A phase I-II study of synchronous chemoradiotherapy for poor prognosis locally advanced bladder cancer.

BACKGROUND: The management of locally advanced bladder cancer remains controversial with poor local control with radiotherapy alone. Synchronous chemotherapy regimens have yielded encouraging results in other primary sites. PATIENTS AND METHODS: Patients with T2-T4a N0/NX M0 bladder cancer were entered into this single centre phase I-II study. Patients received radiotherapy to 55 Gy in 20 fractions over four weeks. Concurrent chemotherapy was given with Mitomycin C 12 mg/m2 day 1 and 5-fluorouracil 500 mg/m2/24 hours weeks one and four of radiotherapy for five or seven days on each occasion. RESULTS: Thirty-one patients entered the trial from March 1998 to December 1999 (22: 5-day; 9: 7-day schedule). Median age was 68 (range 58-79) years, 23 males and 8 females. T2: 9 (29%); T3a: 4 (12%); T3b: 9 (29%); T4: 9 (29%); TCC grade 2: 8 (26%) and grade 3: 23 (74%); 14 of 31 had hydronephrosis. Ten of thirty-one had a GFR < 50 ml/min. Toxicity was mild to moderate with the five-day schedule. More severe toxicity was seen with the seven-day schedule: five of nine patients failed to complete planned therapy. Pathological complete response rate at three months was 74% (5-day regimen) and 50% (7-day regimen). Overall 12-month survival was 65%. CONCLUSION: Chemoradiotherapy with the five-day schedule is feasible with acceptable toxicity in poor prognosis patients. A randomised trial is being launched.

Laparoscopic peritoneal lavage in staging gastric and oesophageal cancer.

AIMS: Accurate staging of gastric, oesophageal and oesophagogastric cancer is essential to avoid unnecessary laparotomies in patients where only palliation is appropriate. This requires a multimodal approach utilizing endoscopy, computed tomography and laparoscopy. Previous authors have found that the presence of free peritoneal tumour cells (FPTCs) detected at laparoscopy or laparotomy confers a poorer prognosis. However, various methods of peritoneal lavage are described. The aim of this study was to evaluate the prognostic value of our technique of peritoneal lavage. MATERIALS AND METHODS: 88 staging laparoscopies with peritoneal lavage were carried out between March 1997 and February 1999 on patients eligible for attempted curative resection of a gastric, oesophageal or oesophagogastric cancer. During laparoscopy the pelvis was irrigated with 200 ml of normal saline, with 100 ml aspirated and examined cytologically. Patients were followed-up until September, 1999. RESULTS: 11 patients had FPTC-positive cytology with a median survival following laparoscopy of 122 days (95% CI 82-161) with only a single patient surviving more than one year. In the FPTC-negative group, median survival was 378 days (95% CI 256,-). Log-rank Chi(2)=16.7, P<0.001. CONCLUSIONS: The presence of FPTCs detected by our technique is a contraindication to attempted curative resection - palliation only (medical or surgical) is appropriate.

Management guidelines for women with normal colposcopy after low grade cervical abnormalities: population study.

OBJECTIVES: To develop an evidence based protocol for the follow up of women with low grade cervical abnormalities for whom treatment is not immediately indicated. DESIGN: Population outcome study. SETTING: Colposcopy clinic of an inner city teaching hospital. PARTICIPANTS: 566 women with low grade cytological abnormalities who were not treated at a first visit to the colposcopy clinic, followed up for a total of 881 years. MAIN OUTCOME MEASURES: Resolution of abnormalities, persistence of disease, and treated disease. RESULTS: Abnormalities resolved in 306 (54.1%) women, whereas 138 (24.4%) had persistent disease and 122 (21.5%) were subsequently treated. Colposcopic opinion, smear test results, age, smoking history, and number of pregnancies were all significantly related to outcome. Logistic regression analysis produced a model that correctly identified 70% of women whose abnormalities resolved. Only 23 of 295 women (7.8%) with a normal cervix on colposcopy and a smear without dyskaryosis at a first visit were treated by the end of the observation period. CONCLUSIONS: Women referred with low grade cytological abnormalities who have a normal cervix on colposcopy and a negative or borderline repeat smear test result may be discharged from the colposcopy clinic. We propose a follow up protocol that could safely avoid unnecessary visits to a clinic.

Histologic and immunologic associations of an HPV16 variant in LoSIL smears.

BACKGROUND: Human papillomavirus type 16 variants have been described and may have different biologic activities: this has implications for the design of HPV vaccines. OBJECTIVES: The aim of this study was to see if the HPV16 variant E-G 131 can be detected in women with preinvasive disease and to consider the histological and immunological implications of such infection. DESIGN: A prospective observational cross-sectional study on a cohort of women with minor cervical cytological abnormalities was performed. METHODS: Samples were tested for HPV DNA by polymerase chain reaction and restriction enzyme digestion. Blood samples were tested for antibodies to HPV16 virus-like particles (VLP) and to determine class I HLA types. Women found to have abnormal colposcopy were treated by large-loop excision of the transformation zone on a see-and-treat basis. RESULTS: Two hundred forty-one women were included in the study. Infection with the variant was detected in 20. 9% of cases and was not associated with any specific HLA type. These cases were more likely to have high-grade CIN than those with wild-type HPV16 or no HPV16 (chi2 = 18.85, P < 0.001). There were significant differences in seropositivity to HPV16 virus-like particles between the three groups (chi2 = 32.43, P < 0.001). CONCLUSIONS: The E-G 131 variant may have increased oncogenic potential by evading host immune responses, but its identification is only weakly predictive of high-grade disease in stepwise logistic regression. The lack of seropositivity to HPV16 VLP has implications for the design of prophylactic vaccines based on VLP to HPV16.