National Cancer Institute®
Last Modified: June 1, 2002
UI - 11851077
AU - de Jong KP; Slooff MJ
TI - [Resection of liver metastasis: higher chance of survival]
SO - Ned Tijdschr Geneeskd 2002 Feb 2;146(5):196-9
AD - Academisch Ziekenhuis, afd. Hepato-Pancreato-Biliaire Chirurgie en Levertransplantatie, Postbus 30.001, 9700 RB Groningen. email@example.com
In patients with colorectal liver metastases, resection is the only intentionally curative therapy. It is stated that follow-up after a resection of primary colorectal malignancies does not favourably influence patient outcome. However, follow-up can identify 12% of patients with isolated liver metastases in whom liver resection should be performed. One third of these patients can be cured by liver surgery. In general, medical care is provided for lower chances of survival and freedom of disease. Local ablative therapies are probably useful, but need to be evaluated in a randomised trial. Tumour progression of hepatocellular carcinomas in patients, during the long waiting time for liver transplantation, necessitates the use of radiofrequency ablation. Minimally invasive techniques for liver resections seem to be promising but need to be evaluated before they can be more widely applied.
UI - 11876687
AU - Faivre-Finn C; Bouvier AM; Mitry E; Rassiat E; Clinard F; Faivre J
TI - Chemotherapy for colon cancer in a well-defined French population: is it under- or over-prescribed?
SO - Aliment Pharmacol Ther 2002 Mar;16(3):353-9
AD - Registre Bourguignon des Cancers Digestifs (INSERM EPI 106), Faculte de Medecine, Dijon, France. firstname.lastname@example.org
BACKGROUND: It has been demonstrated that adjuvant chemotherapy in TNM stage III and palliative chemotherapy are effective treatments for colon cancer. AIM: To determine changes over a 10-year period in the practice of adjuvant and palliative chemotherapy for colon cancer in a well-defined French population. METHODS: Some 4093 patients with colon adenocarcinoma diagnosed between 1989 and 1998 were studied. To estimate the independent effect of the studied variables, a non-conditional logistical regression was performed. RESULTS: The proportion of patients with stage II disease treated with adjuvant chemotherapy increased from 2.3% (1989-90) to 20.5% (1997-98). The corresponding figures for stage III patients were 7.1% and 54.9%. This increase was particularly marked in younger patients, with 47.3% of stage II and 86.1% of stage III patients under the age of 65 years being treated in the 1997-98 period, compared with 4.9% and 24.4% of those over 75 years for the same period (P < 0.0001). The use of palliative chemotherapy increased over time from 13.6% (1989-90) to 38.9% (1997-98). Again, this increase was more dramatic in the younger age group. CONCLUSIONS: The use of adjuvant chemotherapy has increased for stage II disease despite the absence of proven effectiveness. Both adjuvant and palliative chemotherapy are still under-prescribed in patients over the age of 75 years.
UI - 12013294
AU - Rinkus KM; Russell GB; Levine EA
TI - Prognostic significance of nodal disease following preoperative radiation for rectal adenocarcinoma.
SO - Am Surg 2002 May;68(5):482-7
AD - Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
The administration of preoperative radiation (Pre-Op) therapy for adenocarcinoma of the rectum is evolving. The prognostic value of nodal disease found after preoperative therapy is unclear. The purpose of this study is to evaluate the impact of Pre-Op therapy on nodal staging and thus prognosis in patients with operable cancer of the rectum. Retrospective review of 292 cases revealed that 20% (N = 58) received Pre-Op radiation and 33% (N = 97) received Post-Op radiation. Of the Pre-Op group 66% received 5-fluorouracil-based chemotherapy concomitantly (vs 48% Post-Op). Radiation dose averaged 50 Gy for both groups. Node-positive disease was found after Pre-Op therapy at a similar rate to that of Post-Op or surgery-only patients (45% vs 46%, P = 0.95). Fewer nodes were found in Pre-Op resection specimens (6.8 vs 10.0 nodes/specimen, P = 0.003), which altered the fraction of positive nodes (27% Pre-Op vs 18% Post-Op, P = 0.003). The N0 cases had better survival than N+ in both Pre-Op (80% vs 34%, P = 0.0001) and Post-Op (70% vs 40%, P = 0.02) groups. There was no significant difference in survival between Pre-Op versus Post-Op. Pre-Op chemoradiation improved patient survival over radiation alone and should be considered routinely with radiation therapy for rectal cancer. Pre-Op radiotherapy decreases the number of nodes recovered but does not influence the presence of nodal metastasis. Nodal disease remains a strong prognostic indicator of survival after Pre-Op radiation therapy.
UI - 11819841
AU - Makin GB; Breen DJ; Monson JR
TI - The impact of new technology on surgery for colorectal cancer.
SO - World J Gastroenterol 2001 Oct;7(5):612-21
AD - University of Hull Academic Surgical Unit, Castle Hill Hospital, Castle Road, Cottingham HU16 5JQ, United Kingdom.
Advances in technology continue at a rapid pace and affect all aspects of life, including surgery. We have reviewed some of these advances and the impact they are having on the investigation and management of colorectal cancer. Modern endoscopes, with magnifying, variable stiffness and localisation capabilities are making the primary investigation of colonic cancer easier and more acceptable for patients.Imaging investigations looking at primary, metastatic and recurrent disease are shifting to digital data sets, which can be stored, reviewed remotely, potentially fused with other modalities and reconstructed as 3 dimensional (3D) images for the purposes of advanced diagnostic interpretation and computer assisted surgery. They include virtual colonoscopy, trans-rectal ultrasound, magnetic resonance imaging, positron emission tomography and radioimmunoscintigraphy. Once a colorectal carcinoma is diagnosed, the treatment options available are expanding. Colonic stents are being used to relieve large bowel obstruction, either as a palliative measure or to improve the patient's overall condition before definitive surgery. Transanal endoscopic microsurgery and minimally invasive techniques are being used with similar outcomes and a lower mortality, morbidity and hospital stay than open trans-abdominal surgery. Transanal endoscopic microsurgery allows precise excision of both benign and early malignant lesions in the mid and upper rectum. Survival of patients with inoperable hepatic metastases following radiofrequency ablation is encouraging. Robotics and telemedicine are taking surgery well into the 21(st) century. Artificial neural networks are being developed to enable us to predict the outcome for individual patients. New technology has a major impact on the way we practice surgery for colorectal cancer.
UI - 12011134
AU - Ravaioli A; Marangolo M; Pasquini E; Rossi A; Amadori D; Cruciani G;
TI - Tassinari D; Oliverio G; Giovanis P; Turci D; Zumaglini F; Nicolini M; Panzini I Bolus fluorouracil and leucovorin with oxaliplatin as first-line treatment in metastatic colorectal cancer.
SO - J Clin Oncol 2002 May 15;20(10):2545-50
AD - Department of Oncology, Infermi Hospital, Via Settembrini 2, 47900 Rimini, Italy. email@example.com
PURPOSE: A phase II trial investigated the activity and toxicity of a bolus administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV) therapy in patients with untreated advanced colorectal cancer. PATIENTS AND METHODS: Forty-five patients in this multicenter, open, nonrandomized study received oxaliplatin 130 mg/m(2) on the first day of each course and 5-FU and LV 350 mg/m(2) and 20 mg/m(2), respectively, as a daily bolus for 5 days, every 21 days, for a maximum of six courses. RESULTS: Partial responses occurred in 18 patients, giving an intent-to-treat response rate of 40.0%. Median time to response was 12.7 weeks; median duration of response was 18.4 weeks. Median progression-free survival was 5.9 months; median survival was 14 months. The independent prognostic factors for improved overall survival were good performance status and negative carcino-embryonic antigen blood level. Incidences of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m(2). Reversible neurologic toxicity occurred in 44.4% of patients. CONCLUSION: Bolus administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated advanced colorectal cancer is efficacious and safe. In addition to a more favorable safety profile, the 300 mg/m(2) dosage offered improved dose-intensity compared with the initial dosage.
UI - 11938066
AU - Vatra B; Sobhani I; Aparicio T; Girard PM; Puy Montbrun TD; Housset M;
TI - Baillet F; Hecht F; Chossidow D; Soule JC [Anal canal squamous-cell carcinomas in HIV positive patients: clinical features, treatments and prognosis]
SO - Gastroenterol Clin Biol 2002 Feb;26(2):150-6
AD - FAMA de Colo-Proctologie, Hopital Bichat-Claude Bernard, Paris, France.
The prevalence of squamous-cell carcinoma of the anus seems to be increasing in HIV positive patients. Clinical features and prognosis in this population have not been well evaluated.AIMS: To assess the prognosis of anal squamous-cell carcinoma in HIV positive patients as well as clinical features and treatment procedures.METHODS: A series of 20 HIV positive patients presenting with invasive anal squamous-cell carcinoma was retrospectively analyzed. Data have been compared to those obtained from 24 randomly selected HIV negative patients who were followed during the same periods in the same centers for anal carcinoma with similar histopathological features.RESULTS: The follow-up ranged from 10 to 172 months. No difference was observed between the two groups concerning the clinical features leading to anal cancer diagnosis, although HIV positive patients were younger. Anal cancer was more frequently associated with lymph node metastasis in HIV positive (60%) than in HIV negative (17%) patients, although its size was similar in both groups. Radiotherapy was similarly performed in both groups, while chemotherapy was administered less frequently in HIV positive than in HIV negative patients (54% vs 25%). Immediate side effects and mortality at 1 year follow-up were similar in both groups, whereas the objective initial response to therapy (50% versus 88%), the remission rate with anal conservation at 1 year follow-up (45% versus 88%), and the mortality at 3 years were better in HIV negative patients.CONCLUSION: The prognosis of anal squamous-cell carcinoma is poor in HIV positive patients. This correlates with a more advanced tumor stage and an alteration of systemic immunity status at the time of diagnosis and less response rate to treatment. Detection of precancerous lesions and treatment procedures should be evaluated in HIV infected patients.
UI - 12003131
AU - Leung WN; Sun X; Mak NK; Yow CM
TI - Photodynamic effects of mTHPC on human colon adenocarcinoma cells: photocytotoxicity, subcellular localization and apoptosis.
SO - Photochem Photobiol 2002 Apr;75(4):406-11
AD - School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, People's Republic of China. firstname.lastname@example.org
The photodynamic properties of meta-tetra(hydroxyphenyl)chlorin (mTHPC), a promising second-generation photosensitizer, were investigated using a human colon adenocarcinoma cell line (Colo 201 cells). The study on photocytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay showed that mTHPC was an effective photosensitizer on Colo 201 cells. The photocytotoxicity of mTHPC showed both drug and light dose-dependent characteristics. To reach LD50, namely, the dose at which 50% of the cells were killed, only 0.45+/-0.15 microg/mL of mTHPC and 3 J/cm2 of light dose were required. The presence of 10% fetal calf serum in culture medium significantly decreased the incorporation of mTHPC into cells and resulted in the reduction of photodynamic efficacy. Using confocal laser scanning microscopy, mTHPC was first shown to localize in lysosomes rather than in mitochondria. Furthermore, nuclear stainings demonstrated that photodynamic therapy with mTHPC induced apoptosis in Colo 201 cells.
UI - 12025835
AU - Schell SR; Zlotecki RA; Mendenhall WM; Marsh RW; Vauthey JN; Copeland EM
TI - 3rd Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy.
SO - J Am Coll Surg 2002 May;194(5):584-90; discussion 590-1
AD - Department of Surgery, University of Florida College of Medicine, Gainesville 32610-0286, USA.
BACKGROUND: Our institution has previously demonstrated a survival advantage conferred by preoperative neoadjuvant therapy for locally advanced rectal cancers. We now report our results using transanal excision as definitive surgical therapy in a selected group of patients who experienced significant downstaging of T3 rectal cancers after neoadjuvant therapy. STUDY DESIGN: Seventy-four patients diagnosed with locally advanced (T3) rectal cancers were treated with neoadjuvant chemoradiotherapy. After neoadjuvant therapy, 11 (14.9%) patients who had significant downstaging of their tumors were selected to undergo transanal excision of their residual rectal cancers. Intraoperative cryostat evaluation was used to confirm negative margin status, and all patients were subsequently followed with routine endoscopy, transrectal ultrasonography, and digital rectal examinations. RESULTS: Tumors were located between 1 cm and 7 cm from the anal verge (mean 4.3 +/- 0.6 cm), and were located in lateral, anterior, and posterior positions. Mean followup was 55.2 +/- 8.9 months (median 47.9 months). Imaging studies using CT, MRI, transrectal ultrasonography, or combination demonstrated suspicious lymph nodes in three patients. After neoadjuvant therapy, these lymph nodes were no longer demonstrated in two patients. There were no local recurrences, nodal metastases, or operative mortalities. One patient (9%) developed distant metastases (pulmonary nodules), and remains alive 30 months after transanal excision. One patient (9%) experienced sphincter laxity, which was successfully repaired, and is now asymptomatic. One patient (9%) developed postoperative urgency that resolved spontaneously. CONCLUSIONS: In patients who have initial bulky (T3) lesions, and experience significant downstaging after neoadjuvant chemoradiotherapy, transanal excision appears to be a safe and effective treatment, preserving sphincter function and avoiding laparotomy.
UI - 11902493
AU - Yang TS; Hsu KC; Wang HM; Lin YC
TI - Phase II study of a weekly 8-hour 5-fluorouracil and leucovorin infusion for patients with advanced colorectal cancer: dose adjusted according to its toxicity.
SO - Jpn J Clin Oncol 2001 Dec;31(12):610-5
AD - Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan. email@example.com
BACKGROUND: 5-fluorouracil (5-FU) clearly behaves as two different drugs according to the schedules for its administration. A weekly, 8-h 5-FU continuous infusion (CI) regimen may produce a dual effect, because it elicits both a high plasma 5-FU level and also a durable exposure to 5-FU, which may have the advantage of inhibiting both DNA synthesis and RNA activities. The plasma 5-FU level, however, cannot be monitored in most hospitals, so we initiated a pragmatic clinical trial with this weekly 8-h 5-FU Cl regimen and adjusted the drug's dose according to the detected toxicity. METHODS: The initial dose of 5-FU was 1200 mg/m2 and this was escalated by 200 mg/m2 weekly, provided that no evidence of significant (grade 2 or greater) toxicity became apparent. Twenty-six median dose of 5-FU delivered was 1600 mg/m2. The major symptoms precluding dose escalation were nausea and vomiting. Seven patients demonstrated a partial response (26.9%), 11 patients revealed stable disease (42.3%) and eight exhibited progressive disease (30.8%). CONCLUSION: This weekly 8-h CI 5-FU protocol with the adjustment of dose according to toxicity was not able to achieve the same 5-FU dose and response rate as in previous studies with pharmacokinetic monitoring of 5-FU levels. However, with the concurrent administration of intensive anti-emetic premedication, it is still possible to achieve adequate plasma 5-FU levels by adjusting the 5-FU dose according to elicited toxicity.
UI - 12038108
AU - Tersigni R; Alessandroni L; Baiano G; Cavallaro G; Palmieri I; Pantano
TI - F; Tremiterra S [Anastomosis dehiscence in anterior resection of the rectum with total excision of the mesorectum]
SO - Chir Ital 2002 Mar-Apr;54(2):179-84
AD - Dipartimento di Scienze Chirurgiche Unita Operativa di Chirurgia Generale 1a Flajani Azienda Ospedaliera San Camillo, Forlanini, Roma.
Anterior rectal resection with total mesorectal excision is currently regarded as the operation of choice in patients with neoplasms of the extraperitoneal rectum. This operation is associated with a significant incidence of anastomotic dehiscence. Some authors, therefore, advise the execution of a protective stoma. From 1987 to 2000, 241 patients with rectal neoplasma were submitted to radical surgery: 183 to anterior rectal resection (extraperitoneal neoplasms in 129 cases and intraperitoneal neoplasms in 54) and 58 to a Miles operation. The total incidence of anastomotic complications was 8.1% (15 patients). In 12 cases (6.5%) a clinical dehiscence was observed, while in 3 patients (1.6%) an asymptomatic fistula was present. In the patients with symptomatic dehiscence a colostomy was performed in 5 cases (42%), while in 7 cases (58%) a conservative approach was adopted (total parenteral nutrition and antibiotic therapy), with complete healing of the fistula. The incidence of anastomotic complications was 9.3% in extraperitoneal neoplasms and 5.6% in intraperitoneal localizations. In relation to the anastomotic technique adopted, the incidence of dehiscences was 25% after 8 Knight-Griffen anastomoses, 16% after 12 manual anastomoses and 7.3% after 163 end-to-end mechanical anastomoses (P = NS). The percentage of anastomotic complications was greater in the period from 1995 to 1997, compared to the period from 1987 to 1994 (12.6% vs 3.8%, P = NS), due to the routine execution of rectal resection in conjunction with total mesorectal excision, particularly at the beginning of the experience, in 1995. In the last 36 cases from 1998 on the incidence of anastomotic complications was reduced to 8.3%, after the learning phase. No related mortality was observed. On the basis of our experience and the evidence reported in the international literature we do not think the execution of a protective stoma is justified after low and ultra-low colorectal anastomosis, except in selected cases.
UI - 12038109
AU - Cunsolo A; De Cataldis A; De Raffaele E
TI - [The surgeon as a prognostic factor in the treatment of cancer of the rectum]
SO - Chir Ital 2002 Mar-Apr;54(2):185-93
AD - Dipartimento di Discipline Chirurgiche, Rianimatorie e dei Trapianti, Universita degli Studi di Bologna.
The study of prognostic factors in neoplastic rectal surgery is enriched with a new element, namely, the role of the surgeon. The aim of this study was to evaluate whether this was true of our own experience. We selected 118 patients with rectal cancer operated on with a radical intent by two different surgeons and analyzed factors such as sex, age, Dukes' stage, histological type, tumour length, differentiation and type of operation. We studied these factors by univariate and multivariate analysis in relation to local and distant recurrence and survival. We found statistically significant correlations between distant recurrence and tumour stage, differentiation and surgeon, but between local recurrence and tumour stage only. Multivariate analysis showed statistically significant correlations between distant recurrence and tumour stage and differentiation, but between local recurrence and tumour stage only. As regards survival, we found statistically significant differences in relation to stage, histological type, and differentiation. The role of the surgeon appeared to be important when there are differences in experience, training and specialization.
UI - 11793634
AU - North GL
TI - Celecoxib as adjunctive therapy for treatment of colorectal cancer.
SO - Ann Pharmacother 2001 Dec;35(12):1638-43
AD - School of Pharmacy, University of Montana, Missoula, MT, USA. firstname.lastname@example.org
OBJECTIVE: To describe the role of celecoxib as adjunctive therapy in the treatment of familial adenomatous polyposis (FAP), an inherited autosomal dominant predisposition syndrome for colorectal cancer. DATA SOURCES: Literature was evaluated through MEDLINE search (1995-March 2000) and through secondary sources, using the search terms celecoxib, cyclooxygenase-2 inhibitors, and familial adenomatous polyps. DATA SYNTHESIS: Observational studies have found a decreased rate of colorectal cancer in people who regularly took aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs). The Food and Drug NSAID celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, for adjunctive therapy in patients with FAP, based on a six-month, randomized, controlled clinical trial. CONCLUSIONS: Aspirin and other NSAIDs reduce the incidence of colorectal cancer in the general population. Limited clinical studies in patients with FAP using nonaspirin NSAIDs have shown a reduction in polyp burden. A current clinical trial using celecoxib has also shown a reduction in polyp burden in patients with FAP. The long-term clinical impact of using a selective COX-2 inhibitor is not known, since celecoxib has not been studied beyond six months in patients with FAP. By reducing the polyp burden in FAP patients, celecoxib may be useful as adjunctive chemotherapy, in addition to routine endoscopic surveillance and surgery.
UI - 11986771
AU - Casey JL; Napier MP; King DJ; Pedley RB; Chaplin LC; Weir N; Skelton L;
TI - Green AJ; Hope-Stone LD; Yarranton GT; Begent RH Tumour targeting of humanised cross-linked divalent-Fab' antibody fragments: a clinical phase I/II study.
SO - Br J Cancer 2002 May 6;86(9):1401-10
AD - Cancer Research UK Targeting and Imaging Group, Department of Oncology, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
Antibody engineering has made it possible to design antibodies with optimal characteristics for delivery of radionuclides for tumour imaging and therapy. A humanised divalent-Fab' cross-linked with a bis-maleimide linker referred to as humanised divalent-Fab' maleimide was produced as a result of this design process. It is a humanised divalent antibody with no Fc, which can be produced in bacteria and has enhanced stability compared with F(ab')(2). Here we describe a clinical study in patients with colorectal cancer using humanised divalent-Fab' maleimide generated from the anti-carcinoembryonic antigen antibody A5B7 radiolabelled with iodine-131. Ten patients received an i.v. injection of iodine-131-labelled A5B7 humanised divalent-Fab' maleimide, and positive tumour images were obtained by gamma camera imaging in eight patients with known lesions, and one previously undetected lesion was identified. True negative results were obtained in two patients without tumour. Area under the curve analysis of serial blood gamma counting and gamma camera images showed a higher tumour to blood ratio compared to A5B7 mF(ab')(2) used previously in the clinic, implying this new molecule may be superior for radioimmunotherapy. MIRD dose calculations showed a relatively high radiation dose to the kidney, which may limit the amount of activity that could be administered in radioimmunotherapy. However the reduction in immunogenicity was also a major advantage for A5B7 humanised divalent-Fab' maleimide over murine versions of this antibody suggesting that humanised divalent-Fab' maleimide should be a useful vehicle for repeated therapies. Copyright 2002 Cancer Research UK
UI - 11986790
AU - Iacopetta B
TI - Predictive values of sex and tumour site for survival benefit from 5FU in colorectal cancer.
SO - Br J Cancer 2002 May 6;86(9):1524-5; discussion 1525-6
UI - 12040673
AU - Koda K; Miyazaki M
TI - [Evaluation of chemoradiotherapy for the treatment of rectal cancer]
SO - Gan To Kagaku Ryoho 2002 May;29(5):703-8
AD - Dept. of General Surgery, Graduate School of Medicine, Chiba University.
Chemoradiotherapy for the treatment of primary rectal cancers has been regarded as an effective adjuvant for surgical procedures. It has been expected to reduce local recurrence, increase the chance of sphincter-preserving operation and improve survival. However, recent advances in surgical technique for rectal cancers have reduced the local recurrence rate to no more than 10%, where the question may arise of whether adjuvant chemoradiotherapy is indeed necessary. Another matter to be elucidated is why adjuvant chemoradiotherapy does not necessarily improve overall survival for rectal cancers even when the local recurrence rate is reduced. In the treatment of locally recurrent lesions, either heavy ion radiotherapy or proton beam therapy is expected to be an effective alternative to the surgical procedure.
UI - 11905784
AU - Holen KD; Saltz LB
TI - New therapies, new directions: advances in the systemic treatment of metastatic colorectal cancer.
SO - Lancet Oncol 2001 May;2(5):290-7
AD - Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Colorectal cancer is the second leading cause of cancer death and it is clear that patients with metastatic disease have better quality of life and survival when given treatment. Despite four decades of experience of treating patients with fluorouracil, there remains considerable controversy about the optimum dose and scheduling, as well as biomodulation with leucovorin and methotrexate. However, irrespective of the dose and schedule, overall survival times are poor--about 1 year. Disappointingly, oral agents with similar mechanisms to fluorouracil do not improve survival rates in comparison with fluorouracil and leucovorin treatment. Irinotecan and oxaliplatin are newer agents that have improved the response rates for patients with metastatic disease when they are added to flurouracil and leucovorin. The combination of irinotecan, fluorouracil, and leucovorin has also improved overall survival. These are small advances in the fight against colorectal cancer, and further drug development is necessary.
UI - 12001114
AU - Delioukina ML; Prager D; Parson M; Hecht JR; Rosen P; Rosen LS
TI - Phase II trial of irinotecan in combination with amifostine in patients with advanced colorectal carcinoma.
SO - Cancer 2002 Apr 15;94(8):2174-9
AD - University of California at Los Angeles Center for the Health Sciences and Jonsson Comprehensive Cancer Center, Los Angeles, California, USA.
BACKGROUND: Irinotecan is effective in patients with advanced colorectal carcinoma in both first-line and salvage settings but its use can be limited by serious side effects. Amifostine has been shown to reduce the incidence of cisplatin-induced cumulative renal toxicity in patients with advanced ovarian carcinoma and nonsmall cell lung carcinoma. In the current pilot Phase II trial, the authors examined the potential role of amifostine as a protective agent against irinotecan-induced diarrhea and myelosuppression and evaluated an every-2-weeks regimen as an alternative schedule for the administration of irinotecan in patients with previously treated metastatic colorectal carcinoma. METHODS: All patients received amifostine, 740 mg/m2, followed by irinotecan, 250 mg/m2, every 2 weeks. A 6-week cycle of chemotherapy (every 2 weeks for 3 treatments) was chosen to assess toxicity and response. The main objective of the current study was to evaluate the impact of amifostine on gastrointestinal and hematologic toxicity. RESULTS: A total of 22 patients entered the current study. Six of these 22 patients (27%) had WHO Common Toxicity Criteria Grade 3 or 4 diarrhea, including 2 patients (9%) with Grade 4 diarrhea. Eight of 22 patients (36.3%) developed Grade 3 or 4 neutropenia (Grade 4 in 4 of the 22 patients [18%]). Dose reduction was required in 25% of the treatment cycles. Five of the 22 patients (23%) withdrew from the trial due to amifostine toxicity. Of the 15 patients who were evaluable for response, 4 patients (26.6%) had achieved a partial response and 9 (60%) had stable disease as their best response.CONCLUSIONS: The combination of irinotecan with amifostine in patients with previously treated metastatic colorectal carcinoma did not appear to reduce irinotecan toxicity. Amifostine did not appear to interfere with the cytotoxic effect of irinotecan. The results of the current study did demonstrate efficacy and safety of the every-2-weeks irinotecan schedule that was comparable to other established regimens and these results support its feasibility as a reasonable alternative in this disease setting. Copyright 2002 American Cancer Society.
UI - 12014929
AU - Aviv RI; Shyamalan G; Watkinson A; Tibballs J; Ogunbaye G
TI - Radiological palliation of malignant colonic obstruction.
SO - Clin Radiol 2002 May;57(5):347-51
AD - Departments of Radiology, Royal Free Hospital, London, U.K.
PURPOSE: To evaluate the efficacy of colorectal stenting in the palliation of irresectable malignant colonic obstruction. MATERIALS AND METHODS: Fifteen patients underwent colorectal stenting for irresectable colonic malignancy. Sixteen stents were placed successfully in 13 patients. Two stent insertions, one a proximal transverse colon lesion, were unsuccessful. Twelve patients (80%) had clinical or radiological features of imminent obstruction. Three patients were completely obstructed. Eighty-six percent of lesions were within the rectosigmoid colon. RESULTS: Technical and clinical success was 88%. Early, minor complications occurred in two patients (13%). Late complications included migration (13%) and ingrowth (19%). The median survival was 2 months (0.5-12 months). CONCLUSION: Stenting should be considered as definitive treatment in the context of an inoperable malignant stricture of the colon. It has low morbidity and a high technical and clinical success rate and avoids emergency defunctioning surgery in high-risk patients. Copyright 2002 The Royal College of Radiologists.
UI - 11989234
AU - Maehara Y; Kakechi Y; Emi Y; Sumiyoshi Y; Kimura K; Ikeda Y; Kitamura K;
TI - Ono S; Adachi Y; Mori M; Hiramoto Y [Departmental review of surgical cases in the last 17 years: Colonic neoplasms]
SO - Fukuoka Igaku Zasshi 2002 Mar;93(3 Suppl):12-5
UI - 12016748
AU - Hilska M; Gronroos J; Collan Y; Laato M
TI - Surgically treated adenocarcinomas of the right side of the colon during a ten year period: a retrospective study.
SO - Ann Chir Gynaecol Suppl 2001;(215):45-9
AD - Department of Surgery, Turku University Central Hospital, Turku, Finland. email@example.com
BACKGROUND AND AIMS: Colon cancer is one of the most common malignancies in Finland. The purpose of the current study was to analyse the results of surgical treatment of right-sided colon cancers operated in the 1980s at Turku University Central Hospital. In addition, we compared the results to those reported from earlier decades. MATERIAL AND METHODS: One hundred and fifty-three patients with primary proximal colon cancer were operated in 1981-1990. The results were analysed retrospectively from patient records. RESULTS: The crude five-year survival rate of the patients was 48%. The most crucial factor affecting survival was the stage of spreading of the tumour. Obstructive tumours had a poorer prognosis than non-obstructive ones. CONCLUSIONS: The results of surgical treatment of proximal colon cancer were satisfactory at Turku University Central Hospital and slightly better compared to earlier reports.
UI - 12023155
AU - Nuyttens JJ; Robertson JM; Yan D; Martinez A
TI - The variability of the clinical target volume for rectal cancer due to internal organ motion during adjuvant treatment.
SO - Int J Radiat Oncol Biol Phys 2002 Jun 1;53(2):497-503
AD - Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA.
PURPOSE: This study defined the clinical target volume (CTV) for the adjuvant treatment of rectal cancer and applied this definition to multiple CT scans obtained during the typical 5-week course of treatment to measure the modification to the CTV due to internal organ motion that would be needed to define the planning target volume (PTV). METHODS AND MATERIALS: Ten patients with rectal cancer had weekly treatment planning CT scans during adjuvant radiation therapy. All patients were given oral contrast, placed prone on a rigid foam cradle with a depressed area for small bowel exclusion, and instructed to have a full bladder. The CT scans were registered according to the bones of the pelvis, and the CTV was outlined on each CT slice. Movement of the CTV in all dimensions was measured. The CT scan with the lowest and highest bladder volume for each patient was used to calculate the CTV movement due to bladder filling. RESULTS: The largest difference in the CTV occurred 10 cm caudal to the anus, with a standard deviation of 1 cm. Bladder filling displaced the anterior border of the CTV an average of 7 mm over a cranial to caudal length of 2.5 cm. Other borders of the CTV were based on muscle, bone, or major blood vessels and were stable. CONCLUSION: Modification of the CTV to design a PTV can be unequal, with the largest change at the anterior border of the inferior pelvis.
UI - 11810941
AU - Gotsadze DT
TI - [More effective exenteration of small pelvis organs in colorectal cancer: is it possible?]
SO - Khirurgiia (Mosk) 2001;(12):45-8
21 exenterations of small pelvis organs were performed from 1991 to 2000 for locally-spread cancer of the rectum. Temporary passage feces and urine before radical operation was performed in 6 patients. 10 patients underwent infralevator and 11 patients--supralevator exenteration of small pelvis organs. Continent cypass of urine was carried out in all the patients (in 2--delayed), and of feces--in 8 (in 2--delayed). Substitution of the urinary bladder was performed in 11 patients, formation of reservoir with "dry" urinostoma--in 10.
UI - 12044376
AU - Lobo DN; Bostock KA; Neal KR; Perkins AC; Rowlands BJ; Allison SP
TI - Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial.
SO - Lancet 2002 May 25;359(9320):1812-8
AD - Section of Surgery, University Hospital, Queen's Medical Centre, Nottingham, UK. firstname.lastname@example.org
BACKGROUND: Low concentrations of albumin in serum and long gastric emptying times have been returned to normal in dogs by salt and water restriction, or a high protein intake. We aimed to determine the effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection in human beings. METHODS: We randomly allocated ten patients to receive postoperative intravenous fluids in accordance present hospital practice (> or = 3 L water and 154 mmol sodium per day) and ten to receive a restricted intake (< or = 2 L water and 77 mmol sodium per day). All patients had no disease other than colonic cancer. The primary endpoint was solid and liquid-phase gastric emptying time, measured by dual isotope radionuclide scintigraphy on the fourth postoperative day. Secondary endpoints included time to first bowel movement and length of postoperative hospital stay. Analysis was by intention to treat. FINDINGS: Median solid and liquid phase gastric emptying times (T(50)) on the fourth postoperative day were significantly longer in the standard group than in the restricted group (175 vs 72.5 min, difference 56 [95% CI 12-132], p=0.028; and 110 vs 73.5 min, 52 [9-95], p=0.017, respectively). Median passage of flatus was 1 day later (4 vs 3 days, 2 [1-2], p=0.001); median passage of stool 2.5 days later (6.5 vs 4 days, 3 [2-4], p=0.001); and median postoperative hospital stay 3 days longer (9 vs 6 days, 3 [1-8], p=0.001) in the standard group than in the restricted group. One patient in the restricted group developed hypokalaemia, whereas seven patients in the standard group had side-effects or complications (p=0.01). INTERPRETATION: Positive salt and water balance sufficient to cause a 3 kg weight gain after surgery delays return of gastrointestinal function and prolongs hospital stay in patients undergoing elective colonic resection.
UI - 11992391
AU - Mendenhall WM; Morris CG; Rout WR; Zlotecki RA; Lind DS; Hochwald SN;
TI - Schell SR; Copeland EM 3rd Local excision and postoperative radiation therapy for rectal adenocarcinoma.
SO - Int J Cancer 2001;96 Suppl():89-96
AD - Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida 32610-0287, USA. email@example.com
Sixty-seven patients with early-stage adenocarcinoma of the rectum who had lesions thought to be unsuitable for either local excision alone or endocavitary irradiation were treated with local excision followed by postoperative radiation therapy. The purpose of this study was to evaluate the effectiveness of local excision followed by radiation therapy for treatment of rectal adenocarcinoma. The patients were treated between 1974 and 1999; follow-up time was 6 to 273 months (median, 65 months). All living patients had follow-up for at least 2 years. The indications for postoperative irradiation included equivocal or positive margins, invasion of the muscularis propria, endothelial-lined space invasion, poorly differentiated histology, and perineural invasion. Cox proportional hazards regression analysis was performed using six explanatory variables including tumor size, configuration (exophytic vs. ulcerative), histologic differentiation, pathologic T stage, endothelial-lined space invasion, and margin status. The time interval between treatment and development of recurrent disease was in the range of 11 to 48 months. The 5-year results were as follows: local-regional control, 86%; ultimate local-regional control, 93%; distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific survival, 90%. When the Cox proportional hazards regression analysis was performed for these endpoints, margin status influenced absolute survival (P = 0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional control (P = 0.0439). Tumor configuration marginally influenced cause-specific survival (P = 0.0577). None of the variables had an influence on the endpoints' local-regional control, ultimate local-regional control with sphincter preservation, or distant metastasis. Five patients (7%) had severe complications; no complication was fatal. Local excision and postoperative radiation therapy results in a high probability of local-regional control and survival for selected patients with relatively early-stage rectal adenocarcinoma. Patients with ulcerative tumors may have a lower likelihood of cause-specific survival. Copyright 2002 Wiley-Liss, Inc.
UI - 11985979
AU - van der Wal BC; Cleffken BI; Gulec B; Kaufman HS; Choti MA
TI - Results of salvage abdominoperineal resection for recurrent anal carcinoma following combined chemoradiation therapy.
SO - J Gastrointest Surg 2001 Jul-Aug;5(4):383-7
AD - Department of Surgery, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-5614, U.S.A.
Combined chemotherapy and radiation therapy is the standard treatment for epidermoid carcinoma of the anal canal. Failures are often not associated with distant recurrence and are therefore potentially amenable to salvage abdominoperineal resection. The aim of this study was to review our experience with abdominoperineal resection following failure of chemoradiation therapy for epidermoid carcinoma of the anus. Between 1980 and 1998, 17 patients underwent salvage abdominoperineal resection following failure of chemoradiation therapy. Four patients were excluded from survival analysis because resection was performed with palliative intent. Survival curves were based on the method of Kaplan and Meier, and univariate analysis of predictive variables was performed using the log-rank test. Twelve patients underwent abdominoperineal resection for persistent disease and five patients for recurrent disease. No operative deaths occurred, but local complications including perineal wound infection and wound breakdown was seen in 8 of 17 patients and 6 of 17 patients, respectively. Patients undergoing omental flap reconstruction (n = 3) or no pelvic reconstruction (n = 5) had a higher incidence of perineal breakdown compared to those undergoing muscle flap reconstruction (n = 9) (P <0.05). The median follow-up time for the patients operated on with curative intent was 53 months. The 5-year actuarial survival was 47%. Potential prognostic factors that were not found to have an impact on survival included margin status of resection, sphincter invasion, and degree of differentiation. Only pathologic tumor size greater than 5.0 cm (P <0.001) and age over 55 years (P <0.05) adversely affected survival. Selected patients with recurrent or persistent anal carcinoma following chemoradiation therapy can be offered salvage abdominoperineal resection. This operation is associated with a high incidence of local wound complications, and muscle flap reconstruction should be considered when possible. Prolonged survival can be achieved in some patients following salvage resection for epidermoid carcinoma of the anal canal.
UI - 12032824
AU - Kim WJ; Vo QN; Shrivastav M; Lataxes TA; Brown KD
TI - Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line.
SO - Oncogene 2002 May 30;21(24):3864-71
AD - Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Louisiana State University, New Orleans, LA 70112, USA.
Recent findings suggest that DNA alkylating agents trigger cellular responses that overlap those activated after ionizing radiation. Moreover, activation of these responses is dependent upon a functional mismatch repair (MMR) system. These developments led us to test if MMR-deficient cells may be compromised in their ability to activate appropriate cellular signaling pathways after ionizing radiation. An initial experiment to address this notion was to determine the level of radiosensitivity of several MMR-deficient cell lines derived from patients with Hereditary Non-Polyposis Colorectal Cancer (HNPCC). While two of the three HNPCC lines investigated show levels of radiosensitivity consistent with that displayed by normal human fibroblasts, HCT-116 cells display moderate radiosensitivity compared to the other MMR-deficient lines. This increased sensitivity to ionizing radiation correlates with lowered levels of ATM expression in HCT-116. Analysis of genomic DNA from HCT-116 cells determined that these cells possess aberrant methylation of multiple CpG dinucleotides within the proximal promoter region of the ATM gene. The significance of this finding is underscored by our observations that co-culturing HCT-116 cells with the DNA demethylating agent 5-azacytidine reverses promoter methylation, promotes normal levels of ATM expression, and restores normal radiosensitivity. The proximal ATM promoter is a approximately 520 bp region shared with the NPAT gene, and current evidence suggests that this region functions as a bi-directional promoter. We found that, unlike ATM, the methylation status of this intergenic region does not effect the expression of the NPAT gene. In sum, these observations indicate that the ATM gene is a novel target for epigentic silencing through inappropriate methylation of its proximal promoter region.