Biomedical subjects
Publications and source records attributed to N F Hacker.
Significant changes have occurred over the past two decades in the management of vulvar cancer. The most important changes have been the individualization of care for all patients, and the introduction of a multidisciplinary team approach. Radiation has been progressively incorporated into treatment protocols, and more recently chemoradiation has been investigated.
OBJECTIVE: To study whether interleukin-6 (IL-6) changes the expression of the anti-apoptic Bcl-2 protein in the prevention of cis-diaminedichloroplatinum (II) (CDDP)-induced apoptosis of human ovarian cancer cells. METHODS: Comparative studies were performed on 3 ovarian cancer cell lines after 48 hours of exposure to 0.5-50 ng/ml IL-6, 2 micrograms/ml anti-IL-6 monoclonal antibody (anti-IL-6 mAb), 10 microM CDDP, 10 microM CDDP + 0.5-50 ng/ml IL-6, and 10 microM CDDP + 2 micrograms/ml anti-IL-6 mAb. Apoptosis was measured morphologically and by a DNA fragmentation assay. Bcl-2 protein levels were measured by an ELISA. RESULTS: An increase in apoptosis was observed for each cell line after 48 hours of exposure to 10 microM CDDP. Although high doses of IL-6 decreased the percentage of apoptotic cells, this cytokine did not change the expression of the Bcl-2 protein. CONCLUSION: CDDP-induced apoptosis was negatively controlled by IL-6. However, the anti-apoptic Bcl-2 protein level was not changed by IL-6 in the process of apoptosis in the ovarian cancer cell lines.
Uterine papillary serous carcinoma (UPSC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and poor prognosis. We investigated 23 cases of UPSC. p53 expression was studied in archival paraffin-embedded tissue by immunohistochemistry. Eleven tumors (47.8%) showed p53 overexpression whereas 12 tumors (52.2%) were p53 negative. One of 8 stage I/II (12.5%) and 10/15 stage III/IV (66.6%) tumors revealed p53 staining (P = 0.027). The median overall survival was 43.3 months. Patients with advanced-stage (III, IV) disease had a 5-year overall survival probability (5-year OS%) of 24% compared to 100% in those in stages I and II (log-rank, P = 0.018). Myometrial invasion, lymphatic space invasion, or lymph node involvement did not correlate with the 5-year OS of these patients. Patients whose tumors overexpressed p53 had a significantly shorter survival than those whose tumors did not (P = 0.033). This study confirms the influence of p53 overexpression on survival in UPSC patients.
BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an uncommon, aggressive type of endometrial cancer associated with an advanced stage at initial presentation, rapid progression of disease, and poor prognosis. METHODS: Twenty-three patients with UPSC were included in this study. History, treatment, follow-up, and 5-year overall survival probability (5-yr OS%) were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingo-oophorectomy. Positive lymph nodes were found in 10 of 17 patients who underwent pelvic lymphadenectomy. Eight patients had FIGO Stage I/II, whereas 15 patients showed Stage III or IV tumors. After surgery 5 women underwent radiotherapy, 5 chemotherapy, and 8 both radiotherapy and chemotherapy. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. Adjuvant irradiation consisted of vault and external beam irradiation. The median duration of follow-up was 39.4 months (25th and 75th percentiles; 26. 1, 68.1). The median overall survival was 43.3 months (12.9, 75th percentile not reached). Three of 10 patients who received only chemotherapy or radiotherapy are alive, whereas 7/8 patients who received a combination of both are alive with no evidence of disease at the time of reporting. The 5-yr OS% was 80% in those who received radio- and chemotherapy and only 30% in those who were treated with radiotherapy alone (log rank = 0.05). CONCLUSION: These results stress the need to study and evaluate the usefulness of combined chemo- and radiation therapy in patients with uterine serous papillary cancer.
This report describes the classification, clinical profile, etiology, and management of high-grade squamous vulvar intraepithelial-neoplasia (VIN). Recent studies have better defined the progressive potential of high-grade VIN and the relationship of such lesions to squamous vulvar carcinoma. The histologic classification and descriptions have undergone significant refinement over the past decade. The increasing use of more conservative therapeutic approaches to high-grade VIN has demanded greater expertise in clinical evaluation to ensure invasive disease is not missed or undertreated.
In recent years, vulvar cancer management has been revolutionised with a more conservative approach being recommended for the primary lesion, and a more rational approach to the management of the lymph nodes. Treatment has become individualised with consideration being given independently to the optimal approach for the primary lesion and regional lymph nodes. The primary vulvar lesion can be effectively treated by radical local excision, thereby sparing the psychosexual consequences of radical vulvectomy in most patients. Local recurrence occurs in up to 10% cases whether or not radical vulvectomy has been performed, and can usually be effectively treated by further surgery and/or radiation. By contrast, recurrence in the groin is usually fatal, so any patient with a T1 lesion and more than 1 mm stromal invasion should have at least an ipsilateral inguinal-femoral lymphadenectomy performed. Postoperative groin and pelvic radiation should be given for patients with 3 or more micrometastases in lymph nodes, one macrometastasis (> or = 10 mm diameter), or any evidence of extracapsular nodal spread. The future role of lymphatic mapping to decrease the morbidity associated with complete inguinal-femoral lymphadenectomy awaits further investigation.
BACKGROUND: Tumors of borderline malignancy are still a controversial subgroup of ovarian neoplasms. The expression of several cell regulatory proteins was studied to characterize the molecular phenotype of these tumors, and to compare them with their benign and malignant counterparts. METHODS: Specimens from 22 patients with tumors of borderline malignancy (11 serous and 11 mucinous tumors), 12 patients with benign tumors, and 16 patients with invasive ovarian carcinomas were evaluated for expression of epidermal growth factor receptor (EGFR), HER-2/neu, PTP1B, and p53 by immunohistochemical techniques. RESULTS: One or both of the tyrosine kinase growth factor receptors EGFR and HER-2/neu was expressed by 42% of benign, 59% of borderline, and 81% of malignant ovarian tumors. EGFR was expressed in a significantly greater fraction of malignant lesions (69%) than borderline lesions (18%) (P< 0.004). EGFR expression was not observed among the 11 mucinous borderline tumors. HER-2/neu was expressed by 50% of borderline tumors and was not a marker for malignancy. The tyrosine phosphatase PTP1B was expressed by a similar fraction of benign (17%), borderline (27%), and malignant (19%) tumors. The number of cases studied precluded correlation of kinase and phosphatase activity. However, among 12 tumors with PTP1B expression, 9 also expressed EGFR or HER-2/neu. Overexpression of p53 was observed only in malignant serous tumors and was not found in malignant mucinous, borderline, or benign lesions. CONCLUSIONS: Either EGFR or HER-2/neu was detected in a majority of borderline cancers. PTP1B was present only in a minority of these cancers. Frankly malignant serous lesions differed from borderline and benign tumors with regard to expression of EGFR and overexpression of p53.
Basic research in vulvar cancer results in new prognostic variables such as human papillomavirus DNA and epidermal growth factor receptor level. It also suggests that p53 mutants are involved in the pathogenesis of this disease. However, histopathological parameters of the lymph nodes, such as capsule breakthrough are the most significant prognosticators for patient survival.
BACKGROUND: Uterine papillary serous carcinoma (UPSC) is a histologic subtype of endometrial adenocarcinoma that is characterized by its papillary architecture, poor differentiation, and advanced stage at initial presentation. It behaves more aggressively than the more common endometrioid adenocarcinoma of the endometrium. METHODS: The history, treatment and follow-up of 18 women with UPSC were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingoophorectomy. Positive lymph nodes were found in 6 of 14 patients who underwent pelvic lymphadenectomy. Twelve of 18 women with UPSC had FIGO Stage III and IV tumors in contrast to 30 of 236 patients with endometrioid adenocarcinoma (P < 000.1). Subsequent treatment of these women was: radiotherapy, three women; chemotherapy, four, both radiotherapy and chemotherapy, eight. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. None of the patients with Stage I or II UPSC died of tumor during a mean follow-up of 31.6 months (range, 12-68 months). Of the women with Stage III and IV disease, 4 of 12 are alive with no evidence of disease after a mean follow-up of 22.5 months (range, 8-45 months). Eight of 12 women who received chemotherapy are alive with no evidence of disease, 4 of whom had Stage III or IV disease. One of six women who did not receive chemotherapy is alive, three died of tumor, and two of intercurrent disease. CONCLUSION: These results would justify further study of the possible role of platinum-based chemotherapy in patients with uterine papillary serous carcinoma.
Squamous cell cancer of the vulva diagnosed and surgically treated during pregnancy is a rare event. Only a few cases have been described until the present. We report two additional women with Stage II and III disease. The first patient, who had a 5 x 2-cm ulcerated lesion under the clitoris was treated by radical anterior vulvectomy and bilateral groin dissection when 22 weeks pregnant. She had an uneventful pregnancy, was delivered by cesarean section, and is free of disease 39 months after initial surgery. The second patient, who had multifocal lesions with a maximal depth of 1.9 mm of tumor invasion underwent modified radical vulvectomy with bilateral groin dissection when 17 weeks pregnant. Because of a grossly positive groin lymph node, she underwent radiation therapy after cesarean section. She is alive without invasive cancer 28 months after diagnosis. Early histological diagnosis and early treatment are mandatory in the management of suspicious vulvar lesions during pregnancy.
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We describe the case of a 24-year-old woman with a giant cell tumor originating from the distal part of the sacrum, which was almost completely filling the pelvis and extending to the umbilicus. At laparotomy, the tumor was separated from all of the pelvic structures including the ureters. The sigmoid colon was transected and the tumor was dissected down to the pelvic floor. A separate perineal incision was made, the rectovaginal septum was entered, and the posterior vaginal wall was bisected to give better access. It was possible to mobilize the tumor completely after dividing the rectum 5 cm from the anus. All macroscopic tumor was removed in continuity with the sigmoid colon. The ovaries were transposed to the paracolic gutter to avoid artificial menopause following radiation therapy. A sigmoid colostomy was formed. Because histology could not provide definite evidence of complete removal of the tumor, radiation therapy to the sacrum was given. Forty-two months after her surgery, the woman remains free of disease. The abdominoperineal approach should be considered for patients with a large tumor which is fixed to the sacrum.
OBJECTIVE: To evaluate the experience with endometrial carcinoma in women 45 years or younger at the Royal Hospital for Women, Sydney, Australia. METHODS: We evaluated the clinical history, morphology, treatment, and follow-up of 17 premenopausal women 45 years or younger who had been diagnosed with endometrial cancer. All histopathology was reviewed. RESULTS: Sixteen patients received their primary treatment at the Royal Hospital for Women, and one was referred with recurrent disease. Synchronous ovarian malignancies were found in five of 17 cases (29.4%), compared with 11 of 237 (4.6%) women older than 45 (P < .001). Three other patients had secondary ovarian involvement. Five (29%) patients had stage III or IV disease. Thirteen (76.5%) women were alive with no evidence of disease 12-78 months after primary surgery; two were lost to follow-up, but had no evidence of disease at 21 and 29 months, respectively. Two women died of recurrent disease. All but two patients with stage IV disease receiving primary treatment at the Royal Hospital for Women were offered hormone replacement therapy on discharge from the hospital. CONCLUSION: Ovarian and lymph node involvement were common in women 45 years and younger with endometrial cancer. Hormone replacement therapy did not appear to compromise survival.
Between January, 1991 and February, 1993 inclusive, 396 Papanicolaou smears were reported to show Mild Squamous Atypia with or without Human Papilloma Virus (MSA +/- HPV). All women with MSA +/- HPV smears were routinely recalled for colposcopy. To determine the significance of MSA +/- HPV on routine smear screening, the records of all patients were reviewed. Three hundred and thirty-seven women (85.1%) attended the colposcopy clinic and are the subjects analyzed for this report. The remaining 59 (14.9%) failed to attend. Intraepithelial neoplasia was found in 61 patients (18.1%), of whom 27 (8.0%) had a high grade lesion (CIN 2 or 3 or GIN 2). No patient had invasive cancer of the cervix. Only 1 of the 45 pregnant women had a significant lesion. It is concluded that all asymptomatic women with MSA +/- HPV on cervical smear may be managed in accordance with the current NH and MRC recommendations (1) and have a repeat smear in 6 months and colposcopy if the abnormality persists at 12 months.
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BACKGROUND: Developments in ultrasonographic technology have increased the possibilities of ovarian cyst aspiration. The risk of an extension of indications for ovarian cyst aspiration, however, is iatrogenic spread of malignant cells. METHODS: In this article, the diagnostic accuracy and therapeutic effectiveness of ovarian cyst aspiration are discussed, and the potential risk from different forms of tumor spill are considered. RESULTS: Two cases are presented in which a laparoscopic puncture and aspiration of a malignant ovarian cyst were performed. In both cases, there were diagnostic problems with the cytologic assessment. In one case, aspiration of an apparently benign cyst, based on ultrasonographic and laparoscopic findings, yielded cytologically negative fluid, but 8 weeks later an extensively disseminated ovarian carcinoma was found at laparotomy. It is postulated that the time interval between first tumor spill and eventual removal of the diseased ovary is the most important determinant of prognosis. CONCLUSIONS: The conclusion of these case reports is that aspiration of ovarian cysts, except for the purposes of oocyte retrieval, is potentially dangerous and should not be regarded as routinely acceptable clinical practice.
There is a definite trend toward vulvar conservation and individualized management of patients with early vulvar cancer. This approach initially was used only for patients with T1 disease, but with increasing experience with conservative surgery and the integration of postoperative adjuvant radiation when appropriate, some investigators have broadened the indications to include carefully selected patients with T2 lesions. A recent literature review suggests that the local invasive recurrence rate for T1 disease is 7.2% (12 of 165) after radical local excision compared with 6.3% (23 of 365) after radical vulvectomy (P = 0.85). Surgical margins must be at least 1 cm, and the rest of the vulva must be healthy if an increased local recurrence rate is to be avoided. Local recurrences usually can be treated successfully if diagnosed early, but recurrence in the groin is usually fatal. Inguinal-femoral lymphadenectomy should be done on all patients if the primary tumor is more than 2 cm in diameter and in patients with T1 disease in whom the depth of invasion is greater than 1 mm. Separate groin incisions may be used, but pelvic and groin irradiation should be given if there is at least one large node replaced with tumor or multiple nodes containing micrometastases. Careful patient selection is critical if modified operations are used, or an increased rate of recurrence will follow.
BACKGROUND: The evolution of the management of advanced ovarian carcinoma over the last fifteen years has resulted from a number of well-designed randomized trials involving large numbers of patients. MATERIALS AND METHODS: A critical review of long-term follow-up of patients entered onto eleven major randomized trials of advanced ovarian carcinoma has been performed. RESULTS: In the pre-platinum era no long-term survival benefit was obtained with combination compared with single agent chemotherapy. When adding cisplatin to front-line therapy at least a short-term gain in terms of superior response rate and progression-free intervals is obtained compared with non-cisplatin combination chemotherapy. Survival data are more difficult to assess due to the use of cisplatin-containing salvage therapy. Cisplatin-based combination therapy also offers enhanced patient benefit when compared with cisplatin alone. A slight advantage favouring anthracycline-containing therapy is observed, whereas no advantage is obtained with alternating cisplatin and non-cisplatin regimens or by adding BCG. CONCLUSIONS: Platinum-based combination chemotherapy is clearly associated with improved response rates and progression-free survival and, at least in some studies, better overall survival. At least six cycles of therapy should be given. Such approaches should yield long-term survival rates of 10% or better for patients with large-volume disease and 20% or better for small-volume disease.