Duration and characteristics of treatment of premature lambs with natural surfactant.

Premature lambs were treated with 50 mg/kg of natural surfactant lipid by tracheal instillation either at birth or shortly thereafter when respiratory failure was documented. All lambs were delivered by cesarean section and supported on infant ventilators with 100% oxygen under conditions to mimic the care of human infants with the respiratory distress syndrome. The natural surfactant used for therapy was recovered by lavage from sheep lung. Six 120-d gestational age lambs treated at birth had an initial mean oxygen pressure (pO2) value of 270 +/- 35 mm Hg; this fell within 3 h to less than 100 mm Hg. By 8.3 +/- 0.3 h after birth the lambs were in severe respiratory failure with a mean pH less than 7.1 and a mean pCO2 greater than 70 mm Hg. Six untreated lambs had pH values below 7.0 within 40 min of life despite more intensive respiratory support than was given the treated animals. Treatment with natural surfactant of 17 lambs of 120 and 130 d gestational age after early respiratory failure resulted in a prompt increase in pO2 values from about 35 mm Hg to values over 200 mm Hg and a fall in pCO2 values to normal levels in the majority of animals. This response lasted only approximately 3 h, and a second treatment was less predictably effective.

Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix.

PURPOSE: Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent cancer of the cervix, and the combination of these two agents has shown activity and possible synergism in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent cervical cancer to evaluate its activity. PATIENTS AND METHODS: Thirty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m2 administered intravenously over a 3-hour period followed by cisplatin 75 mg/m2 administered intravenously with granulocyte colony-stimulating factor support. The chemotherapy was administered every 3 weeks for a maximum of six courses. RESULTS: Sixteen patients (47%; 95% confidence interval, 30% to 65%) achieved an objective response, including five complete responses and 11 partial responses. Responses occurred in 28% of patients with disease within the radiation field only and in 57% of patients with disease involving other sites. The median duration of response was 5.5 months, and the median times to progression and survival for all patients were 5 and 9 months, respectively. Grade 3 or 4 toxicities included anemia in 18% of patients and granulocytopenia in 15% of patients. Fifty-three percent of patients developed some degree of neurotoxicity; 21% of cases were grade 2 or worse. CONCLUSION: The combination of paclitaxel with cisplatin seems relatively well tolerated and moderately active in patients with metastatic or recurrent cervical cancer. The significant incidence of neurotoxicity is of concern, and alternative methods of administration of the two agents could be evaluated. Then, further study of this combination, alone or with the addition of other active agents, is warranted.

Ras gene activation in malignant cells of human ovarian carcinoma peritoneal fluids.

In this study, we showed, for the first time, the pattern of point mutations at codon 12 of the K-ras, H-ras and N-ras genes, using polymerase chain reaction and restriction fragment length polymorphism analysis in 47 malignant cytologic specimens of ovarian adenocarcinoma peritoneal fluids. Forty-seven % of the samples were found to carry a point mutation at codon 12 of K-ras gene. Also, 21 cystadenoma peritoneal fluids were used as control specimens for the detection of ras mutations. Fourteen % of these samples were found to carry a point mutation at codon 12 of the K-ras gene. The prevalence of K-ras gene mutations were statistically correlated with FIGO and surgical stage of the malignant specimens. Our data demonstrates that the K-ras gene mutations are mainly affected (47%) in the malignant cells of the peritoneal washings or ascites of women with ovarian adenocarcinomas and may have value for the early diagnosis and monitoring of these neoplasms.

Hpv detection in stained cytological cervical specimens and correlation with cytology and histology.

It has been suggested that detection of high risk human papillomavirus (HPV) in low grade cervical intraepithelial neoplasia contributes to transition to high grade lesions and cancer. Currently, the PAP smear is the primary screening tool to identify women with cervical disease, specifically cervical intraepithelial neoplasia (GIN). In the present study we examined the utility of HPV detection and typing by PCR, in women with cytological and/or histological evidence of low grade squamous lesion (LGSL), using stained PAP cervical smears. HPV infection was confirmed in 21 out of the 31 (68%) specimens examined.

Septic lithiasis of the pelvis.

Laparoscopic cholecystectomy has become a standard technique for the treatment of symptomatic cholelithiasis. Despite a significant reduction in the complication rate with increasing experience, bile duct injury and gallstone spillage still occur more frequently with this approach than with the open procedure. Unretrieved gallstones, in particular, have been associated with late infection and the formation of abscesses in virtually every area of the abdominal cavity. We present a rare case of an isolated pelvic abscess that developed in a postmenopausal woman 5 months after laparoscopic cholecystectomy for recurrent cholecystitis. The preoperative differential diagnosis of this case is also discussed.

Endometrial cancer in patients under 30 years of age. A report of two cases.

Two unusual cases of a 22- and a 28-year-old woman, respectively, who were found to have endometrial adenocarcinoma, are presented. The patients experienced abnormal vaginal bleeding and the diagnosis was made by dilatation and curettage. They declined treatment with progestagens, therefore, a total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy were performed in both cases. We emphasize the need of endometrial evaluation in young females with abnormal bleeding before starting any medical treatment. Specific problems of endometrial cancer at young age include delay in diagnosis, difficulty in pathologic interpretation of the curettings and the motivation of most patients to preserve their fertility.

Carcinoembryonic antigen (CEA) in normal and pre-eclamptic pregnancies (values in maternal blood, amniotic fluid and umbilical cord blood).

Values of carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 100 pregnant women divided into 4 groups. In group 1 (49 normal pregnancies) and 2 (17 pre-eclamptic pregnancies), the estimation of CEA was done in maternal vein blood, umbilical cord blood and in amniotic fluid. In group 3 (20 normal pregnancies) CEA was measured separately in blood of the two umbilical vessels as well as in maternal vein blood. In group 4 (14 pregnancies with small-for-date infants) CEA was estimated in umbilical cord blood. The values in amniotic fluid of normal and pre-eclamptic pregnancies were more than 20 times higher than in the other two compartments. A significant correlation was found between the amniotic fluid and umbilical cord blood values (r = 0.500; P < 0.05), as well as between the values in umbilical artery and vein (r = 0.792; P < 0.001). Thus, it is thought that CEA is transferred from the amniotic cavity to the umbilical cord while a part of CEA perhaps is produced by the placenta. Umbilical cord blood values of small-for-date fetuses do not differ significantly from the normal. On the contrary, significantly lower values were obtained in umbilical cord blood and in amniotic fluid of pre-eclamptic women as compared to the normal, but this finding is not useful clinically because of the large standard deviation.

Colposcopically directed biopsy findings in the young female.

STUDY OBJECTIVE: To evaluate the colposcopic findings of cervical alterations in the young sexually active female. DESIGN, SETTING, PARTICIPANTS: Colposcopic examination and follow-up of 51 young sexually active females aged 15-20 yr was conducted due to abnormal cytology or a suspicious abnormality of the cervix. The study was conducted at the Colposcopy Units of the 1(st) and 2(nd) Departments of Obstetrics and Gynecology, University of Athens, Greece. ONTERVENTIONS: Colposcopic examination, LEEP, conization. MEAN OUTCOME MEASURES: Biopsy, human papillomavirus (HPV) typing. RESULTS: Colposcopic examinations were within normal limits in 8 of 51 (15.7%) cases. Cervical alterations were related to HPV infection in 14 cases (27.4%), to cervical intraepithelial neoplasia (CIN) I in 15 (29.4%) cases, to CIN II in 13 (25.5%) cases, and to CIN III in 1 (2.0%) case. Of all CIN I cases, 8 of 15 (53.3%) were HPV positive, and HPV type 11, 16, 18, 31, 33, and 11& 16 were found. In CIN II cases, 5 of 13 (38.4%) were HPV positive, and HPV type 11, 16, 18, and 11 & 31 were found. In the CIN III case, only HPV type 16 was found. CONCLUSIONS: Our findings strongly confirm the necessity of obtaining cervicovaginal smears on all sexually active gynecologic and obstetric teenage patients. Colposcopy plays a major role in the evaluation of the cervix and in the treatment that should be given for any individual CIN lesion.

Conservative management of vaginal intraepithelial neoplasia (VAIN) by laser CO2.

Carbon Dioxide Laser ablation therapy was originally offered to 25 women with Vaginal Intraepithelial Neoplasia (VAIN). The disease was primary in 12 and secondary after a previous hysterectomy in 13 cases. Treatment was accomplished under local anesthesia in 22 cases and was well-tolerated by all patients. The age of the patients ranged from 19 to 68 with a mean age of 44 years. All women were followed-up by cytology and colposcopy within a time period of 35 to 82 months (mean 49 months). Eight patients relapsed resulting in a failure rate of 32%. A second Laser CO2 treatment was offered to these patients with a final cure rate of 84% (21/25). The four cases in which the disease reappeared, after the 2nd treatment, were managed by upper colpectomy (3 cases) and follow-up (1 case). Laser CO2 ablation is an acceptable treatment modality for VAIN considering the promising cure rates and the preservation of the anatomic integrity of the vagina. Close colposcopic follow-up of these patients is necessary for early detection of disease relapses.

Vulvar lichen sclerosus in postmenopausal women: a comparative study for treating advanced disease with clobetasol propionate 0.05%.

BACKGROUND AND OBJECTIVE: Clobetasol propionate 0.05% has been the mainstay in treating vulvar lichen sclerosus (VLS) for the past ten years. The usual length of therapy is two to 12 weeks. We conducted this study to evaluate the efficacy and safety of treating severe lesions of VLS in postmenopausal women for a longer time on a regular basis using clobetasol propionate. MATERIALS AND METHODS: From 1997-2000, 137 women with VLS were examined in the Colposcopy and Laser Surgery Unit of "Alexandra" Hospital. Patients who were premenopausal, had previous therapy, exhibited mild or moderate disease or showed VIN or invasive cancer on vulvar biopsies were excluded from the study. The remaining women were divided into two groups. The first group applied clobetasol propionate 0.05% for three months and afterwards on an "as required" basis, whereas the second group used the ointment for six months on a regular basis. All patients were examined at two, three, six and 12 months following treatment. Signs and symptoms before and after therapy as well as side-effects caused by the ointment were recorded. RESULTS: The mean age of the women was 60.2 years. Fifty-four patients were divided into two categories. In the 6-month follow-up, 59% of the 1st group and 85% of the second had complete response regarding their symptoms whereas on the 12-month follow-up, the respective numbers were 48% and 74%. Concerning the signs, 30% of the first group and 55.5% of the second showed to have complete response after six months and 26% and 41% respectively after 12 months. All differences between the two groups, except the signs after 12 months, were statistically significant. There were no side-effects from the long-term use of clobetasol propionate 0.05%. CONCLUSIONS: Conservative management of severe lesions of VLS in postmenopausal women using clobetasol propionate 0.05% for a long time (6 months) on a regular basis, seems to be a safe and effective therapy. Improvement is observed primarily on the symptoms and less on the signs.

Primary invasive vaginal cancer. Report of 12 cases.

The aim of this study was to describe the clinical features, methods of treatment and results of treatment among patients with primary invasive cancer. Twelve women in whom primary invasive cancer of the vagina was diagnosed between 1996 and 2001 were studied. The mean age of women with primary invasive vaginal cancer was 70.1 years. Half of the patients had advanced stage carcinoma at the time of the diagnosis and 85% of patients had not had a Pap-smear in the last 15 years. Treatment consisted of radiotherapy or a combination of surgery and radiotherapy. Four patients out of six with advanced stage disease died in 30 months. In conclusion, the present study confirms that early detection of the disease could lead to more successful management and therefore better prognosis.

Cervical intraepithelial neoplasia in the young female. Diagnosis and management.

The prevalence of HPV and CIN in young women has increased in recent years. During a 5-year period (1996-2000), 78 sexually active young females, aged 15-20 years, were referred to the Colposcopic Unit of the 1st Department of Obstetrics and Gynecology of the University of Athens in the major University-appointed hospital in Greece, because of an abnormal cytology or a suspicious cervical abnormality in the presence of negative cytology. Colposcopic examinations were found to be within normal limits in 12/78 (15.4%) of cases. Cervical pathology was related in 22 cases (28.2%) to HPV infection, 23 (29.5%) cases to CIN 1, 18 (23.1%) cases to CIN II and 3 (3.8%) to CIN III. No relation between oral contraceptive use and cigarette smoking with HPV infection was found. Our findings strongly confirm the necessity of obtaining cervicovaginal smears on all sexually active gynecologic and obstetric teenage patients.

Malignant rhabdoid tumor of the clitoris in an elderly patient: report of a case.

Malignant rhabdoid tumors of the vulva are rare neoplasms which most of the time show aggressive behavior and a dismal prognosis. We report a case of malignant rhabdoid tumor of the clitoris occurring in an elderly patient. Due to the similarities that these neoplasms show with other low-differentiated tumors, immunohistochemical and ultrastructural assessment should always be conducted so that accurate diagnosis is achieved. Individualized extensive surgical treatment might decrease relapsing disease.

Vaginal intraepithelial neoplasia: report of 102 cases.

BACKGROUND: Vaginal intraepithelian neoplasia (VAIN) is a rare asymptomatic disorder. The aims of the current study were to profile patients with VAIN and to evaluate the response to treatment. MATERIAL AND METHODS: We reviewed the records of 102 patients with VAIN diagnosed from 1990 to 2000. RESULTS: Patients with VAIN, VAIN2 and VAIN3 had the following mean ages 44.5, 47.8 and 61.8 years, respectively (p < 0.001). All patients with VAIN were found to have abnormal Papanicolaou smears. Localization of the lesions to the upper third of the vagina was observed in 80% of the cases. Recurrences following laser ablation and partial vaginectomy reached 21%. Patients with minimal VAIN lesions from whom punch biopsies were obtained had the lowest recurrence rate. Multifocality significantly affected the risk of recurrence (p = 0.03). CONCLUSION: VAIN most often involves the upper third of the vagina and is often multifocal. Patient selection and operator skill have a significant influence on the treatment outcome.

Treating intraepithelial lesions of the uterine cervix by laser CO2. Evaluation of the past, appraisal for the future.

BACKGROUND AND OBJECTIVE: Carbon dioxide laser (CO2) has been widely used in the past for the treatment of squamous intraepithelial lesions (SIL) of the uterine cervix. We present our 10-year experience of using this modality while evaluating its current and future use. MATERIALS AND METHODS: From 1988 to 1998, 3,078 women were treated for an intraepithelial lesion of the uterine cervix (SIL) by laser CO2 either by vaporization or conization. The procedure was performed on an outpatient basis and was well tolerated by the great majority of patients. The mean age of the women treated by vaporization was 27.5 years whereas of those managed by conization, 34.8 years. RESULTS: From the 3,078 women, 750 (24.4%) underwent laser vaporization and the remaining 2,328 (75.6%), conization of the cervix. Complications were minimal and consisted of intraoperative and postoperative bleeding (0.56%), pelvic infections (0.04%) and cervical stenosis (1.1%). Mean follow-up time was 83 months (range 24-142). Relapsing disease (either persistent or recurrent) was detected in 5.6% of the vaporization and 3.9% of the conization group. CONCLUSIONS: The management of SIL of the uterine cervix by laser CO2 offers excellent success rates with minor complications. The preservation of the anatomical integrity of the cervical tissue offers a better follow-up of these patients and the potential for repeat treatment. Although other treatment modalities are available, we believe that laser CO2 represents an excellent surgical tool for the management of intraepithelial lesions of the uterine cervix.

How to avoid suboptimal management of cervical carcinoma by simple hysterectomy.

OBJECTIVE: To determine the reasons leading to an inappropriate simple hysterectomy in the presence of carcinoma of the cervix and to evaluate factors related to survival. METHODS: All preoperative information was abstracted from 63 cervical cancer patients cleared by simple hysterectomy from 1980-1993. Cervical cancer screening history as well as the indication for hysterectomy were analyzed. The 5-year survival was calculated and correlated with the tumour histological subtype and presumed stage of disease. RESULTS: The most common preoperative symptom was abnormal uterine bleeding (73%). The absence of preoperative cytology, an inadequately evaluated abnormal Pap smear and the failure to differentiate from endometrial carcinoma were the main causes leading to an inappropriate simple hysterectomy. The cumulative 5-year survival was 63.5% and was correlated with the presumed stage of disease and the histological subtype. CONCLUSION: Only with close adherence to the cervical cancer screening guidelines and appropriate evaluation of presenting symptoms can we avoid inappropriate management of cervical carcinoma with simple hysterectomy.

Angiogenic properties of carcinoma in situ and microinvasive carcinoma of the uterine cervix.

Neovascularization is a critical step in the growth, progression and metastasis of tumors. The degree of angiogenesis may correlate with disease stage and provide prognostic information in various neoplasms. Microvessel density was studied in 24 patients with severe cervical intraepithelial neoplasias, 15 patients with microinvasive carcinomas (International Federation of Gynecology and Obstetrics IA1) and 15 healthy controls who had undergone hysterectomy for benign conditions. The microvessel density (MVD) in microinvasive squamous cell carcinomas was 40 +/- 2.42 (mean +/- SD) and in squamous carcinomas in situ (CIS) 20.41 +/- 2.29 (p < 0.05). Among patients with CIS and controls (13.33 +/- 1.59) there was also a significant difference in the number of vessels (p < 0.05). No significant correlation was found in relation to depth of invasion and histological grade of the microinvasive carcinomas. It is concluded that microinvasive squamous cell cervical carcinoma is an angiogenetic disorder and it seems that the onset of angiogenesis is an early event, usually in a preinvasive stage.

Vulvar intraepithelial neoplasia (VIN)--diagnostic and therapeutic challenges.

PURPOSE: Vulvar intraepithelial neoplasia (VIN) represents a current diagnostic and therapeutic challenge. The present retrospective study is an institutional experience on the diagnosis and management of VIN. METHODS: One hundred and thirteen women with VIN were reviewed and analyzed. Diagnosis was established by colposcopically directed biopsies whereas treatment was performed by either a surgical or a laser CO2 approach. RESULTS: The mean age of all VIN patients was 47.4 years. The most common symptom was pruritus (60.1%). The majority of the lesions were multifocal (N = 64, 56.6%) and located in the non-hairy part of the vulva (87.6%). VIN management consisted of laser CO2 treatment in 51 patients (45.1%), surgical treatment in 37 (32.7%) whereas 25 VIN, cases were managed by conventional medical treatment. The risk of disease relapse was not associated with VIN grade (p = 0.35) nor with the treatment modality used (p = 0.42). The risk of disease relapse was significantly higher for multifocal lesions (p < 0.001). Long-term follow-up of our patients showed that four patients (3.5%) developed an invasive vulvar carcinoma. CONCLUSION: Our study confirms other reports concerning the diagnostic and treatment difficulties of the management of VIN. Although the benefits of treatment are obvious there seems to be no guarantee that invasion will not occur.

Factors affecting outcome after incomplete excision of cervical intraepithelial neoplasia.

PURPOSE: Conservative treatment for cervical intraepithelial neoplasia (CIN) by ablative or excisional techniques is widely used. However, women with incomplete excision have a variable risk of CIN recurrence. The aim of this study was to identify possible risk factors for recurrence of CIN after large loop excision of the transformation zone (LLETZ) with involved margins of excision. METHODS: All cases of women treated with LLETZ for CIN between 1989-2000, in whom histological evaluation of the excised specimen revealed extension of CIN to the excision margins, were retrospectively studied. A woman was considered to have recurrence when she had histologically confirmed CIN following a second LLETZ or hysterectomy during the follow-up period. The characteristics that were examined as possible risk factors were age, parity, smoking habit, grade of initial lesion and extension to the endo- or ectocervical margin. RESULTS: Treatment failure was diagnosed in 18 out of 65 (27.7%) women with involved margins. The only characteristic that reached statistical significance was age. The mean age of women with recurrence was 35.8 years, whereas the mean age of women without recurrence was 32.8 years (p = 0.044). Also, a trend was evident in women with high-grade initial lesions (CIN II-III) (p = 0.168) and involvement of the endocervical margins (p = 0.149). No differences were observed between the two groups regarding parity and smoking habit. CONCLUSIONS: Increased age is a risk factor for recurrence in women with incomplete excision of CIN after LLETZ. Larger studies are required for definite conclusions.

The prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erb B-2 and cathepsin-D in ovarian cancer patients receiving platinum with cyclophosphamide or paclitaxel chemotherapy.

PURPOSE: To evaluate the prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erbB-2 and cathepsin-D in epithelial ovarian cancer (EOC). METHODS: We analyzed 100 patients with ovarian carcinoma, FIGO Stage IC-IV who underwent primary cytoreductive surgery and received adjuvant chemotherapy with cyclophosphamide and a platinum analogue (CP) (n = 46) or paclitaxel and a platinum analogue (TP) (n = 54). Immunohistochemical expression was studied on paraffin-embedded tissue from the primary tumor. RESULTS: After a median follow-up of 55 months median progression-free survival (PFS) and overall survival (OS) were 16 and 41 months, respectively. Positive bcl-2 staining and absence of cathepsin-D expression were associated with an increased complete response rate in the CP group (p = 0.011 and p = 0.003) but not in the TP group. PFS and OS were not associated with the expression of any of the markers studied. FIGO stage (p = 0.006) and histology (p = 0.047) were the only independent prognostic factors for survival. CONCLUSION: Bcl-2 and cathepsin D expression are associated with response to CP but not TP chemotherapy. P53, bcl-2, c-erb B-2 and cathepsin D expression was not correlated with PFS and OS in our study.