Penny Brasher

A double-blind, crossover trial of intravenous clodronate in metastatic bone pain

After a baseline symptom and laboratory assessment, 24 patients with metastatic bone disease and pain were randomized to receive either a 4-hr intravenous infusion of 2-dichloromethylene bisphosphonate (Cl2MDP), 600 mg in 500 mL of normal saline, or a 4-hr placebo infusion, 500 mL of normal saline. The administration was double blind. After 1 wk, the assessment was repeated and the patients were crossed over to the alternate treatment. After 1 more wk, a final assessment and blinded choice by the patient and investigator took place. Of the 21 evaluable patients, 12 (57%) chose the Cl2MDP and 4 (19%) chose the placebo; 5 (24%) patients did not have a specific preference (p = NS). The investigator chose the Cl2MDP in 14 (67%) cases, placebo in 6 (29%) cases and was unable to discern a difference in 1 (5%) case (p less than 0.05). The patients and investigator made similar selections in 16 (76%) instances. On the visual analogue scale assessments, a significant decrease in pain scores was observed following the Cl2MDP infusion (p less than 0.01) and an increase in activity scores was also demonstrated (p less than 0.01). No significant difference in the daily oral morphine equivalent analgesic requirement was demonstrated for either arm. No difference in clinical and laboratory parameters of toxicity was evident between the placebo and Cl2MDP arms of the trial. Our preliminary findings suggest that Cl2MDP is safe, and has analgesic properties that may prove to be useful in the management of metastatic bone pain.

Breast Implants and Breast Cancer — Reanalysis of a Linkage Study

BACKGROUND In 1992, Berkel and colleagues reported in the Journal the results of their study of the potential association of breast augmentation and breast cancer. The study reported that women who had breast augmentation had a significantly lower subsequent risk of breast cancer (P < 0.01) than the general population, with a standardized incidence ratio of 0.48 overall. Assuming a 10-year induction period (that is, assuming that cancers found within 10 years of the augmentation might have been the result of a process begun before surgery and therefore should not be considered), the reported standardized incidence ratio was 0.16. Problems were later identified involving some of the study methods. This paper reports a second analysis of these data. METHODS We used a data set from Alberta Health Care to identify eligible women with bilateral breast augmentation. Using a combination of deterministic and probabilistic methods, we linked this data set to the Alberta Cancer Registry to identify subsequent breast cancers that developed during the study period. Multiple estimates of standardized incidence ratios were calculated on the basis of differing study-eligibility dates, induction periods, and types of breast-cancer (invasive only or invasive plus in situ). RESULTS The reanalysis found substantial differences in the numbers of person-years at risk, resulting in higher standardized incidence ratios than in the original analysis. The final ratios for all breast cancers, with October 1, 1973, used as the starting date of the study, were 0.76 (95 percent confidence interval, 0.55 to 1.02), 0.85 (95 percent confidence interval, 0.58 to 1.19), and 0.68 (95 percent confidence interval, 0.32 to 1.25) for induction periods of 0, 5, and 10 years, respectively. None of these standardized incidence ratios were significantly different from 1. CONCLUSIONS On the basis of this reanalysis, the incidence of breast cancer among the women who had breast augmentation could not be said to be either significantly higher or lower than that among the general population over the period during which this cohort was followed.

Outcome and Safety of Transrectal US-guided Percutaneous Cryotherapy for Localized Prostate Cancer☆

OBJECTIVES To assess the effectiveness and safety of ultrasound (US)-guided cryotherapy as a primary treatment for localized prostate cancer. MATERIALS AND METHODS A prospective study of percutaneous transrectal US (TRUS)-guided cryotherapy was performed on 71 patients with T1-T3, N0, M0 prostatic cancer: 10 patients underwent two or more procedures. All cases were newly diagnosed and patients had no previous treatment for cancer. For all patients, TRUS biopsies were performed at 5-6 months. Patients were monitored at 6 weeks; 3, 6, 9, and 12 months; and twice yearly thereafter for prostate specific antigen (PSA) levels, complications, and clinical evidence of residual disease. RESULTS Follow-up from 10 to 36 months was available for 70 of 71 patients; one patient died of unrelated disease. Initially, 10 of 69 patients had positive postcryotherapy biopsy results. After repeated treatment, nine of these 10 patients had negative biopsy results and one patient had no follow-up. Overall, 68 of 69 patients had negative biopsy results. At 1 year, 43 of 64 (67%) had an undetectable PSA level. Two patients had proven metastases. Complications include three cases with urethral sloughing requiring transurethral resection of the prostate (TURP). One patient had orchitis. Two patients had persistent incontinence, one as the result of a TURP. There was no death, acute serious morbidity, or fistula formation. Impotence was universal at 6 months, but many patients demonstrated late recovery. CONCLUSION Cryoablation is an imaging-guided percutaneous intervention for prostate cancer that can safely yield disease-free status in a high percentage of patients with localized disease.

ERCP-directed brush cytology prepared by the Thinprep method: test performance and morphology of 149 cases.

Conventionally prepared endobiliary brushings are moderately (42%) sensitive and highly (98%) specific in detecting malignancy. The performance and morphological features of brushings prepared by Thinprep®, a liquid‐based method are mostly unknown. All brushings were retrieved from the laboratory files. Disease was classified as benign or malignant by linkage with the provincial cancer registry and sensitivity, specificity, positive (PPV) and negative predictive values (NPV) calculated. True positives and negatives were reviewed and predictive morphological features analysed by regression tree analysis. Out of 149 brushings, 55 (37%) were positive and 94 (63%) negative. Malignancy was identified in 86 (58%) and benign disease in 63 (42%) of the cases. The sensitivity was 51%, specificity 83%, PPV 80% and NPV 55%. Absolute discriminants of positive and negative brushings were not found, but nuclear cytoplasmic ratio was a useful feature. The performance of Thinprep®‐prepared brushings from this anatomical site was comparable with conventional preparations.

Comparative study of the ThinPrep Pap test and conventional cytology results in a Canadian cohort

Objective:  To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow‐up all test results for a minimum of 2 years and assess performance based on this outcome.

The accuracy and interobserver reproducibility of endometrial dating

Summary Although controversial, diagnosis of luteal phase defect (LPD) includes the morphological assessment of endometrial development. This study was conducted to determine if refresher training in the histological criteria could improve the accuracy and interobserver reproducibility of endometrial dating. Seventy‐eight endometrial biopsies were dated by a reference panel of two pathologists and then reviewed twice by a study panel of four pathologists. In the first review, usual practice was applied. Prior to the second review, they studied a standard document of histological criteria. Samples were dated as proliferative, secretory (post‐ovulatory day, POD), menstrual, and undatable. Accuracy levels based on the reference dating and agreement levels using s values were calculated per review and compared. The s for overall dating was 0.683 in the first review and 0.696 in the second. The respective first and second review s values were 0.736 and 0.771 for proliferative, and 0.794 and 0.764 for secretory. Amongst those dated as secretory in the first and second reviews, respectively, 31 and 28% were assigned the same POD by any two panellists, 68 and 63% were dated to within 1 day, and 77 and 71% were dated to within 2 days. Accuracy levels per panellist for overall dating were very high in both reviews but were low for individual PODs. Accuracy and interobserver reproducibility were unaffected by refresher training, suggesting the limits of histological dating have been reached.

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province

BackgroundSurveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery.MethodsIn this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest.ResultsA colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70 – 79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001).ConclusionsThe majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics.

Investigation of laser cervical cone biopsies negative for premalignancy or malignancy.

Objective. To measure the rate of carbon dioxide, laser cone biopsies negative for premalignancy or malignancy and determine whether the clinical indications were appropriate or the pathology evaluations were correct. Materials and Methods. The patient charts of 95 negative cone biopsies were reviewed by one of the authors to determine the indications for the procedure. All of the slide reviews were done by two of the authors. Following a review of the cone biopsy slides, three deeper sections of the tissue blocks were examined in specimens that were still negative or equivocal for premalignancy. Thereafter, for those still negative the preconization, referral Pap tests, and colposcopic directed tissue samples were reviewed. Results. The overall negative rate of laser cone biopsy was 28% (95/341) and 68% (65/95) were done to investigate high-grade squamous intraepithelial lesions (HGSIL) (cervical intraepithelial neoplasia [CIN] 2,3). There were 25 false negative cone biopsy specimens because of misinterpretation of the original slides or discovery of pathology in additional sections. False positive reporting of some preconization Pap tests or tissue specimens as premalignant when none were seen on review likely resulted in 11 unnecessary conizations. The number of negative cones would thereby be reduced by 36 for a rate of 17% (59/341). Conclusions. The negative rate could be reduced by 11% with routine deeper sectioning of the tissue blocks of the cone biopsy specimen and improved accuracy of pathological interpretation.

The Pap test at follow-up colposcopy examinations: usefulness in the enhanced detection of cervical neoplasia.

Objective. The frequency at which results of the Pap test performed at follow-up colposcopy examinations were more abnormal than the concurrent tissue specimens and the frequency at which the Pap result gain in high-grade squamous intraepithelial lesion (HSIL) resulted in the increased detection of cervical intraepithelial neoplasia 2,3 were investigated. Materials and Methods. Pap test and concurrent tissue samples obtained at all follow-up colposcopy examinations in the year 2000 were coded for comparability of results and were ranked in ascending order from normal to malignant. The frequency at which the Pap test results were more abnormal than the concurrent tissue results was calculated. Results of subsequent cervical investigations were retrieved for all with a Pap test gain in diagnosis of HSIL. Results. In 35% of 2,902 examinations (n = 1,027), the Pap test results were more abnormal than the tissue specimens. The gain in diagnosis was HSIL in 2% (63 of 2,902) and low-grade squamous intraepithelial lesion or better in 33% (964 of 2,902). Among those with a gain in HSIL, cervical intraepithelial neoplasia 2,3 or cancer was tissue-confirmed in 28 samples, for a health benefit of the Pap test of 1.0% (28 of 2,902). Conclusions. The usefulness of the Pap test performed at follow-up colposcopy examinations for the enhanced detection of CIN 2,3 in this cohort is minimal, and the practice safely could be discontinued.

The usefulness of the pap test taken at the first colposcopy examination in the enhanced detection of cervical neoplasia.

Objective. To determine the diagnostic gain, clinical value, and health benefit of the Pap test taken at the first colposcopy examination by investigating the frequency in which the result of the test was more abnormal than the results of the referral Pap test that triggered the examination, the tissue samples taken at that examination, or both. Materials and Methods. The laboratory information system (LIS) was searched for all first colposcopy examinations and their referral Pap tests. The Pap tests and tissue samples were coded for comparability of diagnosis and ranked in ascending order from normal to malignant. The LIS or patient charts, or both, were searched for follow-up information on the more abnormal colposcopy Pap test results. Results. There were 1,633 women having a first colposcopy examination. In 116 (7%), the colposcopy Pap test was more abnormal than the other samples. In 81 (5%), the diagnostic gain was a low-grade squamous intraepithelial lesion, and in 25 (1.5%), the gain was a clinically valuable high-grade squamous intraepithelial lesion (HSIL). High-grade squamous intraepithelial lesion (CIN 2,3) or adenocarcinoma in situ (AIS) was tissue confirmed in 21 of the 116 women, conferring a health benefit of 1.3% on the colposcopy Pap test. Conclusions. The health benefit of the Pap test taken at the first colposcopy examination in terms of the increased detection of HSIL (CIN 2,3) or AIS is minimal and the practice could safely be discontinued.