Early cervical carcinoma: the natural history of lymph node involvement redefined on the basis of thorough parametrectomy and giant section study.

BACKGROUND: Although parametrectomy is the most difficult step in the surgical treatment of cervical carcinoma and is the main cause of postoperative complications, little attention has been given to the patterns of parametrial spread. METHODS: Sixty-nine patients with previously untreated cervical carcinoma (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage IB1, 49 patients [71%]; Stage IB2, 8 patients [12%]; and Stage IIA, 12 patients [17%]; squamous, 59 patients [86%]; and adenocarcinoma, 10 patients [14%]) underwent radical hysterectomy and pelvic +/- aortic lymphadenectomy. Hysterectomy specimens were processed with the giant section technique. To obtain a thorough three-dimensional assessment of the paracervical tissue, both the superficial and deep layers of the cervicovesical ligament (anterior parametrium) and the uterosacral ligament (posterior parametrium) were separated from the uterus and submitted for pathologic evaluation. After resection of the lateral parametrium with hemoclips, the lympho-fatty tissue remaining around the pudendal vessels was removed carefully and referred to as "the distal part of the lateral parametrium." RESULTS: When analyzing all the parametria, lymph nodes were present in 64 patients (93%). Clinically undetected parametrial involvement was found by pathologic examination in 15 Stage IB1 patients (31%), 5 Stage IB2 patients (63%), and 7 Stage IIA patients (58%). Metastases were found in the cardinal, cervicovesical, and sacrouterine ligaments and principally were comprised of lymph node and vascular space invasion. Twenty-five patients (36%) had pelvic lymph node metastases whereas concomitant parametrial involvement was observed in all patients. The overall 5-year survival was 91%, being higher for parametria and lymph node negative patients (100%) than for those with lymph node and/or parametrial metastases (78%). CONCLUSIONS: A three-dimensional pathologic assessment showed that subclinical parametrial spreading of the so-called "early" tumors (Stage IB-IIA) occurred in approximately 30-60% of these patients, and metastasis to the pelvic lymph nodes always was associated with parametrial disease. A better understanding of the patterns of parametrial diffusion will improve knowledge of the natural history of cervical carcinoma and in the future may influence the treatment of these patients. Furthermore, pathologic assessment of cervical carcinoma should be modified to evaluate correctly the parametrial status of each patient. The current routine pathologic evaluation of the parametria makes it very difficult to detect lymph node metastases and tumor emboli.

Lymphatic spread of cervical cancer: an anatomical and pathological study based on 225 radical hysterectomies with systematic pelvic and aortic lymphadenectomy.

To assess the patterns of lymphatic spread in cervical carcinoma, radical hysterectomy with systematic lymphadenectomy was performed in 66 patients FIGO stage IB-IIA <4 cm, and 159 patients stage IB-IIA >4 cm to stage IV. The latter patients were treated with neoadjuvant chemotherapy (NACT). Parametria were evaluated by the giant section technique in 109 patients. In 40 of these, the superficial and deep layers of the vesicouterine ligament, the sacrouterine ligament, and the distal part of the cardinal ligament were separately evaluated. The median number of nodes removed was 48 pelvic (range 20-107) and 22 aortic (range 7-64). Positive nodes were found in 14 (21%) stage IB-IIA <4 cm and in 38 (23%) NACT-treated patients, all having pelvic node metastasis. Aortic nodes were involved in 2 (3%) and 5 (3%) patients, respectively. Solitary metastases were found in the superficial obturator (21% of stage IB-IIA <4 cm and 31% of NACT-treated positive node patients, respectively), external iliac (7 and 3%, respectively), and common iliac nodes (7 and 3%, respectively). Parametrial nodes were found in 59% of giant sections (8% metastatic). The superficial and deep layers of the vesicouterine ligament, the uterosacral ligament, and the distal part of the lateral parametrium revealed the presence of nodes in 33% (no metastatic nodes), 26% (3% metastatic), 5% (no metastatic nodes), and 70% (5% metastatic) of patients, respectively. Overall, parametrial nodes were positive in 12% of stage IB-IIA <4 cm and 7% of NACT-treated patients. The diameter of node metastasis was <10 mm in more than 80% of positive nodes. In conclusion, parametrial nodes were mainly located in the cardinal and vesicouterine ligaments, both being a potential site of metastasis. The superficial obturator, external iliac, common iliac, paracaval, intercavoaortic, and paraaortic nodes were the groups more frequently involved. These data may be useful for tailoring radical hysterectomy and lymphadenectomy according to the primary tumor and the surgeon's intent.

Effect of recombinant human interferon-alpha/2b on epidermal-growth-factor-, estrogen- and progesterone-receptor expression in primary cervical cancer.

The effects of a short period of in vivo systemic rh-IFN-alpha/2b treatment on epidermal-growth-factor(EGFR)-, estrogen(ER)- and progesterone(PR)-receptor content in 11 primary human cervical tumors was investigated by the radioreceptorial technique. EGFR levels were found to be significantly higher in cervical tumors after rh-IFN-alpha/2b treatment with respect to basal levels. In 2 cases, immunohistochemical and cytofluorimetric analysis showed that rh-IFN-alpha/2b treatment induces an increase in EGFR immunoreactivity and in the fraction of EGFR-positive cells. No difference in ER and PR levels in cervical tumors before and after rh-IFN-alpha/2b treatment was observed. Our results suggest that rh-IFN-alpha/2b up-regulates EGFR in primary human cervical tumors in vivo.

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.

Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues: correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor.

OBJECTIVE: The aim of the study was to investigate the biologic significance of p21 expression in normal and neoplastic ovarian tissues. STUDY DESIGN: Western blotting analysis of p21/ras oncoprotein was conducted in a group of 14 normal and cystic ovaries, six benign tumors, 42 primary ovarian cancers, and 15 omental metastases. RESULTS: Levels of p21 were similar in normal and cystic ovaries and in benign tumors, whereas they were significantly higher in malignant tumors than in control tissues (median 1.91, range 0.12 to 5.00 vs median 1.03, range 0.32 to 2.20; p = 0.023) and in omental metastases than in primary ovarian carcinomas (median 3.05, range 0.55 to 5.72 vs median 1.97, range 0.12 to 5.00; p = 0.14). We found no correlation between p21 expression and histopathologic or clinical characteristics. Estrogen receptor-positive and progesterone receptor-positive tumors expressed higher p21 levels than did estrogen receptor-negative and progesterone receptor-negative tumors (p < 0.05), but no correlation with epidermal growth factor receptor status was found. In the univariate analysis of survival p21 positivity showed a negative prognostic value. CONCLUSION: The enhancement of p21 protein is associated in the ovarian tissue with the malignant phenotype and the acquisition of metastatic potential.

High-dose cisplatin and bleomycin neoadjuvant chemotherapy plus radical surgery in locally advanced cervical carcinoma: a preliminary report.

One course of chemotherapy containing cisplatin and bleomycin as a neoadjuvant treatment was given to 26 consecutive patients with previously untreated stage IB (bulky disease)-III cervical carcinoma and followed by radical surgery. After chemotherapy responses were detected in 23 patients (5 complete and 18 partial; overall, 88%) and permitted radical surgery in 21 cases (81%). Surgery consisted of type III-IV radical hysterectomy plus systematic para-aortic and pelvic lymphadenectomy. At histologic examination, complete responses were found in 5 (19%) and partial responses in 16 (62%) cases. The average number of lymph nodes removed was 61 (range, 38-118). A lower than expected incidence of lymph node metastases was detected (2/21, 9.5%). The chemotherapy-induced toxicity was mainly represented by nausea and vomiting. Chemotherapy did not seem to complicate surgery in these circumstances, even though moderate-degree postoperative complications occurred in 48% of cases. Eighteen months median follow-up time (range, 11-23) from hystological diagnosis has been reached in the operated patients, and no recurrences have been detected so far.

[Preoperative cytologic diagnosis of medullary carcinoma of the thyroid]. / La diagnosi citologica preoperatoria nel carcinoma midollare della tiroide.

The Authors emphasize the importance of preoperative aspiration cytology in the diagnosis of 5 medullary types out of 58 thyroid carcinomas observed in the Institute of Pathology of the Università Cattolica del S. Cuore of Rome in the period 1983-88. All the cases were diagnosed preoperatively by mean of a fine-needle aspiration cytological specimen; the case where morphological diagnosis was doubtful were studied with immunohistochemical techniques for calcitonin and CEA. Out of all cases, they report one case of multiple endocrine adenomatosis type II with medullary thyroid carcinoma and pheochromocytoma and another one with cervical node metastases without a clinically detectable thyroid swelling. Therefore, the authors propose the fine-needle aspiration cytology as a simple and important mean in the preoperative diagnostic procedure in case of medullary thyroid carcinoma.