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Biomedical subjects

R C Verschueren

Publications and source records attributed to R C Verschueren.

At least 19 recordsLinked to original sources
PubMed1995

5-Fluorouracil/leucovorin/interferon alpha-2a in patients with advanced colorectal cancer. Effects of maintenance therapy on remission duration.

BACKGROUND: A Phase II study of combination treatment with 5-fluorouracil (5-FU), leucovorin (LV), and interferon alpha-2a (IFN) in patients with previously untreated metastatic colorectal cancer was previously reported by the authors. Therapy was on an outpatient basis and consisted of LV 60 mg orally every 8 hours days 1-3, IFN 18 x 10(6) IU subcutaneously days 1-3, and bolus 5-FU 750 mg/m2 intravenously days 2-3. Treatment was repeated every 14 days, until a maximum of 8 courses was administered. A response rate of 54% [95% confidence interval (CI), 34-72%] was observed. However, remission duration after cessation of therapy was short, with a median duration of 5 months (range, 2 to 13+ months). METHODS: Subsequent to the above study, patients on this induction treatment who achieved remission received maintenance therapy: the above described 3-day regimen every 6 weeks until progression, for a maximum of 2 years. RESULTS: Fifty-three patients were enrolled in the induction regimen and 18 out of 29 patients who achieved remission received maintenance treatment. In 50 assessable patients 3 complete recoveries and 26 partial recoveries were observed for a response rate of 58% (CI, 43-72%). Median remission duration of patients receiving maintenance therapy was 9.4 months (CI, 8.4-10.3 months) compared with 4.7 months (CI, 3.2-6.2 months) for patients without maintenance therapy. Median overall survival of all patients was 16.6 months. Toxicity of maintenance therapy was confined to WHO grade 2. CONCLUSIONS: The high response rate of this 5-FU/LV/IFN regimen holds true in a larger group of patients. The group that received maintenance treatment had a remission duration of just over 9 months, the maintenance regimen added little toxicity.

Adult↗
PubMed1994

Effect of extent of anterior resection and sex on disease-free survival and local recurrence in patients with rectal cancer.

Results are presented following 119 curative resections for rectal cancer performed on 47 women and 72 men. Throughout the study it was policy to remove part of the female genital tract when the rectal tumour impinged on the uterus and/or the posterior vaginal wall. After a median follow-up of 7.5 years, local recurrence occurred in three of 46 women and 15 of 71 men (P = 0.03). The survival rates at 5 years were 71 per cent for women (95 per cent confidence interval 56-83 per cent) and 60 per cent for men (95 per cent confidence interval 50-71 per cent) (P < 0.05). The risk for distant metastasis was comparable, suggesting an influence of local recurrence on survival. Reduction of the local recurrence rate coincides with the higher proportion of anterior extensions of surgery in women (19 of 47) than in men (two of 72).

Adult↗
PubMed1994

The clinical staging of rectal cancer in patients treated by preoperative radiotherapy.

We describe the results of clinical and (or) surgical staging used by the same surgeon to select a group of 41 patients with advanced rectal cancer for preoperative radiotherapy. Fifteen patients with resectable but advanced rectal cancer were subjected to a short course of radiotherapy (30 Gy in 10 days), immediately followed by resection. High dose preoperative radiotherapy (50-56 Gy in 5 weeks) was administered to 26 patients with borderline resectable or fixed cancer. Adequate resection of the tumour was possible in 21 of these 26 patients 4 weeks after the end of the radiotherapy. A total of 36 patients thus underwent resection after preoperative radiotherapy. No radiotherapy related acute or late morbidity was seen. On 31 December 1992 the results were investigated retrospectively. The median time since entering into the study was 87 months (range 27-141). During the follow-up, pelvic recurrence was detected in six patients; one patient had concomitant distant metastases. The local recurrence free survival at 5 years calculated by the Kaplan-Meier method was 72% (95% CI 58-85). Distant metastases without local recurrence developed in 11 patients. The calculated survival at 5 years was 45% (95% CI 30.5-59).

Brain Neoplasms↗
PubMed1994

Long-term disease-free survival after isolated peritoneal metastasis from colonic cancer.

We present the case of a 29-year-old female patient with an isolated peritoneal metastatic mass in the Douglas pouch, following ileocecal resection for a Dukes C2 colon cancer of the caecum. As initial treatment, four courses of continuous infusion with epiadriamycin were administered. The effect on the tumour size was marginal. Palliative radiotherapy (33 Gy) resulted in a reduction of the tumour size and subsequently a wide posterior exenteration could be performed. Five years after the initial diagnosis the patient is still in good health with no evidence of tumour recurrence. We sincerely believe that a maximum effort aiming for cure is warranted in selected patients with localized residual or metastatic peritoneal colon cancer, even if the initial prospects seem less favourable.

Adenocarcinoma↗
PubMed1993

Phase I-II study of the addition of alpha-2a interferon to 5-fluorouracil/leucovorin. Pharmacokinetic interaction of alpha-2a interferon and leucovorin.

5-Fluorouracil (5-FU) activity has been improved by the use of leucovorin (LV) or alpha-2a interferon (alpha-IF). We investigated the feasibility and activity of addition of alpha-IF to a 5-FU/LV regimen. A phase I study with 26 patients (14 previously untreated, 12 previously treated) with disseminated cancer was conducted. 15 patients were treated with 5-FU/LV and 11 with 5-FU/LV/alpha-IF. The 5-FU/LV regimen consisted of escalating doses of 5-FU bolus intravenously on days 2 and 3, combined with repeated oral LV on days 1, 2 and 3. Treatment was every 2 weeks. In the 5-FU/LV/alpha-IF schedule, 18 x 10(6) U alpha-IF subcutaneously daily was added on days 1, 2 and 3. The phase I study was followed by a phase II study of 5-FU/LV/alpha-IF at the established 5-FU dose in 29 previously untreated patients with disseminated colorectal cancer. The optimal 5-FU dose in both parts of the phase I study was 750 mg/m2/day. Mucositis, diarrhea and leucopenia were dose limiting. Although alpha-IF added its own toxicity (fever, flu-like symptoms, fatigue), it did not decrease the optimal dose of 5-FU. In the phase II study 28 patients were evaluable for response: three complete responses and 12 partial responses were observed (response rate 54%, 95% confidence interval, 34 to 72%). Pharmacokinetics of oral LV was performed in patients treated with and without alpha-IF: significantly higher serum levels of LV and 5-methyltetrahydrofolate were found after alpha-IF addition. Influence of alpha-IF on gastrointestinal absorption or renal clearance could be excluded. In conclusion, this 5-FU/LV/alpha-IF combination seems active in metastatic colorectal cancer. The pharmacokinetic interaction between alpha-IF and LV may play a role in the activity of this regimen. Controlled studies are necessary to establish the value of addition of alpha-IF to 5-FU/LV regimens.

Adult↗
PubMed1993

Anaerobes and their fermentation products in faeces of patients with familial adenomatous polyposis before and after subtotal colectomy and ileorectal anastomosis.

In view of the importance of short-chain fatty acids (SCFA) for the colonic epithelial function and their possible relation with the reported spontaneous regression of rectal polyps after subtotal colectomy with ileorectal anastomosis, we compared the SCFA concentrations in faeces of five familial adenomatous polyposis (FAP) patients before, and in 10 FAP patients after operation to each other and to those of 10 healthy controls. Anaerobe cultural counts and concentrations of organic acids were also investigated in the same faecal samples from FAP patients and controls. The preoperative cultural counts were not significantly different from those of the controls. After colectomy, the Bacteroides (P < 0.002; P < 0.02), and bifidobacteria counts (P < 0.02; P < 0.005) were decreased compared to controls and untreated FAP patients. The ratio of acetic acid to total SCFA significantly increased, which coincided with a proportional decrease of the other SCFA. The frequently observed regression of rectal polyps after colectomy cannot be explained from these results. One would rather expect a possible stimulation of polyp growth and dedifferentiation of colonic epithelial cells.

Adenomatous Polyposis Coli↗
PubMed1993

Recent developments in diagnosis and treatment of metastatic carcinoid tumours.

In carcinoid patients a tumour of enterochromaffin cell origin is present, which dependent on the site of origin can result in increased serotonin production. Metastasized carcinoids are often diagnosed by measuring 5-hydroxyindoleacetic acid excretion in the urine. This excretion, however, can be influenced by food intake. On the other hand, serotonin measured in blood platelets is unaffected by food intake and, in addition, is found to be more sensitive. Therapy of metastasized carcinoids is directed at tumour reduction or only reduction of symptoms. Tumour reduction can be achieved surgically or by embolization. Combination chemotherapy has a maximum response percentage of about 33%. Over the last few years, both octreotide and interferon alpha have been used in these patients. They rarely result in a reduction of the tumour size (10-20%). Symptom reduction is achievable in most patients with these agents, however. Recently, increasing knowledge obtained concerning the various serotonin receptors and their antagonists is now being used in the treatment of patients with a metastasized carcinoid. In the future it is expected that the different modalities will be combined increasingly.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Changes in rectal epithelial cell proliferation and intestinal bile acids after subtotal colectomy in familial adenomatous polyposis.

Subtotal colectomy and ileorectal anastomosis in familial adenomatous polyposis patients can induce temporary regression of adenomas in the rectum. The mechanism for this phenomenon is unclear. We evaluated the effect of colectomy on rectal mucosal proliferation, in relation to changes in bile acid metabolism. Four familial adenomatous polyposis patients were studied before and 3-6 months after surgery, and eight others 7-22 years postoperatively. Within 6 months after surgery, the size of the proliferative zone of the colonic crypts was found to be reduced (P less than 0.05). The proliferative activity of total colonic crypts was not affected within this period. More than 7 years postoperatively, increased cell proliferation of total crypts (P less than 0.02), as well as mid (P less than 0.05) and basal (P less than 0.05) crypt compartments, were observed compared to shortly after colectomy. In duodenal bile, deoxycholic acid was absent shortly after operation, whereas several years after operation only a small fraction (2%) was present. Fecal secondary bile acid excretion diminished after colectomy and did not change several years postoperatively. In postoperative stools only, small proportions of ursocholic and ursodeoxycholic acids (about 5% each) were consistently found. As subtotal colectomy causes a temporary decrease in the length of the proliferative zone of rectal crypts toward a normal pattern, this may explain regression of rectal polyps. This temporary effect may be mediated, at least in part, by decreased amounts of cytotoxic secondary bile acids in the rectal lumen.

Adenomatous Polyposis Coli↗
PubMed1992

A phase I-II study of 14-days continuous infusion of 5-fluorouracil with weekly bolus leucovorin in metastatic colorectal carcinoma.

A consecutive phase I and phase II study of a 14-days continuous infusion schedule of 5-fluorouracil with weekly bolus injection leucovorin was performed in 10 and 21 patients, respectively. Chemotherapy courses were repeated every 4 weeks. 1 patient in the phase I study was pretreated, all the others had no prior chemotherapy. 300 mg/m2 continuous infusion of 5-fluorouracil for 14 days could not be combined with any dose of leucovorin 20-200 mg/m2 without severe toxicity, mainly gastrointestinal. A 5-fluorouracil dose of 200 mg/m2 day for 2 weeks, combined with weekly bolus injection of 200 mg/m2 leucovorin was found to be feasible. The phase II study was performed at this dose level. In 21 patients a response rate of 5/21 [23.8%, 95% confidence interval (CI) 8.2-47.1%] was observed, and the overall response rate was 8/29 (27.6%, 95% CI 12.7-47.2%). Responses were observed in patients with liver (4), lung (1), abdominal (1), and multiple (2) metastases. Median survival was 14.5 months. Toxicity was low, mucositis WHO grade 1-2 being most frequent (36/113 courses = 31.9%). Patients' acceptance of this continuous infusion schedule was generally good.

Adult↗
PubMed1992

Recombinant interferon alpha-2b in patients with metastatic apudomas: effect on tumours and tumour markers.

Malignant carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid are tumours with similar clinical features. In patients with unresectable or metastatic tumours leukocyte interferon (IFN) and recombinant human (rh) IFN have demonstrated efficacy. Twenty-four evaluable patients with progressive tumours were treated with 2.5 megaunits rh IFN alpha-2b, administered once daily subcutaneously, for a median duration of 7 months (range 0.5-37+). Two carcinoid patients demonstrated a response in tumour size, 80% showed stable disease (SD). Sixty percent of the carcinoid patients with elevated urinary 5-hydroxyindoleacetic (5-HIAA) levels reached a biochemical partial response of the urinary 5-HIAA levels (median duration 13.5 months). In the patients with an islet cell or medullary tumour and an elevated tumour marker, the marker did not further increase. Of the 12 carcinoid patients evaluable for a symptomatic response, ten (83%) experienced a relieve of symptoms. IFN alpha-2b dose reduction or discontinuation due to toxicity was necessary in three and ten patients, respectively. No neutralising IFN alpha-2b antibodies developed despite prolonged treatment. In conclusion, IFN alpha-2b had a beneficial effect in patients with progressive tumours, while long-term IFN alpha-2b treatment did not augment neutralising antibodies. In view of the IFN alpha-2b-related toxicity, administration of IFN alpha-2b on alternating days may be preferable.

Adenoma, Islet Cell↗
PubMed1991

Chemotherapy and surgery for locally advanced cancer of the cardia and fundus: phase II study with methotrexate and 5-fluorouracil.

Locally advanced cancer of the cardia and fundus might be cured by surgical resection. Poor results after surgery in stage IIIB and stage IV disease prompted a study of neoadjuvant chemotherapy. Treatment included four cycles of high doses of methotrexate (1.5 g/m2) and high doses of 5-fluorouracil (1.5 g/m2) followed by surgery in those patients with lesions then found to be resectable. Twenty patients with tumours staged as IIIB or IV were entered; 17 patients completed the four courses of chemotherapy and 14 underwent re-exploration. Eight patients achieved tumour reduction enabling resection. Five patients underwent total gastrectomy with distal pancreatectomy and splenectomy en bloc and three patients had an oesophagogastrectomy. There were no treatment-related deaths and toxicity was tolerable. Two patients were alive 54 and 41 months after chemotherapy with no evidence of disease. Locoregional recurrence developed in five patients and metastatic disease in one. Their median survival was 22 months.

Adenocarcinoma↗
PubMed1991

[Treatment strategy and results in primary inoperable rectal cancer].

The authors report their experience with laparotomy in patients with rectal carcinoma to identify those patients with locally non-resectable primary cancer of the rectum who may be treated initially by high-dose radiotherapy. The goal of this so-called "staging laparotomy" is to assess mobility and tumor size by means of bimanual palpation, to stage the abdominal cavity and to create total fecal diversion by performing an endcolostomy in order to condition these patients for maximum tolerance during the protracted radiotherapy course (greater than 50 Gy/5-6 weeks). The formation of an endcolostomy seems to avoid severe morbidity and even mortality of high-dose radiotherapy without delay of further surgery. Twenty-two patients with locally advanced rectal carcinoma were treated in this way. The tumor was resectable in 18 of the 20 patients who underwent relaparotomy after high-dose radiotherapy. Six out of the 13 patients with a radical resection died with evidence of disease during the follow-up (2 with local disease). One patient died with no evidence of disease after 5 years and 6 patients are still alive without disease after an average of 37 months (15-67 months).

Adenocarcinoma↗
PubMed1991

The extended Hartmann operation as an elective procedure for rectal cancer. A forgotten operation.

The authors describe their experience with the extended Hartmann procedure as the elective and definitive operation in a selected group of 36 patients having primary adenocarcinoma of the rectum. The operations were carried out between 1st January 1978 and 31st December 1989. The average age of the patients was 70 years (range 37 to 84 years). Ten patients had preoperative radiotherapy because of deep infiltration and (or) fixation of the tumor. In this series the Hartmann procedure was chosen because abdomino-perineal excision was not needed and low anterior resection could not warrant acceptable continence. With a Hartmann procedure the risks of a low colorectal or colo-anal anastomosis were avoided while the perineal excision was abandoned. Eight patients had hepatic metastases. The Dukes' classification of the remaining patients was A in two, B in nine and C in 17 patients. Postoperative morbidity was within acceptable limits for this particular patient group. There was no hospital mortality. Twenty patients had a potentially curative resection prior to 31st December 1987, thus making them available for follow-up of at least 2 years. Ten of these patients have been in follow-up without evidence of disease for an average of 76 months (mean 65 months, range 28-123 months). The authors conclude that the procedure is safe and that the remaining rectal stump does not generate morbidity or discomfort. Considering the fact that only two of the 36 patients had a Dukes' A tumor, the low recurrence rate shows that the Hartmann procedure yields satisfactory pelvic radicality.

Adenocarcinoma↗
PubMed1991

Advanced rectal cancer in the female: reduction of pelvic recurrence by rectal resection en bloc with hysterectomy and/or posterior vaginal wall excision.

The authors report their experience with 20 female patients with advanced rectal cancer in whom rectal excision was combined with concomitant excision of the uterus and/or posterior vaginal wall. Six patients presented with a malignant fistula between the rectum and the genital tract; 10 had pre-operative radiotherapy, with a total dose of 50 Gy in seven patients and 30 Gy in three. The resection was judged as radical in 18 patients; the specimen was staged as a Dukes' B in eight and a Dukes' C in 10 cases. Three patients died within the follow-up period, due to intercurrent disease, without evidence of recurrence. Seven patients have been followed without evidence of disease for an average of 91 months (range 39-143 months). One patient is alive 5 years after surgery with a pelvic recurrence. Seven patients succumbed to distant metastases alone (n = 4) or to a combination of haematogenous metastases and pelvic recurrence (n = 3). The authors make a plea for local radicality in advanced rectal cancer in female patients, to preserve quality of life in most patients and a cure in some.

Adult↗
PubMed1988

Juvenile polyps at the site of a ureterosigmoidostomy. Report of five cases.

Five cases of juvenile polyps at the level of a ureterosigmoidostomy are described. One of the juvenile polyps contained an area of adenomatous tissue. The mechanisms that might cause these polyps are discussed. The mechanisms that might cause these polyps are discussed. The presence of adenomatous tissue in one of the patients may be a step of the polyp cancer sequence at the level of ureteral implantation in the colon. The authors make a plea for a call-up and close follow-up of all patients who have a ureterosigmoidostomy.

Adult↗
PubMed1987

Staging laparotomy for inoperable or borderline operable cancer of the rectum.

The authors report their experience with the staging laparotomy as a means of identifying and preparing patients for high-dose preoperative radiotherapy. Twelve patients had clinically unresectable cancers of the rectum. The goal of the staging laparotomy is to assess mobility and tumor size by means of bimanual palpation, to stage the abdominal cavity, and to fashion an end colostomy at the level of the descending colon. Eight patients ultimately underwent radical resection. Three died during follow-up due to hematogenic metastases without recurrent pelvic disease. Five patients are alive with no evidence of disease and have been followed for an average of 34 months (range, 20 to 64 months).

Adult↗