Alessandro Bovicelli

Neoadjuvant Chemotherapy in Cervical Carcinoma Regulators of Cell Cycle, Apoptosis, and Proliferation as Determinants of Response to Therapy and Disease Outcome

To evaluate whether cellular markers predict the responsiveness to neoadjuvant chemotherapy (NAC) in cervical cancer, 21 patients with stages I and II cervical carcinomas treated by NAC before surgery were followed up for a mean of 52.3 months. Pre-NAC biopsy and operative specimens were subjected to counting of apoptotic (AI/V) and mitotic (MI/V) indices, detection of human papillomavirus (HPV) DNA, and immunohistochemical analysis of cell cycle and proliferation markers (p21, p53, pRb, proliferating cell nuclear antigen [PCNA], Ki-67) and multidrug resistance gene (MDR1), as related to NAC response (RAC), recurrence-free (RFS), and overall (OS) survival. Adenosquamous histology and lymph node involvement were significant determinants of nonsurvival. All carcinomas contained HPV DNA. In univariate analysis, p21, pRb, and MDRI in the biopsy specimen and PCNA, Ki-67, and pRb in the surgical sample significantly predicted RAC, while age, AI/V number of lymph nodes removed, and MI/V predicted RFS. Highly significant predictors of OS were AI/V number of lymph nodes removed, post-NAC MDR1 expression, MI/V and recurrence. Multivariate analysis confirmed the strong post-NAC effects of histologic type, AI/V, and MDR1 expression for RFS, and recurrence, age, and Ki-67 expression for OS. NAC responders with slightly decreased AI/V and increased MI/V had a poor prognosis.

Epithelial Ovarian Cancer: The Role of Cell Cycle Genes in the Different Histotypes

Cancer is frequently considered to be a disease of the cell cycle; alterations in different families of cell cycle regulators cooperate in tumor development. Molecular analysis of human tumors has shown that cell cycle regulators are frequently mutated in human neoplasms, which underscores how important the maintenance of cell cycle commitment is in the prevention of human cancer. The regulatory pathways controlling cell cycle phases include several oncogenes and tumor suppressor genes which display a range of abnormalities with potential usefulness as markers of evolution or treatment response in epithelial ovarian cancer. This review summarizes the current knowledge about these aberrations in malignant tumors of the ovary. We sought to focus our attention on the genes involved in the development of tumors arising from the ovarian epithelium, which are the most common types of ovarian malignancies.

Factors associated with cone margin involvement in CIN patients undergoing conization-equivalent electrosurgical procedure.

Background. Most studies of cervical conization have considered the frequency of complications and the outcome of follow‐up. The determinants of cone margin positivity have been inadequately described. In a series of CIN patients undergoing conization‐equivalent electrosurgical procedure, we evaluated the factors associated with (i) any cone margin involvement, and (ii) endocervical margin involvement (with or without other locations) as contrasted with all other conditions.

Decreased incidence of cervical Cancer in medicare-eligible California women

OBJECTIVE To determine if the incidence of invasive cervical cancer relative to carcinoma in situ decreased in Medicare‐eligible women. METHODS A retrospective cohort was amassed from the California Cancer Registry database. The hypothesis was prospectively specified. Mean ratio of invasive (International Federation of Gynecology and Obstetrics Stages I–IV) to in situ cervical carcinoma in 1988–1990 versus 1991–1995 was stratified by age (24 or younger, 25–44, 45–64, 65 or older) and race (all races, whites, blacks, Hispanics, Asian/Pacific Islanders). RESULTS The mean ratio of invasive to in situ cervical cancer incidence for women at least 65 years old was lower in 1991–1995 compared with 1988–1990 (P < .001, 95% confidence interval 0.893, 0.954); and had decreased more than observed for women aged 45–64 and 25–44, for all races combined, and for white women. The decreased ratio of invasive to in situ cancer for blacks, Hispanics, and Asian/Pacific Islanders at least 65 years old was no different than the decreased ratio in younger women. CONCLUSION In California, in the 5 years after the 1990 change in Medicare funding statutes for cervical cytology screening, the ratio of invasive cervical cancer to in situ disease decreased more in Medicare‐eligible patients than in younger women.

Amniotic Fluid Index and Labor Length of Pregnancies Induced Beyond 41 Weeks of Gestation with Unfavorable Cervix

We evaluated if the response to prostaglandin E2 (PGE2) induction, in pregnancies completing 41 gestational weeks, is correlated to amniotic fluid index (AFI) values. A follow-up was performed from the time of the induction to the time of delivery of 63 pregnancies resulting in a spontaneous delivery showing unfavorable cervical examination at 41 weeks of gestation. This was induced by means of intracervical administration of PGE2 gel (Dinoprostone 0.5 mg). If the cervix was still unfavorable after 12 h, another gel administration followed. The number of PGE2 administration and AFI were both used as variables to correlate the time remaining before the delivery and the probability of delivery (Kaplan-Meier and Cox algorithms). Gestational age, parity, neonatal weight, and APGAR 5′ were used as covariates. A cut-off of AFI >6 better discriminates two groups regarding the probability of delivery at paired hours from the beginning of the induction. A statistically significant difference was demonstrated in only those patients which did not deliver within 12 h (44 cases). Multivariate analysis (Cox regression) yielded an adjusted odds ratio associated to the probability of delivery of 0.47 (0.23–0.95, 95% CI, p value = 0.0354) for AFI≤6 vs. AFI >6.

Electrochemotherapy pre-treatment in primary squamous vulvar cancer. Our preliminary experience

Previous studies showed a local tumor control of 80% in patients with relapsed squamous cell vulvar cancer (V‐SCC) treated with electrochemotherapy. These results encouraged electrochemotherapy use as neo‐adjuvant treatment in V‐SCC. The objective of this study was to evaluate the effectiveness of electrochemotherapy in reducing tumor burden in V‐SCC.

The Cell Cycle and the Molecular Biology of Cancer

Human malignant tumors are characterized by abnormal proliferation resulting from alterations in cell-cycle regulatory mechanisms. The regulatory pathways controlling cell-cycle phases include several oncogenes and tumor suppressor genes, which display a range of abnormalities with potential usefulness as markers of evolution or treatment response in cancer. This chapter summarizes the current knowledge about these aberrations in malignant transformation.

The Holistic Approach to Female Cancer Patients

For years, the doctor has fundamentally been an autonomous professional figure. He took care of his patients, carried out diagnostic investigations, and did the autopsies hen the inevitable happened—a clinician and a pathologist practically united in one single person. Then, the growth of knowledge, which has taken place in recent years, has profoundly modified the structure of the medical class so that currently, the profession is characterized by the existence of numerous specialties and subspecialties. This has been followed by the creation of distinct professional figures, clinician on the one hand and pathologist on the other, which has contributed in large measure to the growth of knowledge in medicine, which has resulted in large benefits in contrast to some minor problems. In this regard, separating the fields of specialization has determined, in reality, separation of the culture and the language, creating a deep rift. Unfortunately, there are numerous realities, in which the clinician and the pathologist operate in different structures, and therefore, interact very little or not at all.