Francesco Battaglia

Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival

Between January 1986 and September 1988, 75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB–III) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM). Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR). Pretreatment characteristics were analyzed for response to NAC. Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall. None of the biological parameters studied was related to chemoresponsiveness. Patients achieving CR or PR had a significantly improved 3‐year survival rate compared with those who did not respond. After NAC, radical surgery was possible in all responding patients. The median number of lymph nodes removed was 60. A lower than expected incidence of lymph node metastases was detected. None of the clinical and pathologic features considered was significantly correlated with the lymph node status. Twelve of the 62 operated patients had disease recurrence. Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence. A 3‐year, disease‐free survival of 89%, 73%, and 43% for Stage IB–IIA, IIB, and III, respectively, was found. Among the operated patients these rates increased to 100%, 81%, and 66% for Stage IB–IIA, IIB, and III, respectively. A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress.

Epidermal growth factor receptor in human breast cancer: correlation with steroid hormone receptors and axillary lymph node involvement

Epidermal growth factor (EGF-R) estrogen (ER) and progesterone (PR) receptors were evaluated in 89 primary breast cancers and 23 axillary lymph node metastases. About 57% of primary and 72.2% of metastatic tumors were EGF-R positive and median EGF-R levels were higher in metastatic deposits than in primary breast tumors (P less than 0.05). An inverse distribution of EGF-R and steroid hormone receptor positive tumors was found (chi 2 = 10.87; P less than 0.001 for PR and chi 2 = 5.01; P less than 0.05 for ER) and an interesting correlation between EGF-R expression in primary tumor and axillary lymph node involvement was demonstrated (chi 2 = 21.4; P less than 0.001). Immunohistochemical studies with a monoclonal antibody against EGF-R revealed the presence of EGF-R only in malignant cells. Our data suggest that EGF-R could identify a class of more aggressive breast tumors endowed with a higher metastatic potential and may therefore represent an unfavorable prognostic parameter in breast cancer.

Epidermal growth factor receptor expression in gynecological malignancies

Epidermal growth factor receptor (IEGF-R) levels were analyzed in 72 gynecological tumor specimens. Measurable EGR-R levels were found in a significant percentage of ovarian and uterine tumors. Moreover, all vulvar epidermoid carcinomas and uterine sarcomas analyzed were EGF-R positive. In all tumor types examined, scattered EGF-R levels were observed. Higher EGF-R levels were found in metastatic than in primary ovarian tumors. Moreover, EGF-R were found to be more expressed in less differentiated than in well-moderately differentiated endometrial tumors. Our results suggest a role of EGF or EGF-like substances in regulating the growth of gynecological malignancies, and indicate EGF-R expression as a possible prognostic factor.

Receptors for Epidermal Growth Factor and Steroid Hormones in Human Breast Cancer

Epidermal growth factor (EGF) seems to play an important role in regulating the proliferation of human breast cancer. Fifty-five primary breast tumors and 7 lymph node metastases were simultaneously assayed for the presence of EGF receptors (EGFR), estrogen receptors (ER), and progesterone receptors (PR). Overall, 42% (23/55) of the tumors were EGFR positive. EGFR were more frequently present in ER- and PR-negative than in ER- and PR-positive tumors. In particular, a negative correlation between EGFR and PR (chi 2 = 6.8; p greater than 0.01) was observed. All metastatic tumors were EGFR negative, and in all cases but 1 the levels of EGFR were higher in metastatic than in primary tumors. Our results suggest the presence of a subclass of breast tumors, the growth of which is primarily regulated by EGF or EGF-like substances rather than by steroid hormones. In this group, not amenable to endocrine therapy, EGF receptors should represent a target for therapeutic intervention.

Oral condyloma lesions in patients with extensive genital human papillomavirus infection

OBJECTIVES The incidence, location, and morphologic appearances of human papillomavirus oral lesions in patients with genital condylomatosis were investigated with clinical, colposcopic, and histologic examination as diagnostic procedures. The human papillomavirus types were also evaluated with filter in situ hybridization. STUDY DESIGN One hundred one patients, 66 female and 35 male, with genital condyloma underwent an oral cavity examination. Ninety-nine (99%) practiced orogenital sex, and all were asymptomatic for oral lesions. RESULTS Ninety-one underwent biopsy; histologic studies gave a diagnosis of condyloma in 48% of 101 specimens collected. In 8 of 91 (9%) oral lesions were suspected by naked-eye examination; they were confirmed histologically in all eight. Of 83 patients suspected of having oral condyloma on colposcopic examination, 38 (46%) were confirmed histologically. Thus 38 of 46 patients (83%) had oral condyloma not visible to the naked eye. Colposcopically, oral lesions appeared filiform (50%), moruloid (26%), and mixed (24%). Twenty cytologic oral samples were also collected for deoxyribonucleic filter in situ hybridization analysis. Human papillomavirus deoxyribonucleic genital types were observed in 45% (9/20) of all oral scrapings collected, and all were histologically confirmed. CONCLUSION Our data indicate that genital human papillomavirus types are capable of establishing a local infection in the oral cavity and demonstrate a high incidence of human papillomavirus oral lesions in patients with genital condyloma.

Bilateral ovarian pregnancy after intrauterine insemination and controlled ovarian stimulation.

OBJECTIVE To report a case of bilateral ovarian pregnancy in a young patient who had previously undergone intrauterine insemination (IUI) and controlled ovarian stimulation (COS). DESIGN Case report. SETTING University hospital. PATIENT(S) A 34-year-old woman who had previously undergone IUI and COS. INTERVENTION(S) Emergency exploratory laparotomy for circulatory collapse. About 350 mL of bloody fluid was collected in the pelvic cavity. The left ovary was about 6 cm in diameter and was completely involved by a darkish hemorrhagic ovarian mass; the right ovary was involved by a 4-cm mass. A left ovariectomy and a partial resection of the right ovary with preservation of two-thirds of ovarian tissue was performed. MAIN OUTCOME MEASURE(S) IUI and COS outcome. RESULT(S) The pathologic diagnosis was considered, and bilateral ovarian pregnancy was confirmed according to the diagnostic criteria described by Spiegelberg. CONCLUSION(S) Diagnosis of primary ovarian pregnancy is very difficult because of its rarity and asymptomatic state before rupture. However, early diagnosis is fundamental to avoid more serious complications and an emergency invasive procedure.

Steroid hormone receptors in carcinoma of the cervix: Lack of response to an antiestrogen

Levels of estrogen (ER) and progesterone (PR) receptors were measured in 81 patients with primary cervical cancer. In 10 patients, receptor levels were evaluated before and after a short course of tamoxifen treatment. Fifty-six percent of cervical tumors contained ER, and 58%, PR. Receptor level and expression were not related to any clinical and histological characteristic. Moreover, both survival time and response to neoadjuvant chemotherapy did not correlate with the presence of ER and PR. Tamoxifen treatment did not influence ER and PR levels. Our results suggest that steroid hormone receptors are of little value in the management of cervical cancer, and that in this neoplasia, ER is probably not functional.

IMMUNOSUPPRESSIVE ACIDIC PROTEIN AND CA 125 LEVELS IN PATIENTS WITH OVARIAN CANCER

The serum levels of immunosuppressive acid protein (IAP) and CA 125 were determined in 98 patients with ovarian cancer, in 20 patients with benign ovarian tumors and in a group of normal postmenopausal women as controls. On the basis of the mean values of normal controls (346.46 +/- 133.26 micrograms/ml), the IAP threshold was fixed at 613 micrograms/ml. Increased IAP levels were found in 70.4% of patients with ovarian cancer, in 25% of benign tumors and in 4.5% of normal women. Elevated levels of CA 125 were observed in 66.6% of cancers, in 40% of benign tumors and in 6.9% of controls. In particular, in early stage ovarian cancer the combined assay of the two markers increased by about 30% with respect to CA 125 alone. The simultaneous determination of IAP and CA 125 allowed an overall sensitivity of 84% without any significant reduction of specificity.

Feasibility and Safety of Vaginal Myomectomy: A Prospective Pilot Study

STUDY OBJECTIVE Classic myomectomy was performed via laparotomy. More recently, laparoscopic myomectomy has become a valuable treatment option. Vaginal myomectomy is a surgical procedure that has recently been evaluated. However, few trials have been reported in past literature. The aim of this study was to evaluate feasibility and complication rate of patients submitted to vaginal myomectomy. DESIGN Prospective study with review of literature (Canadian Task Force classification II-2). SETTING Department of Obstetrics and Gynecology, S. Filippo Neri Hospital of Rome, Italy. PATIENTS Consecutive patients with symptomatic myomas who refused hysterectomy. INTERVENTIONS After preoperative assessment, patients were submitted to vaginal myomectomy using posterior colpotomy. MEASUREMENTS AND MAIN RESULTS Operative time, perioperative complications, and hospital stay were prospectively recorded. Follow-up examinations were performed at 1 and 12 months postoperatively. Data on possible symptoms, fertility, and pregnancy outcome during follow-up periods were recorded. Myomectomy was completed vaginally in 17 (94%) of 18 patients. Mean operating time was 48 +/- 22 minutes; mean operative blood loss and hospital stay were 210 +/- 350 mL and 3.5 +/- 2.4 days, respectively. Only 2 (11%) patients required blood transfusion. Three patients have conceived spontaneously. CONCLUSION Vaginal myomectomy is a feasible and safe surgical procedure, with low morbidity and short hospital stay, and could represent a valid alternative to open or laparoscopic myomectomy in selected cases.

Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer.

The immunohistochemical expression of HER-2/neu and cytofluorimetric data were retrospectively analyzed in a group of primary advanced ovarian cancers. Thirty-three out of 94 (35%) cases showed a specific p185/neu immunoreaction. No correlation between p185/neu expression and any of the clinico-pathologic parameters examined was observed. As far as cytofluorimetric data are concerned, 38 out of 69 (55%) of the tumors were diploid (DNA index = 1) while 31 (45%) were aneuploid (DNA index from 1.10 to 2.50 with a median value of 1.50). Ovarian tumors were defined as of low and high S-phase fraction in 68% and 32% of the cases, respectively. Tumor ploidy and S-phase fraction did not correlate with the clinico-pathologic characteristics or p185/neu oncoprotein expression. Aneuploid tumors had a higher S-phase fraction (mean: 15.81 ± 13.44) than diploid tumors (mean: 8.89 ± 7.98) (P < 0.01). p185/neu expression failed to affect significantly both overall and progression free survival. On the other hand tumor ploidy was found to be related to the prognosis of advanced ovarian cancer patients although the difference was not statistically significant. As far as progression free survival is concerned, the median time to recurrence was not reached for diploid cases whereas it was 21 months for aneuploid cases (P < 0.05). The 5-year survival for patients with a low S-phase fraction (58%) was significantly higher than for patients with high S-phase fraction tumors (28%) (P < 0.01). Median time to recurrence was 48 and 17 months for low and high S-phase fraction tumor patients, respectively (P < 0.05). However, in a multivariate analysis both tumor ploidy and S-phase fraction did not retain their prognostic value. The assessment of the role of the parameters examined in improving the prognostic characterization of ovarian cancer patients should be investigated in large multicenter clinical trials.