Beth E. Juliar

A Longitudinal Study of Genital Human Papillomavirus Infection in a Cohort of Closely Followed Adolescent Women

BACKGROUND We performed a study to better characterize the natural history of genital human papillomavirus (HPV) infection in a cohort of closely followed adolescent women. METHODS A cohort of 60 adolescent women was followed over a 2.2-year period, on average. A median of 41.5 self-collected vaginal and clinician-obtained cervical swabs were obtained from each subject. RESULTS HPV was detected in 45.3% of all adequate specimens, by use of a polymerase chain reaction/reverse blot strip assay. Oncogenic--or high-risk (HR)--HPV types were detected in 38.6% of specimens, and nononcogenic--or low-risk (LR)--types were detected in 19.6% of specimens. During the entire study period, 49 of 60 subjects tested positive for HPV (cumulative prevalence, 81.7%). The most frequently detected HR types were HPV types 52, 16, and 59. Infections with multiple HPV types were common. The median duration of persistence of a specific HPV type was 168 days, and HR types were more persistent than LR types. Abnormal cervical cytological results occurred in 37% of the adolescent women and were significantly associated with HR HPV infection. CONCLUSIONS The cumulative prevalence of HPV infection in sexually active adolescent women is extremely high, involves numerous HPV types, and frequently results in cervical dysplasia.

Effect of screening colonoscopy on colorectal cancer incidence and mortality.

BACKGROUND & AIMS Colonoscopy is used widely for colorectal cancer (CRC) screening; however, its long-term impact on the incidence and mortality of CRC is not known. METHODS We assessed CRC incidence and mortality in a group of asymptomatic average-risk patients who underwent screening colonoscopy between 1989 and 1993 at a university hospital. By using standardized incidence ratios and standardized mortality ratios, we compared our observed CRC rates with expected rates from the Surveillance, Epidemiology, and End Results (SEER) data. RESULTS The cohort comprised 715 patients (mean age, 61 +/- 6.5 y; 59% male; 95% Caucasian) with 10,492 patient-years of follow-up. There were 12 cases of CRC: 5 found at baseline and 7 found after a median follow-up period of 8 years (range, 3-16 y). When the first 2 years of follow-up were excluded, there were 7 incident cases of CRC (95% confidence interval [CI], 2-13) over 9075 person-years of follow-up. The expected number based on SEER data was 21. The incidence rate was 0.77 cases per 1000 person-years, and the standardized incidence ratio was 0.33 (95% CI, 0.10-0.62), consistent with a relative risk reduction in CRC incidence of 67%. Three patients died from CRC (95% CI, 0-9). The expected number of deaths based on SEER data was 9. The mortality rate was 0.29 per 1000 person-years, and the standardized mortality ratio was 0.35 (95% CI, 0.0-1.06), consistent with a relative reduction in CRC death of 65%. CONCLUSIONS In this average-risk cohort, CRC incidence and mortality were reduced after screening colonoscopy. These results provide additional evidence for the effectiveness of colonoscopy as a primary CRC screening modality.

Variation in polyp detection rates at screening colonoscopy

BACKGROUND Variation in polyp detection among endoscopists has been used to justify the need for establishing quality standards for colonoscopy performance. OBJECTIVE To measure variation in polyp detection rates (PDRs) among endoscopists who perform screening colonoscopy and to identify associated factors. DESIGN Cross-sectional analysis of summary-level data. SETTING Endoscopy practices in central Indiana. SUBJECTS Twenty-five endoscopists and their patients. MAIN OUTCOME MEASUREMENTS Mean procedure time (MPT); proportions of patients with any polyp, any adenoma, any polyp > or =1.0 cm, and multiple adenomas; and variation in PDRs and identification of outliers. Multiple linear regression analysis identified factors that accounted for the variation in PDRs. RESULTS A total of 2664 screening colonoscopies (1108 women and 1556 men) were performed. The mean patient age was 59 years; the mean proportion of women was 42%; the MPT was 17.1 minutes. Adenoma detection rates ranged from 7% to 44% (P < .001) and from 0% to 13% for large polyps, which was not statistically significant (P = .07). For all polyp categories, only 1 to 3 high outlier endoscopists (ie, higher than mean PDRs) were identified. Models that included the number of procedures, mean age, percentage of women, and MPT accounted for 36% to 56% of the variation in PDRs. In all models, only MPT was significantly associated with PDRs. LIMITATIONS Whether each endoscopists cohort was at comparable risk for colorectal neoplasia was uncertain. In comparison with individual-level data, analysis of summary-level data is limited. CONCLUSIONS PDRs vary widely among endoscopists, although only a few (high) outliers were identified. Variation in PDRs was associated only with MPT. Further research is needed to determine the clinical importance of and reasons for this variation.

Weekly Paclitaxel and Gemcitabine in Advanced Transitional-Cell Carcinoma of the Urothelium: A Phase II Hoosier Oncology Group Study

PURPOSE To evaluate the efficacy and toxicity of weekly paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma (TCC) of the urothelial tract. PATIENTS AND METHODS Patients with advanced unresectable TCC were enrolled onto this multicenter, community-based, phase II trial. Initially, patients were treated with paclitaxel 110 mg/m(2) and gemcitabine 1,000 mg/m(2) by intravenous infusion on days 1, 8, and 15 every 28 days. Patients who had an objective response or stable disease continued treatment for a maximum of six courses. Paclitaxel was decreased to 90 mg/m(2) and gemcitabine was decreased to 800 mg/m(2) for the last 12 patients because of a concerning incidence of pulmonary toxicity in the first 24 patients. RESULTS Thirty-six patients were enrolled between September 1998 and March 2003. Twenty-four patients received the higher doses of paclitaxel and gemcitabine, and 12 patients received the lower doses. Twenty-five (69.4%) of 36 patients had major responses to treatment, including 15 patients (41.7%) with complete responses. With a median follow-up time of 38.7 months, the median survival time was 15.8 months. Grade 3 and 4 toxicities included granulocytopenia (36.1%), thrombocytopenia (8.3%), and neuropathy (16.7%). Five patients (13.9%) had grades 3 to 5 pulmonary toxicity, and one patient had grade 2 pulmonary toxicity. CONCLUSION Weekly paclitaxel and gemcitabine is an active regimen in the treatment of patients with advanced TCC. However, because of the high incidence of pulmonary toxicity associated with this schedule of paclitaxel and gemcitabine, we recommend against the use of this regimen in this patient population.

The Combined Percentage of Gleason Patterns 4 and 5 Is the Best Predictor of Cancer Progression After Radical Prostatectomy

PURPOSE Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. PATIENTS AND METHODS Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. RESULTS A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. CONCLUSION The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.

Phase II Study of Paclitaxel Plus Gemcitabine Salvage Chemotherapy for Germ Cell Tumors After Progression Following High-Dose Chemotherapy With Tandem Transplant

PURPOSE To determine long-term survival and potential cure with salvage chemotherapy with paclitaxel plus gemcitabine after progression after both cisplatin combination chemotherapy and subsequent high-dose chemotherapy with tandem transplantation. PATIENTS AND METHODS One hundred eighty-four patients received salvage high-dose chemotherapy at Indiana University (Indianapolis, IN) from February 1996 to December 2004. After further evidence of progressive disease, 32 patients were subsequently treated with paclitaxel 100 mg/n2 over 1 hour plus gemcitabine 1,000 mg/m2 over 30 minutes, days 1, 8, and 15 every 4 weeks for a maximum of six courses. This is a retrospective review of this patient population. Patients were evaluated for response, duration of response, and survival. Patients were ineligible if they received prior paclitaxel or gemcitabine. RESULTS Ten (31%) of 32 patients achieved objective response, including four partial remissions (2- to 6-month duration) and six complete responses (CRs). Four of these six CRs (12.5% of total patient population) are continuously disease free (NED) with paclitaxel plus gemcitabine alone (no postchemotherapy surgery) at more than 20, 40, 44, and 57 months from start of paclitaxel plus gemcitabine, respectively. One additional CR is currently NED more than 63 months after paclitaxel plus gemcitabine with two subsequent resections of carcinoma. CONCLUSION Long-term disease-free survival is possible with paclitaxel plus gemcitabine in this patient population that progressed after high-dose chemotherapy, and had not received prior paclitaxel or gemcitabine.

The prevalence of chlamydia, gonorrhea, and trichomonas in sexual partnerships: implications for partner notification and treatment.

Background: Treatment of sex partners by patient-delivered partner therapy (PDPT) may prove to be an effective strategy in reducing reinfection and preventing the sequelae of sexually transmitted infections (STIs). However, limited data exists regarding STIs within sexual partnerships (dyads). Objective: The objective of this study was to determine the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), and Trichomonas vaginalis (TV) in sexual dyads to estimate the potential yield and limitations of PDPT. Methods: Male and female STI clinic attendees were invited to participate. Index subjects and partners were interviewed and tested for CT, GC, and TV. All partners were sought regardless of infection status of the index subject. Results: Of 210 dyads, the prevalence in index subjects was CT, 46%; GC, 18%; and TV, 14%. Considering the partners of 72 CT-only-infected index subjects, 57% had CT, 6% had GC, and 11% had TV. Considering the partners of 35 index subjects with GC or GC–CT coinfection, 57% had GC and/or CT; however, in 20% of partners, unsuspected TV was present. Among 74 dyads with uninfected index subjects, 26% of partners had an STI. Among the partners of 19 index subjects with TV only, 11% had CT, 5% had GC, and 37% had TV. Conclusion: In our clinic population, a substantial number of partners had infections different from or in addition to those infections in the index. Many of these infected partners would not be diagnosed and treated using PDPT. Partners of index attendees without detected infection were at high risk (26%) for STI, mostly CT.

Maximum tumor diameter is an independent predictor of prostate-specific antigen recurrence in prostate cancer

Maximum tumor diameter has been shown to correlate with multiple predictors of clinical outcome in prostate cancer. In the current study, we prospectively analyze whether maximum tumor diameter is a significant predictor of prostate-specific antigen (PSA) recurrence. The study population consisted of 364 patients who underwent radical prostatectomy for prostate cancer. Prostatectomy specimens were evaluated by whole-mount processing of the entire prostate. Maximum tumor diameter was measured from the whole-mount sections of the prostate. Spearmans coefficient of rank correlation was used to correlate tumor diameter with continuous variables. T-tests or analysis of variance (ANOVA) tests were performed to determine if tumor diameter was significantly associated with other clinical and pathologic variables. The effect of clinical and pathologic variables on time to recurrence was analyzed using Cox regression. The mean tumor diameter for all patients was 1.73 cm (range, 0.02–4.40 cm). Maximum tumor diameter was associated with preoperative PSA (r=0.22, P<0.0001), prostate weight (r=−0.12, P=0.028), tumor volume (r=0.87, P<0.0001), Gleason score (r=0.29, P<0.0001), and pathologic stage (P<0.0001). Cox multiple regression was performed to test the prognostic value of maximum tumor diameter adjusting for pathologic stage, Gleason score, and surgical margin status. Increased maximum tumor diameter was associated with shorter time to PSA recurrence (hazard ratio=1.70, 95% confidence interval 1.13–2.56, P=0.01), controlling for risk factors, Gleason score, and surgical margin status. We conclude that maximum tumor diameter is a significant predictor of biochemical recurrence in patients with prostate cancer.

The influence of extent of surgical margin positivity on prostate specific antigen recurrence

Background: Positive surgical margins are an adverse prognostic factor in patients undergoing prostatectomy for prostate cancer. The extent of margin positivity varies and its influence on clinical outcome is uncertain. Aims: To evaluate the linear extent of margin positivity and the number and location of positive sites as prognostic indicators in a series of prostatectomy specimens evaluated with the whole mount technique. Methods: Eighty six consecutive margin positive prostatectomy specimens were evaluated, and all pathology data were collected prospectively. The linear extent of margin positivity was measured with an ocular micrometer and the total extent of all positive sites was summed. The total number of sites with positive margins and anatomical sites of the positive margins were analysed. Results: The linear extent of margin positivity ranged from 0.01 to 68 mm (mean, 6.8; median, 3.0) and was associated with prostate specific antigen (PSA) recurrence in univariate logistic regression (p = 0.031). In addition, the extent of margin positivity weakly correlated with preoperative PSA (p = 0.017) and tumour volume (p = 0.013), but not with age, prostate weight, Gleason score, pathological stage, or perineural invasion. The total number of positive sites was significantly higher in patients with PSA recurrence (p = 0.037). The location of the positive margin site was not associated with PSA recurrence. The extent of margin positivity correlated with PSA recurrence in univariate analysis, although it had only marginal predictive value when adjusted for Gleason score (p = 0.076). Conclusions: The extent of margin positivity correlates with PSA recurrence in univariate analysis, although it has no predictive value independent of Gleason score.

Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders

Spleen is a common site of extramedullary hematopoiesis. Extramedullary hematopoiesis seen in non-neoplastic conditions can occasionally be extensive and raise concerns for a myeloid neoplasm. We compared the morphologic and immunohistochemical features of splenic hematopoietic proliferations seen in neoplastic myeloid disorders (eg chronic myeloproliferative disorders, myelodysplastic/myeloproliferative disorders and acute myeloid leukemias) to extramedullary hematopoiesis seen in a variety of reactive conditions. In all, 80 spleen specimens were reviewed. The presence of each marrow-derived lineage, dysplasia and immunohistochemical results were evaluated (CD34, CD117, myeloperoxidase, CD68, p53, TdT, CD42b and hemoglobin). Neoplastic hematopoietic proliferations in chronic myeloproliferative disorders are characterized by trilineage hematopoiesis with significant dysplasia in all cell lineages. Acute myeloid leukemia showed an increase in immature forms, which were highlighted by immunohistochemistry. Reactive extramedullary hematopoiesis showed variability in histologic features. Post-bone marrow transplant and thrombotic thrombocytopenic purpura/hemolytic–uremic syndrome spleens showed extramedullary hematopoiesis with some morphologic features of immaturity, which could simulate chronic myeloproliferative disorder. However, they lacked characteristic immunohistochemical features of neoplastic myeloid disorders such as positivity for CD34 or CD117.