another 18% of the variance. Conclusion: The importance of participation in activities on rectal cancer survivors’ QOL is underappreciated. We recommend revising QOL instruments used in cancer care and research to include questions about participation in activities. Interventions should address maintenance of preferred activities and adoption of new, fulfilling activities. PMID:28241904

  2. Prone-position thoracoscopic resection of posterior mediastinal lymph node metastasis from rectal cancer.

    PubMed

    Shirakawa, Yasuhiro; Noma, Kazuhiro; Koujima, Takeshi; Maeda, Naoaki; Tanabe, Shunsuke; Ohara, Toshiaki; Fujiwara, Toshiyoshi

    2015-02-12

    Mediastinal lymph node metastasis from colorectal cancer is rare, and barely any reports have described resection of this pathology. We report herein a successful thoracoscopic resection of mediastinal lymph node metastasis in a prone position. A 65-year-old man presented with posterior mediastinal lymph node metastasis after resection of the primary rectal cancer and metachronous hepatic metastasis. Metastatic lymph nodes were resected completely using thoracoscopic surgery in the prone position, which provided advantages of minimal invasiveness, good surgical field, and reduced ergonomic burden on the surgeon. Thoracoscopic resection in the prone position was thought to have the potential to become the standard procedure of posterior mediastinal tumors.

  3. Genetic variation in C-reactive protein (CRP) in relation to colon and rectal cancer risk and survival

    PubMed Central

    Slattery, Martha L.; Curtin, Karen; Poole, Elizabeth M.; Duggan, David J.; Samowitz, Wade S.; Peters, Ulrike; Caan, Bette J.; Potter, John D.; Ulrich, Cornelia M.

    2011-01-01

    Background C-reactive protein (CRP), a biomarker of inflammation has been shown to be influenced by genetic variation in the CRP gene. Methods In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n=1574 cases, 1970 controls) and rectal (n=791 cases, 999 controls) were conducted. We evaluated four CRP tagSNPs: rs1205 (G>A, 3’ UTR); rs1417938 (T>A, intron); rs1800947 (G>C, L184L); and rs3093075 (C>A, 3’ flanking). Results The CRP rs1205 AA genotype was associated with an increased risk of colon cancer (OR 1.3, 95%CI 1.1-1.7), whereas the rs3093075 A allele was associated with a reduced risk of rectal cancer (OR 0.7, 95%CI 0.5-0.9). The strongest association for the rs1205 polymorphism and colon cancer was observed among those with KRAS2 mutations (OR 1.5, 95%CI 1.1-2.0). The CRP rs1205 AA genotype also was associated with an increased risk of CIMP+ rectal tumors (OR 2.5, 95% CI 1.2-5.3); conversely, the rs1417938 A allele was associated with a reduced risk of CIMP+ rectal tumors (OR 0.5, 95%CI 0.3-0.9). We observed interactions between CRP rs1800947 and BMI and family history of CRC in modifying risk of both colon and rectal cancer. Conclusions These data suggest that genetic variation in the CRP gene influences risk of both colon and rectal cancer development. PMID:20949557

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

    PubMed

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

    2015-07-15

    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.

  5. 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.

  6. 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

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

    ClinicalTrials.gov

    2014-12-22

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

  8. The degree of extramural spread of T3 rectal cancer: an appeal to the American Joint Committee on Cancer.

    PubMed

    Zinicola, R; Pedrazzi, G; Haboubi, N; Nicholls, R J

    2017-01-01

    The T3 category of the TNM classification includes over 60% of all rectal tumours and encompasses the greatest variance in cancer-specific end-points than any other T category. The most recent edition of the cancer staging handbook of the American Joint Committee on Cancer (AJCC) dated 2010 does not divide T3 tumours into subgroups which reflect cancer-specific outcome more sensitively. The original aim of the present study was to review the literature to assess the influence of the degree of extramural extent of T3 rectal cancer on local recurrence and survival. An article written by the authors was accepted for publication but was withdrawn immediately after they became aware of the publication of the 4th edition of the TNM Supplement by the Union for International Cancer Control dated 2012, which was not accessible by the search system used. This article dealt with the subdivision of the T3 category although this was not included in the most up-to-date AJCC guidelines and was stated to be 'entirely optional'. Medline, PubMed and Cochrane Library searches were performed to identify all studies that investigated the degree of extramural spread and its relationship to survival and local recurrence. Twenty-two studies were identified of which 12 assessed the degree of histopathological extramural spread measured in millimetres. In 18 of the 22 studies the degree of extramural spread was a statistically significant prognostic factor for survival and local recurrence. Analysis of the studies indicated that the subdivision of category T3 rectal cancer into two subgroups of extramural spread ≤ 5 mm or more than 5 mm resulted in markedly different survival and local recurrence rates. The data were insufficient to allow validation of any greater subdivision. Measurement of the extent of extramural spread by MRI before any treatment agreed with the histopathological measurement in the surgical specimen to within 1 mm. The extent of extramural spread in T3 rectal

  9. Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven

    PubMed Central

    Holman, Fabian A.; Haddock, Michael G.; Gunderson, Leonard L.; Kusters, Miranda; Nieuwenhuijzen, Grard A. P.; van den Berg, Hetty A.; Nelson, Heidi

    2016-01-01

    Background The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. Methods In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. Results A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. Conclusions An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and

  10. 17-Week Delay Surgery after Chemoradiation in Rectal Cancer with Complete Pathological Response

    PubMed Central

    Santos, Marisa D.; Gomes, Manuel T.; Moreno, Filipa; Rocha, Anabela; Lopes, Carlos

    2015-01-01

    Neoadjuvant chemoradiation (CRT) followed by curative surgery still remains the standard of care for locally advanced rectal cancer (LARC). The main purpose of this multimodal treatment is to achieve a complete pathological tumor response (ypCR), with better survival. The surgery delay after CRT completion seems to increase tumor response and ypCR rate. Usually, time intervals range from 8 to 12 weeks, but the maximum tumor regression may not be seen in rectal adenocarcinomas until several months after CRT. About this issue, we report a case of a 52-year-old man with LARC treated with neoadjuvant CRT who developed, one month after RT completion, an acute myocardial infarction. The need to increase the interval between CRT and surgery for 17 weeks allowed a curative surgery without morbidity and an unexpected complete tumor response in the resected specimen (given the parameters presented in pelvic magnetic resonance imaging (MRI) performed 11 weeks after radiotherapy completion). PMID:26579325

  11. 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

  12. 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.

  13. 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

  14. Amount, type, and timing of recreational physical activity in relation to colon and rectal cancer in older adults: the Cancer Prevention Study II Nutrition Cohort.

    PubMed

    Chao, Ann; Connell, Cari J; Jacobs, Eric J; McCullough, Marjorie L; Patel, Alpa V; Calle, Eugenia E; Cokkinides, Vilma E; Thun, Michael J

    2004-12-01

    Physical activity has consistently been associated with lower risk of colon cancer, but information is limited on the amount, type, and timing of activities. The relationship between physical activity and rectal cancer is unclear. We examined characteristics of recreational physical activity in relation to colon and rectal cancer in the Cancer Prevention Study II Nutrition Cohort of 70,403 men and 80,771 women (median age, 63 years); 940 colon and 390 rectal cancers were identified from enrollment in 1992 to 1993 through August 1999. The multivariate-adjusted rate ratios (95% confidence intervals) associated with any recreational physical activity compared with none were 0.87 (0.71-1.06) for colon cancer and 0.70 (0.53-0.93) for rectal cancer. Colon cancer risk decreased significantly with increasing total hours (P for trend without reference group = 0.007) and metabolic equivalent hours (P for trend = 0.006) per week of activities. No clear decrease in rectal cancer risk was seen with increasing hours per week of physical activity. Rate ratios (95% confidence intervals) were 0.72 (0.52-0.98) for <2 hours, 0.68 (0.47-0.97) for 2 to 3 hours, 0.59 (0.41-0.83) for 4 to 6 hours, and 0.83 (0.59-1.16) for >/=7 hours per week of physical activity compared with none. Past exercise, as reported in 1982, was not associated with risk of either colon or rectal cancer. We conclude that increasing amounts of time spent at recreational physical activity are associated with substantially lower risk of colon cancer and that recreational physical activity is associated with lower risk of rectal cancer in older men and women.

  15. ‘I–We’ boundary fluctuations in couple adjustment to rectal cancer and life with a permanent colostomy

    PubMed Central

    McCarthy, Molly; Fergus, Karen; Miller, Debbie

    2016-01-01

    This study investigates couples’ adjustment to rectal cancer and a colostomy using the ‘Classification System of Couple Adjustment to Cancer’, a framework delineating fluctuations in couples’ sense of ‘I’ and ‘We’ in response to cancer. Nine couples affected by rectal cancer and adjusting to life with a colostomy were interviewed. A theoretical thematic analysis of the transcripts was conducted; nearly all ‘I–We’ shifts of the Classification System of Couple Adjustment to Cancer were observed – often in unique ways in response to rectal cancer–specific challenges – and one new shift was described. The results provide a novel and experientially grounded means of conceptualizing complex dyadic coping processes. PMID:28070388

  16. Pancreatic Metastasis from Rectal Cancer that was Diagnosed by Endoscopic Ultrasonography-guided Fine Needle Aspiration (EUS-FNA)

    PubMed Central

    Sano, Itsuki; Katanuma, Akio; Yane, Kei; Kin, Toshifumi; Nagai, Kazumasa; Yamazaki, Hajime; Koga, Hideaki; Kitagawa, Koh; Yokoyama, Kensuke; Ikarashi, Satoshi; Takahashi, Kuniyuki; Maguchi, Hiroyuki; Omori, Yuko; Shinohara, Toshiya

    2017-01-01

    Pancreatic metastasis from colorectal cancer is rare, and there have been only a few reports of its preoperative diagnosis by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with immunohistochemical staining. We herein describe the case of a 77-year-old woman in whom a solitary mass in the pancreatic tail was detected 11 years after rectal cancer resection. The patient also had a history of pulmonary tumor resection. We performed EUS-FNA and a histopathological examination showed adenocarcinoma with CD20+, CD7-, and CDX2+ (similar to her rectal cancer). EUS-FNA enabled a histopathological examination, including immunohistochemical staining, which helped to confirm the diagnosis of pancreatic and pulmonary metastasis from rectal cancer. PMID:28154274

  17. 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

  18. 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

  19. Rectal Dose-Volume Differences Using Proton Radiotherapy and a Rectal Balloon or Water Alone for the Treatment of Prostate Cancer

    SciTech Connect

    Vargas, Carlos Mahajan, Chaitali; Fryer, Amber; Indelicato, Daniel; Henderson, Randal H.; McKenzie, Craig C.; Horne, David C.; Chellini, Angela; Lawlor, Paula C.; Li Zuofeng; Oliver, Kenneth; Keole, Sameer

    2007-11-15

    Purpose: To describe dose-volume values with the use of water alone vs. a rectal balloon (RB) for the treatment of prostate cancer with proton therapy. Materials and Methods: We analyzed 30 proton plans for 15 patients who underwent CT and MRI scans with an RB or water alone. Simulation was performed with a modified MRI endorectal coil and an RB with 100 mL of water or water alone. Doses of 78-82 gray equivalents were prescribed to the planning target volume. The two groups were compared for three structures: rectum, rectal wall (RW), and rectal wall 7 cm (RW7) at the level of the planning target volume. Results: Rectum and RW volumes radiated to low, intermediate, and high doses were small: rectum V10, 33.7%; V50, 17.3%; and V70, 10.2%; RW V10, 32.4%; V50, 20.4%; and V70, 14.6%. The RB effectively increased the rectal volume for all cases (139.8 {+-} 44.9 mL vs. 217.7 {+-} 32.2 mL (p < 0.001). The RB also decreased the volume of the rectum radiated to doses V10-V65 (p {<=} 0.05); RW for V10-V50; and RW7 for V10-V35. An absolute rectum V50 improvement >5% was seen for the RB in 5 of 15 cases, for a benefit of 9.2% {+-} 2.3% compared with 2.4% {+-} 1.3% for the remaining 10 cases (p < 0.001). Similar benefit was seen for the rectal wall. No benefit was seen for doses {>=}70 gray equivalents for the rectum, RW, or RW7. No benefit of {<=}1% was seen with an RB in 46% for the rectum V70 and in 40% for the rectal wall V70. Conclusions: Rectum and rectal wall doses with proton radiation were low whether using water or an RB. Selected patients will have a small but significant advantage with an RB; however, water alone was well tolerated and will be an alternative for most patients.

  20. 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.

  1. Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer

    PubMed Central

    Restivo, Angelo; Cocco, Ivana Maria Francesca; Casula, Giuseppe; Scintu, Francesco; Cabras, Francesco; Scartozzi, Mario; Zorcolo, Luigi

    2015-01-01

    Background: Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer. Methods: Two hundred and forty-one patients with stage II–III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups: group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored. Results: Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19% P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13% P=0.196). Aspirin use was also associated with a better 5-year progression-free survival (86.6% vs 67.1% hazard rate (HR)=0.20; 95% CI=0.07–0.60) and overall survival (90.6% vs 73.2% HR=0.21; 95% CI=0.05–0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06–4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10–0.86). Conclusions: Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials. PMID:26372700

  2. 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.

  3. 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

  4. [A Case of Rectal Cancer Successfully Treated with Surgery and Stereotactic Radiotherapy for Metachronous Lung Metastases].

    PubMed

    Oshima, Yu; Hosoda, Yohei; Tachi, Hidekazu; Sugimoto, Takashi; Okabe, Asami; Nishiyama, Kazuhiro; Ogura, Nobuko; Komoto, Izumi; Kiyochi, Hidenori; Tsunekawa, Shoji; Tanaka, Toru; Taki, Yoshiro; Imamura, Masayuki

    2016-11-01

    A 64-year-old woman underwent polypectomy for a rectal polyp(Isp). Pathological findings were invasion of the submucosa( 3,500 mm diameter), and she underwent anterior resection for rectal cancer(RS, pT1b, pN0, cM0, Stage I )without adjuvant chemotherapy. Lung masses were found in her right(8mm)and left lung(7mm). The tumors enlarged during the 4 month follow-up period. We decided to perform left partial pneumonectomy. The tumor was diagnosed as a lung metastasis from colon cancer by pathology. Because the right tumor was located towards the center, performing right pneumonectomy would have been quite invasive and we feared occult metastases. We decided to apply SRT(50 Gy)to the right tumor. The tumor shrunk and became a scar after treatment. There were no complications such as radiation pneumonitis. The patient was in good health without any recurrence for 12 months after SRT. Surgical resection is an optimal method to control lung metastasis from colon cancer if the lesion is operable. However, in the case of a tumor centrally located, surgical resection may cause deterioration of lung function. There are also cases with contraindications for surgery due to co-morbidities. In addition, there is no consensus on observation periods to exclude occult metastases. SRT can be an effective treatment for lung metastases from colon cancer when there are bilateral lung metastases and no metastases outside the lungs.

  5. Management of Rectal Cancer: Short- vs. Long-Course Preoperative Radiation

    SciTech Connect

    Mohiuddin, Mohammed Marks, John; Marks, Gerald

    2008-11-01

    There is considerable debate on the optimum approach to neoadjuvant therapy in rectal cancer. This review of major published studies of short-course preoperative radiation and the more conventional approach of long-course neoadjuvant chemoradiation was undertaken in an effort to understand the potential advantages and disadvantages of each of these approaches. Studies were evaluated with regard to patient selection, clinical outcomes, and toxicities. Short-course preoperative radiation has shown a clear advantage over surgery alone in reducing local recurrence rates and improving survival of patients with rectal cancer. However, studies using short-course preoperative treatment have included a significant number of early (30%; Stage I/II) and more proximal cancers yet appear to have higher positive margin rates, higher abdominoperineal resection rates, and lower aggregate survival than patients treated with long-course neoadjuvant chemoradiation. Although long-course preoperative chemoradiation is associated with higher rates of reversible acute toxicity, there appears to be more significant and a higher rate of late gastrointestinal toxicity observed in short-course preoperative radiation studies. Patient convenience and lower cost of treatment, however, can be a significant advantage in using a short-course treatment schedule. Selective utilization of either of these approaches should be based on extent of disease and goals of treatment. Patients with distal cancers or more advanced disease (T3/T4) appear to have better outcomes with neoadjuvant chemoradiation, especially where downstaging of disease is critical for more complete surgical resection and sphincter preservation.

  6. VNN1 overexpression is associated with poor response to preoperative chemoradiotherapy and adverse prognosis in patients with rectal cancers

    PubMed Central

    Chai, Chi-Yung; Zhang, Yimin; Song, Junlong; Lin, Shih-Chun; Sun, Shengrong; Chang, I-Wei

    2016-01-01

    Background: Colorectal cancer is prevalent worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a public dataset of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that VNN1 was the most significantly upregulated gene among those related to nitrogen compound metabolic process (GO:0006807). Therefore, we analyzed the clinicopathological correlation and prognostic impact of VNN1 protein (pantetheinase), which encoded by VNN1 gene. Methods: VNN1 immunostaining was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by surgery, which were bisected into high- and low-expression subgroups. Furthermore, statistical analyses were performed to correlate the relationship between VNN1 immunoreactivity and clinicopathological features, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: High VNN1 immunoexpression was significantly associated with advanced pre-treatment and post-treatment disease and poor response to CCRT (all P ≤ .026). In addition, VNN1 overexpression was linked to adverse DSS, LRFS and MeFS in univariate analysis and served as an independent prognosticator indicating worse DSS and LRFS in multivariate analysis (all P ≤ .019). Conclusion: VNN1 may play a crucial role in rectal cancer progression and responsiveness to CCRT, and serve as a novel prognostic biomarker. Additional studies to clarify the molecular pathway are essential for developing potential VNN1-targeted therapies for rectal cancer. PMID:27830030

  7. 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

  8. Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer.

    PubMed

    Mardjuadi, Feby Ingriani; Carrasco, Javier; Coche, Jean-Charles; Sempoux, Christine; Jouret-Mourin, Anne; Scalliet, Pierre; Goeminne, Jean-Charles; Daisne, Jean-François; Delaunoit, Thierry; Vuylsteke, Peter; Humblet, Yves; Meert, Nicolas; van den Eynde, Marc; Moxhon, Anne; Haustermans, Karin; Canon, Jean-Luc; Machiels, Jean-Pascal

    2015-09-01

    Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5%, H1 = 17%, α = 0.05, β = 0.2). From 19 enrolled patients, 17 (89%) were evaluable for pathology assessment. Although no pCR was observed, seven patients (41%) had grade 3 Dworak pathological tumor regression. The regimen was safe and was associated with 95% of sphincter-preservation rate. No NRAS, BRAF, or PI3KCA mutation was found in this study, but one patient (5%) showed loss of PTEN expression. The quantification of plasma EGFR ligands during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration (p < 0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF-α (p = 0.03) but lower plasma EGF (p = 0.003) compared to those with grade 0-2 Dworak. Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression. However, pCR rate remained modest. Given that the primary endpoint of our study was not reached, we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting.

  9. Local advanced rectal cancer perforation in the midst of preoperative chemoradiotherapy: A case report and literature review

    PubMed Central

    Takase, Nobuhisa; Yamashita, Kimihiro; Sumi, Yasuo; Hasegawa, Hiroshi; Yamamoto, Masashi; Kanaji, Shingo; Matsuda, Yoshiko; Matsuda, Takeru; Oshikiri, Taro; Nakamura, Tetsu; Suzuki, Satoshi; Koma, Yu-Ichiro; Komatsu, Masato; Sasaki, Ryohei; Kakeji, Yoshihiro

    2017-01-01

    Standard chemoradiotherapy (CRT) for local advanced rectal cancer (LARC) rarely induce rectal perforation. Here we report a rare case of rectal perforation in a patient with LARC in the midst of preoperative CRT. A 56-year-old male was conveyed to our hospital exhibiting general malaise. Colonoscopy and imaging tests resulted in a clinical diagnosis of LARC with direct invasion to adjacent organs and regional lymphadenopathy. Preoperative 5-fluorouracil-based CRT was started. At 25 d after the start of CRT, the patient developed a typical fever. Computed tomography revealed rectal perforation, and he underwent emergency sigmoid colostomy. At 12 d after the surgery, the remaining CRT was completed according to the original plan. The histopathological findings after radical operation revealed a wide field of tumor necrosis and fibrosis without lymph node metastasis. We share this case as important evidence for the treatment of LARC perforation in the midst of preoperative CRT. PMID:28138443

  10. 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

  11. High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers

    PubMed Central

    Tunio, Mutahir Ali; Rafi, Mansoor; Hashmi, Altaf; Mohsin, Rehan; Qayyum, Abdul; Hasan, Mujahid; Sattar, Amjad; Mubarak, Muhammad

    2010-01-01

    AIM: To determine the feasibility and safety of high dose rate intraluminal brachytherapy (HDR-ILBT) boost during preoperative chemoradiation for rectal cancer. METHODS: Between 2008 and 2009, thirty-six patients with locally advanced rectal cancer (≥ T3 or N+), were treated initially with concurrent capecitabine (825 mg/m2 oral twice daily) and pelvic external beam radiotherapy (EBRT) (45 Gy in 25 fractions), then were randomized to group A; HDR-ILBT group (n = 17) to receive 5.5-7 Gy × 2 to gross tumor volume (GTV) and group B; EBRT group (n = 19) to receive 5.4 Gy × 3 fractions to GTV with EBRT. All patients underwent total mesorectal excision. RESULTS: Grade 3 acute toxicities were registered in 12 patients (70.6%) in group A and in 8 (42.1%) in group B. Complete pathologic response of T stage (ypT0) in group A was registered in 10 patients (58.8%) and in group B, 3 patients (15.8%) had ypT0 (P < 0.0001). Sphincter preservation was reported in 6/9 patients (66.7%) in group A and in 5/10 patients (50%) in group B (P < 0.01). Overall radiological response was 68.15% and 66.04% in Group A and B, respectively. During a median follow up of 18 mo, late grade 1 and 2 sequelae were registered in 3 patients (17.6%) and 4 patients (21.1%) in the groups A and B, respectively. CONCLUSION: HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers, with higher response rates, downstaging and with manageable acute toxicities. PMID:20845511

  12. 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

  13. Feasibility of transanal endoscopic total mesorectal excision for rectal cancer: results of a pilot study

    PubMed Central

    Oh, Jae Hwan; Park, Sung Chan; Kim, Min Jung; Park, Byung Kwan; Hyun, Jong Hee; Chang, Hee Jin; Han, Kyung Su

    2016-01-01

    Purpose To evaluate the feasibility of transanal total mesorectal excision (TME) in patients with rectal cancer. Methods This study enrolled 12 patients with clinically node negative rectal cancer located 4–12 cm from the anal verge who underwent transanal endoscopic TME with the assistance of single port laparoscopic surgery between September 2013 and August 2014. The primary endpoint was TME quality; secondary endpoints included number of harvested lymph nodes and postoperative complications within 30 days (NCT01938027). Results The 12 patients included 7 males and 5 females, of median age 59 years and median body mass index 24.2 kg/m2. Tumors were located on average 6.7 cm from the anal verge. Four patients (33.3%) received preoperative chemoradiotherapy. Median operating time was 195 minutes and median blood loss was 50 mL. There were no intraoperative complications and no conversions to open surgery. TME was complete or nearly complete in 11 patients (91.7%). Median distal resection and circumferential resection margins were 18.5 mm and 10 mm, respectively. Median number of harvested lymph nodes was 15. Median length of hospital stay was 9 days. There were no postoperative deaths. Six patients experienced minor postoperative complications, including urinary dysfunction in 2, transient ileus in 3, and wound abscess in 1. Conclusion This pilot study showed that high-quality TME was possible in most patients without serious complications. Transanal TME for patients with rectal cancer may be feasible and safe, but further investigations are necessary to evaluate its long-term functional and oncologic outcomes and to clarify its indications. PMID:27757396

  14. 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

  15. Fortune of temporary ileostomies in patients treated with laparoscopic low anterior resection for rectal cancer

    PubMed Central

    Haksal, Mustafa; Okkabaz, Nuri; Atici, Ali Emre; Civil, Osman; Ozdenkaya, Yasar; Erdemir, Ayhan; Aksakal, Nihat

    2017-01-01

    Purpose The current study aims to analyze the risk factors for the failure of ileostomy reversal after laparoscopic low anterior resection for rectal cancer. Methods All patients who underwent a laparoscopic low anterior resection for rectal cancer with a diverting ileostomy between 2007 and 2014 were abstracted. The patients who underwent and did not undergo a diverting ileostomy procedure were compared regarding patient, tumor, treatment related parameters, and survival. Results Among 160 (103 males [64.4%], mean [± standard deviation] age was 58.1 ± 11.9 years) patients, stoma reversal was achieved in 136 cases (85%). Anastomotic stricture (n = 13, 52.4%) was the most common reason for stoma reversal. These were the risk factors for the failure of stoma reversal: Male sex (P = 0.035), having complications (P = 0.01), particularly an anastomotic leak (P < 0.001), or surgical site infection (P = 0.019) especially evisceration (P = 0.011), requirement for reoperation (P = 0.003) and longer hospital stay (P = 0.004). Multivariate analysis revealed that male sex (odds ratio [OR], 7.82; P = 0.022) and additional organ resection (OR, 6.71; P = 0.027) were the risk factors. Five-year survival rates were similar (P = 0.143). Conclusion Fifteen percent of patients cannot receive a stoma reversal after laparoscopic low anterior resection for rectal cancer. Anastomotic stricture is the most common reason for the failure of stoma takedown. Having complications, particularly an anastomotic leak and the necessity of reoperation, limits the stoma closure rate. Male sex and additional organ resection are the risk factors for the failure in multivariate analyses. These patients require a longer hospitalization period, but have similar survival rates as those who receive stoma closure procedure. PMID:28090504

  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. 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.

  18. Short-course radiation versus long-course chemoradiation for rectal cancer.

    PubMed

    Minsky, Bruce D; Rödel, Claus; Valentini, Vincenzo

    2012-10-01

    The 2 broad approaches to preoperative therapy for rectal cancer are chemoradiation and short-course radiation. The outcomes of these 2 approaches reported in nonrandomized trials are not comparable because patients selected for treatment with short-course radiotherapy included those with cT1-3 disease, whereas patients selected for chemoradiation included those with T3 and/or N+ disease. However, more recent trials of short-course radiation have included patients with cT3 and/or N+ disease who also underwent sequential or postoperative chemotherapy, allowing a more relevant comparison with chemoradiation. This article compares the 2 preoperative approaches and addresses their emerging roles.

  19. [A case with liver resection of metastasis from rectal cancer after FOLFOX4+bevacizumab treatment].

    PubMed

    Kojima, Taiki; Matsui, Takanori; Uemura, Takanori; Fujimitsu, Yasunobu; Kure, Narihiro; Kojima, Hiroshi

    2008-10-01

    We report a 59-year-old woman with rectal cancer who underwent low anterior resection in March 2007. After curative operation at Stage IIIb(pT3N2M0), multiple liver metastasis was diagnosed in May 2007. Chemotherapy with FOLFOX4+bevacizumab was performed from June to August in 2007, and liver resection(left lobectomy and partial resection)was performed in September 2007. Bevacizumab was newly available from June 2007 in Japan, and liver resection after bevacizumab administration was safely performed.

  20. Neoadjuvant treatment for rectal cancer-A value-based proposition.

    PubMed

    Massarweh, Nader N; Artinyan, Avo; Chang, George J

    2016-09-01

    Over the last decade, the use of neoadjuvant chemo-radiation has been an integral part of the care of patients with locally advanced rectal cancer. However, emerging data are beginning to challenge the current treatment paradigm of neoadjuvant chemo-radiation followed by radical resection and subsequent adjuvant chemotherapy. Going forward, the challenge will be to identify patients for whom radiation can be safely omitted and those for whom it can potentially provide added oncologic value. J. Surg. Oncol. 2016;114:304-310. © 2016 Wiley Periodicals, Inc.

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

    PubMed

    2012-07-18

    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.

  2. 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

  3. Nitrates in drinking water and the risk of death from rectal cancer: does hardness in drinking water matter?

    PubMed

    Chang, Chih-Ching; Chen, Chih-Cheng; Wu, Deng-Chuang; Yang, Chun-Yuh

    2010-01-01

    The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and increased risk of death from rectal cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of nitrate on development of rectal cancer. A matched case-control study was used to investigate the relationship between the risk of death from rectal cancer and exposure to nitrate in drinking water in Taiwan. All rectal cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N), Ca, and Mg in drinking water was collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO(3)-N exposure level was <0.38 ppm, the adjusted odds ratio (OR) (95% CI) for rectal cancer occurrence was 1.15 (1.01-1.32) for individuals who resided in municipalities served by drinking water with a NO(3)-N exposure > or =0.38 ppm. There was no apparent evidence of an interaction between drinking water NO(3)-N levels with low Mg intake via drinking water. However, evidence of a significant interaction was noted between drinking-water NO(3)-N concentrations and Ca intake via drinking water. Our findings showed that the correlation between NO(3)-N exposure and risk of rectal cancer development was influenced by Ca in drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO(3)-N exposure and risk of rectal cancer occurrence. Increased knowledge of the mechanistic interaction between Ca and NO(3)-N in reducing

  4. A system biology approach for understanding the miRNA regulatory network in colon rectal cancer.

    PubMed

    Pradhan, Meeta; Nagulapalli, Kshithija; Ledford, Lakenvia; Pandit, Yogesh; Palakal, Mathew

    2015-01-01

    In this paper we present a systems biology approach to the understanding of the miRNA-regulatory network in colon rectal cancer. An initial set of significant genes in Colon Rectal Cancer (CRC) were obtained by mining relevant literature. An initial set of cancer-related miRNAs were obtained from three databases: miRBase, miRWalk, Targetscan and GEO microarray experiment. First principle methods were then used to generate the global miRNA-gene network. Significant miRNAs and associated transcription factors in the global miRNA-gene network were identified using topological and sub-graph analyses. Eleven novel miRNAs were identified and three of the novel miRNAs, hsa-miR-630, hsa-miR-100 and hsa-miR-99a, were further analysed to elucidate their role in CRC. The proposed methodology effectively made use of literature data and was able to show novel, significant miRNA-transcription associations in CRC.

  5. Synergistic effects of AKAP95, Cyclin D1, Cyclin E1, and Cx43 in the development of rectal cancer

    PubMed Central

    Qi, Fengjie; Yuan, Yangyang; Zhi, Xuehong; Huang, Qian; Chen, Yuexin; Zhuang, Wenxin; Zhang, Dengcheng; Teng, Bogang; Kong, Xiangyu; Zhang, Yongxing

    2015-01-01

    Objective: To explore the expression of A-kinase anchor protein 95 (AKAP95), Cyclin D1, Cyclin E1, and Connexin43 (Cx43) in rectal cancer tissues and assess the associations between each of the proteins and pathological parameters, as well as their inter-relationships. Methods: AKAP95, Cyclin D1, Cyclin E1, and Cx43 protein expression rates were evaluated by immunohistochemistry in 50 rectal cancer specimens and 16 pericarcinoma tissues. Results: The positive rates of AKAP95, Cyclin E1, and Cyclin D1 proteins were 54.00 vs. 18.75%, 62.00 vs. 6.25%, and 72.00 vs. 31.25% in rectal cancer specimens and pericarcinoma tissues, respectively, representing statistically significant differences (P < 0.05). The positive rate of Cx43 protein expression in rectal cancer tissues was 44.00% and 62.50% in pericarcinoma tissues, and the difference between them was not significant (P > 0.05). No significant associations were found between protein expression of AKAP95, Cyclin E1, Cyclin D1, and Cx43, and the degree of differentiation, histological type, and lymph node metastasis of rectal cancer (P > 0.05). However, significant correlations were obtained between the expression rates of AKAP95 and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43 protein, and Cyclin D1 and Cx43, respectively (P < 0.05). Conclusion: AKAP95, Cyclin E1, and Cyclin D1 protein expression rates were significantly higher in rectal cancer tissues compared with pericarcinoma samples, suggesting an association between these proteins and the development and progression of rectal cancer. In addition, the significant correlations between the proteins (AKAP95 and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43 protein, and Cyclin D1 and Cx43) indicate the possible synergistic effects of these factors in the development and progression of rectal cancer. PMID:25973052

  6. Trihalomethanes in drinking water and the risk of death from rectal cancer: does hardness in drinking water matter?

    PubMed

    Kuo, Hsin-Wei; Chen, Pei-Shih; Ho, Shu-Chen; Wang, Li-Yu; Yang, Chun-Yuh

    2010-01-01

    The objectives of this study were (1) to examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of rectal cancer development and (2) to determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of TTHM on risk of developing rectal cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to rectal cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All rectal cancer deaths in the 53 municipalities from 1998 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from the Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for rectal cancer occurrence was 1.04 (0.88-1.22) for individuals who resided in municipalities served by drinking water with a TTHM exposure >or=4.9 ppb. There was no evidence of an interaction of drinking-water TTHM levels with low Ca intake via drinking water. However, evidence of an interaction was noted between drinking-water TTHM concentrations and Mg intake via drinking water. Our findings showed that the correlation between TTHM exposure and risk of rectal cancer is influenced by Mg in drinking water. Increased knowledge of the interaction between Mg and TTHM in reducing rectal cancer risk will aid

  7. Discriminating cancer-related and cancer-unrelated chemoradiation-response genes for locally advanced rectal cancers

    PubMed Central

    Guo, You; Cheng, Jun; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Zhang, Juan; Yan, Haidan; Cai, Hao; Gao, Qiao; Jiang, Weizhong; Guo, Zheng

    2016-01-01

    For patients with locally advanced rectal cancer (LARC) treated with preoperation chemoradiation (pCRT), identifying differentially expressed (DE) genes between non-responders and responders is a common approach for investigating mechanisms of chemoradiation resistance. However, some of such DE genes might be irrelevant to cancer itself but simply reflect the pharmacokinetic differences of the normal tissues. In this study, we adopted the RankComp algorithm to identify DE genes for each of LARC sample compared with its own normal state. Then, we identified genes with significantly different deregulation frequencies between the non-responders and responders, defined as cancer-related pCRT-response genes. Pathway enrichment and protein-protein interaction analyses showed that these genes specifically and intensively interacted with currently known effective genes of pCRT, involving in DNA replication, cell cycle and DNA repair. In contrast, after excluding the cancer-related pCRT-response genes, the other DE genes between non-responders and responders were enriched in many pathways of drug and protein metabolisms and transports, and interacted with both the known effective genes and pharmacokinetic genes. Hence, these two types of DE genes should be distinguished for investigating mechanisms of pCRT response in LARCs. PMID:27845363

  8. 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.

  9. 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.

  10. 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.

  11. Risk Factors Associated With Sphincter-Preserving Resection in Patients With Low Rectal Cancer

    PubMed Central

    Cong, Zhi-Jie; Hu, Liang-Hao; Xing, Jun-Jie; Zhang, Wei; Fu, Chuan-Gang; Yu, En-Da; Zhong, Ming

    2014-01-01

    Abdominoperineal resection (APR) and sphincter-preserving resection (SPR) are the two primary surgical options for rectal cancer. Retrospectively we collected rectal cancer patients for SPR and APR observation between 2005 and 2007. The patient-related, tumor-related, and surgery-related variables of the SPR and APR groups were analyzed by using logistic regression techniques. The mean distance from the anal verge (DAV) of cancer is significantly higher in SPR than that in APR (P < 0.001). In cancers with DAV <40 mm (SPR, 40 versus APR, 110), multivariate analysis shows that surgeon procedure volume (odds ratio [OR] = 0.244; 95% confidence interval [CI]: 0.077–0.772; P = 0.016) and neoadjuvant radiotherapy (OR = 0.031; 95% CI: 0.002–0.396; P = 0.008) are factors influencing SPR. In cancers with DAV ranging from 40 mm to 59 mm (SPR 190 versus APR 50), analysis shows that patient age (OR = 2.139; 95% CI: 1.124–4.069; P = 0.021), diabetes (OR = 2.657; 95% CI: 0.872–8.095; P = 0.086), and colorectal surgeon (OR = 0.122, 95% CI: 0.020–0.758; P = 0.024), are influencing factors for SPR. The local recurrence and disease-free survival reveal no significant difference. A significant difference exists in DAV, surgeon specialization, procedure volume, age, diabetes, and neoadjuvant radiotherapy between SPR and APR. PMID:25058761

  12. Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: science, opinions and experiences from the experts of surgery.

    PubMed

    van de Velde, C J H; Boelens, P G; Tanis, P J; Espin, E; Mroczkowski, P; Naredi, P; Pahlman, L; Ortiz, H; Rutten, H J; Breugom, A J; Smith, J J; Wibe, A; Wiggers, T; Valentini, V

    2014-04-01

    The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?

  13. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer.

    PubMed

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-08-10

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients.

  14. The evaluation of the oxidative stress for patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer

    PubMed Central

    Serbanescu, GL; Gruia, MI; Bara, M; Anghel, RM

    2017-01-01

    Hypothesis: Nowadays, rectal cancer is an important healthcare challenge that affects many thousands of people each year worldwide, being diagnosed especially after the age of 50 years. Objective: This study attempted to evaluate the oxidative stress in patients with rectal cancer. Methods and results: 30 patients from the “Prof. Dr. Al. Trestioreanu” Institute of Oncology in Bucharest were treated with neoadjuvant radiochemotherapy during 2014 and 2016 and were included in the clinical study. Blood samples were obtained in dynamics during the treatment. From the blood samples, the serum was separated and used to identify the biochemical oxidative stress parameters. Results: Regarding the determination of lipid peroxides, albumin thiols, the cuprum oxidase activity of ceruloplasmin, the values registered in the dynamic of the treatment highlighted their increase to a maximum at the treatment’s endpoint due to an important oxidative stress. Regarding the serum values for total antioxidants, the results pointed out the activation of the natural protection systems, which in time were overwhelmed, due to the installed oxidative stress. Conclusion: Part of the cytotoxic effect of radiotherapy was due to the production of oxidative stress. The cell was constantly exposed to the cytotoxic action of the reactive oxygen species. The obtained results indicated the dual relation to which the tumoral cell exposed itself and the installed oxidative stress, respectively, the oxidative stress being a cause or a consequence of the malign transformation. Abbreviations: CT = computed tomography, MRI = magnetic resonance imaging, ESMO = European Society for Medical Oncology, ECOG = performance status scale PMID:28255388

  15. [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.

  16. Progress in the treatment of locally advanced clinically resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-12-01

    There have been significant developments in the adjuvant treatment of locally advanced clinically resectable (T3 and/or N+) rectal cancer. Postoperative systemic chemotherapy plus concurrent pelvic irradiation (chemoradiation) significantly improves local control and survival compared with surgery alone. The German Rectal Cancer Trial confirmed that when chemoradiation is delivered preoperatively there is a significant decrease in acute and late toxicity and a corresponding increase in local control and sphincter preservation. Despite these advances, controversies remain. Among these controversies are the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery after chemoradiation can be modified based on tumor response. Are there more accurate imaging techniques and/or molecular markers to help identify patients with positive pelvic nodes with the goal of reducing the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve outcome and modify the need for pelvic irradiation? This review examines the advances in chemoradiation as well as addresses these and other opportunities for improvement.

  17. The evaluation of the oxidative stress for patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

    PubMed

    Serbanescu, G L; Gruia, M I; Bara, M; Anghel, R M

    2017-01-01

    Hypothesis: Nowadays, rectal cancer is an important healthcare challenge that affects many thousands of people each year worldwide, being diagnosed especially after the age of 50 years. Objective: This study attempted to evaluate the oxidative stress in patients with rectal cancer. Methods and results: 30 patients from the "Prof. Dr. Al. Trestioreanu" Institute of Oncology in Bucharest were treated with neoadjuvant radiochemotherapy during 2014 and 2016 and were included in the clinical study. Blood samples were obtained in dynamics during the treatment. From the blood samples, the serum was separated and used to identify the biochemical oxidative stress parameters. Results: Regarding the determination of lipid peroxides, albumin thiols, the cuprum oxidase activity of ceruloplasmin, the values registered in the dynamic of the treatment highlighted their increase to a maximum at the treatment's endpoint due to an important oxidative stress. Regarding the serum values for total antioxidants, the results pointed out the activation of the natural protection systems, which in time were overwhelmed, due to the installed oxidative stress. Conclusion: Part of the cytotoxic effect of radiotherapy was due to the production of oxidative stress. The cell was constantly exposed to the cytotoxic action of the reactive oxygen species. The obtained results indicated the dual relation to which the tumoral cell exposed itself and the installed oxidative stress, respectively, the oxidative stress being a cause or a consequence of the malign transformation. Abbreviations: CT = computed tomography, MRI = magnetic resonance imaging, ESMO = European Society for Medical Oncology, ECOG = performance status scale.

  18. 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.

  19. COX-2 verexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

    SciTech Connect

    Smith, Fraser M.; Reynolds, John V. . E-mail: reynoldsjv@stjames.ie; Kay, Elaine W.; Crotty, Paul; Murphy, James O.; Hollywood, Donal; Gaffney, Eoin F.; Stephens, Richard B.; Kennedy, M. John

    2006-02-01

    Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). Methods and Materials: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. Results: Good response (TRG 1 + 2), moderate response (TRG 3), and poor response (TRG 4 + 5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3 + 4) to treatment than were those with normal COX-2 expression (p = 0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p = 0.0007, chi-square test). Conclusions: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.

  20. 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.

  1. [A case of liver metastasis of rectal cancer demonstrating complete response to 5-FU + Leucovorin + UFT].

    PubMed

    Ishida, Hideyuki; Ohsawa, Tomonori; Takeuchi, Ikuya; Nakada, Hiroshi; Inokuma, Shigehisa; Hoshino, Takanobu; Daijo, Hashimoto

    2002-04-01

    Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme that metabolizes 5-fluorouracil (5-FU). We report a patient with metachronous liver metastasis from rectal cancer with low expression of DPD, who demonstrated complete response to chemotherapy comprising 5-FU, Leucovorin, and UFT. A 53-year-old man underwent macroscopically curative proctectomy with coloanal anastomosis for lower rectal cancer (Curability B). The DPD level in the primary tumor determined by an enzyme-linked immunosorbent assay was extremely low (10.3 U/mg.protein). Three months postoperatively, 5-FU (333 mg/m2) + Leucovorin (200 mg/m2) therapy (once a week for 3 weeks with a one-week rest interval, repeatedly) was started as an adjuvant therapy. However, computed tomography demonstrated a solitary liver metastasis 3 cm in size 1 month later. Chemotherapy was continued with dose escalation of 5-FU (500 mg/m2) and with oral administration of UFT-E (400 mg/body, daily). Five months later, computed tomography did not detect the liver metastasis, and this finding was maintained for two months (complete response). This case provides evidence that a low expression of DPD in the primary lesion is related to a favorable response of liver metastasis to 5-FU-based systemic chemotherapy.

  2. STED super-resolution microscopy of clinical paraffin-embedded human rectal cancer tissue.

    PubMed

    Ilgen, Peter; Stoldt, Stefan; Conradi, Lena-Christin; Wurm, Christian Andreas; Rüschoff, Josef; Ghadimi, B Michael; Liersch, Torsten; Jakobs, Stefan

    2014-01-01

    Formalin fixed and paraffin-embedded human tissue resected during cancer surgery is indispensable for diagnostic and therapeutic purposes and represents a vast and largely unexploited resource for research. Optical microscopy of such specimen is curtailed by the diffraction-limited resolution of conventional optical microscopy. To overcome this limitation, we used STED super-resolution microscopy enabling optical resolution well below the diffraction barrier. We visualized nanoscale protein distributions in sections of well-annotated paraffin-embedded human rectal cancer tissue stored in a clinical repository. Using antisera against several mitochondrial proteins, STED microscopy revealed distinct sub-mitochondrial protein distributions, suggesting a high level of structural preservation. Analysis of human tissues stored for up to 17 years demonstrated that these samples were still amenable for super-resolution microscopy. STED microscopy of sections of HER2 positive rectal adenocarcinoma revealed details in the surface and intracellular HER2 distribution that were blurred in the corresponding conventional images, demonstrating the potential of super-resolution microscopy to explore the thus far largely untapped nanoscale regime in tissues stored in biorepositories.

  3. Matched case-control analysis comparing oncologic outcomes between preoperative and postoperative chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Byoung Chul; Park, In Ja; Kim, Chan Wook; Lim, Seok-Byung; Yu, Chang Sik

    2017-01-01

    Purpose To investigate patterns of recurrence and oncologic outcomes after recurrence between preoperative and postoperative chemoradiotherapy (CRT). Methods Records of patients with stage II or III locally advanced rectal cancer seen between January 2000 and December 2010 were analyzed. The outcomes for patients undergoing preoperative CRT followed by radical resection (n = 466) were compared with outcomes of patients matched for sex, age, and stage who had surgery and then postoperative CRT (n = 466). Recurrence rates and sites, treatment of recurrence, and oncologic outcomes after recurrence were investigated. The rate of sphincter preservation and permanent stoma formation were also evaluated. Results Recurrence occurred in 124 and 140 patients in the pre- and postoperative CRT groups, respectively. The local and systemic recurrence rates were 3.6% and 20.8%, respectively, in the preoperative CRT group and 3.0% and 25.3%, respectively, in the postoperative CRT group (P = 0.245). Time to recurrence was longer in the postoperative CRT group (19 months vs. 24.2 months, P = 0.029). The overall rates of sphincter preservation (sphincter preservation operation and postoperative permanent stoma formation) did not significantly different between the two groups (P = 0.381). The 5-year overall survival rate after recurrence did not differ between the two groups (25.6% vs. 18.6%, P = 0.051). Conclusion Preoperative and postoperative CRT are both safe and suitable treatment methods for rectal cancer, so the choice can be tailored to the patient's situation. PMID:28382292

  4. 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

  5. Decision-making in rectal and colorectal cancer: systematic review and qualitative analysis of surgeons' preferences.

    PubMed

    Broc, Guillaume; Gana, Kamel; Denost, Quentin; Quintard, Bruno

    2017-04-01

    Surgeons are experiencing difficulties implementing recommendations not only owing to incomplete, confusing or conflicting information but also to the increasing involvement of patients in decisions relating to their health. This study sought to establish which common factors including heuristic factors guide surgeons' decision-making in colon and rectal cancers. We conducted a systematic literature review of surgeons' decision-making factors related to colon and rectal cancer treatment. Eleven of 349 identified publications were eligible for data analyses. Using the IRaMuTeQ (Interface of R for the Multidimensional Analyses of Texts and Questionnaire), we carried out a qualitative analysis of the significant factors collected in the studies reviewed. Several validation procedures were applied to control the robustness of the findings. Five categories of factors (i.e. patient, surgeon, treatment, tumor and organizational cues) were found to influence surgeons' decision-making. Specifically, all decision criteria including biomedical (e.g. tumor information) and heuristic (e.g. surgeons' dispositional factors) criteria converged towards the factor 'age of patient' in the similarity analysis. In the light of the results, we propose an explanatory model showing the impact of heuristic criteria on medical issues (i.e. diagnosis, prognosis, treatment features, etc.) and thus on decision-making. Finally, the psychosocial complexity involved in decision-making is discussed and a medico-psycho-social grid for use in multidisciplinary meetings is proposed.

  6. 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

  7. 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

  8. Response to chemoradiotherapy and lymph node involvement in locally advanced rectal cancer

    PubMed Central

    García-Flórez, Luis J; Gómez-Álvarez, Guillermo; Frunza, Ana M; Barneo-Serra, Luis; Fresno-Forcelledo, Manuel F

    2015-01-01

    AIM: To establish the association between lymph node involvement and the response to neoadjuvant therapy in locally advanced rectal cancer. METHODS: Data of 130 patients with mid and low locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation followed by radical surgery over a 5-year period were reviewed. Tumor staging was done by endorectal ultrasound and/or magnetic resonance imaging. Tumor response to neoadjuvant therapy was determined by T-downstaging and tumor regression grading (TRG). Pathologic complete response (pCR) is defined as the absence of tumor cells in the surgical specimen (ypT0N0). The varying degrees TRG were classified according to Mandard’s scoring system. The evaluation of the response is based on the comparison between previous clinico-radiological staging and the results of pathological evaluation. χ2 and Spearman’s correlation tests were used for the comparison of variables. RESULTS: Pathologic complete response (pCR, ypT0N0, TRG1) was observed in 19 cases (14.6%), and other 18 (13.8%) had only very few residual malignant cells in the rectal wall (TRG2). T-downstaging was found in 63 (48.5%). Mean lymph node retrieval was 9.4 (range 0-38). In 37 cases (28.5%) more than 12 nodes were identified in the surgical specimen. Preoperative lymph node involvement was seen in 77 patients (59.2%), 71 N1 and 6 N2. Postoperative lymph node involvement was observed in 41 patients (31.5%), 29 N1 and 12 N2, while the remaining 89 were N0 (68.5%). In relation to ypT stage, we found nodal involvement of 9.4% in ypT0-1, 22.2% in ypT2 and 43.7% in ypT3-4. Of the 37 patients considered “responders” to neoadjuvant therapy (TRG1 and 2), there were only 4 N+ (10.8%) and the remainder N0 (89.2%). In the “non responders” group (TRG 3, 4 and 5), 37 cases were N+ (39.8%) and 56 (60.2%) were N0 (P < 0.001). CONCLUSION: Response to neoadjuvant chemoradiation in rectal cancer is associated with lymph node involvement. PMID:26425268

  9. Paf15 expression correlates with rectal cancer prognosis, cell proliferation and radiation response

    PubMed Central

    Yan, Rong; Zhu, Kun; Dang, Chengxue; Lan, Ke; Wang, Haonan; Yuan, Dawei; Chen, Wei; Meltzer, Stephen J.; Li, Kang

    2016-01-01

    Paf15, which participates in DNA repair, is overexpressed in numerous solid tumors. Blocking of Paf15 inhibits the growth of many types of cancer cells; while simultaneously enhancing cellular sensitivity to UV radiation. However, its expression and function in rectal cancer (RC) remain unknown. The current study was undertaken to assess the association of Paf15 expression with RC prognosis, as well as to explore the participation of Paf15 in the response of RC cells to irradiation. Increased Paf15 expression was observed in RC tissues and associated with pTNM stage and poor survival. In vitro, Paf15 induced increased RC cell proliferation while accelerating cell cycle progression, inhibiting cell death, and protecting against gamma radiation-induced DNA damage in RC cells. In conclusion, increased Paf15 expression is associated with increased RC proliferation, decreased patient survival, and a worse radiotherapeutic response. PMID:27246972

  10. 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

  11. The Role of Robotic Surgery for Rectal Cancer: Overcoming Technical Challenges in Laparoscopic Surgery by Advanced Techniques.

    PubMed

    Park, Seungwan; Kim, Nam Kyu

    2015-07-01

    The conventional laparoscopic approach to rectal surgery has several limitations, and therefore many colorectal surgeons have great expectations for the robotic surgical system as an alternative modality in overcoming challenges of laparoscopic surgery and thus enhancing oncologic and functional outcomes. This review explores the possibility of robotic surgery as an alternative approach in laparoscopic surgery for rectal cancer. The da Vinci® Surgical System was developed specifically to compensate for the technical limitations of laparoscopic instruments in rectal surgery. The robotic rectal surgery is associated with comparable or better oncologic and pathologic outcomes, as well as low morbidity and mortality. The robotic surgery is generally easier to learn than laparoscopic surgery, improving the probability of autonomic nerve preservation and genitourinary function recovery. Furthermore, in very complex procedures such as intersphincteric dissections and transabdominal transections of the levator muscle, the robotic approach is associated with increased performance and safety compared to laparoscopic surgery. The robotic surgery for rectal cancer is an advanced technique that may resolve the issues associated with laparoscopic surgery. However, high cost of robotic surgery must be addressed before it can become the new standard treatment.

  12. [Experience with radiofrequency ablation in the treatment of unresectable pelvic recurrence of rectal cancer].

    PubMed

    Mátrai, Zoltán; Fehér, István; Péley, Gábor; Rényi Vámos, Ferenc; Farkas, Emil; Sulyok, Zoltán; Kovács, Tibor; Köves, István

    2005-02-01

    More than half of colorectal cancers are located in the rectum, and the number of such cancers is increasing. In Hungary colorectal cancers are diagnosed predominantly in advanced stages. In the last five years 736 patients with colorectal cancer were operated on at our Department, with the following stage distribution: Dukes A 10%, BI 10%, B2 31%, C 36% and D 13%. The local recurrence rate is decreasing since the introduction of total mesorectal excision and preoperative radiation. Effective treatment options are however poor for unresectable pelvic recurrences. Chemo- and radiotherapy have severe limitations in this advanced stage cancer. In recent years there are a few publications on the minimal-invasive radiofrequency tumour ablation (RFTA) technique, which is an effective treatment for primary and metastatic liver carcinomas and is a new palliative for the local treatment of pelvic recurrence. The aim of this study was to assess the response to treatment using ultrasound-guided radiofrequency ablation in two patients with unresectable pelvic recurrent rectal cancer.

  13. 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.

  14. Long-term Effect of Radiotherapy in Rectal Cancer Patients with Mucinous Tumor: A Large Population Based Study

    PubMed Central

    Guan, Xu; Jia, Senhao; Chen, Wei; Jiang, Zheng; Liu, Zheng; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

    2017-01-01

    Due to distinct biological behavior of mucinous adenocarcinoma (MAC) and signet ring cell cancer (SRC), the efficacy of radiotherapy on long-term outcome for rectal cancer (RC) patients with mucinous tumors is still unclear. Here, we identified 1808 RC patients with MAC/SRC from Surveillance, Epidemiology, and End-Results (SEER) database from 2004 to 2013. Patients were divided into two subgroups according to different therapeutic strategies, including surgery alone and surgery combined with radiotherapy. Kaplan–Meier methods and Cox regression models were used to access the influence of therapeutic strategy on long-term survival outcomes. The 5-year and 10-year cancer specific survival (CSS) were improved in stage II and III patients who underwent surgery and radiotherapy compared with patients who underwent surgery alone. These results were further confirmed following propensity score matching. In addition, radiotherapy was deemed as independent good prognostic factor in patient with MAC/SRC. In subgroup analysis, the result also demonstrated that long-term survival was improved following radiotherapy. However, there was no prognostic difference between preoperative and postoperative radiotherapy. In conclusion, radiotherapy could improve survival for RC patients with MAC and SRC, but only for patients in stage II and III. This finding supported the application of radiotherapy in clinical practice. PMID:28272410

  15. 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

  16. 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

  17. Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response.

    PubMed

    McCoy, Melanie J; Hemmings, Chris; Anyaegbu, Chidozie C; Austin, Stephanie J; Lee-Pullen, Tracey F; Miller, Timothy J; Bulsara, Max K; Zeps, Nikolajs; Nowak, Anna K; Lake, Richard A; Platell, Cameron F

    2017-02-03

    Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3+, CD8+ and CD3+ cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response.

  18. Preliminary report of a new treatment strategy for advanced pelvic malignancy: surgical resection and radiation therapy using afterloading catheters plus an inflatable displacement prosthesis in the treatment of advanced primary and recurrent rectal cancer

    SciTech Connect

    Edington, H.D.; Hancock, S.; Coe, F.L.; Sugarbaker, P.H.

    1986-09-01

    An unsolved problem in colon and rectal surgery involves the treatment of locally invasive primary and recurrent rectal cancer. An approach is described that uses intracavitary iridium-192 sources in combination with a pelvic displacement prosthesis to augment external beam radiation doses to sites of residual disease identified at surgery. This approach should permit administration of tumoricidal doses of radiation to positive surgical margins minimizing radiation toxicity to the small bowel. The radiation source and all prosthetic materials are removed at the bedside within 2 weeks of surgery, ensuring accurate radiation dosimetry, minimizing infectious complications, and sparing the patient the need for full high-dose pelvic irradiation.

  19. Automatic segmentation software in locally advanced rectal cancer: READY (REsearch program in Auto Delineation sYstem)-RECTAL 02: prospective study.

    PubMed

    Gambacorta, Maria A; Boldrini, Luca; Valentini, Chiara; Dinapoli, Nicola; Mattiucci, Gian C; Chiloiro, Giuditta; Pasini, Danilo; Manfrida, Stefania; Caria, Nicola; Minsky, Bruce D; Valentini, Vincenzo

    2016-07-05

    To validate autocontouring software (AS) in a clinical practice including a two steps delineation quality assurance (QA) procedure.The existing delineation agreement among experts for rectal cancer and the overlap and time criteria that have to be verified to allow the use of AS were defined.Median Dice Similarity Coefficient (MDSC), Mean slicewise Hausdorff Distances (MSHD) and Total-Time saving (TT) were analyzed.Two expert Radiation Oncologists reviewed CT-scans of 44 patients and agreed the reference-CTV: the first 14 consecutive cases were used to populate the software Atlas and 30 were used as Test.Each expert performed a manual (group A) and an automatic delineation (group B) of 15 Test patients.The delineations were compared with the reference contours.The overlap between the manual and automatic delineations with MDSC and MSHD and the TT were analyzed.Three acceptance criteria were set: MDSC ≥ 0.75, MSHD ≤1mm and TT sparing ≥ 50%.At least 2 criteria had to be met, one of which had to be TT saving, to validate the system.The MDSC was 0.75, MSHD 2.00 mm and the TT saving 55.5% between group A and group B. MDSC among experts was 0.84.Autosegmentation systems in rectal cancer partially met acceptability criteria with the present version.

  20. Automatic segmentation software in locally advanced rectal cancer: READY (REsearch program in Auto Delineation sYstem)-RECTAL 02: prospective study

    PubMed Central

    Dinapoli, Nicola; Mattiucci, Gian C.; Chiloiro, Giuditta; Pasini, Danilo; Manfrida, Stefania; Caria, Nicola; Minsky, Bruce D.

    2016-01-01

    To validate autocontouring software (AS) in a clinical practice including a two steps delineation quality assurance (QA) procedure. The existing delineation agreement among experts for rectal cancer and the overlap and time criteria that have to be verified to allow the use of AS were defined. Median Dice Similarity Coefficient (MDSC), Mean slicewise Hausdorff Distances (MSHD) and Total-Time saving (TT) were analyzed. Two expert Radiation Oncologists reviewed CT-scans of 44 patients and agreed the reference-CTV: the first 14 consecutive cases were used to populate the software Atlas and 30 were used as Test. Each expert performed a manual (group A) and an automatic delineation (group B) of 15 Test patients. The delineations were compared with the reference contours. The overlap between the manual and automatic delineations with MDSC and MSHD and the TT were analyzed. Three acceptance criteria were set: MDSC ≥ 0.75, MSHD ≤1mm and TT sparing ≥ 50%. At least 2 criteria had to be met, one of which had to be TT saving, to validate the system. The MDSC was 0.75, MSHD 2.00 mm and the TT saving 55.5% between group A and group B. MDSC among experts was 0.84. Autosegmentation systems in rectal cancer partially met acceptability criteria with the present version. PMID:27302924

  1. 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

  2. Definitive high-dose radiotherapy with concurrent chemotherapy for locally advanced rectal cancer

    PubMed Central

    Kim, Min-Jeong; Kim, Eun Seok; Yeo, Seung-Gu

    2016-01-01

    Abstract Background: Standard management for locally advanced rectal cancer (LARC) involves preoperative chemoradiotherapy (CRT) and radical surgery. However, this level of treatment may be unnecessary for a subgroup of LARC patients. Previous reports have shown that approximately 20% of LARC patients experience a complete tumor response to preoperative CRT. Post-CRT nonoperative management of these patients may prevent morbidities associated with radical surgery. To our knowledge, this case report firstly presents the favorable long-term outcomes of a LARC patient who underwent definitive aim CRT. Methods: The patient was 73 years’ old, and staging workups revealed T3N2bM0 rectal adenocarcinoma. He agreed to receive CRT, but refused surgery. A radiotherapy (RT) dose of 64.8 Gy was prescribed, which was higher than conventional (50.4 Gy) preoperative aim RT. The regimen of concurrent chemotherapy was the same as that used in preoperative aim CRT: 2 cycles of 5-fluorouracil and leucovorin. Results: Three months after CRT completion, a complete tumor response was identified clinically. Colonoscopic biopsy after 1 year showed no tumor cells. This patient is alive after 4 years with no evidence of recurrence or severe toxicity. Conclusion: The long-term outcomes of this case indicate the feasibility of definitive high-dose RT with concurrent chemotherapy for LARC. PMID:27749573

  3. Anastomotic leak rate after low anterior resection for rectal cancer after chemoradiation therapy.

    PubMed

    Phillips, Benjamin R; Harris, Lisa J; Maxwell, Pinckney J; Isenberg, Gerald A; Goldstein, Scott D

    2010-08-01

    Anastomotic leak may be the most concerning complication after colorectal anastomosis. To compare open with laparoscopic rectal resection, we must have accurate leak rates in patients who have received neoadjuvant chemoradiation therapy to serve as a benchmark for comparison. All patients who had preoperative chemoradiation therapy with rectal resection and low pelvic anastomosis for cancer in a single colorectal practice over a 7-year period were retrospectively reviewed. All patients had proximal diversion and a contrast enema study before stoma reversal. Eighty-seven consecutive patients were included in the study. Average age was 58 years. Fifty-nine per cent of patients were male. Sixty-six per cent were smokers. Pathologic T stage was 5 per cent T0, 16 per cent T1, 28 per cent T2, 47 per cent T3, and 5 per cent T4. Seventy-five per cent of patients were pathologically lymph node-negative. Average time to stoma reversal was 122 days. Total anastomotic leak rate was 10.3 per cent (8% clinical leaks). Five (56%) patients with leak successfully underwent reversal of their diverting stoma (average time to reversal, 290 days). Patients who had the complication of anastomotic leakage had less likelihood of stoma reversal and a significantly prolonged time to stoma reversal.

  4. Synchronous rectal and gastric cancer in a fighter pilot: aeromedical concerns.

    PubMed

    Gu, Guo-Li; Wei, Xue-Ming; Xu, Xian-Rong; Li, De-Chang; Wang, Shi-Lin; Gu, Jin

    2013-06-01

    Synchronous cancer of the stomach and rectum is very rare. In a special population of pilots, especially fighter pilots, synchronous rectal and gastric cancer is much more uncommon. We herein report a case of synchronous carcinoma of the rectum and stomach. The patient was a 44-year-old male fighter pilot who complained with bloody stool and altered bowel habits. He was diagnosed with hereditary nonpolyposis colorectal cancer with a definite family history, and subsequently he underwent simultaneous low anterior resection and distal gastrectomy with D2 lymphadenectomy. Postoperative pathologic assessment showed a poorly differentiated gastric adenocarcinoma with signet ring cell components (pT2N1M0; stage IIb) and a moderately differentiated rectal adenocarcinoma with myxoid components (pT3N0M0; stage IIa). Both tumors showed positive expression of p53, Ki-67, VEGF, carcinoembryonic antigen, MRP, TS, P-gp, and TopoII, and negative expression of c-erbB2, CD34, CD31, D2-40, S-100, FVIII, MLH1, MSH2, and MSH6 oncoproteins. Six cycles of XELOX chemotherapy and 50 Gy/25 f radiotherapy were delivered postoperatively. Now, he has returned to his work under medical observation for about 6 months. From this patient's diagnosis and treatment, we think that the gene screening should be used in pilot selection. According to the result of gene screening, we can give pertinence examinations to the target organ of genes. It is very necessary for pilots to keep keen vigilance at gastrointestinal tumors because they have to face many high-risk factors in working. As to pilots, the selection of operation should be individualized.

  5. Is Preoperative Chemoradiotherapy Beneficial for Sphincter Preservation in Low-Lying Rectal Cancer Patients?

    PubMed

    Park, In Ja; Yu, Chang Sik; Lim, Seok-Byung; Lee, Jong Lyul; Kim, Chan Wook; Yoon, Yong Sik; Park, Seong Ho; Kim, Jin Cheon

    2016-05-01

    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 no beneficial

  6. 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

  7. Robotic Versus Laparoscopic Surgery for Rectal Cancer after Preoperative Chemoradiotherapy: Case-Matched Study of Short-Term Outcomes

    PubMed Central

    Kim, Yong Sok; Kim, Min Jung; Park, Sung Chan; Sohn, Dae Kyung; Kim, Dae Yong; Chang, Hee Jin; Nam, Byung-Ho; Oh, Jae Hwan

    2016-01-01

    Purpose Robotic surgery is expected to have advantages over laparoscopic surgery; however, there are limited data regarding the feasibility of robotic surgery for rectal cancer after preoperative chemoradiotherapy (CRT). Therefore, we evaluated the short-term outcomes of robotic surgery for rectal cancer. Materials and Methods Thirty-three patients with cT3N0-2 rectal cancer after preoperative CRT who underwent robotic low anterior resection (R-LAR) between March 2010 and January 2012 were matched with 66 patients undergoing laparoscopic low anterior resection (L-LAR). Perioperative clinical outcomes and pathological data were compared between the two groups. Results Patient characteristics did not differ significantly different between groups. The mean operation time was 441 minutes (R-LAR) versus 277 minutes (L-LAR, p < 0.001). The open conversion rate was 6.1% in the R-LAR group and 0% in the L-LAR group (p=0.11). There were no significant differences in the time to flatus passage, length of hospital stay, and postoperative morbidity. In pathological review, the mean number of harvested lymph nodes was 22.3 in R-LAR and 21.6 in L-LAR (p=0.82). Involvement of circumferential resection margin was positive in 16.1% and 6.7%, respectively (p=0.42). Total mesorectal excision (TME) quality was complete in 97.0% in R-LAR and 91.0% in L-LAR (p=0.41). Conclusion In our study, short-term outcomes of robotic surgery for rectal cancer after CRT were similar to those of laparoscopic surgery in respect to bowel function recovery, morbidity, and TME quality. Well-designed clinical trials are needed to evaluate the functional results and long-term outcomes of robotic surgery for rectal cancer. PMID:25779367

  8. 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

  9. Long-term survival of a patient with metachronous rectal metastasis from primary cecal cancer who underwent repetitive resection and chemotherapy: a case report.

    PubMed

    Shimazaki, Jiro; Nakachi, Takeshi; Tabuchi, Takanobu; Ubukata, Hideyuki; Tabuchi, Takafumi

    2014-04-23

    There are few reported cases of colorectal metastasis from cancers of other organs, particularly other segments of the colon. Here we describe the long-term survival of a 68-year-old male patient with metachronous rectal metastasis from cecal cancer who underwent repetitive resection and chemotherapy. The patient underwent ileocecal resection and hepatectomy for cecal cancer with liver metastasis (T3, N1a, M1a, Stage IVA) in 2006. The patient subsequently underwent splenectomy for splenic metastasis in 2007. In August 2008, barium enema revealed compression of the rectal wall, and abdominal computed tomography (CT) detected a mass along the rectum extending into the pelvis. Rectal metastasis from cecal cancer was suspected and Hartmann's operation with bilateral seminal vesicle dissection was performed. Histological examination of the excised tumor revealed moderately differentiated adenocarcinoma formed in the muscularis propria of the rectum and infiltrating the connective tissue between the seminal vesicle and rectum. However, no tumor was detected in the rectal mucosa or submucosa. These histological findings supported the diagnosis of rectal metastasis from cecal cancer. The patient has been monitored at our clinic for 60 months after surgical removal of the rectal metastasis. The findings from this case should alert oncologists to the potential danger of rectal metastasis from primary colon cancer and the benefits of timely complete resection in terms of improved patient outcomes.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. [Rectal cancer: locoregional recurrence in relation to surgical and complementary treatment].

    PubMed

    Asteria, C R; Valanzano, R; Marcucci, T; Tonelli, F

    2005-01-01

    Much recent data have been published on the risk of local recurrence (LR) following curative surgery for rectal cancer and the impact of adjuvant therapy. On the other hand, improvements in surgical techniques, as the total mesorectal excision, have apparently reduced the risk of LR. Furthermore, in selected cases, neoadjuvant therapy seems to reduce much more the incidence of LR. A list of prognostic factors which affect the onset of LR, other than the different procedures, was considered. To investigate such evidences a retrospective analysis was undertaken in our series, focusing on examination of the employed techniques as potential predictors of local recurrence. Thus, in a 18-yr-period (1986-2003), two hundred and ninety-five patients who had undergone elective curative surgical resection of rectal cancer were included in the study. The demographic, operative and follow-up data were collected retrospectively. All patients underwent total mesorectal excision, whereas neoadjuvant therapy was performed in a selected series of patients, according to defined entry criteria patterns. Results evidenced LR in 7.1% of patients and occurred between 6 months to 8 year following surgery. Comparisons were made between patients who had different surgical procedures; indeed sphyncter saving procedures correlated with a higher incidence of LR rather than abdomino-perineal resection. Pelvic recurrences were observed more frequently compared to the anastomotic ones. A limited number of patients with LR underwent surgery due to the associated condition of metastatic lesions; the follow-up related to such series evidenced a mortality rate of 57% within 3 year from reoperation. A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest that preoperative radiotherapy may be employed only for those patients who are at a higher risk for local recurrence.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. On a prolonged interval between rectal cancer (chemo)radiotherapy and surgery

    PubMed Central

    Glimelius, Bengt

    2017-01-01

    Preoperative radiotherapy (RT) or chemoradiotherapy (CRT) is often required before rectal cancer surgery to obtain low local recurrence rates or, in locally advanced tumours, to radically remove the tumour. RT/CRT in tumours responding completely can allow an organ-preserving strategy. The time from the end of the RT/CRT to surgery or to the decision not to operate has been prolonged during recent years. After a brief review of the literature, the relevance of the time interval to surgery is discussed depending upon the indication for RT/CRT. In intermediate rectal cancers, where the aim is to decrease local recurrence rates without any need for down-sizing/-staging, short-course RT with immediate surgery is appropriate. In elderly patients at risk for surgical complications, surgery could be delayed 5–8 weeks. If CRT is used, surgery should be performed when the acute radiation reaction has subsided or after 5–6 weeks. In locally advanced tumours, where CRT is indicated, the optimal delay is 6–8 weeks. In patients not tolerating CRT, short-course RT with a 6–8-week delay is an alternative. If organ preservation is a goal, a first evaluation should preferably be carried out after about 6 weeks, with planned surgery for week 8 if the response is inadequate. In case the response is good, a new evaluation should be carried out after about 12 weeks, with a decision to start a ‘watch-and-wait’ programme or operate. Chemotherapy in the waiting period is an interesting option, and has been the subject of recent trials with promising results. PMID:28256956

  1. On a prolonged interval between rectal cancer (chemo)radiotherapy and surgery.

    PubMed

    Glimelius, Bengt

    2017-03-01

    Preoperative radiotherapy (RT) or chemoradiotherapy (CRT) is often required before rectal cancer surgery to obtain low local recurrence rates or, in locally advanced tumours, to radically remove the tumour. RT/CRT in tumours responding completely can allow an organ-preserving strategy. The time from the end of the RT/CRT to surgery or to the decision not to operate has been prolonged during recent years. After a brief review of the literature, the relevance of the time interval to surgery is discussed depending upon the indication for RT/CRT. In intermediate rectal cancers, where the aim is to decrease local recurrence rates without any need for down-sizing/-staging, short-course RT with immediate surgery is appropriate. In elderly patients at risk for surgical complications, surgery could be delayed 5-8 weeks. If CRT is used, surgery should be performed when the acute radiation reaction has subsided or after 5-6 weeks. In locally advanced tumours, where CRT is indicated, the optimal delay is 6-8 weeks. In patients not tolerating CRT, short-course RT with a 6-8-week delay is an alternative. If organ preservation is a goal, a first evaluation should preferably be carried out after about 6 weeks, with planned surgery for week 8 if the response is inadequate. In case the response is good, a new evaluation should be carried out after about 12 weeks, with a decision to start a 'watch-and-wait' programme or operate. Chemotherapy in the waiting period is an interesting option, and has been the subject of recent trials with promising results.

  2. Comparison of non-Gaussian and Gaussian diffusion models of diffusion weighted imaging of rectal cancer at 3.0 T MRI

    PubMed Central

    Zhang, Guangwen; Wang, Shuangshuang; Wen, Didi; Zhang, Jing; Wei, Xiaocheng; Ma, Wanling; Zhao, Weiwei; Wang, Mian; Wu, Guosheng; Zhang, Jinsong

    2016-01-01

    Water molecular diffusion in vivo tissue is much more complicated. We aimed to compare non-Gaussian diffusion models of diffusion-weighted imaging (DWI) including intra-voxel incoherent motion (IVIM), stretched-exponential model (SEM) and Gaussian diffusion model at 3.0 T MRI in patients with rectal cancer, and to determine the optimal model for investigating the water diffusion properties and characterization of rectal carcinoma. Fifty-nine consecutive patients with pathologically confirmed rectal adenocarcinoma underwent DWI with 16 b-values at a 3.0 T MRI system. DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models (IVIM-mono, IVIM-bi and SEM) on primary tumor and adjacent normal rectal tissue. Parameters of standard apparent diffusion coefficient (ADC), slow- and fast-ADC, fraction of fast ADC (f), α value and distributed diffusion coefficient (DDC) were generated and compared between the tumor and normal tissues. The SEM exhibited the best fitting results of actual DWI signal in rectal cancer and the normal rectal wall (R2 = 0.998, 0.999 respectively). The DDC achieved relatively high area under the curve (AUC = 0.980) in differentiating tumor from normal rectal wall. Non-Gaussian diffusion models could assess tissue properties more accurately than the ADC derived Gaussian diffusion model. SEM may be used as a potential optimal model for characterization of rectal cancer. PMID:27934928

  3. 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.

  4. Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

    PubMed Central

    Andreoni, Bruno; Chiappa, Antonio; Bertani, Emilio; Bellomi, Massimo; Orecchia, Roberto; Zampino, MariaGiulia; Fazio, Nicola; Venturino, Marco; Orsi, Franco; Sonzogni, Angelica; Pace, Ugo; Monfardini , Lorenzo

    2007-01-01

    Background This study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003. Methods A consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed. Results Of the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001). Conclusion A prospective, uniform follow-up policy used in a single institution

  5. A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

    PubMed Central

    Hashida, Hiroki; Satake, Hironaga; Kaihara, Satoshi

    2017-01-01

    It has been reported that many patients with lung metastasis of colorectal cancer (CRC) underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI) plus bevacizumab (BV) therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped. PMID:28203168

  6. Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?

    PubMed

    Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

    2015-06-01

    Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes.

  7. Alcohol and the risk of colon and rectal cancer with mutations in the K-ras gene.

    PubMed

    Bongaerts, Brenda W C; de Goeij, Anton F P M; van den Brandt, Piet A; Weijenberg, Matty P

    2006-04-01

    The first metabolite of alcohol, acetaldehyde, may trigger replication errors and mutations in DNA, which may predispose to developing colorectal cancer (CRC). In a prospective study on colon and rectal cancer, we investigated the following hypotheses: alcohol consumption is associated with an increased risk of mutations in the K-ras oncogene, and beer consumption is associated with an increased risk of G-->A mutations in this gene. Therefore, we studied the associations between consumption of alcohol and alcoholic beverages and the risk of CRC without and with specific K-ras gene mutations. In 1986, 120,852 men and women, aged 55-69 years, completed a questionnaire on risk factors for cancer. The case-cohort approach was used for data processing and analyses. After 7.3 years of follow-up, excluding the first 2.3 years, complete data from 4,076 subcohort members, 428 colon and 150 rectal cancer patients, were available for data analyses. Incidence rate ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Compared to abstaining, a total alcohol consumption of 30.0 g/day and more was associated with the risk of colon and rectal cancer with and without a K-ras mutation in both men and women. Independent from alcohol intake, liquor consumption when compared to nonliquor consumption was associated with an increased risk of rectal cancer with a wild type K-ras in men (RR: 2.25, 95% CI: 1.0-5.0). Beer consumption was not clearly associated with the risk of colon and rectal tumors harboring G-->A mutations in the K-ras gene in men. This association could not be assessed in women because of sparse beer consumption. In conclusion, alcohol does not seem to be involved in predisposing to CRC through mutations in the K-ras gene, and specifically beer consumption is not associated with colon and rectal tumors harboring a G-->A mutation.

  8. CorRECTreatment: A Web-based Decision Support Tool for Rectal Cancer Treatment that Uses the Analytic Hierarchy Process and Decision Tree

    PubMed Central

    Karakülah, G.; Dicle, O.; Sökmen, S.; Çelikoğlu, C.C.

    2015-01-01

    Summary Background The selection of appropriate rectal cancer treatment is a complex multi-criteria decision making process, in which clinical decision support systems might be used to assist and enrich physicians’ decision making. Objective The objective of the study was to develop a web-based clinical decision support tool for physicians in the selection of potentially beneficial treatment options for patients with rectal cancer. Methods The updated decision model contained 8 and 10 criteria in the first and second steps respectively. The decision support model, developed in our previous study by combining the Analytic Hierarchy Process (AHP) method which determines the priority of criteria and decision tree that formed using these priorities, was updated and applied to 388 patients data collected retrospectively. Later, a web-based decision support tool named corRECTreatment was developed. The compatibility of the treatment recommendations by the expert opinion and the decision support tool was examined for its consistency. Two surgeons were requested to recommend a treatment and an overall survival value for the treatment among 20 different cases that we selected and turned into a scenario among the most common and rare treatment options in the patient data set. Results In the AHP analyses of the criteria, it was found that the matrices, generated for both decision steps, were consistent (consistency ratio<0.1). Depending on the decisions of experts, the consistency value for the most frequent cases was found to be 80% for the first decision step and 100% for the second decision step. Similarly, for rare cases consistency was 50% for the first decision step and 80% for the second decision step. Conclusions The decision model and corRECTreatment, developed by applying these on real patient data, are expected to provide potential users with decision support in rectal cancer treatment processes and facilitate them in making projections about treatment options

  9. 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.

  10. 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}.

  11. Predictive Factors of Tumor Response After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

    SciTech Connect

    Moureau-Zabotto, Laurence; Farnault, Bertrand; de Chaisemartin, Cecile; Esterni, Benjamin; Lelong, Bernard; Viret, Frederic; Giovannini, Marc; Monges, Genevieve; Delpero, Jean-Robert; Bories, Erwan; Turrini, Olivier; Viens, Patrice; Salem, Naji

    2011-06-01

    Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. Methods and Materials: From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Conclusions: Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5ng/ml, and use of capecitabine were associated with tumor downstaging.

  12. 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.

  13. Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancer

    PubMed Central

    McCoy, M J; Hemmings, C; Miller, T J; Austin, S J; Bulsara, M K; Zeps, N; Nowak, A K; Lake, R A; Platell, C F

    2015-01-01

    Background: Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component. Whether Tregs play an inhibitory role in chemoradiotherapy (CRT) response in rectal cancer remains unknown. Methods: Foxp3+, CD3+, CD4+, CD8+ and IL-17+ cell density in post-CRT surgical samples from 128 patients with rectal cancer was assessed by immunohistochemistry. The relationship between T-cell subset densities and clinical outcome (tumour regression and survival) was evaluated. Results: Stromal Foxp3+ cell density was strongly associated with tumour regression grade (P=0.0006). A low stromal Foxp3+ cell density was observed in 84% of patients who had a pathologic complete response (pCR) compared with 41% of patients who did not (OR: 7.56, P=0.0005; OR: 5.27, P=0.006 after adjustment for presurgery clinical factors). Low stromal Foxp3+ cell density was also associated with improved recurrence-free survival (HR: 0.46, P=0.03), although not independent of tumour regression grade. Conclusions: Regulatory T cells in the tumour microenvironment may inhibit response to neoadjuvant CRT and may represent a therapeutic target in rectal cancer. PMID:26645238

  14. A novel approach to inoperable or recurrent rectal cancer by chemoembolization. A new arrow in our quiver?

    PubMed Central

    Bini, Roberto; Comelli, Simone; Leli, Renzo; Vaudano, Giacomo Paolo; Savio, Daniele; Viora, Tiziana; Addeo, Alfredo

    2016-01-01

    Purpose Assess the feasibility, safety and efficacy of TACE with irinotecan loaded micro particles (debiri) for the treatment of locally advanced rectal cancer patients. Results We assessed the Edmonton Symptom Assessment System (ESAS). The tool is designed to assess nine common symptoms in cancer patients: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The ESAS score was 7 in 10/12 (83%) patients before treatment and 6 in 2/12 (16.5%) patients. After treatment in 6/12 (50%) patients the score dropped to 3; 3/12 (33%) reported 4, 1/12 (8%) reported 2. All patients experienced local control disease with a degree of citoreduction; in 4 cases (33%) we observed outstanding responses with a dramatic reduction in the tumors size which led us to surgical radical resections. Materials and methods We run a prospective mono-institutional study where we recruited, 12 non- consecutive patients with histology confirmation of rectal cancer, inoperable and not treatable due to severe comorbidities, or pelvic recurrence/progression after curative treatment, chemotherapy, radiotherapy and/or surgery. Their performance status (PS) ECOG was 2-3. Twelve patients (10 male and 2 female) with a median age 71 (range 56-89) were recruited in the study. Conclusions The study has met the primary endpoint and showed encouraging activity. Debiri could be a possible option for locally advanced/inoperable or recurred rectal cancer patients. Further trials are warranted to validate this methodic in early stages. PMID:27303924

  15. 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.

  16. Human Phosphatidylethanolamine-Binding Protein 4 Promoted the Radioresistance of Human Rectal Cancer by Activating Akt in an ROS-Dependent Way

    PubMed Central

    Qiu, Jianming; Yang, Guangen; Lin, Ali; Shen, Zhong; Wang, Dong; Ding, Lei

    2014-01-01

    Human phosphatidylethanolamine-binding protein 4(hPEBP4) is a novel anti-apoptosis molecule associated with the resistance of tumors to apoptotic agents. Here we sought to investigate the role of hPEBP4 in the radioresistance of rectal cancer. Immunohistochemistry analysis showed hPEBP4 was expressed in 27/33 of rectal cancer specimens, but only in 2/33 of neighboring normal mucosa. Silencing the expression of hPEBP4 with siRNA significantly reduced the clonogenic survival and enhanced the apoptosis of rectal cancer cells on irradiation. Instead, forced overexpression of hPEBP4 promoted its survival and decreased the apoptosis. Western blot showed hPEBP4 could increase the radiation-induced Akt activation, for which reactive oxygen specimen(ROS) was required. The radioresistance effect of hPEBP4 was reversed after given LY-294002 to inhibit Akt activation or antioxidant to abolish the ROS production. We also confirmed that effect of hPEBP4 in vivo with nude mice. Thus we concluded that hPEBP4, specifically expressed in rectal cancer cells, is associated with radioresistance of rectal cancer, implying that modulation of hPEBP4 may have important therapeutic implications in radiotherapy of rectal cancer. PMID:24594691

  17. 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

  18. [A case of metachronous multiple lung metastases and intraabdominal lymph node metastases of rectal cancer responding to S-1].

    PubMed

    Kakisaka, Tatsuhiko; Aiki, Fusayoshi; Matsuhisa, Tadashi; Hattori, Atsuo; Kazui, Keizou

    2010-04-01

    A 70-year-old man was referred to our hospital with bowel obstruction because of rectal cancer. High anterior resection of rectum and lymph node dissection was performed. The rectal cancer was in stage III, and the patient selected no adjuvant chemotherapy. At 1-year follow-up, the CEA level was 17. 6 ng/mL, and CT revealed multiple lung metastases and paraaortic and parailiac lymph node metastases. S-1, 100 mg/body, was administered for 4 weeks followed by 2 drug-free weeks. After 3 courses, the CEA level was 4. 5 ng/mL, and metastatic lesions were remarkably reduced in the CT findings. After 10 courses, the CEA level was hovering around 6 ng/mL, and CT showed no recurrent foci. The effect of S-1 treatment was PR, and no severe side effect was observed throughout the treatment.

  19. [A Case of Local Recurrence and Lung Metastasis from a Rectal Cancer Treated with Systemic Chemotherapy and Cyberknife].

    PubMed

    Uchino, Tairin; Mishima, Hideyuki; Osawa, Takaaki; Matsumura, Tatsuki; Komaya, Kenichi; Kimura, Kengo; Ando, Keiichi; Saito, Takuya; Ishiguro, Seiji; Ohashi, Norifumi; Arikawa, Takashi; Komatsu, Shunichiro; Miyachi, Masahiko; Mizumatsu, Shinichiro; Sano, Tsuyoshi

    2015-11-01

    A 73-year-old man underwent abdominoperineal resection for a rectal cancer. He developed a hip pain 3 years and 6 months after the surgery. A CT scan revealed a local recurrence in the perineum and multiple lung metastases in the bilateral lung. He received systemic chemotherapy consisting of XELOX with bevacizumab. Thereafter, the hip pain was slightly relieved. The hip pain worsened 1 year and 6 months after the recurrence. The border between the perineal tumor and skin was very narrow, and conventional radiation therapy could cause a perineal skin necrosis and subsequent poor wound healing. Therefore, we selected a Cyberknife treatment. The hip pain was relieved and a CT scan showed a reduction of the perineal tumor's size after the Cyberknife treatment. A Cyberknife treatment may be effective and promising as palliation for patients with local recurrence of rectal cancer.

  20. Practice Guideline for the Surveillance of Patients After Curative Treatment of Colon and Rectal Cancer.

    PubMed

    Steele, Scott R; Chang, George J; Hendren, Samantha; Weiser, Marty; Irani, Jennifer; Buie, W Donald; Rafferty, Janice F

    2015-08-01

    Current evidence suggests improved rates of curative secondary treatment following identification of recurrence among patients who participate in a surveillance program after initial curative resection of colon or rectal cancer. The newer data show that surveillance CEA, chest and liver imaging,and colonoscopy can also improve survival through early diagnosis of recurrence; thus, these modalities are now included in the current guideline. Although the optimum strategy of surveillance for office visits, CEA, chest and liver imaging, and colonoscopy is not yet defined, routine surveillance does improve the detection of recurrence that can be resected with curative intent. Recommended surveillance schedules are shown in Table 4. However, the factors to be considered when recommending surveillance include underlying risk for recurrence, patient comorbidity, and the ability to tolerate major surgery to resect recurrent disease or palliative chemotherapy, performance status, physiologic age, preference, and compliance. The success of surveillance for early detection of curable recurrence will depend on patient and provider involvement to adhere to the surveillance schedule and avoid unnecessary examination. It should be noted that, after curative resection of colorectal cancer, patients are still at risk for other common malignancies(lung, breast, cervix, prostate) for which standard screening recommendations should be observed and measures to maintain general health (risk reduction for cardiovascular disease, eg, cessation of smoking, control of blood pressure and diabetes mellitus, balanced diet, regular exercise and sleep, and flu vaccines) should be recommended.

  1. [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.

  2. Prognostic Impact of Immunonutritional Status Changes During Preoperative Chemoradiation in Patients With Rectal Cancer

    PubMed Central

    Lee, Yong Joon; Kim, Woo Ram; Han, Jeonghee; Han, Yoon Dae; Cho, Min Soo; Hur, Hyuk; Lee, Kang Young; Kim, Nam Kyu

    2016-01-01

    Purpose Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (<5, 5–10, and >10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification. Results No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (<5); only 15% had a high dPNI (>10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978). Conclusion The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes. PMID:28119863

  3. Rectal bleeding and prolapse… not always benign diseases rather anal cancer. The importance of a correct decision making since primary care

    PubMed Central

    COCORULLO, G.; TUTINO, R.; FALCO, N.; FONTANA, T.; SALAMONE, G.; LICARI, L.; GULOTTA, G.

    2016-01-01

    Rectal bleeding is very common in general population with a prevalence of 10–20 %. Primary care physicians have to stratify patients basing on urgency and on the colo-rectal cancer risk and to conduct a decision making for the correct management. We report a case of a 61-years-old woman, complaining rectal bleeding and an anal mass attended to their family doctor who does a visit but without a digital rectal examination and diagnosed a hemorrhoidal prolapse suggesting medical therapy. For the persistence of symptoms she comes to our service from emergency attention. Inspection and digital rectal examination revealed an anal mass. CT scan was performed showing a large anal mass involving half anal circumference. Histologic samples showed an epithelial proliferation compatible with a squamous carcinoma. Oncological consult was requested and a chemo-radiotherapy treatment was proposed. This case report highlights the difficulty when physicians assess patients with anorectal complaints in differentiating anal cancer from benign disease, presumably because symptoms are similar. Primary care physicians must maintain a high index of suspicion of cancer in high-risk population. Sensitization of these colleagues is required since digital rectal examination is of inestimable value to verify the presence of a rectal or an anal mass. PMID:27734798

  4. 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.

  5. Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation

    PubMed Central

    Huh, Jung Wook; Kim, Hee Cheol; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

    2016-01-01

    Abstract This study evaluated the predictive and prognostic value of expression of mismatch repair (MMR) protein, including MLH1, MSH2, and MSH6 in rectal cancer patients with preoperative chemoradiotherapy. MMR protein expression was measured by immunohistochemistry in both pretreatment biopsies (pre-) and pathologic specimens (post-) from 209 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and radical surgery. The patients were followed for a median period of 44 months. A pathologic complete response (pCR) was observed in 30 patients (14.4%). The expression levels of MLH1, MSH2, and MSH6 were not significantly different between the pCR and non-pCR groups. A multivariate analysis revealed that tumor differentiation, postoperative chemotherapy, and pre-MSH6 expression were independent predictors of overall survival; ypN category and perineural invasion were independent predictors of disease-free survival. The pre-MSH6 expression was significantly associated with tumor budding and expression of all MMR proteins. On multivariate analysis, ypN category and post-MSH6 expression were independent predictors for local recurrence. In our study, we observed the independent prognostic value of MSH6 expression in pretreatment tissue on overall survival and MSH6 expression after chemoradiation on local recurrence. Constitutive MSH6 expression before and after preoperative therapy may be a useful tool for prediction of oncologic outcome in locally advanced rectal cancer. PMID:26817916

  6. 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.

  7. 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.

  8. The Importance of Preoperative Staging of Rectal Cancer Using Multiparametric MRI. A Systematic Review

    PubMed

    Bauer, Ferdinand

    2016-01-01

    A correct preoperative stadialization of rectal carcinoma has a direct influence upon its therapeutic strategy, resulting in a significant improvement of the survival rate and life quality after the treatment. The therapeutic strategy refers to the option of undergoing or not preoperative radiochemotherapy before the total mesorectal excision (TME). The technical advances in the magnetic resonance domain makes possible the multiparametric examinations (mp MRI) with medical equipments (3T models are common) good enough to obtain images having an excellent quality, which allow a correct diagnosis of the local tumour spread. These multiparametric examinations include T2 multiplan sequences and T1 sequences, which offer valuable morphological information due to the high resolution of anatomic structures and DWI functional sequences, with a decisive role in tracing residual tumours after post-surgery radiochemotherapy. The functional examination using DWI is the only highly accurate non-invasive diagnostic method which can differentiate the fibrosis from vital tumoral remnants. The dynamic contrast-enhanced examination (DCE) combined with DWI and volumetry can give supplementary information as to the complete and incomplete response to RCT, and is efficient in detecting a local recurrence after TME. Also, MRI is the only diagnostic method which has the necessary accuracy to assess the meso-rectal fascia, which represents the circumferential resection margin (CRM) in the case of TME. With the help of MRI we can measure with a precision similar to histology the minimal distance to the mesorectal fascia, essential in planning the surgical treatment, and more important than the T stadialization. This allows the selection of patients with an unfavourable prognosis factor who would benefit from radiotherapy or from RCT. The evaluation of other prognostic factors as the condition of nodes, their number and primary site, and the extramural venous invasion (EMVI) have an

  9. PET-Based Treatment Response Evaluation in Rectal Cancer: Prediction and Validation

    SciTech Connect

    Janssen, Marco H.M.; Oellers, Michel C.; Stiphout, Ruud G.P.M. van; Riedl, Robert G.; Bogaard, Jorgen van den; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido

    2012-02-01

    Purpose: To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders. The predictive strength of the model was validated in a second patient group, treated and imaged identical to the patients on which the predictive model was based. Methods and Materials: Fifty-one rectal cancer patients were prospectively included in this study. All patients underwent fluorodeoxyglucose (FDG) PET-computed tomography (CT) imaging both before the start of chemoradiotherapy (CRT) and after 2 weeks of treatment. Preoperative treatment with CRT was followed by a total mesorectal excision. From the resected specimen, the tumor regression grade (TRG) was scored according to the Mandard criteria. From one patient group (n = 30), the metabolic treatment response was correlated with the pathological treatment response, resulting in a receiver operating characteristic (ROC) curve based cutoff value for the reduction of maximum standardized uptake value (SUV{sub max}) within the tumor to differentiate pathological responders (TRG 1-2) from nonresponders (TRG 3-5). The applicability of the selected cutoff value for new patients was validated in a second patient group (n = 21). Results: When correlating the metabolic and pathological treatment response for the first patient group using ROC curve analysis (area under the curve = 0.98), a cutoff value of 48% SUV{sub max} reduction was selected to differentiate pathological responders from nonresponders (specificity of 100%, sensitivity of 64%). Applying this cutoff value to the second patient group resulted in a specificity and sensitivity of, respectively, 93% and 83%, with only one of the pathological nonresponders being false positively predicted as pathological responding. Conclusions: For rectal cancer, an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT. The presented predictive model could be used to

  10. Relationship between diversion colitis and quality of life in rectal cancer

    PubMed Central

    Son, Dong Nyoung; Choi, Dong Jin; Woo, Si Uk; Kim, Jin; Keom, Bo Ra; Kim, Chul Hwan; Baek, Se Jin; Kim, Seon Hahn

    2013-01-01

    AIM: To investigated the incidence of diversion colitis (DC) and impact of DC symptoms on quality of life (QoL) after ileostomy reversal in rectal cancer. METHODS: We performed a prospective study with 30 patients who underwent low anterior resection and the creation of a temporary ileostomy for the rectal cancer between January 2008 and July 2009 at the Department of Surgery, Korea University Anam Hospital. The participants totally underwent two rounds of the examinations. At first examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom were performed 3-4 mo after the ileostomy creations. At second examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom and QoL were performed 5-6 mo after the ileostomy reversals. Clinicopathological data were based on the histopathological reports and clinical records of the patients. RESULTS: At the first examination, all of the patients presented with inflammation, which was mild in 15 (50%) patients, moderate in 11 (36.7%) and severe in 4 (13.3%) by endoscopy and mild in 14 (46.7%) and moderate in 16 (53.3%) by histology. At the second examination, only 11 (36.7%) and 17 (56.7%) patients had mild inflammation by endoscopy and histology, respectively. There was no significant difference in DC grade between the endoscopic and the histological findings at first or second examination. The symptoms detected on the first and second questionnaires were mucous discharge in 12 (40%) and 5 (17%) patients, bloody discharge in 5 (17%) and 3 (10%) patients, abdominal pain in 4 (13%) and 2 (7%) patients and tenesmus in 9 (30%) and 5 (17%) patients, respectively. We found no correlation between the endoscopic or histological findings and the symptoms such as mucous discharge, bleeding, abdominal pain and tenesmus in both time points. Diarrhea was detected in 9 patients at the second examination; this number correlated with the severity of DC (0%, 0%, 66.7%, 33.3% vs 0%, 71.4%, 23

  11. Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

    PubMed

    Palma, Pablo; Cuadros, Marta; Conde-Muíño, Raquel; Olmedo, Carmen; Cano, Carlos; Segura-Jiménez, Inmaculada; Blanco, Armando; Bueno, Pablo; Ferrón, J Antonio; Medina, Pedro

    2013-01-01

    Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced

  12. 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.

  13. Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer

    PubMed Central

    Marone, Pietro; de Bellis, Mario; D’Angelo, Valentina; Delrio, Paolo; Passananti, Valentina; Di Girolamo, Elena; Rossi, Giovanni Battista; Rega, Daniela; Tracey, Maura Claire; Tempesta, Alfonso Mario

    2015-01-01

    The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery. PMID:26140096

  14. Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases

    PubMed Central

    Kumamoto, Kensuke; Endo, Shungo; Isohata, Noriyuki; Nirei, Azuma; Nemoto, Daiki; Utano, Kenichi; Saito, Takuro; Togashi, Kazutomo

    2017-01-01

    A 70-year-old man who was diagnosed with unresectable advanced rectal cancer with multiple liver metastases, received oxaliplatin-based treatment with bevacizumab as first-line chemotherapy and irinotecan-based treatment with bevacizumab as second-line chemotherapy for a total of 17 months. The patient was treated with regorafenib (160 mg/day for 3 weeks) as third-line chemotherapy. Following completion of one course of regorafenib treatment, the patient complained of abdominal distension. Computed tomography (CT) examination identified liver atrophy and massive ascites, while no such symptoms were observed prior to the regorafenib treatment. Blood testing revealed increases in the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The patient was admitted to the Aizu Medical Center (Aizuwakamatsu, Japan). Approximately 2,000 ml of ascitic fluid were aspirated daily for 1 week by abdominal puncture. The patient was administered oral diuretics, including 20 mg/day of furosemide and 25 mg/day of spironolactone. Albumin was administered to correct the albumin deficit. The levels of AST, ALT and ALP were decreased from the peak value reported on admission and the patient was discharged from our hospital 16 days following treatment initiation. The CT examination after 1 month revealed that the volume of the liver had been restored and the ascites had disappeared. Furthermore, almost all the liver metastases were reduced in size. The carcinoembryonic antigen level, which was elevated prior to regorafenib treatment, also decreased to normal. PMID:28123730

  15. Clinical implications of preoperative chemoradiotherapy prior to laparoscopic surgery for locally advanced low rectal cancer

    PubMed Central

    Kondo, Keisaku; Shimbo, Taiju; Tanaka, Keitaro; Yamamoto, Masashi; Narumi, Yoshifumi; Okuda, Junji; Uchiyama, Kazuhisa

    2017-01-01

    The present study aimed to evaluate whether preoperative chemoradiotherapy (CRT) has any adverse effects on laparoscopic surgery (LS) for locally advanced low rectal cancer (LARC). The study was performed at the Osaka Medical College Hospital, and included patients who were operated on between July 2006 and December 2013. The short-term outcomes in 156 patients who underwent surgery for LARC following CRT were evaluated, of whom 152 underwent LS. Among the patients who were followed for >40 months, 77 patients (the CRT group) were compared with 39 patients who underwent LS without CRT (the surgery-alone group) for long-term outcomes. The total number of patients who received sphincter-preserving surgery was 74%. No positive longitudinal resection margins were identified, and only 1.3% had identifiable positive circumferential resection margins. The complication rate was 14%, and no serious complications occurred. There were no significant differences between the CRT and the surgery-alone groups in terms of the 5-year relapse-free survival rate (70.1 vs. 61.5%; P=0.81) or the 5-year overall survival rate (88.3 vs. 69.2%; P=0.06). However, the 5-year local recurrence-free survival rate was significantly improved in the CRT group patients (96.1 vs. 79.5%; P=0.009). In conclusion, our results have demonstrated that LS with preoperative CRT appears to be feasible and safe, and may have beneficial effects on local recurrence. PMID:28123724

  16. Complete Response after Chemoradiotherapy in Rectal Cancer (Watch-and-Wait): Have we Cracked the Code?

    PubMed

    Glynne-Jones, R; Hughes, R

    2016-02-01

    Patients with locally advanced rectal cancer receive preoperative chemoradiation as the standard of care, producing a pathological complete response in 10-20% and a complete clinical response (CCR) in 20-30%. Small observational studies suggest a selective non-operative management with rigorous surveillance is an option and is increasingly being advocated in many parts of the world for patients who achieve a CCR or near CCR. The assumption is that oncological outcomes for good responders, who are observed, compare favourably with patients subjected to radical surgery. Late regrowth of the primary is rare, almost invariably endoluminal and, hence, can be salvaged. However, concerns remain among some surgeons and oncologists regarding the reproducibility of published results in routine practice. We have previously reviewed this topic. The aim of this brief overview was to re-assess the feasibility and safety of a non-operative approach based on the currently available literature. We make recommendations as to the quality of care required to undertake this management. Significant heterogeneity remains in the initial inclusion criteria, staging and restaging methods, study design, timing of assessment, duration and rigour of follow-up of the trials reviewed - all of which obscure the validity of the results.

  17. Predictive Response Value of Pre- and Postchemoradiotherapy Variables in Rectal Cancer: An Analysis of Histological Data.

    PubMed

    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.

  18. Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases.

    PubMed

    Kumamoto, Kensuke; Endo, Shungo; Isohata, Noriyuki; Nirei, Azuma; Nemoto, Daiki; Utano, Kenichi; Saito, Takuro; Togashi, Kazutomo

    2017-01-01

    A 70-year-old man who was diagnosed with unresectable advanced rectal cancer with multiple liver metastases, received oxaliplatin-based treatment with bevacizumab as first-line chemotherapy and irinotecan-based treatment with bevacizumab as second-line chemotherapy for a total of 17 months. The patient was treated with regorafenib (160 mg/day for 3 weeks) as third-line chemotherapy. Following completion of one course of regorafenib treatment, the patient complained of abdominal distension. Computed tomography (CT) examination identified liver atrophy and massive ascites, while no such symptoms were observed prior to the regorafenib treatment. Blood testing revealed increases in the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The patient was admitted to the Aizu Medical Center (Aizuwakamatsu, Japan). Approximately 2,000 ml of ascitic fluid were aspirated daily for 1 week by abdominal puncture. The patient was administered oral diuretics, including 20 mg/day of furosemide and 25 mg/day of spironolactone. Albumin was administered to correct the albumin deficit. The levels of AST, ALT and ALP were decreased from the peak value reported on admission and the patient was discharged from our hospital 16 days following treatment initiation. The CT examination after 1 month revealed that the volume of the liver had been restored and the ascites had disappeared. Furthermore, almost all the liver metastases were reduced in size. The carcinoembryonic antigen level, which was elevated prior to regorafenib treatment, also decreased to normal.

  19. 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.

  20. The Role of Diverting Stoma After an Ultra-low Anterior Resection for Rectal Cancer

    PubMed Central

    Seo, Seok In; Kim, Gwon Sik; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Lim, Seok-Byung; Kim, Jin Cheon

    2013-01-01

    Purpose A diverting stoma is known to reduce the consequences of distal anastomotic failure following colorectal surgery. The aim of this study was to evaluate the efficacy of a diverting stoma after an ultra-low anterior resection (uLAR) for rectal cancer. Methods Between 2000 and 2007, 836 patients who underwent an uLAR were divided into two groups, depending on the fecal diversion: 246 received fecal diversion, and 590 had no diversion. Patient- and disease-related variables were compared between the two groups. Results Thirty-two of the 836 patients (3.8%) had immediate anastomosis-related complications and required reoperation. Anastomosis leakage comprised 72% of the complications (23/32). The overall immediate complication rate was significantly lower in patients with a diverting stoma (0.8%, 2/246) compared to those without a diverting stoma (5.1%, 30/590; P = 0.005). The fecal diversion group had lower tumor location, lower anastomosis level, and more preoperative chemo-radiation therapy (P < 0.001). In total, 12% of patients in the diverting stoma group had complications either in making or reversing the stoma (30/246). Conclusion The diverting stoma decreased the rate of immediate anastomosis-related complications. However, the rate of complications associated with the diverting stoma was non-negligible, so strict criteria should be applied when deciding whether to use a diverting stoma. PMID:23700573

  1. Anastomotic salvage after rectal cancer resection using the Turnbull–Cutait delayed anastomosis

    PubMed Central

    Hallet, Julie; Bouchard, Alexandre; Drolet, Sébastien; Milot, Hélène; Desrosiers, Emilie; Lebrun, Aude; Grégoire, Roger Charles

    2014-01-01

    Background Turnbull–Cutait abdominoperineal pull-through followed by delayed coloanal anastomosis (DCA) was first described in 1961. Studies have described its use for challenging colorectal conditions. We reviewed our experience with Turnbull–Cutait DCA as a salvage procedure for complex failure of colorectal anastomosis. Methods We performed a retrospective cohort study from October 2010 to September 2011, with analysis of postoperative morbidity and mortality. Results Seven DCAs were performed for anastomotic complications (3 chronic leaks, 2 rectovaginal fistulas, 1 colovesical fistula, 1 colonic ischemia) following surgery for rectal cancer. Six patients had a diverting ileostomy constructed as part of previous treatment for anastomotic complications before the salvage procedure. No anastomotic leaks were observed. All procedures but 1 were completed successfully. One patient who underwent DCA subsequently required an abdominoperineal resection and a permanent colostomy for postoperative extensive colonic ischemia. No 30-day mortality occurred. Conclusion Salvage Turnbull–Cutait DCA appears to be a safe procedure and could be offered to patients with complex anastomotic complications. This procedure could be added to the surgeon’s armamentarium as an alternative to the creation of a permanent stoma. PMID:25421083

  2. Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands

    SciTech Connect

    Treurniet-Donker, A.D.; van Putten, W.L.; Wereldsma, J.C.; Bruggink, E.D.; Hoogenraad, W.J.; Roukema, J.A.; Snijders-Keilholz, A.; Meijer, W.S.; Meerwaldt, J.H.; Wijnmaalen, A.J. )

    1991-04-15

    The authors assessed the potential benefit of postoperative radiation therapy for rectal cancer in a two-arm, prospective multicenter trial. One hundred seventy-two patients who had undergone surgical resection for rectal adenocarcinoma were randomly assigned to either treatment consisting of external irradiation to a dose of 5000 cGy in 5 weeks or a control group (no adjuvant therapy). It was assumed that the number of cells remaining after radical surgery would be low and that the dose of 5000 cGy would be adequate in eradicating the majority of those cells. The number of local recurrences was lower in the treated group of patients, but the difference was not statistically significant. It was assumed that if a significant reduction in the number of local recurrences could be obtained, improved (disease-free) survival would result. No influence on disease-free or overall survival could be detected. These results were in agreement with those reported in Europe and the US, and it was concluded that postoperative radiation therapy alone cannot be justified as a routine procedure in the primary management of resectable rectal cancer.

  3. Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands.

    PubMed

    Treurniet-Donker, A D; van Putten, W L; Wereldsma, J C; Bruggink, E D; Hoogenraad, W J; Roukema, J A; Snijders-Keilholz, A; Meijer, W S; Meerwaldt, J H; Wijnmaalen, A J

    1991-04-15

    The authors assessed the potential benefit of postoperative radiation therapy for rectal cancer in a two-arm, prospective multicenter trial. One hundred seventy-two patients who had undergone surgical resection for rectal adenocarcinoma were randomly assigned to either treatment consisting of external irradiation to a dose of 5000 cGy in 5 weeks or a control group (no adjuvant therapy). It was assumed that the number of cells remaining after radical surgery would be low and that the dose of 5000 cGy would be adequate in eradicating the majority of those cells. The number of local recurrences was lower in the treated group of patients, but the difference was not statistically significant. It was assumed that if a significant reduction in the number of local recurrences could be obtained, improved (disease-free) survival would result. No influence on disease-free or overall survival could be detected. These results were in agreement with those reported in Europe and the US, and it was concluded that postoperative radiation therapy alone cannot be justified as a routine procedure in the primary management of resectable rectal cancer.

  4. Meat intake, cooking methods and risk of proximal colon, distal colon and rectal cancer: the Norwegian Women and Cancer (NOWAC) cohort study.

    PubMed

    Parr, Christine L; Hjartåker, Anette; Lund, Eiliv; Veierød, Marit B

    2013-09-01

    Red and processed meat intake is an established risk factor for colorectal cancer (CRC), but epidemiological evidence by subsite and sex is still limited. In the population-based Norwegian Women and Cancer cohort, we examined associations of meat intake with incident proximal colon, distal colon and rectal cancer, in 84,538 women who completed a validated food frequency questionnaire (FFQ) during 1996-1998 or 2003-2005 (baseline or exposure update) at age 41-70 years, with follow-up by register linkages through 2009. We also examined the effect of meat cooking methods in a subsample (n = 43,636). Multivariable hazard ratios (HRs) were estimated by Cox regression. There were 459 colon (242 proximal and 167 distal), and 215 rectal cancer cases with follow-up ≥ 1 (median 11.1) year. Processed meat intake ≥60 vs. <15 g/day was associated with significantly increased cancer risk in all subsites with HRs (95% confidence interval, CI) of 1.69 (1.05-2.72) for proximal colon, 2.13 (1.18-3.83) for distal colon and 1.71 (1.02-2.85) for rectal cancer. Regression calibration of continuous effects based on repeated 24-hr dietary recalls, indicated attenuation due to measurement errors in FFQ data, but corrected HRs were not statistically significant due to wider CIs. Our study did not support an association between CRC risk and intake of red meat, chicken, or meat cooking methods, but a high processed meat intake was associated with increased risk of proximal colon, distal colon and rectal cancer. The effect of processed meat was mainly driven by the intake of sausages.

  5. 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 ...

  6. [A Case of Unresectable Advanced Rectal Cancer with a Pancreatic Tumor That Was Successfully Treated with FOLFIRINOX].

    PubMed

    Yabe, Nobushige; Murai, Shinji; Ozawa, Hiroki; Yokose, Takahiro; Oto, Ippei; Yoshikawa, Takahisa; Kitasato, Kenjiro; Shimizu, Hirotomo; Kojima, Kenji; Hasegawa, Hirotoshi; Kitagawa, Yuko

    2016-11-01

    A 72-year-old man was admitted to our hospital department in September 2014 because of a positive fecal occult blood test.Colonoscopy showed a type 2 tumor in half of the AV 15 cm rectosigmoid colon.Histology of the biopsy indicated a moderately differentiated adenocarcinoma, and the RAS gene test found wild type.On CT examination, there were multiple liver lung metastases and a 30mm diameter tumor with pancreatic duct extension to the pancreatic body.A PET-CT examination had a high SUVmax at the same site.Because of the location of the tumor EUS-FNA was not used.However, the possibility of pancreatic body cancer could not be denied after the CT examination.Treatment by radical resection was impossible because of the spread of the cancer so we selected chemotherapy.Undeniable pancreatic metastasis of rectal cancer, pancreatic cancer was used as a prognostic factor as double cancer of rectal cancer and pancreatic cancer, from that UGT1A1 test side effects appearance was a low-risk decision, was selected FOLFIRINOX in the treatment regimen.After 25 cycles, the pancreatic body tumor and liver metastases and also the primary tumor were reduced, the multiple lung metastases disappeared, and disease control was good.Side effects were diarrhea on the day of administration of irinotecan, but this was controllable by administering oral loperamide when starting the infusion.Grade 3 or more peripheral neuropathy has not developed, and this regimen is continuing.Pancreatic cancer is a solid cancer with a poor prognosis; if you do not reach the tissue diagnosis of metastatic pancreatic cancer, was a case in which no choice but to select a regimen to carcinoma of the prognostic.

  7. Time to lowest postoperative carcinoembryonic antigen level is predictive on survival outcome in rectal cancer

    PubMed Central

    Yu, Huichuan; Luo, Yanxin; Wang, Xiaolin; Bai, Liangliang; Huang, Pinzhu; Wang, Lei; Huang, Meijin; Deng, Yanhong; Wang, Jianping

    2016-01-01

    This study was to investigate whether the time to the lowest postoperative CEA can predict cancer survival. We enrolled 155 rectal cancer patients in this retrospective and longitudinal cohort study. Deepness of response (DpR) of CEA refers to the relative change of the lowest postoperative CEA level from baseline, and time to DpR (TTDpR) refers to the time from surgery to the lowest postoperative CEA level. The median of TTDpR and DpR was 4.5 (range, 3.0–18.0) weeks and −67% (range, −99% to 114%) respectively. Patients with TTDpR 4.5 weeks. Using TTDpR as a continuous variable, the HR of DFS and OS was 1.13 (95% CI 1.06–1.22, P = 0.001) and 1.17 (95% CI 1.07–1.29, P = 0.001) respectively. On multivariate analysis, the predictive value of prolonged TTDpR remained [adjusted HRs: 1.12 (95% CI 1.03–1.21, P = 0.006) and 1.17 (95% CI 1.06–1.28, P = 0.001)]. These findings remained significant in patients with normal preoperative CEA. Our results showed prolonged TTDpR of CEA independently predicted unfavorable survival outcomes, regardless of whether preoperative CEA was elevated or not. PMID:27658525

  8. XRCC2 as a predictive biomarker for radioresistance in locally advanced rectal cancer patients undergoing preoperative radiotherapy

    PubMed Central

    Qin, Chang-Jiang; Song, Xin-Ming; Chen, Zhi-Hui; Ren, Xue-Qun; Xu, Kai-Wu; Jing, Hong; He, Yu-Long

    2015-01-01

    XRCC2 has been shown to increase the radioresistance of some cancers. Here, XRCC2 expression was investigated as a predictor of preoperative radiotherapy (PRT) treatment response in locally advanced rectal cancer (LARC). XRCC2 was found to be overexpressed in rectal cancer tissues resected from patients who underwent surgery without PRT. In addition, overall survival for LARC patients was improved in XRCC2-negative patients compared with XRCC2-positive patients after treatment with PRT (P < 0.001). XRCC2 expression was also associated with an increase in LARC radioresistance. Conversely, XRCC2-deficient cancer cells were more sensitive to irradiation in vitro, and a higher proportion of these cells underwent cell death induced by G2/M phase arrest and apoptosis. When XRCC2 was knocked down, the repair of DNA double-strand breaks caused by irradiation was impaired. Therefore, XRCC2 may increases LARC radioresistance by repairing DNA double-strand breaks and preventing cancer cell apoptosis. Moreover, the present data suggest that XRCC2 is a useful predictive biomarker of PRT treatment response in LARC patients. Thus, inhibition of XRCC2 expression or activity represents a potential therapeutic strategy for improving PRT response in LARC patients. PMID:26320178

  9. Intermediate neoadjuvant radiotherapy for T3 low/middle rectal cancer: postoperative outcomes of a non-controlled clinical trial

    PubMed Central

    Bisceglia, Giovanni; Mastrodonato, Nicola; Tardio, Berardino; Mazzoccoli, Gianluigi; Corsa, Pietro; Troiano, Michele; Parisi, Salvatore

    2014-01-01

    Background The benefits of adjuvant radiotherapy in rectal carcinoma are well known. However, there is still considerable uncertainty about the optimal radiation treatment. There is an ongoing debate about the choice between very short treatments immediately followed by surgical resection and prolonged treatments with delayed surgery. In this paper, we describe an interim analysis of a non-controlled clinical trial in which radiotherapy delivered with intermediate dose/duration was followed by surgery after about 2 weeks to improve local control and survival after curative radiosurgery for cT3 low/middle rectal cancer. Methods Preoperative radiotherapy (36 Gy in 3 weeks) was delivered in 248 consecutive patients with cT3NxM0 rectal adenocarcinoma within 10 cm from the anal verge, followed by surgery within the third week after treatment completion. Results 166 patients (66.94%) underwent anterior resection, 80 patients (32.26%) the Miles' procedure and 2 patients (0.8%) the Hartmann's procedure. Local resectability rate was 99.6%, with 226 curative-intent resections. The overall rate of complications was 27.4%. 5-year oncologic outcomes were evaluated on 223 patients. The median follow-up time was 8.9 years (range 5-17.4 years); local recurrence (LR) rate and distal recurrence (DR) rate after 5 years were 6.28% and 21.97%, respectively. Overall survival was 74.2%; disease free survival was 73.5%; local control was 93.4 % and metastasis-free survival was 82.1%. Conclusions preoperative radiotherapy with intermediate dose/duration and interval between radiotherapy and surgery achieves high local control in patients with cT3NxM0 rectal cancer, and high DR rate seems to be the major limitation to improved survival. PMID:25373926

  10. 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

  11. 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.

  12. Impact of chemotherapy on eosinophilia-associated advanced rectal cancer: A case report and review of the literature

    PubMed Central

    Inoue, Maki; Kadono, Jun; Sugita, Hiroshi; Nakazono, Toshihiro; Motoi, Shunsuke; Kitazono, Iwao; Goto, Yuko; Fukukura, Yoshihiko; Yoshimitsu, Makoto; Misaka, Takaharu; Imoto, Yutaka

    2016-01-01

    The present study reports a case of eosinophilia-associated rectal cancer that was successfully stabilized using chemotherapy, and reviews the mechanisms of eosinophilia and the importance of chemotherapy. A 65-year-old man, who had previously been diagnosed with suspected rectal cancer, presented with the chief complaint of melena. Eosinophilia, abnormal blood coagulation, and elevated carcinoembryonic antigen and carbohydrate antigen 19–9 tumor marker levels were observed, and the patient was subsequently diagnosed with advanced rectal cancer accompanied by multiple lymph node metastases that extended from the para-aortic lymph nodes to the left axillary lymph nodes. The complication of deep vein thrombosis was also observed. Tumor hemorrhage was exacerbated, and thus, Hartmann's procedure was performed. Pathological findings included poorly- to moderately-differentiated adenocarcinoma; however, no eosinophil infiltration was observed within the tumor. Following surgery, the eosinophilia and lymph node metastasis were exacerbated, and an oxaliplatin plus capecitabine chemotherapy regimen was initiated. The patient's eosinophil count and tumor marker levels normalized, and the lymph nodes decreased in size; however, re-enlargement of the lymph nodes was observed 6 months after surgery. The patient was then administered a chemotherapeutic regimen of irinotecan/fluorouracil/folinic acid + bevacizumab, and stable disease was maintained until pleural and peritoneal dissemination were observed at 22 months post-surgery. Following a rapid deterioration in condition, the patient succumbed to the disease at 23 months post-surgery. The present case indicates that although eosinophilia-associated colon cancer exhibits a poor prognosis, early chemotherapeutic intervention may improve this. PMID:28105235

  13. 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

  14. 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

  15. Cancer of the uterine cervix: dosimetric guidelines for prevention of late rectal and rectosigmoid complications as a result of radiotherapeutic treatment

    SciTech Connect

    Pourquier, H.; Dubois, J.B.; Delard, R.

    1982-11-01

    This paper is the report of a dosimetric study of 41 rectal and rectosigmoid complications after radiotherapeutic treatment (1974-1978) of 287 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit applicator) at different doses depending on tumor stage. Dosimetric measurements were expressed as the maximum rectal dose and mean rectal dose on the anterior surface of the rectum, as proposed by the Groupe Europeen de Curietherapie. Rectal doses were also studied as a function of intracavitary irradiation and intracavitary + external irradiation (maximum rectal and mean cummulative doses for each). The results show a significant difference in the state of the patients with and without complications, based on the dose reaching the rectum. The maximum and the mean cumulative rectal doses serve as one of the primary indicators for predicting complications. These values should therefore be determined before placement of intracavitary sources or, at the latest, before the second intracavitary applications. We have shown that there is no fixed threshold dose, but that it varies from one region to another, depending on level of external irradiation. Our results argue in favor of adapting individual patient therapy based on simple precautions, which are adjustable to all treatment modalities. This method could lead to complete elimination of late rectal and rectosigmoid complications arising from radiotherapeutic treatment of cervical uterine cancer.

  16. Cancer of the uterine cervix: dosimetric guidelines for prevention of late rectal and rectosigmoid complications as a result of radiotherapeutic treatment

    SciTech Connect

    Pourquier, H.; Dubois, J.B.; Delard, R.

    1982-11-01

    This paper is the report of a dosimetric study of 41 rectal and rectosigmoid complications after radiotherapeutic treatment (1974-1978) of 287 cervical uterine tumors. Treatment consisted of external irradiation (25 MeV linear accelerator) and intracavitary irradiation (Fletcher-Suit applicator) at different doses depending on tumor stage. Dosimetric measurements were expressed as the maximum rectal dose and mean rectal dose on the anterior surface of the rectum, as proposed by the Groupe Europeen de Curietherapie. Rectal doses were also studied as a function of intracavitary irradiation + external irradiation (maximum rectal and mean cumulative doses for each).The results show a significant difference in the state of the patients with and without complications, based on the dose reaching the rectum. The maximum and the mean cumulative rectal doses serve as one of the primary indicators for predicting complications. These values should therefore be determined before placement of intracavitary sources or, at the latest, before the second intracavitary application. We have shown that there is no fixed threshold dose, but that it varies from one region to another, depending on level of external irradiation. Our results argue in favor of adapting individual patient therapy based on simple precautions, which are applicable to all treatment modalities. This method could lead to complete elimination of late rectal and rectosigmoid complications arising from radiotherapeutic treatment of cervical uterine cancer.

  17. High-performance size-based microdevice for the detection of circulating tumor cells from peripheral blood in rectal cancer patients.

    PubMed

    Sun, Wenjie; Jia, Chunping; Huang, Ting; Sheng, Weiqi; Li, Guichao; Zhang, Honglian; Jing, Fengxiang; Jin, Qinghui; Zhao, Jianlong; Li, Gang; Zhang, Zhen

    2013-01-01

    Since individualized therapy becomes more and more important in the treatment of rectal cancer, an accurate and effective approach should be established in the clinical settings to help physicians to make their decisions. Circulating tumor cells (CTCs), originated from either primary or metastatic cancer, could provide important information for diagnosis and monitoring of cancer. However, the implication and development of CTCs are limited due to the extreme rarity of these tumor cells. In this study we fabricated a simple and high-performance microfluidic device, which exploited numerous filtered microchannels in it to enrich the large-sized target tumor cells from whole blood. A very high CTC capture efficiency (average recovery rate: 94%) was obtained in this device at the optimum flow rate of 0.5 mL/h and channel height of 5 µm. Additionally, we used this device for detecting CTCs in 60 patients with rectal cancer. The CTC counts of rectal cancer patients were significantly higher than those in healthy subjects. Furthermore, the CTC counts detected by this device were significantly higher than those by EpCAM bead-based method for rectal cancer patients with various stage. Especially, for localized rectal cancer patients, the positive rates of samples with more than 3 CTCs per 5 mL blood by use of microdevice vs. EpCAM-based ones were 100% vs. 47%, respectively. Thus, this device provides a new and effective tool for accurate identification and measurement of CTCs in patients with rectal cancer, and has broad potential in clinical practice.

  18. 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

  19. 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

  20. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    SciTech Connect

    Yeo, Seung-Gu; Kim, Dae Yong; Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju

    2012-02-01

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  1. 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.

  2. 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.

  3. Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

    PubMed Central

    Zhang, Lu-Ning; Xiao, Wei-Wei; Xi, Shao-Yan; OuYang, Pu-Yun; You, Kai-Yun; Zeng, Zhi-Fan; Ding, Pei-Rong; Zhang, Hui-Zhong; Pan, Zhi-Zhong; Xu, Rui-Hua; Gao, Yuan-Hong

    2016-01-01

    Background Tumor deposits (TDs) were reported to be poor prognoses in colorectal carcinoma, but the significance in locally advanced rectal cancer (LARC) (T3-4/N+) following neoadjuvant chemoradiotherapy (neo-CRT) and surgery is unclear. Since adjuvant chemotherapy showed no benefit for LARC following neo-CRT, it is of great value to investigate whether TDs can identify the subgroup of patients who may benefit from adjuvant chemotherapy. Methods Between 2004 and 2012, 310 LARC patients following neo-CRT and surgery were retrospectively reviewed. Overall survival (OS), disease-free survival (DFS), distant metastasis free survival (DMFS) and local recurrence free survival (LRFS) were evaluated by Kaplan-Meier method, log-rank test and Cox models. Results TDs-positive patients showed adverse OS, DFS and DMFS (all P≤0.001), but not LRFS (P = 0.273). In multivariate analysis, TDs continued to be associated with poor OS (HR = 2.44, 95% CI 1.32-4.4, P = 0.004) and DFS (HR = 1.99, 95% CI 1.21-3.27, P = 0.007), but not DMFS (HR = 1.77, 95% CI 0.97-3.20, P = 0.061) or LRFS (HR = 1.85, 95% CI 0.58-5.85, P = 0.298). Among TDs-positive patients, adjuvant chemotherapy significantly improved OS (P = 0.045) and DMFS (P = 0.026), but not DFS (P = 0.127) or LRFS (P = 0.862). Conclusions TDs are predictive of poor survival in LARC after neo-CRT. Fortunately, TDs-positive patients appear to benefit from adjuvant chemotherapy. PMID:26695441

  4. 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.

  5. 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

  6. 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.

  7. Laparoscopic total mesorectal excision of low rectal cancer with preservation of anal sphincter: A report of 82 cases

    PubMed Central

    Zhou, Zong-Guang; Wang, Zhao; Yu, Yong-Yang; Shu, Ye; Cheng, Zhong; Li, Li; Lei, Wen-Zhang; Wang, Tian-Cai

    2003-01-01

    AIM: To assess the feasibility and efficacy of laparoscopic total mesorectal excision (LTME) of low rectal cancer with preservation of anal sphincter. METHODS: From June 2001 to June 2003, 82 patients with low rectal cancer underwent laparoscopic total mesorectal excision with preservation of anal sphincter. The lowest edge of tumors was below peritoneal reflection and 1.5-7 cm from the dentate line (1.5-5 cm in 48 cases, 5-7 cm in 34 cases). RESULTS: LTME with anal sphincter preservation was performed on 82 randomized patients with low rectal cancer, and 100% sphincter preservation rate was achieved. There were 30 patients with laparoscopic low anterior resection (LLAR) at the level of the anastomosis below peritoneal reflection and 2 cm above from the dentate line; 27 patients with laparoscopic ultralow anterior resection (LULAR) at the level of anastomoses 2 cm below from the dentate line; and 25 patients with laparoscopic coloanal anastomoses (LCAA) at the level of the anastomoses at or below the dentate line. No defunctioning ileostomy was created in any case. The mean operating time was 120 min (ranged from 110-220 min), and the mean operative blood loss was 20 mL (ranged from 5-120 mL). Bowel function was restored and diet was resumed on day 1 or 2 after operation. The mean hospital stay was 8 d (ranged from 5-14). Postoperative analgesics were used in 45 patients. After surgery, 2 patients had urinary retention, one had anastomotic leakage, and another 2 patients had local recurrence one year later. No interoperative complication was observed. CONCLUSION: LTME with preservation of anal sphincter is a feasible, safe and minimally invasive technique with less postoperative pain and rapid recovery, and importantly, it has preserved the function of the sphincter. PMID:12854145

  8. Impact of anastomotic leakage on long-term oncologic outcome and its related factors in rectal cancer

    PubMed Central

    Noh, Gyoung Tae; Ann, Yeo Shen; Cheong, Chinock; Han, Jeonghee; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young; Kim, Nam Kyu

    2016-01-01

    Abstract Anastomotic leakage (AL) is a well-known cause of morbidity after low anterior resection (LAR) for rectal cancer, but its impact on oncologic outcome is not well understood. The aim of this study is to investigate the impact of AL on long-term oncologic outcome and to identify factors associated with AL that may affect prognosis after LAR for rectal cancer. A retrospective analysis of patients who underwent curative resection for rectal cancer without diverting stoma was performed. To investigate AL related factors that may be associated with oncologic outcome, Clavien-Dindo grades, prognostic nutritional indices (PNI) and inflammatory indices were included. One hundred and one patients out of a total of 1258 patients developed postoperative AL, giving an AL rate of 8.0%. Patients with AL showed poorer disease-free survival (DFS), than patients without AL (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.1–2.5; P = 0.01). In patients who developed AL, age over 60 (HR = 2.2; 95% CI: 1.1–4.7; P = 0.033), advanced pathologic stage (HR = 2.4; 95% CI: 1.4–4.0; P = 0.001), suppressed neutrophil-proportion (≤80%) (HR = 2.6; 95% CI: 1.2–5.8; P = 0.019) and PNI <36 (HR = 3.5; 95% CI: 1.2–9.6; P = 0.018) were associated with poorer DFS. AL was associated with poorer DFS. In patients with AL, a suppressed neutrophil-proportion and decreased PNI below 36 were associated with tumor recurrence. PMID:27472726

  9. SU-E-T-29: A Dosimetric Study of Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost for Rectal Cancer

    SciTech Connect

    Sun, T; Lin, X; Yin, Y; Liu, T

    2015-06-15

    Purpose: To compare the dosimetric differences among fixed field intensity-modulated radiotherapy (IMRT) and double-arc volumetricmodulated arc therapy (VMAT) plans with simultaneous integrated boost in rectal cancer. Methods: Ten patients with rectal cancer previously treated with IMRT were included in this analysis. For each patient, two treatment techniques were designed for each patient: the fixed 7 fields IMRT and double-arc VMAT with RapidArc technique. The treatment plan was designed to deliver in one process with simultaneous integrated boost (SIB). The prescribed doses to the planning target volume of the subclinical disease (PTV1) and the gross disease (PTV2) were 45 Gy and 55 Gy in 25 fractions, respectively. The dose distribution in the target, the dose to the organs at risk, total MU and the delivery time in two techniques were compared to explore the dosimetric differences. Results: For the target dose and homogeneity in PTV1 and PTV2, no statistically differences were observed in the two plans. VMAT plans showed a better conformity in PTV1. VMAT plans reduced the mean dose to bladder, small bowel, femur heads and iliac wings. For iliac wings, VMAT plans resulted in a statistically significant reduction in irradiated volume of 15 Gy, 20 Gy, 30 Gy but increased the 10 Gy irradiated volume. VMAT plans reduced the small bowel irradiated volume of 20 Gy and 30 Gy. Compared with IMRT plans, VMAT plans showed a significant reduction of monitor units by nearly 30% and reduced treatment time by an average of 70% Conclusion: Compared to IMRT plans, VMAT plans showed the similar target dose and reduced the dose of the organs at risk, especially for small bowel and iliac wings. For rectal cancer, VMAT with simultaneous integrated boost can be carried out with high quality and efficiency.

  10. 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.

  11. Correlations of Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Morphologic, Angiogenic, and Molecular Prognostic Factors in Rectal Cancer

    PubMed Central

    Hong, Hye-Suk; Kim, Se Hoon; Park, Hae-Jeong; Park, Mi-Suk; Kim, Won Ho; Kim, Nam Kyu; Lee, Jae Mun; Cho, Hyeon Je

    2013-01-01

    Purpose To investigate the correlations between parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and prognostic factors in rectal cancer. Materials and Methods We studied 29 patients with rectal cancer who underwent gadolinium contrast-enhanced, T1-weighted DCE-MRI with a three Tesla scanner prior to surgery. Signal intensity on DCE-MRI was independently measured by two observers to examine reproducibility. A time-signal intensity curve was generated, from which four semiquantitative parameters were calculated: steepest slope (SLP), time to peak (Tp), relative enhancement during a rapid rise (Erise), and maximal enhancement (Emax). Morphologic prognostic factors including T stage, N stage, and histologic grade were identified. Tumor angiogenesis was evaluated in terms of microvessel count (MVC) and microvessel area (MVA) by morphometric study. As molecular factors, the mutation status of the K-ras oncogene and microsatellite instability were assessed. DCE-MRI parameters were correlated with each prognostic factor using bivariate correlation analysis. A p-value of <0.05 was considered significant. Results Erise was significantly correlated with N stage (r=-0.387 and -0.393, respectively, for two independent data), and Tp was significantly correlated with histologic grade (r=0.466 and 0.489, respectively). MVA was significantly correlated with SLP (r=-0.532 and -0.535, respectively) and Erise (r=-0.511 and -0.446, respectively). MVC was significantly correlated with Emax (r=-0.435 and -0.386, respectively). No significant correlations were found between DCE-MRI parameters and T stage, K-ras mutation, or microsatellite instability. Conclusion DCE-MRI may provide useful prognostic information in terms of histologic differentiation and angiogenesis in rectal cancer. PMID:23225808

  12. Stage II/III rectal cancer with intermediate response to preoperative radiochemotherapy: Do we have indications for individual risk stratification?

    PubMed Central

    2010-01-01

    Background Response to preoperative radiochemotherapy (RCT) in patients with locally advanced rectal cancer is very heterogeneous. Pathologic complete response (pCR) is accompanied by a favorable outcome. However, most patients show incomplete response. The aim of this investigation was to find indications for risk stratification in the group of intermediate responders to RCT. Methods From a prospective database of 496 patients with rectal adenocarcinoma, 107 patients with stage II/III cancers and intermediate response to preoperative 5-FU based RCT (ypT2/3 and TRG 2/3), treated within the German Rectal Cancer Trials were studied. Surgical treatment comprised curative (R0) total mesorectal excision (TME) in all cases. In 95 patients available for statistical analyses, residual transmural infiltration of the mesorectal compartment, nodal involvement and histolologic tumor grading were investigated for their prognostic impact on disease-free (DFS) and overall survival (OS). Results Residual tumor transgression into the mesorectal compartment (ypT3) did not influence DFS and OS rates (p = 0.619, p = 0.602, respectively). Nodal involvement after preoperative RCT (ypN1/2) turned out to be a valid prognostic factor with decreased DFS and OS (p = 0.0463, p = 0.0236, respectively). Persistent tumor infiltration of the mesorectum (ypT3) and histologic tumor grading of residual tumor cell clusters were strongly correlated with lymph node metastases after neoadjuvant treatment (p < 0.001). Conclusions Advanced transmural tumor invasion after RCT does not affect prognosis when curative (R0) resection is achievable. Residual nodal status is the most important predictor of individual outcome in intermediate responders to preoperative RCT. Furthermore, ypT stage and tumor grading turn out to be additional auxiliary factors. Future clinical trials for risk-adapted adjuvant therapy should be based on a synopsis of clinicopathologic parameters. PMID:20388220

  13. Immunohistochemical Markers as Predictors of Histopathologic Response and Prognosis in Rectal Cancer Treated with Preoperative Adjuvant Therapy: State of the Art

    PubMed Central

    2017-01-01

    We explain the state of the art of the immunohistochemical markers of response in rectal cancers treated with neoadjuvant medical therapies and its implication with prognosis. Neoadjuvant chemoradiotherapy is widely used to improve the outcome of patients with locally advanced rectal cancer, and the evaluation of the effects of medical therapy is to date based on histomorphological examination by applying four grading systems of response to therapy (tumor regression grade (TRG)). The need to identify immunohistochemical markers that could ensure a better assessment of response and possibly provide additional prognostic information has emerged. We identified p53, p27kip1, Ki67, matrix metalloprotease-9, survivin, Ki67 proliferative index, CD133, COX2, CD44v6, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase as the most common markers studied in literature to date, and we explained their prognostic potential and their implications in the evaluation of the response to preoperative therapies in rectal cancers. PMID:28326100

  14. 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

  15. Successful resection of metachronous para-aortic, Virchow lymph node and liver metastatic recurrence of rectal cancer.

    PubMed

    Takeshita, Nobuyoshi; Fukunaga, Toru; Kimura, Masayuki; Sugamoto, Yuji; Tasaki, Kentaro; Hoshino, Isamu; Ota, Takumi; Maruyama, Tetsuro; Tamachi, Tomohide; Hosokawa, Takashi; Asai, Yo; Matsubara, Hisahiro

    2015-11-28

    A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, cSS, cN0, cH0, cP0, cM0 cStage II, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, pSS, pN3, pH0, pP1, pM1 (para-aortic lymph node, dissemination) fStage IV. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography (CT) detected an 11 mm of liver metastasis in the postero-inferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of para-aortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in para-aortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine alone and continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome (Grade 3), we managed to

  16. Long-term outcomes of surgery alone versus surgery following preoperative chemoradiotherapy for early T3 rectal cancer

    PubMed Central

    Cho, Seung Hyun; Choi, Gyu-Seog; Kim, Gab Chul; Seo, An Na; Kim, Hye Jung; Kim, Won Hwa; Shin, Kyung-Min; Lee, So Mi; Ryeom, Hunkyu; Kim, See Hyung

    2017-01-01

    Abstract Recently, a few studies have raised the question of whether preoperative chemoradiotherapy (PCRT) is essential for all T3 rectal cancers. This case-matched study aimed to compare the long-term outcomes of surgery alone with those of PCRT + surgery for magnetic resonance imaging (MRI)-assessed T3ab (extramural depth of invasion ≤5 mm) and absent mesorectal fascia invasion (clear MRF) in mid/lower rectal cancer patients. From January 2006 to November 2012, 203 patients who underwent curative surgery alone (n = 118) or PCRT + surgery (n = 85) were enrolled in this retrospective study. A 1:1 propensity score-matched analysis was performed to eliminate the inherent bias. Case-matching covariates included age, sex, body mass index, histologic grade, carcinoembryonic antigen, operation method, follow-up period, tumor height, and status of lymph node metastasis. The end-points were the 5-year local recurrence (LR) rate and disease-free-survival (DFS). After propensity score matching, 140 patients in 70 pairs were included. Neither the 5-year LR rate nor the DFS was significantly different between the 2 groups (the 5-year LR rate, P = 0.93; the 5-year DFS, P = 0.94). The 5-year LR rate of the surgery alone was 2% (95% confidence interval [CI] 0.2%–10.9%) versus 2% (95% CI 0.2%–10.1%) in the PCRT + surgery group. The 5-year DFS of the surgery alone was 87% (95% CI 74.6%–93.7%) versus 88% (95% CI 77.8%–93.9%) in the PCRT + surgery group. In patients with MRI-assessed T3ab and clear MRF mid/lower rectal cancer, the long-term outcomes of surgery alone were comparable with those of the PCRT + surgery. The suggested MRI-assessed T3ab and clear MRF can be used as a highly selective indication of surgery alone in mid/lower T3 rectal cancer. Additionally, in those patients, surgery alone can be tailored to the clinical situation. PMID:28328820

  17. 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

  18. Implications for determining the optimal treatment for locally advanced rectal cancer in elderly patients aged 75 years and older.

    PubMed

    Wan, Jue-feng; Zhu, Ji; Li, Gui-chao; Sun, Wen-jie; Zhang, Zhen

    2015-10-06

    Patients were excluded if they were older than 75 years of age in most clinical trials. Thus, the optimal treatment strategies in elderly patients with locally advanced rectal cancer (LARC) are still controversial. We designed our study to specifically evaluate the cancer specific survival of four subgroups of patients according to four different treatment modalities: surgery only, radiation (RT) only, neoadjuvant RT and adjuvant RT by analyzing the Surveillance, Epidemiology, and End Results (SEER)-registered database. The results showed that the 5-year cancer specific survival (CSS) was 52.1% in surgery only, 27.7% in RT only, 70.4% in neoadjuvant RT and 60.4% in adjuvant RT, which had significant difference in univariate log-rank test (P < 0.001) and multivariate Cox regression (P < 0.001). Thus, the neoadjuvant RT and surgery may be the optimal treatment pattern in elderly patients, especially for patients who are medically fit for the operation.

  19. 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

  20. The clinicopathologic relevance and prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy

    PubMed Central

    He, Ming-ming; Luo, Hui-yan; Wang, Feng-hua; Zhang, Dong-sheng; Li, Yu-hong; Xu, Rui-hua

    2016-01-01

    The clinicopathologic relevance and prognostic value of tumor deposits in colorectal cancer has been widely demonstrated. However, there are still debates in the prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy. In this study, rectal cancer with preoperative radiotherapy followed by resection of primary tumors registered in Surveillance, Epidemiology and End Results (SEER) database from 2010-2012 were analyzed. There were 4,813 cases eligible for this study, and tumor deposits were found in 514 (10.7%) cases. The presence of tumor deposits was significantly associated with some aggressive characteristics, including poorer tumor differentiation, more advanced ypT category, ypN category and ypTNM stage, distant metastasis, elevated carcinoembryonic antigen, higher positive rates of circumferential resection margin and perineural invasion (all P < = 0.001). Tumor deposit was also an independent negative prognostic factor for cancer-specific survival in rectal cancer with preoperative radiotherapy (adjusted HR and 95% CI: 2.25 (1.51 – 3.35)). N1c category had significant worse survival compared with N0 category (adjusted HR and 95% CI: 2.41 (1.24 – 4.69)). In conclusion, tumor deposit was a significant and independent prognostic factor, and the N1c category by the 7th edition of AJCC/TNM staging system was applicable in rectal cancer with preoperative radiotherapy. PMID:27655707

  1. Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer

    PubMed Central

    2013-01-01

    Background As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Methods Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. Results From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. Conclusions This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. Trial registration: German Clinical Trials Register DRKS00003273. PMID:23336502

  2. 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.

  3. Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region

    SciTech Connect

    Spindler, Karen-Lise Garm . E-mail: kalgsp@vgs.vejleamt.dk; Nielsen, Jens Nederby; Lindebjerg, Jan; Brandslund, Ivan; Jakobsen, Anders

    2006-10-01

    Purpose: Epidermal growth factor receptor (EGFR) has been associated with radioresistance in solid tumors. Recently a polymorphism in the Sp1 recognition site of the EGFR promoter region was identified. The present study investigated the predictive value of this polymorphism for the outcome of chemoradiation in locally advanced rectal cancer. Methods and Materials: The study included 77 patients with locally advanced T3 rectal tumors. Treatment consisted of preoperative radiation therapy at a total tumor dose of 65 Gy and concomitant chemotherapy with Uftoral. Blood samples from 63 patients were evaluated for Sp1 -216 G/T polymorphism by polymerase chain reaction analysis. Forty-eight primary tumor biopsies were available for EGFR immunostaining. Patients underwent surgery 8 weeks after treatment. Pathologic response evaluation was performed according to the tumor regression grade (TRG) system. Results: Forty-nine percent had major response (TRG1-2) and 51% moderate response (TRG 3-4) to chemoradiation. The rates of major response were 34% (10/29) in GG homozygote patients compared with 65% (22/34) in patients with T containing variants (p = 0.023). Fifty-eight percent of biopsies were positive for EGFR expression (28/48). The major response rates with regard to EGFR immunostaining were not significantly different. EGFR-positive tumors were found in 83% of the GG homozygote patients compared with 38% of patients with TT or GT variants (p = 0.008). Conclusions: There was a significant correlation between EGFR Sp1 -216 G/T polymorphism and treatment response to chemoradiation in locally advanced rectal cancer. Further investigations of a second set of patient and other treatment schedules are warranted.

  4. Systematic Review of Anastomotic Leakage Rate According to an International Grading System Following Anterior Resection for Rectal Cancer

    PubMed Central

    Ye, Guang-Yao; Yu, Min-Hao; Gao, Yun-He; Li, Zhao-Shen; Yu, En-Da; Zhong, Ming

    2013-01-01

    Background A generally acceptable definition and a severity grading system for anastomotic leakages (ALs) following rectal resection were not available until 2010, when the International Study Group of Rectal Cancer (ISGRC) proposed a definition and a grading system for AL. Methods A search for published data was performed using the MEDLINE database (2000 to December 5, 2012) to perform a systematic review of the studies that described AL, grade AL according to the grading system, pool data, and determine the average rate of AL for each grade after anterior resection (AR) for rectal cancer. Results A total of 930 abstracts were retrieved; 40 articles on AR, 25 articles on low AR (LAR), and 5 articles on ultralow AR (ULAR) were included in the review and analysis. The pooled overall AL rate of AR was 8.58% (2,085/24,288); the rate of the asymptomatic leakage (Grade A) was 2.57%, that of AL that required active intervention without relaparotomy (Grade B) was 2.37%, and that of AL that required relaparotomy (Grade C) was 5.40%. The pooled rate of AL that required relaparotomy was higher in AR (5.40%) than in LAR (4.70%) and in ULAR (1.81%), which could be attributed to the higher rate of protective defunctioning stoma in LAR (40.72%) and ULAR (63.44%) compared with that in AR (30.11%). Conclusions The new grading system is simple that the ALs of each grade can be easily extracted from past publications, therefore likely to be accepted and applied in future studies. PMID:24086552

  5. [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.

  6. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

    2009-11-01

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

  7. Prediction of Anastomotic Leakage After Laparoscopic Low Anterior Resection in Male Rectal Cancer by Pelvic Measurement in Magnetic Resonance Imaging

    PubMed Central

    Tashiro, Jo; Ishii, Toshimasa; Oka, Yasuo; Suzuki, Asami; Kondo, Hiroka; Yamaguchi, Shigeki

    2017-01-01

    Objective: Anastomotic leakage after laparoscopic low anterior resection in male rectal cancer patients with a narrow pelvis cannot be easily resolved. The objective of this study is to assess numerical information of narrow pelvis and to determine whether prediction of morbidity can be possible. Methods: Retrospective medical record review was performed. From July 2007 to January 2013, 43 consecutive male patients with low rectal cancer who underwent laparoscopic low anterior resection were divided into the anastomotic leakage–negative group and anastomotic leakage–positive group. Eleven anatomic parameters were measured from preoperative magnetic resonance imaging of pelvis and a new index called “pelvic index” was calculated. Results: The pelvic index (difference between the interspinous distance and the diameter of the mesorectum divided by the depth of the cavity of the lesser pelvis) in the leakage-positive group was significantly smaller than that in the negative group (P=0.038). Comparison between those 2 groups at the border of the cut-off value of the pelvic index (13.0) showed a significant difference. Conclusions: Preoperative assessment by the pelvic index can predict the narrow pelvis and risk of anastomotic leakage. PMID:28092330

  8. Influence of enteral glutamine on inflammatory and hormonal response in patients with rectal cancer during preoperative radiochemotherapy.

    PubMed

    Rotovnik Kozjek, N; Kompan, L; Žagar, T; Mrevlje, Ž

    2017-03-08

    We conducted a randomized double-blind placebo-controlled study evaluating the influence of 5 weeks' duration of 30 g enteral glutamine supplementation on inflammatory and hormonal responses in 73 patients with rectal cancer undergoing preoperative radiochemotherapy. Plasma levels of inflammatory and hormonal parameters were controlled at the beginning and at the end of supplementation. Enteral glutamine resulted in modulation of inflammatory and hormonal responses as shown by a decreased plasma interleukin 6 and cortisol levels in glutamine compared with placebo group: 5.5±3.8 versus 11.1±19.9 ng/l (P=0.02) for IL-6 and 386±168.4 to 312.7±111.7 nmol/l (P=0.03) for cortisol. We conclude that enteral glutamine exhibits some anti-inflammatory activity and, consequently, leads to a lower hormonal stress response during radiochemotherapy in patients with rectal cancer.European Journal of Clinical Nutrition advance online publication, 8 March 2017; doi:10.1038/ejcn.2017.11.

  9. Nodal tumor response according to the count of peripheral blood lymphocyte subpopulations during preoperative chemoradiotherapy in locally advanced rectal cancer

    PubMed Central

    Heo, Jaesung; Oh, Young-Taek; Noh, O Kyu; Chun, Mison; Park, Jun-Eun; Cho, Sung-Ran

    2016-01-01

    Purpose The objective of this prospective study was to evaluate the relationship between the circulating lymphocyte subpopulation counts during preoperative chemoradiotherapy (CRT) and tumor response in locally advanced rectal cancer. Materials and Methods From August 2015 to June 2016, 10 patients treated with preoperative CRT followed by surgery were enrolled. Patients received conventional fractionated radiotherapy (50.4 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. The absolute blood lymphocyte subpopulation was obtained prior to and after 4 weeks of CRT. We analyzed the association between a tumor response and change in the lymphocyte subpopulation during CRT. Results Among 10 patients, 2 (20%) had evidence of pathologic complete response. In 8 patients with clinically node positive, 4 (50%) had nodal tumor response. All lymphocyte subpopulation counts at 4 weeks after CRT were significantly lower than those observed during pretreatment (p < 0.01). A high decrease in natural killer (NK) cell, count during CRT (baseline cell count − cell count at 4 weeks) was associated with node down staging (p = 0.034). Conclusion Our results suggest that the change of lymphocyte subset to preoperative CRT may be a predictive factor for tumor response in rectal cancer. PMID:27927012

  10. Does Extending the Waiting Time of Low-Rectal Cancer Surgery after Neoadjuvant Chemoradiation Increase the Perioperative Complications?

    PubMed Central

    Timudom, Kittinut; Phothong, Natthawut; Akaraviputh, Thawatchai; Chinswangwatanakul, Vitoon; Pongpaibul, Ananya; Petsuksiri, Janjira; Ithimakin, Suthinee

    2016-01-01

    Background. Traditionally, rectal cancer surgery is recommended 6 to 8 weeks after completing neoadjuvant chemoradiation. Extending the waiting time may increase the tumor response rate. However, the perioperative complication rate may increase. The purpose of this study was to determine the association between extending the waiting time of surgery after neoadjuvant chemoradiation and perioperative outcomes. Methods. Sixty patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by radical resection at Siriraj hospital between June 2012 and January 2015 were retrospectively analyzed. Demographic data and perioperative outcomes were compared between the two groups. Results. The two groups were comparable in term of demographic parameters. The mean time interval from neoadjuvant chemoradiation to surgery was 6.4 weeks in Group A and 11.7 weeks in Group B. The perioperative outcomes were not significantly different between Groups A and B. Pathologic examination showed a significantly higher rate of circumferential margin positivity in Group A than in Group B (30% versus 9.3%, resp.; P = 0.04). Conclusions. Extending the waiting to >8 weeks from neoadjuvant chemoradiation to surgery did not increase perioperative complications, whereas the rate of circumferential margin positivity decreased. PMID:27738430

  11. Effect of High-Dose-Rate {sup 192}Ir Source Activity on Late Rectal Bleeding After Intracavitary Radiation Therapy for Uterine Cervix Cancer

    SciTech Connect

    Suzuki, Osamu Yoshioka, Yasuo; Isohashi, Fumiaki; Morimoto, Masahiro; Kotsuma, Tadayuki; Kawaguchi, Yoshifumi; Konishi, Koji; Nakamura, Satoaki; Shiomi, Hiroya; Inoue, Takehiro

    2008-08-01

    Purpose: This retrospective study analyzed the effect of the activity of high-dose-rate (HDR) {sup 192}Ir source on late rectal bleeding after HDR intracavitary radiotherapy (ICRT) in patients with uterine cervix cancer. Methods and Materials: One hundred thirty-two patients who underwent HDR-ICRT and external beam radiotherapy (EBRT) were analyzed. The rectal point dose in ICRT was calculated by inserting a lead wire into the rectal lumen and summed with the whole-pelvic EBRT dose. The rectal biologic effective dose (BED) was calculated. The relationship between averaged source activity or the BED and late rectal bleeding were analyzed. Results: Three-year actuarial rectal bleeding probabilities were 46% ({>=}100 Gy{sub 3}) and 18% ({<=} 100 Gy{sub 3}), respectively (p < 0.005). When patients were divided into four groups according to rectal BED ({>=} or {<=}100 Gy{sub 3}) and source activity ({>=} or {<=}2.4 cGy.m{sup 2}.h{sup -1}), the group with both a high BED and high activity showed significantly greater probability (58% at 3 years; p < 0.005). It was noted that the probability of the group with BED of 100 Gy{sub 3} or greater was high, but that was not the case with 2.4 cGy.m{sup 2}.h{sup -1} or less. Conclusion: This is the first clinical report concerning the source activity effect of HDR {sup 192}Ir on late rectal bleeding in patients undergoing HDR-ICRT. This suggests that when source activity is higher than 2.4 cGy.m{sup 2}.h{sup -1}, ICRT should be performed with more caution not to exceed 100 Gy{sub 3} in total.

  12. Evolution of motion uncertainty in rectal cancer: implications for adaptive radiotherapy

    NASA Astrophysics Data System (ADS)

    Kleijnen, Jean-Paul J. E.; van Asselen, Bram; Burbach, Johannes P. M.; Intven, Martijn; Philippens, Marielle E. P.; Reerink, Onne; Lagendijk, Jan J. W.; Raaymakers, Bas W.

    2016-01-01

    Reduction of motion uncertainty by applying adaptive radiotherapy strategies depends largely on the temporal behavior of this motion. To fully optimize adaptive strategies, insight into target motion is needed. The purpose of this study was to analyze stability and evolution in time of motion uncertainty of both the gross tumor volume (GTV) and clinical target volume (CTV) for patients with rectal cancer. We scanned 16 patients daily during one week, on a 1.5 T MRI scanner in treatment position, prior to each radiotherapy fraction. Single slice sagittal cine MRIs were made at the beginning, middle, and end of each scan session, for one minute at 2 Hz temporal resolution. GTV and CTV motion were determined by registering a delineated reference frame to time-points later in time. The 95th percentile of observed motion (dist95%) was taken as a measure of motion. The stability of motion in time was evaluated within each cine-MRI separately. The evolution of motion was investigated between the reference frame and the cine-MRIs of a single scan session and between the reference frame and the cine-MRIs of several days later in the course of treatment. This observed motion was then converted into a PTV-margin estimate. Within a one minute cine-MRI scan, motion was found to be stable and small. Independent of the time-point within the scan session, the average dist95% remains below 3.6 mm and 2.3 mm for CTV and GTV, respectively 90% of the time. We found similar motion over time intervals from 18 min to 4 days. When reducing the time interval from 18 min to 1 min, a large reduction in motion uncertainty is observed. A reduction in motion uncertainty, and thus the PTV-margin estimate, of 71% and 75% for CTV and tumor was observed, respectively. Time intervals of 15 and 30 s yield no further reduction in motion uncertainty compared to a 1 min time interval.

  13. SU-E-J-153: MRI Based, Daily Adaptive Radiotherapy for Rectal Cancer: Contour Adaptation

    SciTech Connect

    Kleijnen, J; Burbach, M; Verbraeken, T; Weggers, R; Zoetelief, A; Reerink, O; Lagendijk, J; Raaymakers, B; Asselen, B

    2014-06-01

    Purpose: A major hurdle in adaptive radiotherapy is the adaptation of the planning MRI's delineations to the daily anatomy. We therefore investigate the accuracy and time needed for online clinical target volume (CTV) adaptation by radiation therapists (RTT), to be used in MRI-guided adaptive treatments on a MRI-Linac (MRL). Methods: Sixteen patients, diagnosed with early stage rectal cancer, underwent a T2-weighted MRI prior to each fraction of short-course radiotherapy, resulting in 4–5 scans per patient. On these scans, the CTV was delineated according to guidelines by an experienced radiation oncologist (RO) and considered to be the gold standard. For each patient, the first MRI was considered as the planning MRI and matched on bony anatomy to the 3–4 daily MRIs. The planning MRI's CTV delineation was rigidly propagated to the daily MRI scans as a proposal for adaptation. Three RTTs in training started the adaptation of the CTV conform guidelines, after a two hour training lecture and a two patient (n=7) training set. To assess the inter-therapist variation, all three RTTs altered delineations of 3 patients (n=12). One RTT altered the CTV delineations (n=53) of the remaining 11 patients. Time needed for adaptation of the CTV to guidelines was registered.As a measure of agreement, the conformity index (CI) was determined between the RTTs' delineations as a group. Dice similarity coefficients were determined between delineations of the RTT and the RO. Results: We found good agreement between RTTs' and RO's delineations (average Dice=0.91, SD=0.03). Furthermore, the inter-observer agreement between the RTTs was high (average CI=0.94, SD=0.02). Adaptation time reduced from 10:33 min (SD= 3:46) to 2:56 min (SD=1:06) between the first and last ten delineations, respectively. Conclusion: Daily CTV adaptation by RTTs, seems a feasible and safe way to introduce daily, online MRI-based plan adaptation for a MRL.

  14. Diffusion-Weighted Magnetic Resonance Imaging in Monitoring Rectal Cancer Response to Neoadjuvant Chemoradiotherapy

    SciTech Connect

    Barbaro, Brunella; Vitale, Renata; Valentini, Vincenzo; Illuminati, Sonia; Vecchio, Fabio M.; Rizzo, Gianluca; Gambacorta, Maria Antonietta; Coco, Claudio; Crucitti, Antonio; Persiani, Roberto; Sofo, Luigi; Bonomo, Lorenzo

    2012-06-01

    Purpose: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials: The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T{sub 2}- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm{sup 2}/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results: Low pretreatment ADCs (<1.0 Multiplication-Sign 10{sup -3}mm{sup 2}/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC {>=}1.4 Multiplication-Sign 10{sup -3}mm{sup 2}/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Conclusion: Diffusion-weighted magnetic resonance imaging seems to be a promising

  15. Predictors for Rectal and Intestinal Acute Toxicities During Prostate Cancer High-Dose 3D-CRT: Results of a Prospective Multicenter Study

    SciTech Connect

    Vavassori, Vittorio; Fiorino, Claudio . E-mail: fiorino.claudio@hsr.it; Rancati, Tiziana; Magli, Alessandro; Fellin, Gianni; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Valdagni, Riccardo

    2007-04-01

    Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with {>=}70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered. Results: Of 1,132 patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for

  16. Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial

    PubMed Central

    Yothers, Greg; O’Connell, Michael J.; Beart, Robert W.; Wozniak, Timothy F.; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini; Eakle, Janice F.; Robertson, John M.; Moore, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Sharif, Saima; Roh, Mark S.; Wolmark, Norman

    2015-01-01

    Background: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. Methods: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. Results: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3–4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. Conclusions: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity. PMID:26374429

  17. Image-guided method for TLD-based in vivo rectal dose verification with endorectal balloon in proton therapy for prostate cancer

    SciTech Connect

    Hsi, Wen C.; Fagundes, Marcio; Zeidan, Omar; Hug, Eugen; Schreuder, Niek

    2013-05-15

    Purpose: To present a practical image-guided method to position an endorectal balloon that improves in vivo thermoluminiscent dosimeter (TLD) measurements of rectal doses in proton therapy for prostate cancer. Methods: TLDs were combined with endorectal balloons to measure dose at the anterior rectal wall during daily proton treatment delivery. Radiopaque metallic markers were employed as surrogates for balloon position reproducibility in rotation and translation. The markers were utilized to guide the balloon orientation during daily treatment employing orthogonal x-ray image-guided patient positioning. TLDs were placed at the 12 o'clock position on the anterior balloon surface at the midprostatic plane. Markers were placed at the 3 and 9 o'clock positions on the balloon to align it with respect to the planned orientation. The balloon rotation along its stem axis, referred to as roll, causes TLD displacement along the anterior-posterior direction. The magnitude of TLD displacement is revealed by the separation distance between markers at opposite sides of the balloon on sagittal x-ray images. Results: A total of 81 in vivo TLD measurements were performed on six patients. Eighty-three percent of all measurements (65 TLD readings) were within +5% and -10% of the planning dose with a mean of -2.1% and a standard deviation of 3.5%. Examination of marker positions with in-room x-ray images of measured doses between -10% and -20% of the planned dose revealed a strong correlation between balloon roll and TLD displacement posteriorly from the planned position. The magnitude of the roll was confirmed by separations of 10-20 mm between the markers which could be corrected by manually adjusting the balloon position and verified by a repeat x-ray image prior to proton delivery. This approach could properly correct the balloon roll, resulting in TLD positioning within 2 mm along the anterior-posterior direction. Conclusions: Our results show that image-guided TLD-based in vivo

  18. Is It Time to Tailor the Prediction of Radio-Induced Toxicity in Prostate Cancer Patients? Building the First Set of Nomograms for Late Rectal Syndrome

    SciTech Connect

    Valdagni, Riccardo; Kattan, Michael W.; Rancati, Tiziana; Yu Changhong; Vavassori, Vittorio; Fellin, Giovanni; Cagna, Elena; Gabriele, Pietro; Mauro, Flora Anna; Baccolini, Micaela; Bianchi, Carla; Menegotti, Loris; Monti, Angelo F.; Stasi, Michele; Giganti, Maria Olga; and others

    2012-04-01

    Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer. Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events). Results: Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy. Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach.

  19. The degree of extramural spread of T3 rectal cancer: a plea to the UICC and AJCC.

    PubMed

    Zinicola, R; Pedrazzi, G; Haboubi, N; Nicholls, R J

    2017-03-01

    The above article, published online on 15 July 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, Neil Mortensen, and John Wiley & Sons Limited. After acceptance the authors were made aware of a contribution to a prior publication of the UICC, TNM Supplement: A commentary on uniform use, 4th Edition, ed. C. Wittekind (Wiley, 2012), p. 195, which renders the central argument of their article invalid. They have therefore asked for it to be withdrawn. A modified version of the paper was published in the January 2017 issue (volume 19; issue 1) with the title "The degree of extramural spread of T3 rectal cancer: an appeal to the American Joint Committee on Cancer".

  20. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study

    SciTech Connect

    Valentini, Vincenzo . E-mail: vvalentini@rm.unicatt.it; Morganti, Alessio G.; Gambacorta, M. Antonietta; Mohiuddin, Mohammed; Doglietto, G. Battista; Coco, Claudio; De Paoli, Antonino; Rossi, Carlo; Di Russo, Annamaria; Valvo, Francesca; Bolzicco, Giampaolo; Dalla Palma, Maurizio

    2006-03-15

    Purpose: The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence. However, a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis. In these patients, local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity. The aim of this multicenter phase II study is to evaluate the response rate, resectability rate, local control, and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis. Methods and Materials: Patients with histologically proven pelvic recurrence of rectal carcinoma, with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses {<=}55 Gy; age {>=}18 years; performance status (PS) (Karnofsky) {>=}60, and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2) including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8 Gy). During the radiation treatment, concurrent chemotherapy was delivered (5-fluorouracil, protracted intravenous infusion, 225 mg/m{sup 2}/day, 7 days per week). Four to 6 weeks after the end of chemoradiation, patients were evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed between 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using Raltitrexed, 3 mg/square meter (sm), every 3 weeks, for a total of 5 cycles. Patients were staged using the computed tomography (CT)-based F

  1. Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales

    PubMed Central

    Siddiqui, Muhammed R S; Bhoday, Jemma; Battersby, Nicholas J; Chand, Manish; West, Nicholas P; Abulafi, Al-Mutaz; Tekkis, Paris P; Brown, Gina

    2016-01-01

    AIM To define good and poor regression using pathology and magnetic resonance imaging (MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer. METHODS A systematic review was performed on all studies up to December 2015, without language restriction, that were identified from MEDLINE, Cochrane Controlled Trials Register (1960-2015), and EMBASE (1991-2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words used included “tumour regression”, “mrTRG”, “poor response” and “colorectal cancers”. Clinical studies using either MRI or histopathological tumour regression grade (TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures. RESULTS Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemo-radiotherapy (CRT) was 37.7% (95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR

  2. Spontaneous rupture of the renal pelvis presenting as an urinoma in locally advanced rectal cancer

    PubMed Central

    Garg, Pankaj Kumar; Mohanty, Debajyoti; Rathi, Vinita; Jain, Bhupendra Kumar

    2014-01-01

    A 29-year-old gentleman underwent a transverse colostomy for intestinal obstruction caused by advanced rectal carcinoma. On the 5th postoperative day, the patient developed a painful swelling on the right side of the abdomen. The contrast enhanced computed tomography of the abdomen revealed a right sided hydronephrosis, a large rent in the renal pelvis, and a large retroperitoneal fluid collection on the right side. Percutaneous nephrostomy and pigtail catheter drainage of the urinoma led to resolution of abdominal swelling. Development of a urinoma as a consequence of rectal carcinoma is highly unusual. Prompt imaging for confirmation of diagnosis, decompression of the renal pelvicalyceal system, and drainage of the urinoma limits morbidity. PMID:24749123

  3. Metastasis to the Glans Penis: An Unusual Site of Rectal Cancer Recurrence.

    PubMed

    Nunes, Beatriz; Matias, Margarida; Alves, António; Jorge, Marília

    2015-01-01

    Secondary malignancy of the penis is a rare clinical condition, often associated with disseminated genitourinary malignancies. The prognosis is poor and the treatment options include penectomy, local surgical excision, radiation therapy, chemotherapy and supportive therapy. Neither of these therapeutic options lead to superior treatment outcomes in the literature. The authors report the case of a 66 year-old man with a metastasis to the glans penis from a rectal adenocarcinoma, diagnosed two years after radical treatment for primary disease. The patient underwent palliative treatment with radiotherapy and chemotherapy, remaining asymptomatic and disease-free at one year follow-up. Close follow-up of patients with history of rectal adenocarcinoma is very important. Radiochemotherapy is a feasible and effective therapeutic option for penile metastasis, addressing both disease control and symptomatic improvement.

  4. Systematic review and meta-analysis of preoperative chemoradiotherapy with or without oxaliplatin in locally advanced rectal cancer

    PubMed Central

    Zheng, Jiabin; Feng, Xingyu; Hu, Weixian; Wang, Junjiang; Li, Yong

    2017-01-01

    Abstract Background: Preoperative chemoradiotherapy has become the current standard regimen for locally advanced rectal cancer (LARC). However, the additional benefit of oxaliplatin to preoperative chemotherapy was still controversial. On one hand, oxaliplatin may improve the tumor response rate of even prolong the survival time. On the other hand, it can bring a series of adverse effects. Opinions vary from studies to studies. We aim to perform a meta-analysis to evaluate the efficacy, safety, and long-term survival of oxaliplatin in preoperative chemoradiotherapy for LARC. Method: To identify clinical trials fusing oxaliplatin in preoperative chemoradiotherapy for LARC published until December 2015, we searched PubMed, the Cochrane Library, and the Springer Link databases by combining various key words. We also search for relevant ASCO conferences. Data were extracted from every study to perform a meta-analysis using STATA 12.0 software. Result: Eleven articles or ASCO abstracts from 8 studies with a total of 5597 patients were included. Adding oxaliplatin to preoperative chemoradiotherapy can significantly improve the ypCR rate [risk ratio (RR) = 1.208, 95% confidence interval (95% CI): 1.070–1.364, P = 0.002, I2 = 14.5%], and decrease the preoperative metastasis (RR = 0.494, 95% CI: 0.256–0.954, P = 0.036, I2 = 53.9%) and local recurrence rate (RR = 0.761, 95% CI: 0.616–0.941, P = 0.012, I2 = 26.1%). What's more, oxaliplatin can prolong the disease-free survival (DFS) [hazard ratio (HR) = 0.867, 95% CI: 0.741–0.992, P = 0.000, I2 = 16.3%]. However, oxaliplatin can increase the chemoradiotherapy-related toxicities (RR = 1.858, 95% CI 1.427–2.419, P = 0.000, I2 = 84.7%). There was no significant difference between the groups with and without oxaliplatin in operation rate, R0 resection rate, sphincter preservation rate, permanent stoma rate, postoperative complication, mortality, and overall

  5. Real-time in vivo rectal wall dosimetry using plastic scintillation detectors for patients with prostate cancer

    PubMed Central

    Wootton, Landon; Kudchadker, Rajat; Lee, Andrew; Beddar, Sam

    2014-01-01

    We designed and constructed an in vivo dosimetry system using plastic scintillation detectors (PSDs) to monitor dose to the rectal wall in patients undergoing intensity-modulated radiation therapy for prostate cancer. Five patients were enrolled in an Institutional Review Board–approved protocol for twice weekly in vivo dose monitoring with our system, resulting in a total of 142 in vivo dose measurements. PSDs were attached to the surface of endorectal balloons used for prostate immobilization to place the PSDs in contact with the rectal wall. Absorbed dose was measured in real time and the total measured dose was compared with the dose calculated by the treatment planning system on the daily CT image dataset. The mean difference between measured and calculated doses for the entire patient population was −0.4% (standard deviation 2.8%). The mean difference between daily measured and calculated doses for each patient ranged from −3.3% to 3.3% (standard deviation ranged from 5.6% to 7.1% for 4 patients and was 14.0% for the last, for whom optimal positioning of the detector was difficult owing to the patient’s large size). Patients tolerated the detectors well and the treatment workflow was not compromised. Overall, PSDs performed well as in vivo dosimeters, providing excellent accuracy, real-time measurement, and reusability. PMID:24434775

  6. Factors affecting morbidity, mortality and survival in patients undergoing surgery for rectal cancer in a district general hospital.

    PubMed Central

    Macadam, Robert; Yeomans, Neil; Wilson, Jonathan; Case, William; White, Clive; Lovegrove, John; Lyndon, Philip

    2005-01-01

    INTRODUCTION: This is a review of elective rectal cancer surgery during 1993-1999 at a single district general hospital to investigate the variables that affect