Wilhelm Graf

Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer

BACKGROUND The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients. PATIENTS AND METHODS Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physicians evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03). CONCLUSIONS The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study

PURPOSE: The Swedish Rectal Cancer Trial has unequivocally demonstrated that preoperative high-dose (5 × 5 Gy) radiotherapy reduces local failure rates and improves overall survival. This will have an impact on the primary treatment of rectal cancer. This study investigates the effect of preoperative high-dose radiotherapy on long-term bowel function in patients treated with anterior resection. METHODS: A questionnaire was answered by 92 percent (203/220) of patients who were included in the Swedish Rectal Cancer Trial and who were alive after a minimum of five years. Thirty-two patients were excluded, mainly because of postoperative stomas and dementia, which left 171 for analysis. RESULTS: Median bowel frequency per week was 20 in the irradiated group (n=84) and 10 in the surgery-alone group (n=87;P<0.001). Incontinence for loose stools (P<0.001), urgency (P<0.001), and emptying difficulties (P<0.05) were all more common after irradiation. Sensory functions such as “discrimination between gas and stool” and “ability to safely release flatus” did not, however, differ between groups. Thirty percent of the irradiated group stated that they had an impaired social life because of bowel dysfunction, compared with 10 percent of the surgery-alone group (P<0.01). CONCLUSIONS: The study indicates that high-dose radiotherapy influences long-term bowel function, thus emphasizing the need for finding predictive factors for local recurrence to exclude patients with a very high probability for cure with surgery alone and to use optimized radiation techniques.

Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial

BACKGROUND Injection of a bulking agent in the anal canal is an increasingly used treatment for faecal incontinence, but efficacy has not been shown in a controlled trial. We aimed to assess the efficacy of injection of dextranomer in stabilised hyaluronic acid (NASHA Dx) for treatment of faecal incontinence. METHODS In this randomised, double-blind, sham-controlled trial, patients aged 18-75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomisation was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. Patients in the active treatment group are still being followed up. This trial was registered with ClinicalTrials.gov, number NCT00605826. FINDINGS 278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2·36, 95% CI 1·24-4·47, p=0·0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess). INTERPRETATION Anal injection of NASHA Dx is an effective treatment for faecal incontinence. A refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might further increase the acceptance of this minimally invasive treatment. FUNDING Q-Med AB.

Short-term preoperative radiotherapy results in down-staging of rectal cancer: a study of 1316 patients

BACKGROUND AND PURPOSE This study was undertaken to investigate down-staging effects after short-term, high-fractionated preoperative radiotherapy. MATERIAL AND METHODS The relationships between preoperative radiotherapy 25-25.5 Gy given over 5-7 days and clinical variables (sex, age, tumour level, metastatic disease, and tumour size) and the risk of lymph node metastases were examined in 1316 patients with rectal adenocarcinoma by uni-, and multivariate analyses. RESULTS Irradiated specimens contained smaller tumours (P < 0.00001) and nodal metastases were less common (P < 0.001). In a logistic regression model, tumour size in cm was positively related to the risk for nodal spread (odds ratio, OR = 1.14, 95% confidence limits, CL, of OR 1.08-1.22). In the same model, radiotherapy decreased the risk for nodal involvement (OR 0.73, 95% CL 0.58-0.92. This risk was particularly reduced when the time interval between start of radiotherapy and surgery equalled 10 days or more. CONCLUSIONS These results demonstrate a down-staging effect by a short course of preoperative radiotherapy which should be considered in the interpretation of radiotherapy trials and in the recruitment of patients for further postoperative adjuvant treatment.

Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study

Patients with peritoneal or local metastases from colorectal cancer have a poor prognosis. However, aggressive treatments by debulking surgery and infusional intraperitoneal (i.p.) chemotherapy have been tried and appear to benefit selected patients. We assayed the effects of debulking surgery and i.p. chemotherapy with respect to survival and compared the results with matched control patients treated by intravenous (i.v.) chemotherapy. In all, 18 patients with peritoneal and/or local metastases from colorectal adenocarcinoma underwent debulking surgery followed by 5-fluorouracil (5-FU) 550 mg m−2 day−1 i.p. and leucovorin (LV) 60 mg m−2 day−1 i.v. The chemotherapy was started the day after surgery and was given daily for 6 days and repeated monthly for totally eight courses. The control patients, matched for age, gender, performance status and metastatic site, were randomly selected from controlled clinical chemotherapy trials and treated with i.v. 5-FU+LV or i.v. methotrexate+5-FU+LV. There was no treatment-related mortality. The median survival among i.p. patients was 32 months compared to 14 months in the control group. In all, 11 patients who underwent macroscopically radical surgery had a longer survival than those who were not radically operated (P=0.02). These results indicate that patients with peritoneal metastases and/or locally advanced cancers but without distant metastases may benefit from cytoreductive surgery combined with i.p. chemotherapy.

Evaluation of a Questionnaire in the Assessment of Patients with Faecal Incontinence and Constipation

BACKGROUND A self-reported questionnaire may be a useful instrument in assessing patients with faecal incontinence and constipation. METHODS Reliability, discrimination, validity, and sensitivity were evaluated in 16 control subjects 36 patients with faecal incontinence, and in 38 with constipation. The reliability was measured by a test-retest procedure (kappa (kappa) statistics or Spearman rank test), and validity by comparing the questionnaire and a diary. Discrimination was assessed by comparing the patient groups with the controls, and sensitivity by comparing selected answers before and after treatment. RESULTS Overall reliability (faecal incontinence group, mean kappa = 0.57; constipation group, mean kappa = 0.60; controls, mean kappa = 0.95) and validity were judged acceptable. In the incontinence group occurrence of faecal incontinence per se was reproducible (kappa = 0.66), as was the need to wear a pad (kappa = 0.85). Stool frequency, percentage toilet time spent straining and digitation was reproducible in patients with constipation (kappa = 0.80, r = 0.56; p < 0.001, kappa = 0.83 respectively). Several items distinguished both patient groups from healthy controls (p < 0.05 to p < 0.001). Sensitivity to surgical treatment was seen in several items in both patient groups. CONCLUSIONS The questionnaire appears to be a valid measure of symptoms in faecal incontinence and constipation with sufficient discriminatory capacity.

Does surgical repair of a rectocele improve rectal emptying

PURPOSE: This study was undertaken to assess results of surgical repair of rectocele and to identify possible determinants of outcome from patients history and preoperative defecography. Another aim was to evaluate how surgery affects rectal evacuation. METHOD: Thirty-four women with constipation and rectal emptying difficulties underwent surgery with a transanal technique. A preoperative defecography was performed in each patient. They were followed up after a median of 10 (range, 2–60) months with a questionnaire (n=34) and a defecography (n=31). Computer-based image analysis of defecographies was used to evaluate rectal evacuation. RESULTS: In 27 patients (79 percent), the result of surgery was good with subjectively improved emptying. The need for vaginal or perineal digitation preoperatively was related to a good result (P<0.05), whereas a previous hysterectomy (P<0.01) and a large rectal area on defecography (P<0.01) related to a poor result. Preoperative use of enemas, motor stimulants, or several types of laxatives also related to a poor outcome (P<0.05). Surgical treatment resulted in reduction of the rectocele (P<0.001), an elevated position of the anorectal junction (P<0.05), and improved rectal evacuation on defecographies (P<0.001). CONCLUSIONS: Surgical repair reduces the size of the rectocele and improves rectal emptying. These changes are accompanied by a symptomatic improvement in the majority of patients. Preoperative patient data and defecography may help in selecting patients for surgery.

Endoanal ultrasound or magnetic resonance imaging for preoperative assessment of anal fistula: a comparative study

To compare endoanal ultrasound (EUS) with a 10‐MHz probe vs. bodycoil magnetic resonance imaging (MRI) in the preoperative evaluation of anal fistula.

Septic complications and prognosis after surgery for rectal cancer.

AbstractPURPOSE: The influence of septic complications on long-term prognosis after surgery for rectal cancer is controversial. This study was performed to investigate whether an abdominal or perineal septic complication was associated with rectal cancer recurrence. METHODS: A total of 228 patients who had undergone curative resection for rectal cancer from 1973 to 1992 were reviewed. The patients were divided into groups of those who developed either an intra-abdominal abscess or a perineal infection after surgery (infection group) and those who did not (noninfection group). RESULTS: There was no clear difference in the overall incidence of tumor recurrence between the infection group (19/53, 36 percent) and the noninfection group (46/175, 26 percent; P = 0.25). However, the incidence of local recurrence was higher in the infection group (12/53, 23 percent) than in the noninfection group (16/175, 9 percent; P = 0.02). This increased risk was restricted to patients with a perineal infection (10/30, 33 percent; P = 0.003 vs. the noninfection group), whereas patients with an abdominal infection (3/24, 13 percent) did not differ from the noninfection group. CONCLUSION: Patients with a perineal infection after an abdominoperineal resection have an increased incidence of local recurrence. However, there was no association between abdominal sepsis and prognosis after surgery for rectal cancer.

A pilot study of factors influencing bowel function after colorectal anastomosis.

PURPOSE: This study was undertaken to assess subjective bowel function after anterior resection and to search for clinical characteristics that might affect the functional results. METHODS: A total of 70 patients answered a questionnaire concerning bowel function a median of 65 months after anterior resection, and 40 patients responded to the same questionnaire a median of 60 months after colonic resection. RESULTS: Median frequency of bowel movements per 24 hours was two (range, 0.2–9) after rectal resection and one (range, 0.4–6) after colonic resection (P<0.001). Incontinence for loose stools (P<0.01), need to wear a pad (P<0.05), and need to return to the toilet after defecation (P<0.05) was more common in the rectal resection group. In the latter group, advanced age, use of descending or transverse colon for anastomosis, and large amount of intraoperative bleeding was associated with fecal incontinence (P<0.05). Preoperative radiotherapy was correlated with a high bowel frequency (P=0.003). CONCLUSIONS: These data indicate that alterations of subjective bowel function frequently observed after colorectal anastomosis may be affected by both surgical technique and adjuvant radiotherapy.