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NCI CANCERLIT® Search: Therapy of Colorectal Cancer - September 2001
Last Modified: November 1, 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21263452
AU - Giardiello C; Angelone G; Iodice G; Finelli R; Cristiano S; Tramontano G; Sarrantonio G
TI - [Diagnosis, therapy, and follow up in synchronous colorectal cancer of the colon]
SO - G Chir 2001 Apr;22(4):122-4
The authors report their experience with synchronous colorectal cancers (CRC). They underline the role of pre-operative diagnosis to improve surgical results and overall survival. The endoscopic surveillance allows the identification of neoplasms missed at previous examinations. In selected cases intraoperative colonoscopy may prove to be helpful.

2
UI - 21362746
AU - Tonus C; Strassmann G; Debertshauser D; Kolotas C; Walter S; Zamboglou N; Nier H
TI - [Intraoperative radiotherapy--progress with a CT-assisted navigation system]
SO - Chirurg 2001 Jun;72(6):731-5
AD - Klinik fur Allgemein-, Visceral-, Gefass- und Thorax-Chirurgie, Chirurgische Klinik I, Klinikum Offenbach. Liutkus.Tonus@t-online.de
INTRODUCTION: The fact that conventional intraoperative radiotherapy (IORT) does not give the opportunity for exact documentation of the applied radiation volume and dose distribution has been criticised. We would like to introduce a system for surgical navigation and documentation of the flab positioning for intraoperative brachytherapy in afterloading flab technique. METHODS: Our system consists of an electromagnetic 3D digitizer and a PC workstation. Preoperatively taken spiral CT scans of the tumour region are used for navigation and documentation of the flab positioning, analogous to the procedure in neuronavigation. Registration is done via an external reference system attached to the iliac bone of the patient. RESULTS: The mean accuracy of digitalization of the 100 spheres in a pelvis model is about 2.6 +/- 0.5-3.7 +/- 0.9 mm. Mean navigation accuracy is 2.4 +/- 0.8-3.3 +/- 0.8 mm. These figures correspond to the clinical experience of our surgeons. CONCLUSIONS: The optimization of the flab positioning by CT-guided navigation and the more accurate documentation of the dose volume and distribution in the patient is an important step towards improving the quality of individual radiotherapy. We are of the opinion that surgical navigation in the pelvic region should be subject to additional investigation in order to optimize the procedure.

3
UI - 21341902
AU - Benoist S; Taffinder N; Gould S; Ziprin P; Chang A; Darzi A
TI - [Transanal endoscopic microsurgery: a forgotten minimally invasive technique]
SO - Gastroenterol Clin Biol 2001 Apr;25(4):369-74
AD - Service de Chirurgie Generale et Digestive, Hopital Lariboisiere, Paris France.
OBJECTIVES: The aim of this study was to evaluate transanal endoscopic microsurgery in patients with benign and malignant rectal tumours with special reference to feasibility, morbidity, and recurrence rate.METHODS: Forty-three patients underwent transanal endoscopic microsurgical excision of rectal tumours between 1996 and 2000. The histological diagnosis was benign adenoma in 30 and invasive carcinoma in 13. The mean height of the tumour above the anal verge was 11.2 +/- 3 cm and the mean diameter of the lesion was 3.4 +/- 1.5 cm.RESULTS: The mean operative time was 85 +/- 26 min and in one case (2%), it was necessary to convert to an anterior resection. The morbidity rate was 18%. Mean hospital stay was 3.9 +/- 2.4 days. Complete excision of the tumour with histological confirmation was achieved in 42 cases (98%). With a mean follow-up of 26 months, benign tumour recurrence was observed in one patient (3%). Of the 13 patients with carcinoma, two had immediate further radical resection. For the remaining 11 patients, with a mean follow-up of 19 months, the recurrence rate was 75% for T2 tumours and nil for T1 tumours.CONCLUSIONS: Transanal endoscopic microsurgery is safe and feasible technique which should have a useful place in the management of sessile adenomas of the mid and upper rectum. Its role in the management of rectal cancer is limited, although it may be appropriate for carefully selected cases.

4
UI - 21379549
AU - Regenet N; Pessaux P; Tuech JJ; Burtin P; du Plessis R; Arnaud JP
TI - [Abdominoperineal resection for locally recurrent rectal cancers following anterior resection]
SO - Ann Chir 2001 Jul;126(6):541-8
AD - Departement de chirurgie viscerale, CHU Angers, 4, rue Larrey, 49033 Angers, France.
STUDY AIM: The aim of this retrospective study was to evaluate the short and long term results of abdominoperineal resection for local recurrence following low anterior resection of a rectal adenocarcinoma and to determine the prognostic factors. PATIENTS AND METHODS: From January 1978 to December 1996, 35 patients (17 women, 18 men) with a mean age of 59.4 years, underwent an abdominoperineal resection for local recurrence after low anterior resection of a rectal adenocarcinoma. The primary tumor was below the peritoneum in 29 cases, and the mean security margin was 3 cm under the tumor. Tumor staging at the time of primary surgery included 23 Dukes B, 11 Dukes C, and 1 Dukes D. The mean time elapsed between low anterior resection and local recurrence was 16.4 months. The histological diagnosis of recurrence was obtained preoperatively in 29 cases (82.8%). RESULTS: Resection was curative in 12 patients and palliative only in 23 patients. The recurrence was intramural in 3 cases, extramural in 10 cases, and mixed in 22 cases. Ten patients had an extended "en bloc" resection including one or several adjacent organs, and a synchronous metastasis was resected in 2 cases. The mortality rate was 2.8% (n = 1) and the morbidity rate was 23% (n = 8). The 1-year and 5-year survival rates were respectively 77 and 30.2% with the univariate analysis of prognosis factors of survival, there were four pretherapeutic factors (age, staging of the primary tumor, delay of the recurrence, CEA rate) and four therapeutic factors (curative resection, extramural recurrence, staging of the recurrence, postoperative radiotherapy). The curative or not curative type of resection was the only independent predictor of survival with multivariate analysis. CONCLUSION: The results of this study seem to justify an abdominoperineal resection for local recurrence after low anterior resection whenever possible. Long-term results may possibly be improved by using adjuvant treatment.

5
UI - 21370460
AU - Sasson AR; Sigurdson ER
TI - Management of locally advanced rectal cancer.
SO - Surg Oncol 2000 Dec;9(4):193-204
AD - Department of Surgical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
The treatment of rectal cancer typically involves a multidisciplinary approach. A minority of patients will have tumors that are full thickness, involve adjacent structures, or have metastatic disease to regional lymph nodes. The combination of adjuvant therapy and surgical resection is the mainstay of treatment for locally advanced carcinoma of the rectum. This article will review the role of adjuvant chemotherapy and radiotherapy in patients with high risk tumors. The operative considerations in advanced rectal cancers will be reviewed. In particular, the role of mesorectal excision and exenterative surgery will be discussed.

6
UI - 21341878
AU - Saurin JC
TI - [Clinical follow-up and treatment of patients with familial adenomatous polyposis]
SO - Gastroenterol Clin Biol 2001 Apr;25(4 Suppl):B31-7
AD - Federation des Specialites Digestives, Hopital Edouard-Herriot, 5, place d'Arsonval, 69437 Lyon Cedex 03.

7
UI - 21341880
AU - Louvet C
TI - [New chemotherapies for colorectal cancer treatment]
SO - Gastroenterol Clin Biol 2001 Apr;25(4 Suppl):B51-6
AD - Oncologie - Medecine Interne, Hopital Saint-Antoine, 184, rue du Faubourg-St-Antoine, 75012 Paris, France.

8
UI - 21376186
AU - Myerson RJ; Valentini V; Birnbaum EH; Cellini N; Coco C; Fleshman JW; Gambacorta MA; Genovesi D; Kodner IJ; Picus J; Ratkin GA; Read TE
TI - A phase I/II trial of three-dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1299-308
AD - Radiation Oncology Center, Washington University School of Medicine, St. Louis MO 63110, USA. myerson@wustl.edu
BACKGROUND: Improving the response to preoperative therapy may increase the likelihood of successful resection of locally advanced rectal cancers. Historically, the pathologic complete response (pCR) rate has been < approximately 10% with preoperative radiation therapy alone and < approximately 20% with concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Thirty-seven patients were enrolled on a prospective Phase I/II protocol conducted jointly at Washington University, St. Louis and the Catholic University of the Sacred Heart, Rome evaluating a three-dimensionally (3D) planned boost as part of the preoperative treatment of patients with unresectable or recurrent rectal cancer. Preoperative treatment consisted of 4500 cGy in 25 fractions over 5 weeks to the pelvis, with a 3D planned 90 cGy per fraction boost delivered once or twice a week concurrently (no time delay) with the pelvic radiation. Thus, on days when the boost was treated, the tumor received a dose of 270 cGy in one fraction while the remainder of the pelvis received 180 cGy. When indicated, nonaxial beams were used for the boost. The boost treatment was twice a week (total boost dose 900 cGy) if small bowel could be excluded from the boost volume, otherwise the boost was delivered once a week (total boost dose 450 cGy). Patients also received continuous infusion of 5-fluorouracil (1500 mg/m(2)-week) concurrently with the radiation as well as postoperative 5-FU/leucovorin. RESULTS: All 37 patients completed preoperative radiotherapy as planned within 32--39 elapsed days. Twenty-seven underwent proctectomy; reasons for unresectability included persistent locally advanced disease (6 cases) and progressive distant metastatic disease with stable or smaller local disease (4 cases). Actuarial 3-year survival was 82% for the group as a whole. Among resected cases the 3-year local control and freedom from disease relapse were 86% and 69%, respectively.Twenty-four of the lesions (65%) achieved an objective clinical response by size criteria, including 9 (24%) with pCR at the primary site (documented T0 at surgery). The most important factor for pCR was tumor volume: small lesions with planning target volume (PTV) < 200 cc showed a 50% pCR rate (p = 0.02).There were no treatment associated fatalities. Nine of the 37 patients (24%) experienced Grade 3 or 4 toxicities (usually proctitis) during preoperative treatment. There were an additional 7 perioperative and 2 late toxicities. The most important factors for small bowel toxicity (acute or late) were small bowel volume (> or = 150 cc at doses exceeding 4000 cGy) and large tumor (PTV > or = 800 cc). For rectal toxicity the threshold is PTV > or = 500 cc. CONCLUSION: 3D planned boost therapy is feasible. In addition to permitting the use of nonaxial beams for improved dose distributions, 3D planning provides tumor and normal tissue dose-volume information that is important in interpreting outcome. Every effort should be made to limit the treated small bowel to less than 150 cc. Tumor size is the most important predictor of response, with small lesions of PTV < 200 cc most likely to develop complete responses.

9
UI - 21376187
AU - Benson R; Wong CS; Cummings BJ; Brierley J; Catton P; Ringash J; Abdolell M
TI - Local excision and postoperative radiotherapy for distal rectal cancer.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1309-16
AD - Department of Oncology, Addenbrooke's Hospital, United Kingdom, Cambridge, UK.
PURPOSE: To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma. MATERIALS AND METHODS: Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and "elective" where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1--8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38--60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3--5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10--165 months). RESULTS: Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery). CONCLUSION: The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.

10
UI - 21393500
AU - Araki Y; Isomoto H; Shirouzu K
TI - Dihydropyrimidine dehydrogenase activity and thymidylate synthase level are associated with response to 5-fluorouracil in human colorectal cancer.
SO - Kurume Med J 2001;48(2):93-8
AD - Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
In the recent studies associated with the modulation of 5-fluorouracil (5-FU) and the development of new antifolates, attentions have been focused on the expression of the target enzymes, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), that affect tumor sensitivity and resistance to drugs. In order to evaluate predictability of therapeutic efficacy by intratumoral enzyme activity, we investigated the role of TS content and DPD activity in tumor sensitivity of 5-FU. Surgical specimens were obtained from 51 patients with colorectal cancer and used to measure TS content and DPD activity. TS content and DPD activity in tissues were measured by [3H]-FdUMP binding assay and radioenzymatic assay, respectively. The sensitivity to 5-FU in tumor specimens was determined by collagen-gel droplet embedded-drug sensitivity test (CD-DST). The TS content and DPD activity did not correlate with Dukes' staging. There was no correlation between TS content and DPD activity in any tumors. Simple linear regression analysis showed that neither DPD activity (r = -0.267, p > 0.05) nor TS content (r = -0.277, p > 0.05) in tumors had a significant correlation with 5-FU effectiveness independently. Four out of 24 patients, highly responsive to 5-FU, showed low levels in both DPD and TS. The patients with high value in either DPD activity or TS content proved not to respond to 5-FU. In conclusion, these results demonstrate that both tumor DPD activity and TS content are the factors predicting 5-FU responsiveness in colorectal cancer.

11
UI - 21395129
AU - Aschele C
TI - [1st Multidisciplinary Colorectal Cancer Congress. Effectiveness of pre-operative radiotherapy in combination with total mesorectal excision. Preliminary results of the Netherland study of rectal cancer]
SO - Tumori 2001 May-Jun;87(3):A1-2
AD - Divisione di Oncologia Medica, Azienda Ospedaliera di Padova.

12
UI - 21416726
AU - Ohue M; Mori T; Takahashi K; Yamaguchi T
TI - [Minimally invasive treatment of colorectal cancer]
SO - Gan To Kagaku Ryoho 2001 Aug;28(8):1077-82
AD - Dept. of Surgery, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bukyou-ku, Tokyo 113-8677, Japan.
It may be widely interpreted that minimally invasive treatment of colorectal cancer includes endoscopic mucosal resection, transanal endoscopic microsurgery (TEM), laparoscopic surgery and open reduction-surgery as well as adjuvant treatments such as chemotherapy, radiotherapy and thermotherapy. With the development of medical technology and instruments, we have now a wide and new range of choices for each cancer stage of patients. However, it is not yet clear that minimally invasive treatment necessarily leads to better results in survival and recurrent rates of the patients, as compared with conventional surgery. We should therefore take into full consideration the lingering problems in selecting the new therapies. In this paper, we show the strong and weak points of laparoscopic surgery, TEM, right hemi-colectomy preserving Bauhin's valve and adjuvant radiotherapy for lower rectal cancer, and discuss ongoing problems.

13
UI - 21255261
AU - Kronborg O
TI - Colonic screening and surveillance.
SO - Best Pract Res Clin Gastroenterol 2001 Apr;15(2):301-16
AD - Department A, Odense University Hospital, Odense C, DK-5000, Denmark.
Screening for colorectal cancer has not obtained worldwide acceptance in spite of its proven survival benefit for average-risk persons and some high-risk groups. The incidence of and mortality from colorectal cancer are worrying in Europe as well as in the USA, Australia and Japan. The best evidence-based studies are those published on screening using faecal occult blood tests, endoscopic methods and different tumour markers having been evaluated to a lesser degree. Feasibility studies are necessary before massive screening can be undertaken because the results obtained from randomized studies may not be reproduced to a satisfactory degree in average- as well as high-risk populations. Primary prevention by dietary intervention and drugs has been studied in great detail, so far without any major breakthrough. This chapter will address different screening methods in populations with a varying risk of colorectal cancer, together with providing a short review of prevention and intervention strategies. Copyright 2001 Harcourt Publishers Ltd.

14
UI - 21255262
AU - Rembacken B; Fujii T; Kondo H
TI - The recognition and endoscopic treatment of early gastric and colonic cancer.
SO - Best Pract Res Clin Gastroenterol 2001 Apr;15(2):317-36
AD - Department of Gastroenterology, Centre for Digestive Diseases, The General Infirmary at Leeds, Great George Street, Leeds, LS16 8LT, UK.
As the prognosis of both gastric and colonic cancer remains poor, the challenge is to detect lesions at an early and treatable stage. The benefit of early detection is not only improved survival, but also that patients may be treated with endoscopic mucosal resection, a low-cost, low-morbidity and low-mortality alternative to surgery. In spite of the increasing use of endoscopy in the West, we are not detecting as many early cancers as in Japan. This chapter will discuss the possible reasons for this discrepancy and give a practical guide to 'Japanese endoscopy techniques'. Finally, we have compiled a comprehensive review of the indications, techniques and complications of endoscopic mucosal resection. Throughout the chapter, controversies have been highlighted to give an insight into the limits of our knowledge and stimulate future research. Copyright 2001 Harcourt Publishers Ltd.

15
UI - 21141601
AU - Kucher MD; Ioffe OIu; Sheveliuk SB; Denisov MO
TI - [The usage of the laser induced fluorescence in laparoscopy]
SO - Klin Khir 2000 Dec;(12):24-5
Optic biopsy (the laser-induced fluorescence) was applied in laparoscopic surgery in 14 patients with colonic malignancy. There were investigated 66 lymph nodes. Trustworthiness of the laser induced fluorescence was 80.7%.

16
UI - 21141602
AU - Bondar' GV; Borota AV; Zolotukhin SE; Oleinikov KN; Psaras GG; Vasil'ev SD
TI - [Intensive therapy and strategy of management of patients with rectal cancer after the colonic descending to the perineum]
SO - Klin Khir 2000 Dec;(12):26-8
Optimal tactic for management of the patients on various stages of treatment was elaborated together with surgical procedure, basing on the experience of 3500 operations conduction for cancer recti, mainly abdominal resection with colon descendant to perineum. Methods of preoperative preparation and anesthesiological support were stated as well as the tactics of postoperative management of patients.

17
UI - 21141603
AU - Ievtushenko OI; Sorokin BV; Kolesnyk OO; Korobko VB; Pryimak VV
TI - [The ways of the efficacy raising in surgical treatment of patients with colonic cancer]
SO - Klin Khir 2000 Dec;(12):29-30
The indications extension for the radical surgical intervention conduction in elderly and senile patients and with locally spreading colonic cancer had promoted the result of their treatment improvement.

18
UI - 21183436
AU - Bondar' GV; Basheev VKh; Zolotukhin SE; Psaras GG; Borota AV; Efimochkin OE; Bukhteev SV
TI - [Methods of inversion closure of transient colostomy]
SO - Klin Khir 2000 Jun;(6):15-7
The method of inversive excision of colostomy, securing access to noninflamed tissues of intestine and pericolostomic region for consequent suturing made in accordance to requirements. While using the method purulent-inflammatory complications had occurred in less than 5% of patients and insufficiency of anastomotic sutures--in 3.4%.

19
UI - 21183463
AU - Erko IP
TI - [The transverse colon descending via the small intestine mesentery in rectal cancer]]
SO - Klin Khir 2000 Jun;(6):63-4

20
UI - 21193593
AU - Bonetti A; Zaninelli M; Leone R; Franceschi T; Fraccon AP; Pasini F; Sabbioni R; Cetto GL; Sich D; Brienza S; Howell SB
TI - Use of the ratio of time to progression following first- and second-line therapy to document the activity of the combination of oxaliplatin with 5-fluorouracil in the treatment of colorectal carcinoma.
SO - Ann Oncol 2001 Feb;12(2):187-91
AD - Department of Oncology, Azienda Ospedaliera and University of Verona, Italy. abonetti@sfm.univr.it
BACKGROUND: It has been proposed that the activity of a second-line treatment regimen can be documented by showing that the time to progression (TTP) following second-line therapy is longer than the TTP following first-line therapy in the same patients. PATIENTS AND METHODS: The ratio of TTP during first and second-line therapy, identified as the growth modulation index (GMI), was determined in 34 patients with advanced colorectal cancer. First-line chemotherapy consisted of one of several schedules of leucovorin (LV)-modulated 5-fluorouracil (5-FU) or raltitrexed. Second-line therapy consisted of the combination of LV-modulated 5-FU and oxaliplatin (1-OHP). Patients were switched to second-line therapy upon evidence of progressive disease following first-line therapy. RESULTS: Median TTP following first-line therapy was 13 weeks (95% confidence interval (CI): 7.6-18.7), while median TTP following second-line therapy was 31 weeks (95% CI: 21.3-41.0). Sixteen patients (47%; 95% CI: 35%-59%), showed a GMI > or = 1.33, while the remaining 18 patients (53%; 95% CI: 40%-66%) had a GMI < 1.33. Log-rank analysis of the Kaplan-Meier curves of TTP following first- versus second-line therapy demonstrated a statistically significant difference in favour of second-line therapy (P = 0.0081). CONCLUSIONS: This study demonstrates the utility of the GMI as a tool for assessing the activity of novel second-line therapeutic programs.

21
UI - 21193597
AU - Backus HH; Dukers DF; van Groeningen CJ; Vos W; Bloemena E; Wouters D; van Riel JM; Smid K; Giaccone G; Pinedo HM; Peters GJ
TI - 5-Fluorouracil induced Fas upregulation associated with apoptosis in liver metastases of colorectal cancer patients.
SO - Ann Oncol 2001 Feb;12(2):209-16
AD - Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
BACKGROUND: In vitro, thymidylate synthase (TS) inhibition by 5-fluorouracil (5-FU) induces thymineless apoptosis possibly via Fas receptor Fas ligand interactions and cell-cycle arrest. In colorectal cancer patients we evaluated whether 5-FU administration also resulted in apoptosis and cell-cycle arrest and which proteins might be involved. PATIENTS AND METHODS: Biopsy specimens were taken from 36 patients 2, 22 or 46 hours after administration of 500 mg/m2 5-FU, and from 12 control patients who did not receive 5-FU. In frozen tissue-sections from liver metastases immunohistochemistry was performed with antibodies directed against p53, p21, E2F2, Rb, Ki67 and TS (cell-cycle related) and bax, BCL-2, BCL-x, mcl-1, PARP, caspase-3, Fas receptor and Fas ligand (apoptosis related). Apoptosis was determined by M30 immunostaining, which recognises a cleavage product of cytokeratin 18. RESULTS: Fas receptor expression was 50% higher (P = 0.036) 46 hours after 5-FU administration compared to the control group. This was associated with a 12% increase (P < 0.02) in M30 positive tumour cells and with elevation of caspase-3 and PARP expression. The expression of Ki67 and E2F2 was 30% lower after 46 hours compared to the control group, whereas TS was 56% lower after 2 hours and 32% higher again after 46 hours. No differences in the expression of the other proteins were found. CONCLUSIONS: These results suggest that 5-FU decreases proliferation status and induces apoptosis possibly via the Fas pathway. Since Fas mediated cell killing is important for cytotoxic T cells this indicates that clinical studies combining immunotherapy for activation of T cells and chemotherapy using 5-FU might be very effective.

22
UI - 21193599
AU - Hanke B; Riedel C; Lampert S; Happich K; Martus P; Parsch H; Himmler B; Hohenberger W; Hahn EG; Wein A
TI - CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).
SO - Ann Oncol 2001 Feb;12(2):221-6
AD - Research Group Gerontology, Humboldt University, Berlin, Germany. Bert.Hanke@gmx.net
BACKGROUND: There have been contradictory reports on the benefit of CEA and CA 19-9 measurements in patients with metastatic colorectal cancer using palliative chemotherapy. The object of this study was to examine the diagnostic accuracy of monitoring of palliative chemotherapy by means of CEA and CA 19-9. PATIENTS AND METHODS: The tumour markers CEA and CA 19-9 were subjected to serial measurement in patients with metastatic colorectal cancer (n = 90) using palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-FU with FA and were compared with objective response according to WHO criteria. 85 patients could be evaluated. 43 patients (51%) initially had elevated CEA (> or = 10 ng/ml) and 33 patients (39%) elevated CA19-9 (> or = 50 IE/ml). In 24 patients (28%), both markers were initially increased. With CEA positive patients, 143 cycles of chemotherapy were carried out, which showed the following response in the various cycles: 21 episodes with progressions (ePD), 69 episodes with no change (eNC), 53 episodes with partial/complete remission (ePR/eCR). With CA 19-9 positive patients, 100 cycles of chemotherapy were carried out with the following results: 21 episodes with progressions (ePD), 48 episodes with eNC, and 31 episodes with ePR/eCR. RESULTS: A CEA rise by at least 50% differentiated between ePD versus eNC/ePR/eCR with a sensitivity of 76% and specificity of 90%. With CEA decreases of at least 30% in 99% of these patient episodes (78 of 79), a tumour progression could be excluded. Patients with an initial drop in CEA after the first cycle of chemotherapy of at least 50% of the initial level had a significantly higher probability of achieving an ePR/eCR in further therapy (relative risk 2.9; P = 0.002). With an CA 19-9 increase of at least 30%, a sensitivity progression of 62% and a specifity of 90% could be calculated. A CA 19-9 decrease of at least 60% excludes a progression in 95% of the patient episodes. CONCLUSIONS: A CEA or CA 19-9 rise is only conditionally appropriate for recording progressions. A progression however, can be excluded with falling levels with high diagnostic accuracy, in which CEA offers a greater degree of certainty than CA 19-9. With a drop in CEA 79 of 143 (= 55%) of the CT scans could be saved, in which case 78 of 79 patient episodes (99%) were correctly assessed as 'no progression'. In patients with an increased CEA and CA 19-9 the CEA determination is sufficient for the further monitoring. A confirmation of these results by multicenter trials can result in a considerable decrease of monitoring costs for palliative treatment.

23
UI - 21193612
AU - Haller DG
TI - Combination chemotherapy for colon cancer: de gustibus non est disputandum.
SO - Ann Oncol 2001 Feb;12(2):278

24
UI - 21237429
AU - Dodd MJ; Miaskowski C; Paul SM
TI - Symptom clusters and their effect on the functional status of patients with cancer.
SO - Oncol Nurs Forum 2001 Apr;28(3):465-70
AD - School of Nursing, Department of Physiological Nursing, University of California, San Francisco, USA.
PURPOSE/OBJECTIVES: To determine the effect of the symptom cluster of pain, fatigue, and sleep insufficiency on functional status during three cycles of chemotherapy. DESIGN: Prospective, longitudinal. SETTING: 23 outpatient offices and clinics. SAMPLE: 93 patients with cancer. The typical participant was female (72%), married/partnered (65%), white (87%), and middle-aged (55.4 years), with an average of 14.8 years of education. METHODS: The Quality of Life-Cancer (QOL-CA) version instrument and the Karnofsky Performance Scale (KPS) were completed by 93 outpatients receiving chemotherapy at baseline (Time 1) and at the end of the third cycle (Time 2). Three items (pain, tires easily, sleeps enough to meet needs) from the QOL-CA questionnaire were used to measure the symptom cluster. MAIN RESEARCH VARIABLES: Symptom cluster, outcome, functional status, chemotherapy. FINDINGS: A hierarchical multiple regression model explained 48.4% of the variance in functional status. The KPS at Time 1 explained 30.8% of the variance in KPS at Time 2 (p < 0.001). After KPS at Time 1 was partialled out from KPS at Time 2, the four independent variables entered in the next step were considered predictors of the change in functional status between Time 1 and Time 2. Age explained 11.8% of the change (p = 0.001), pain explained 10.7% of the change (p = 0.002), and fatigue explained 7.3% of the change (p = 0.011). Sleep insufficiency statistically was not significant, only explaining 1% of the change (p = 0.344). CONCLUSION: This study provides beginning insights into the effect of a symptom cluster on patients' functional status. IMPLICATIONS FOR NURSING PRACTICE: Healthcare professionals need to be aware of the presence of symptom clusters and their possible synergistic adverse effect on patients' future morbidity.

25
UI - 21236087
AU - Lorenz W; Stinner B; Bauhofer A; Rothmund M; Celik I; Fingerhut A; Koller M; Lorijn RH; Nystrom PO; Sitter H; Schein M; Solomkin JS; Troidl H; Wyatt J; Wittmann DH; Lucerne Group for Consensus-assisted Development of the Study Protocol on Prevention of Abdominal Sepsis: Example G-CSF
TI - Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol of a controlled clinical trial developed by consensus of an international study group. Part one: rationale and hypothesis.
SO - Inflamm Res 2001 Mar;50(3):115-22
AD - Institute of Theoretical Surgery, University of Marburg,Germany.
GENERAL DESIGN: Presentation of a novel study protocol to evalue the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). The rationale and hypothesis are presented in this part of the protocol of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group). OBJECTIVE: Part one of this protocol describes the concepts of three major sections of the study: Definition of optimum and sub-optimal recovery after operation. Recovery, as an outcome, is not a simple univariate endpoint, but a complex construction of mechanistic variables (i. e. death, complications and health status assessed by the surgeon), quality of life expressed by the patient, and finally a weighted outcome judgement by both the patient and the surgeon (true endpoint). Its conventional early assessment within 14-28 days is artificial: longer periods (such as 6 months) are needed for the patient to state: "I am now as well as I was before". Identification of suitable target patients: the use of biological response modifiers (immune modulators) in addition to traditional prophylaxes (i. e. antibiotics, heparin, volume substitutes) may improve postoperative outcome in appropriate selected patients with reduced host defence and increased immunological stress response, but these have to be defined. Patients classified as ASA 3 and 4 (American Society for Anaesthesiologists) and with colorectal cancer will be studied to prove this hypothesis. Choice of biological response modifier: Filgrastim has been chosen as an example of a biological response modifier because it was effective in a new study type, clinic-modelling randomised trials in rodents, and has shown promise in some clinical trials for indications other than preoperative prophylaxis. It has also enhanced host defence and has been anti-inflammatory in basic research. CONCLUSION: The following hypothesis will be tested in patients with operations for colorectal cancer and increased preoperative risk (ASA 3 and 4): is the outcome as evaluated by the hermeneutic endpoint (quality of life expressed by the patient) and mechanistic endpoints (mortality rate, complication rate, relative hospital stay, assessed by the doctor) improved in the group receiving filgrastim prophylaxis in comparison with the placebo group? Quality of life will be the first primary endpoint in the hierarchical, statistical testing of confirmatory analysis.

26
UI - 21371748
AU - Iacomino G; Tecce MF; Grimaldi C; Tosto M; Russo GL
TI - Transcriptional response of a human colon adenocarcinoma cell line to sodium butyrate.
SO - Biochem Biophys Res Commun 2001 Aug 3;285(5):1280-9
AD - Istituto di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche, via Roma 52 A/C, Avellino, 83100, Italy.
Taking advantage of the DNA array screening technology, we analysed the effect of sodium butyrate on mRNA transcription in human HT29 colon adenocarcinoma cells. Out of 588 mRNA species analysed, only 119 resulted expressed. Among these, 60 exhibited a variable degree of modulation after butyrate treatment. Genes linked to the cell growth, apoptosis and oxidative metabolism appeared the most significantly affected. Furthermore, many of the differentially expressed genes are transcription factors and this may account for the variability of the biological effects of butyrate. The pattern of butyrate-affected genes may represent a reference in further analyses of gene expression of intestinal cells and tissues. Copyright 2001 Academic Press.

27
UI - 21394578
AU - Kapiteijn E; Marijnen CA; Nagtegaal ID; Putter H; Steup WH; Wiggers T; Rutten HJ; Pahlman L; Glimelius B; van Krieken JH; Leer JW; van de Velde CJ; Dutch Colorectal Cancer Group
TI - Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.
SO - N Engl J Med 2001 Aug 30;345(9):638-46
AD - Department of Surgery, Leiden University Medical Center, The Netherlands.
BACKGROUND: Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer. We conducted a multicenter, randomized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision. METHODS: We randomly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision (924 patients) or to total mesorectal excision alone (937 patients). The trial was conducted with the use of standardization and quality-control measures to ensure the consistency of the radiotherapy, surgery, and pathological techniques. RESULTS: Of the 1861 patients randomly assigned to one of the two treatment groups, 1805 were eligible to participate. The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone (P=0.84). Among the 1748 patients who underwent a macroscopically complete local resection, the rate of local recurrence at two years was 5.3 percent. The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group (P<0.001). CONCLUSIONS: Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a standardized total mesorectal excision.

28
UI - 21394586
AU - Nelson H; Sargent DJ
TI - Refining multimodal therapy for rectal cancer.
SO - N Engl J Med 2001 Aug 30;345(9):690-2

29
UI - 21421624
AU - Villar F; Buecher B; Lehur PA
TI - [Is there a role for rectal conservation in familial adenomatous polyposis?]
SO - Gastroenterol Clin Biol 2001 May;25(5):559-60
AD - Clinique Chirurgicale II, Centre Hospitalo-Universitaire de Nantex, Place Alexic-Ricordeau, BP 1005, 44093 Nantes Cedex 01, France.

30
UI - 21411399
AU - Chen MJ; Chung-Faye GA; Searle PF; Young LS; Kerr DJ
TI - Gene therapy for colorectal cancer: therapeutic potential.
SO - BioDrugs 2001;15(6):357-67
AD - CRC Institute for Cancer Studies, University of Birmingham, Birmingham, B15 2TA, England. m.chen@bham.ac.uk
Colorectal cancer is a leading cause of cancer mortality in Western countries. Gene therapy has been proposed as a potential novel treatment modality for colorectal cancer, but it is still in an early stage of development. The preclinical data have been promising and numerous clinical trials are underway. This brief review aims to summarise the current status of clinical trials of different gene therapy strategies, including immune stimulation, mutant gene correction, prodrug activation and oncolytic virus therapy, for patients with colorectal cancer. Data from phase I trials have proven the safety of the reagents but have not yet demonstrated significant therapeutic benefit. In order to achieve this and extend the scope of the treatment, continuing efforts should be made to improve the antitumour potency, efficiency of gene delivery and accuracy of gene targeting.

31
UI - 21404875
AU - Harris GJ; Senagore AJ; Lavery IC; Fazio VW
TI - The management of neoplastic colorectal obstruction with colonic endolumenal stenting devices.
SO - Am J Surg 2001 Jun;181(6):499-506
AD - Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. mrguyharris@aol.com
BACKGROUND: Colonic endolumenal stenting (CELS) to treat obstructing colorectal neoplasms was first described in 1991. The aim of this study was to review the published world literature and make recommendations for its use in current clinical practice. METHODS: Suitable English language reports were identified using a Medline search. RESULTS: CELS can been successfully accomplished in 64% to 100% of obstructing malignant colonic lesions. Distal lesions are more common and theoretically more easy to stent although lesions within the ascending colon have been successfully managed. Minor complications include transient anorectal pain and rectal bleeding, however, significant complications of stent dislocation and colonic perforation are also well recognized. CONCLUSION: CELS can aid the palliative management of malignant colorectal obstruction. Its role in relieving obstruction prior to resection remains to be defined. Increasing experience has allowed the safe placement of stents and relief of obstruction of virtually any lesion throughout the large bowel.

32
UI - 21410080
AU - Lyass S; Zamir G; Matot I; Goitein D; Eid A; Jurim O
TI - Combined colon and hepatic resection for synchronous colorectal liver metastases.
SO - J Surg Oncol 2001 Sep;78(1):17-21
AD - Department of Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel. lyass@md2.huji.ac.il
BACKGROUND AND OBJECTIVES: The surgical strategy for the treatment of resectable synchronous hepatic metastases of colorectal cancer remains controversial. This study was performed to assess the outcome of combined resection of colorectal cancer and liver metastases. METHODS: The perioperative data, morbidity, and survival of the patients who underwent combined colon and liver resections for synchronous colorectal liver metastases from 1988 to 1999 were compared to the parameters of the patients who underwent colon resection followed by resection of liver metastases in a staged setting. RESULTS: 198 hepatic resections were performed, of which 112 procedures in 103 patients were done for metastatic colorectal carcinoma. Twenty six patients (25%) had combined hepatic and colon resection and were compared to 86 patients with metachronous metastases who underwent colon and hepatic resection in the staging setting. Postoperative morbidity was 27 and 35%, respectively. There was no hospital mortality in the combined group vs. 2.3% in the staged group. Blood loss, intensive care unit (ICU) stay and length of postoperative stay (LOS) were similar in both groups. The 5 years cumulative survival of the group after combined surgery was 28% vs. 27% of the group after isolated hepatic resections (P = 0.21). CONCLUSION: Combined colon and hepatic resection is a safe and efficient procedure for the treatment of synchronous colorectal liver metastases. It can be performed with acceptable morbidity and no perioperative mortality. The survival after combined procedure is comparable to the one achieved after staged procedure of colon resection followed by liver resection. Copyright 2001 Wiley-Liss, Inc.

33
UI - 20290421
AU - Elsaleh H; Joseph D; Grieu F; Zeps N; Spry N; Iacopetta B
TI - Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer.
SO - Lancet 2000 May 20;355(9217):1745-50
AD - Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia. helsaleh@cyllene.uwa.edu.au
BACKGROUND: Adjuvant chemotherapy can improve 5-year survival in Dukes' C colorectal carcinoma. Improved selection of patients who will respond to adjuvant treatments is required. We investigated whether site of tumour origin, sex, and presence of microsatellite instability (MSI) phenotype were associated with a survival benefit from adjuvant chemotherapy. METHODS: We analysed data for 656 consecutive patients with Dukes' C colorectal carcinoma, with median follow-up of 54 months (range 7-104) and mean age 66.7 years (SD 12.9). We screened tumour samples by PCR for deletions in the BAT-26 mononucleotide repeat to establish MSI status. Details of chemotherapy and survival were obtained by review of hospital and health-department records. Adjuvant chemotherapy (fluorouracil and levamisole) was given with curative intent to 272 (42%) patients. FINDINGS: Striking survival benefits were seen for patients who had right-sided tumours and who received adjuvant chemotherapy compared with those who did not (48 vs 27% alive at end of study [95% CI 0.25-0.56], p<0.0001), for women (53 vs 33% [0.25-0.56], p<0.0001), and for patients with MSI tumours (90 vs 35% [0.01-0.53], p=0.0007). MSI-positive tumours were slightly more frequent in women than in men (10 vs 7%). Right-sided tumours were more frequently MSI positive than left-sided tumours (20 vs 1%). Men with right-sided tumours benefited from chemotherapy (37 vs 12% [0.24-0.69], p=0.0007) but men with left-sided tumours did not. INTERPRETATION: The survival benefits seen in patients treated with adjuvant chemotherapy suggest that data from previous trials of adjuvant chemotherapy should be reassessed and the predictive value of MSI status confirmed. Validation of our results will allow better selection of patients for chemotherapy.

34
UI - 20475794
AU - Rosell R; Abad A
TI - Tumour site, sex, and survival in colorectal cancer.
SO - Lancet 2000 Sep 2;356(9232):857; discussion 858

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