Nirit Yarom

Neoadjuvant Chemohormonal Therapy in Poor-Prognosis Localized Prostate Cancer

OBJECTIVES To conduct a trial of neoadjuvant chemohormonal therapy and radical prostatectomy for patients with poor-prognosis localized prostate cancer (prostate-specific antigen [PSA] value 20 ng/mL or greater, Gleason score 8 or higher, and clinical stage T2c or greater), who are at high risk for local and systemic relapse. METHODS Complete androgen blockage and four cycles of docetaxel (70 mg/m2) on day 2 and estramustine (280 mg three times daily) on days 1 to 5 every 21 days were given to 22 patients before radical prostatectomy and nerve preservation. RESULTS Patient characteristics, as median (range), were as follows: age 61 (49 to 70) years, PSA value 21.2 (3.2 to 71.6) ng/mL, and Gleason sum 7 (6 to 9). Clinical stage was T3a-c in 14 patients (64%), T2c in 4 (18%), T2b in 3 (14%), and T1c in 1 (4%). Presurgery characteristics after chemohormonal therapy were as follows: PSA value 0.21 (0.05 to 0.6) ng/mL, clinical stage T1c in 14 patients (63.7%), T2a in 6 (27.3%), and T3a in 2 (9%). The pathologic specimens revealed viable disease in all patients, organ-confined disease in 14 (63.6%), specimen-confined disease in 16 (72.7%), seminal vesicle disease in 9 (40.9%), and lymph node involvement in 4 (18.1%). To date, at a median follow-up of 23.6 (12.1 to 54.7) months, 10 patients (45.4%) relapsed, with PSA doubling time of 1.5 (0.4 to 34.3) months. Of the relapsed patients, 8 (89%) had organ/specimen involvement. CONCLUSIONS The neoadjuvant chemohormonal approach with nerve-preservation surgery is feasible in patients with poor-prognosis localized prostate cancer. It leads to clinical tumor downstaging. The pattern of relapse suggests that local therapy, with radiotherapy for patients with surgical or capsular involvement, and additional systemic therapy should be integrated.

A similar cell-specific pattern of HOXA methylation in normal and in cancer tissues.

HOX genes are developmental genes that determine anterior–posterior embryonic pattern and govern the process of differentiation. Inappropriate expression of HOX genes has been implicated in developmental abnormalities and hematopoietic malignancies. In addition, HOX genes silencing by DNA methylation has been reported in cancers and related to disease aggressiveness and outcome. On the other hand, accumulating evidence suggests that epigenetic changes at HOX genes are linked to normal development and differentiation. To better understand the relationship between HOXA methylation and cancer, we analyzed the methylation pattern of HOXA genes in human primary breast and colon carcinomas, normal tissues and normal white blood cells. Genome-wide methylation arrays of breast cancers and white blood cells demonstrated similar methylation patterns. Quantitative methylation analysis of seven representative HOXA genes revealed various levels of methylation in both normal tissues and cancers. Analysis of epithelial-enriched normal breast tissue and stroma indicated that the stroma was the major origin of HOXA methylation. Furthermore, in selected dense breast cancers, minimal increase in methylation of several HOXA genes did not correlate with the predominance of malignant epithelial cells in these tumors. Our results suggest that methylation of the HOXA cluster may be a normal developmental and cell type specific process rather than a cancer specific mechanism.

A comparative study on two different pathological methods to retrieve lymph nodes following gastrectomy

BACKGROUND The number of lymph nodes harvested during gastrectomy depends on the extension of lymphadenectomy and the method of lymph node retrieval. AIM The objective of this study was to evaluate two methods of lymph node retrieval in specimens of gastric cancer. METHODS The number of lymph nodes was compared using two different techniques. The technique used in the first group was manual dissection following formalin fixation, and the techniques used in the second group was fat-clearing by acetone. RESULTS Both groups were comparable for demographic and pathological variables. The average number of harvested nodes was 19.3 ± 10 for the manual group as compared to 26.1 ± 14 in the acetone group (P = 0.003). The differences in the average number of positive nodes did not reach statistical significance (4.6 compared to 6.9 nodes). CONCLUSION The acetone clearing technique enables the evaluation of a larger number of nodes. An increase, but statistically non significant, number of positive nodes was noted in the acetone group.

Progression after docetaxel-based chemotherapy in androgen-independent prostate cancer

To assess the clinical pattern of progression and prostate‐specific antigen doubling time (PSA‐DT) after exposure to docetaxel‐based chemotherapy in patients with androgen‐independent prostate cancer (AIPC).