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Mixed müllerian tumors (MMT) of the uterus have been reported following the use of tamoxifen. Rarely, these tumors lead to an uterine inversion. The surgical approach of a uterine inversion forms a therapeutic challenge. In this article, a case of uterine inversion due to a MMT is reported, together with a literature review regarding the developing mechanisms and management.

The aim of this study was to compare the preoperative findings of abdominal/pelvic CT and MRI with the preoperative clinical International Federation of Obstetrics and Gynecology (FIGO) staging and postoperative pathology report in patients with primary cancer of the cervix. Thirty-six patients with surgical-pathological proven primary cancer of the cervix were retrospectively studied for preoperative staging by clinical examination, CT, and MR imaging. Studied parameters for preoperative staging were the presence of tumor, tumor extension into the parametrial tissue, pelvic wall, adjacent organs, and lymph nodes. The CT was performed in 32 patients and MRI (T1- and T2-weighted images) in 29 patients. The CT and MR staging were based on the FIGO staging system. Results were compared with histological findings. The group is consisted of stage 0 (in situ):1, Ia:1, Ib:8, IIa:2, IIb:12, IIIa:4, IVa:6, and IVb:2 patients. The overall accuracy of staging for clinical examination, CT, and MRI was 47, 53, and 86%, respectively. The MRI incorrectly staged 2 patients and did not visualize only two tumors; one was an in situ (stage-0) and one stage-Ia (microscopic) disease. The MRI is more accurate than CT and they are both superior to clinical examination in evaluating the locoregional extension and preoperative staging of primary cancer of the cervix.

More and more malignancies are identified by laparoscopy. Concerns have been risen about the safety of these procedures, especially after the publications on trocar metastases. General laparoscopic techniques should include safety measures in order to reduce the risk of implantation metastasis.

Malignant mixed müllerian tumour (MMMT) of the ovary is a rare and aggressive tumour with a poor prognosis. We present a case of a 57-year-old woman with a large pelvic mass, omental cake, ascites and pleural effusions, clinically highly suspect of an ovarian neoplasm. Paracentesis and ultrasound-guided biopsy of the ovary were negative for malignant disease. Therefore a CT-guided true cut biopsy was performed. The latter gave a histopathologic diagnosis of an endometrioid adenocarcinoma of the ovary. However after cytoreductive surgery anatomopathologic examination revealed a malignant mixed müllerian tumour of the ovary with heterologous differentiation. Apparently only one of the two components was found in the puncture. Adjuvant chemotherapy, active against the sarcomatous and the carcinomatous component, was given. At present the patient is well and disease free 35 months after the initial diagnosis. Cytological examination of ascites may be negative in the presence of malignant disease. If a tumour consists of two components, puncture can miss one, which may lead to undertreatment. Punctures should be discouraged as a diagnostic tool in patients in whom an ovarian malignancy is suspected.

An ovarian mass in a premenopausal patient has many differential diagnoses. In young patients the mass is most likely to be benign. Sometimes patients with an abdominal mass will present as acute abdomen. If the patients have an IUD and a positive test for serum HCG, an ectopic ovarian pregnancy has to be suspected. However one also has to take into consideration the possibility of an ovarian germ cell tumour. The latter occurs in young patients, presents as an ovarian mass and can produce HCG. The preoperative and even intraoperative diagnosis are difficult. In these cases where there is a suspected ovarian mass and no clear diagnosis a laparoscopic approach should be considered. Patients with an ovarian pregnancy have a good prognosis for future fertility and therefore conservative surgical management is advocated. The approach and treatment modalities of an ovarian pregnancy are discussed.

Primary squamous cell carcinoma of the breast is a rare neoplasm. We herein report two cases of primary squamous cell carcinoma of the breast, each with a different clinical manifestation. A 75-year-old patient with bilateral breast cancer and a 73-year-old woman with a mastitis carcinomatosa. Histopathology revealed that both tumours were squamous cell carcinomas. In the first case there was a coexisting adenocarcinoma in the contralateral breast. The diagnostic and therapeutic challenges are discussed in a review of the literature. The initial management of primary squamous cell carcinoma should be slightly different to that of more common types of breast cancer.

Intracystic papillary carcinoma of the male breast is a very rare disease with only a few cases reported in the literature. A case is described and the additional value of MRI is discussed. To our knowledge, this is the first report regarding the MRI findings of an intracystic papillary carcinoma of the male breast.

We present a case of extreme pancytopenia in a 27-year-old pregnant woman. The initial picture was compatible with a severe hematological problem in the category of aplastic anemia, paroxysmal nocturnal hemoglobinuria or even acute leukemia. The further biochemical investigations revealed, however, a folate deficiency. Nowadays this is a very rare cause of pancytopenia. Next to this she also had a Vitamin B(12) deficiency due to intrinsic factor failure. The recent literature is discussed.

Mucoepidermoid carcinoma is a very rare primary tumour of the breast. Until now only 17 cases have been described in the literature. Generally these malignancies have a good prognosis, especially if well differentiated. We report a case of low-grade which recurred as high-grade after 32 months. She also developed a poorly differentiated adenocarcinoma in the other breast 12 years after her initial treatment. At present the patient is well without any sign of disease for 156 months. A literature review of this rare entity is presented.

A case of a 23-year-old woman, with an uncomplicated term pregnancy, who developed subcutaneous emphysema 12 hours after the delivery on a specially designed chair is reported. Subcutaneous emphysema is an uncommon delivery complication, with a favourable outcome. The pathophysiology and treatment modalities of this rare phenomenon are discussed.

Objectives: To assess the feasibility of a one-stop colposcopy clinic for the management of women with low-grade smear abnormalities. Secondly, to determine whether the approach of immediate information of biopsy results combined with treatment if indicated helps to reduce patient anxiety and improve overall patient satisfaction with the colposcopy process., Design: Prospective study following the introduction of a "one-stop" process for the management of women with low grade smear abnormalities., Subjects: First 118 women managed in a "one-stop" clinic during an 8-month period., Methods: Assessment of patient anxiety via self-completed questionnaires and comparison of anxiety scores with a control group managed via a standard clinic., Results: The median waiting time for results in the one-stop clinic was 120 min (range: 100-165). All women in both groups felt anxious at the time of the clinic visit. However, after 1 week the majority of patients managed via the one-stop process felt slight anxiety only (P=0.0001) as opposed to those patients in the control group who remained anxious (P=NS). In addition, all women said they would prefer the one-stop approach for further smear abnormalities if a further colposcopic examination was warranted., Conclusion: A one-stop colposcopy clinic is feasible for the management of women with low-grade smear abnormalities. In addition, it delivers a quality service, optimises patient management, reduces anxiety and is the patient's choice.

Objective: The present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and angiogenesis in cervical cancer and their impact on clinical outcome., Study Design: Tumours from 111 patients were assessed by immunohistochemistry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for the quantification of the mitotic index and the microvessel density (CD 31). The results were correlated with various histopathologic characteristics and survival., Results: The multiple Cox's regression analysis for overall survival of all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO stage (P=0.070). Subanalysis was performed for the patients where the lymph node status was known (n=79). Adding the lymph node status gave as best model for overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic index (P=0.044). However, they hardly influenced the association., Conclusion: In the apoptotic pathway of cervical cancer, bcl-2 is one of most important proteins. It can probably not only mediate cell death but also regulate cell growth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future.

Idiopathic granulomatous mastitis is a very rare benign breast disease, which mimics breast cancer both clinically and mammographically. Most cases have an unknown aetiology, however, we found an alpha-1-antitrypsin deficiency. A literature review is presented and the controversies in diagnosis and management are discussed.

Objective: The aim of this study was to define the role of surgery in managing patients with a primary squamous vaginal cancer., Methods: A retrospective review was conducted of patients with primary invasive vaginal cancer managed at one institution over a 25-year period. The results were compared with those of all major publications of the past 20 years., Results: A total of 84 patients were reviewed. Forty-five (66%) were of squamous origin. The median follow-up was 45 months (range: 0.6-268). The patients were primarily treated by surgery in 67% and by radiotherapy alone in 33% of cases. The 5- and 10-year overall survival was, respectively, 74 and 58%. For stage I the figures were 91 and 70%. These survival rates compared favorably with those of published series of cases managed by radiotherapy alone. Univariate analysis showed that age (P = 0.004), size (P = 0.009), site (P = 0.016), lymph node status (P = 0.022), FIGO stage (P = 0.027), and treatment (P = 0.003) were relevant prognostic factors. Multiple regression analysis, however, revealed that only age (P = 0.009) and size (P = 0.037) were independent prognostic variables., Conclusions: Stage I and II squamous vaginal cancer patients have good outcomes in terms of survival and local tumor control if they are managed by initial surgery followed by selective radiotherapy., (Copyright 2001 Academic Press.)

Congenital diaphragmatic hernia is a rare condition in adulthood. It is even more exceptional when located on the right side. We describe a case of right-sided congenital diaphragmatic hernia in a 74-year old woman. The diagnosis was only made when the patient developed an acute intestinal obstruction after a laparotomy for a gynaecological benign tumour. The treatment of this condition is discussed. In our opinion, in elderly, the advantages of an elective operation in asymptomatic congenital diaphragmatic hernia have to outweigh the risks of the operation. However, if the patient shows symptoms of pulmonary dysfunction or motility disorders of the gut, or even when he has to undergo a laparotomy for a different reason, we advise to repair the hernia in order to prevent complications.

Objectives: Inguinal metastasis is a hitherto unreported presenting feature of fallopian tube adenocarcinoma., Case: We describe a case of a 69-year-old patient whose first manifestation of fallopian tube adenocarcinoma was an enlarged inguinal lymph node. This was excised and confirmed to be metastatic adenocarcinoma. She was investigated by diagnostic laparoscopy and subsequently underwent laparotomy with total abdominal hysterectomy, omentectomy, and pelvic and para-aortic lymph node dissection. All but two of the lymph nodes extirpated were negative., Conclusions: Fallopian tube adenocarcinoma may rarely present with metastatic inguinal lymphadenopathy., (Copyright 2001 Academic Press.)

Objective: To evaluate the proliferation activity in CIN III lesions and Ia1 carcinoma according to the risk of recurrence., Study Design: The proliferation markers PCNA (proliferating cell nuclear antigen) and mitotic index were studied in 75 patients with CIN III and in 20 patients with an Ia1 squamous carcinoma of the cervix by staining representative tissue sections for the PCNA and assessing the mitotic index. Associations between the studied proliferation markers and various histopathologic characteristics as well as recurrence were assessed., Results: Three groups of PCNA were constituted: <20, 20--40, > OR =40% positive tumour nuclei, which contained, respectively, 45 (47%), 29 (31%), and 21 (22%) patients. Microinvasive carcinomas have a higher proliferation activity than CIN III (PCNA P=0.005; mitotic index P=0.094). For CIN III, there was a significantly lower risk for recurrence in the group with lower mitotic activity, compared to the group with higher mitotic activity (Kaplan-Meier: log-rank testing P=0.044). Significance was, however, not reached for the different PCNA categories (Kaplan-Meier, log-rank test P=0.068). Multiple regression analysis showed that in our population of CIN III lesions, only age of diagnosis and treatment modality were relevant (independent) prognostic indicators for recurrence., Conclusions: In CIN III lesions there is evidence for an association between proliferation activity and the risk of recurrence. The observed crude association weakens when adjusting for age at diagnosis and treatment modality. Apparently this feature is associated with more aggressive biological behaviour and could be used to identify women who are at higher risk of recurrence.

The current report describes a 57-year-old patient with multiple bone metastases 14 years after her initial treatment for breast cancer. The only therapy the patient received for her osteolytic lesions was oral clodronate (800 mg/daily), as she refused any other kind of treatment. On bone scintigraphy the number of visible bone metastases diminished slowly and after two years only a few minor lesions could be seen. Together with this report the value of oral clodronate as anti-osteolytic therapy in breast cancer patients is discussed.

Worldwide there is a strong relation between the presence of human papillomavirus (HPV) and the development of cervical cancer. This study investigated the prevalence and genotype of HPV in women with normal smears, women with premalignant lesions and women with cervical cancer in Antwerp, Belgium. Type-specific polymerase chain reaction (PCR) for HPV types 16 and 18 and general primer PCR (GP5+/6+) was performed on DNA extracted from paraffin-embedded tissue from women with lesions or fresh material from controls. HPV was detected in 11% of controls, 61% of women with atypia, 77% of women with CIN lesions and 88% of women with cervical carcinoma (chi2 trend, 273, p<0.001). The odds ratio for high-risk HPV types was 9.3 for atypia (95%CI. 4.3-19.8), 33.6 for CIN lesions (95%CI, 19.3-58.6) and 78.8 for cervical cancer (95%CI, 39.2-158.3). In total, 19 different HPV genotypes were detected, including five low risk HPV types. Seven of the 14 high-risk HPV types were detected in cervical cancer patients. Based on our study it is suggested that a prophylactic vaccine based on a cocktail of a limited number of high-risk HPV types should be considered in order to protect most women from developing cervical cancer.

A 74-year-old patient with recurrent Paget's disease of the vulva in the gluteus maximus island myocutaneous flap 11 years after a hemivulvectomy with reconstruction is presented. This report is only the second case of recurrent noninvasive Paget's disease in a reconstructive flap. The English literature on this subject is reviewed with special attention to the biological behavior of these tumors.

Vaginal melanoma is a rare and highly malignant disease. This report describes the characteristics and clinical course of all patients treated at one institute (Northern Gynaecological Oncology Centre, UK) over the last 25 years. Of a total of nine patients identified with a primary malignant vaginal melanoma, only one patient survived for more than five years. A literature review revealed only 21 reported cases with a survival greater than five years. The most important factor for survival appears to be the tumour size. Treatment modality varied equally within the group of long-term survivors (27% radical surgery, 27% wide local excision, 27% radiotherapy, 14% wide local excision and radiotherapy, and 5% unknown therapy). The prognosis of patients with primary malignant melanoma is poor, regardless of primary therapy (conservative or radical). Conservative treatment and accurate investigation of every discoloured lesion is recommended.

To investigate the relation between the prevalence of human papillomavirus (HPV) and age in cervical cancer patients, material from 93 patients with Ia-IIb cervical carcinoma was analyzed for the presence of HPV by both type-specific and general primer polymerase chain reaction. Patients were divided into 2 groups: 64 years or younger, and 65 years and older. There was no statistically significant difference in either the prevalence of HPV DNA or distribution of genotypes amongst the 2 groups. Therefore, HPV detection can be equally well used in the management and follow-up of elderly cervical cancer patients., (Copyright 2001 S. Karger AG, Basel)

Objective: The aim of this study was to analyse the vascular endothelial growth factor (VEGF) expression in a series of cervical carcinomas and to compare the results with the microvessel density (MVD) and clinicopathological features., Study Design: The immunoreactivity for VEGF was studied in 130 invasive cervical carcinomas and in 22 patients with a carcinoma in situ of the cervix. The results were compared with the MVD., Results: Staining for VEGF of less then 50% per slide occurred in 80% of the invasive carcinomas and in 82% of the in situ carcinomas. The median MVD was 261 vv/mm(2) (range: 11-1000) in the invasive group and 146 vv/mm(2) (range: 25-536) in the in situ group. Unlike the microvessel density there was no association between VEGF expression and survival. The MVD was higher in VEGF poorer (<50%) tumours (P=0.055). Beside tumour histology (P=0.012) there were no other significant relationships between the remaining histopathological findings and VEGF expression., Conclusion: Tissue VEGF expression has no prognostic value in contrast with the MVD in patients with invasive cervical cancer.

Objective: To evaluate the performance of karyometry and histometry in the prediction of survival, recurrence and response of early-stage invasive cervical carcinoma., Study Design: Nuclear morphometry, chromatin texture and tissue architecture (characterized by syntactic structure analysis) were measured using a semiautomated image analysis system on 46 cases of Feulgen-stained tissue sections. The performance of the features was compared to that of clinical features, reported to be the best prognosticators until now, such as age, lympho-vascular permeation, histologic type, stage and grade. A K nearest neighbor classifier was used for classification., Results: In the prediction of three-year survival, recurrence and response, syntactic structure analysis proved to be the best performer. Classification rates were, respectively, 100%, 94.4% and 94.5%. In all classifications, karyometric and histometric features outperformed clinical features. In general, the best performing features described differences in second-order population statistics (standard deviations)., Conclusion: The results show that a quantitative analysis based on nuclear morphology, chromatin texture and histology can be considered an excellent aid in the prognosis of invasive cervical carcinoma. The measurements are not hampered by the need to undertake complete resections and are suited to daily practice when implemented in a semiautomated image analysis system.

Retrospective analyses suggest that a subgroup of patients with Stage III and IV ovarian carcinoma can be treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The absolute indications for neo-adjuvant chemotherapy appear to be Stage IV disease (excluding pleural fluid) or metastases of more than 1 g at sites where resection is impossible. In patients with an estimated total metastatic tumor load of >100 g, the presence of at least two of the following relative indications for neo-adjuvant chemotherapy are considered to be necessary: 1) uncountable (>100) peritoneal metastases, 2) estimated metastatic tumor load of >1000 g, 3) presence of large (>10 g) peritoneal metastatic plaques, 4) large volume ascites, and 5) World Health Organization (WHO) status II or III. Interval debulking surgery in patients with suboptimal primary debulking surgery has been proven effective in increasing overall survival and progression-free survival in a large prospective, randomized trial of the European Organization for Research and Treatment of Cancer (EORTC). The strategy of neo-adjuvant chemotherapy, followed by interval debulking surgery, should be confirmed in a prospective randomized trial. The EORTC 55971 trial is currently addressing this issue. We will review the studies on primary chemotherapy, interval debulking surgery, and the indications for primary chemotherapy followed by interval debulking surgery, and ongoing trials., (Copyright 2000 Wiley-Liss, Inc.)

The authors report a case of false positive diagnosis of iliac vein thrombosis on duplex ultrasound. The misreading of the duplex scan was based on the presence of an incompressible common femoral vein. External compression on the iliac veins, caused by enormous postoperative lymphoceles, was responsible for the false positive diagnosis.

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Since 1989, we have been treating advanced epithelial ovarian cancer with neoadjuvant chemotherapy instead of primary cytoreductive surgery in approximately half of the patients with stage III-IV disease. Selection of neoadjuvant chemotherapy was based on disease-related characteristics (eg, metastatic tumor load, stage of disease, performance status). Since 1993, open laparoscopy also has been used to aid in evaluating operability. A retrospective analysis of 338 patients was conducted to compare outcomes during 1989 to 1998, when neoadjuvant chemotherapy was used, with those observed during 1980 to 1988, when all patients underwent primary cytoreductive surgery. Crude 3-year survival rates were higher and postoperative mortality rates were lower during the second time period compared with the first. Overall, the results suggest that neoadjuvant chemotherapy results in survival rates in selected patients with advanced ovarian cancer that are comparable with those associated with primary cytoreductive surgery. Patients with stage IV disease, total metastatic tumor load greater than 1,000 g, uncountable plaque-shaped peritoneal metastases, and/or a poor performance status are probably the best candidates for this alternative approach. A prospective randomized study of neoadjuvant chemotherapy and primary cytoreductive surgery is ongoing.

Primary malignant melanomas of the urethra are extremely rare. Clinically they are usually mistaken for other malignant diseases or even benign lesions. The case of a 66-year-old woman is reported, who presented with local bleeding of the urethra. Macroscopically a polypoid tumor was seen on the meatus externus of the urethra. A biopsy was taken and the histology report revealed a malignant melanoma. There were no signs of metastases and therefore the treatment consisted of a wide local excision only. A review of literature regarding therapy and prognosis is presented.

The occurrence of disseminated tumors of the appendix is a rare event. Usually appendix tumors are very small, located on the inside of the appendix, and can be pathologically diagnosed. Adenocarcinoid is an uncommon variant of carcinoid tumors that usually arises in the appendix. This report describes a case of a primary adenocarcinoid of the appendix in a patient who was preoperatively diagnosed to have uterus myomatosus but was intraoperatively found to instead have disseminated ovarian carcinoma. This case demonstrates that the clinical picture can be misleading, and that surgeons therefore always have to wait for the final pathological report before making a final diagnosis.

Superficial pubic collateral veins are the result of iliac vein occlusion due to previous thrombosis. They can be accompanied by deep crossover veins. We present a patient with thrombophlebitis of superficial pubic collateral veins after a hysteroscopic procedure.

Objective: The purpose of this study was to determine risk factors for trocar implantation metastasis after diagnostic laparoscopy in patients with primary or recurrent advanced ovarian cancer., Study Design: Eighty-three women with primary advanced ovarian cancer and 21 women with recurrent ovarian cancer undergoing a laparoscopy for a tissue diagnosis and for assessment of operability were included in the study. The occurrence of implantation metastasis at the trocar incision scars was analyzed according to clinicopathologic characteristics., Results: A recurrence developed at the trocar site in 7 (58%) of 12 patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in 2 (2%) of 92 patients undergoing a laparoscopy with closure of all layers (odds ratio, 63; 95% confidence interval, 10.3-385; P <.001). The International Federation of Gynecology and Obstetrics stage at initial presentation, tumor histologic type, tumor differentiation, maximal tumor diameter at the time of diagnosis, estimated weight of the metastatic tumor, residual tumor after cytoreductive surgery, surgical characteristics, and type of chemotherapy were well balanced among both groups. Patients with implantation metastasis had significantly more ascites (median, 700 mL vs 300 mL; P =.032) and a longer interval between the start of platinum-based chemotherapy or cytoreductive surgery (median, 6 days vs 17 days; P <.01) compared with patients without abdominal wall recurrence. A palpable abdominal wall metastasis developed in none of the patients undergoing a laparoscopy with closure of all layers of the abdomen followed by cytoreductive surgery or chemotherapy within 1 week after the laparoscopy. Kaplan-Meier survival analysis showed that patients with abdominal wall implantation metastasis had a survival rate similar to that of the other patients., Conclusions: Laparoscopy with careful closure of the peritoneum, rectus sheath, and skin followed by chemotherapy or cytoreductive surgery with excision of the trocar trajectories within 1 week is safe in patients with disseminated ovarian cancer.

Objective: We sought to investigate whether angiogenesis can predict the risk of recurrence of cervical intraepithelial neoplasia after treatment., Study Design: Microvessel density was studied in 75 patients with grade 3 cervical intraepithelial neoplasia and in 20 patients with microinvasive squamous carcinoma (International Federation of Gynecology and Obstetrics stage IA1) of the uterine cervix by staining representative tissue sections with the specific endothelial marker anti-CD31. The microvessel density was determined with a digital image analyzer. The results were correlated with clinical and histopathologic data., Results: The mean vessel density was 264 per field (range, 86-674 per field) in grade 3 cervical intraepithelial neoplasia and 378 per field (range, 161-848 per field; P = .001) in microinvasive squamous carcinoma. Thirteen patients with grade 3 cervical intraepithelial neoplasia had recurrent cervical intraepithelial neoplasia (microvessel density, recurrent vs nonrecurrent; not significant). Multiple regression analysis in the noninvasive group confirmed that the mean vessel density (P = .121) had no prognostic value. Furthermore, it showed that the age at diagnosis (P = .011), menopausal status (P = .052), and treatment modality (P = .022) proved to be independent prognostic factors for recurrence., Conclusions: During the progression from noninvasive to microinvasive cervical carcinoma, the microvessel density increases significantly. However, the vessel density does not predict recurrence of noninvasive lesions.

We present three cases of chest wall resection for locally recurrent breast cancer and a Medline review of the current literature. In selected cases full thickness resection of the chest wall may be used as a salvage procedure to improve the quality of life and prolong the survival at low morbidity and mortality.

We report a case of a 23-year-old woman diagnosed as having an epithelioid sarcoma of the vulva. She was treated by a clitoris-sparing hemivulvectomy and lymph node sampling of the ipsilateral groin. Vulvar reconstruction was performed with a rectus abdominis myocutaneous flap. Four years after the operation there is no evidence of disease and the patient has a normal sex life. The English literature on this subject is reviewed with special attention to the biological behavior and therapeutic approach., (Copyright 1999 Academic Press.)

Objective: This study was aimed at comparison of neoadjuvant chemotherapy with primary debulking surgery in advanced ovarian carcinoma., Methods: Retrospective analysis of 285 patients with advanced ovarian carcinoma treated between 1980 and 1997 was performed., Results: In the period 1980-1988 all patients underwent primary debulking surgery and 82% were cytoreduced to less than 0.5 cm largest residual tumor mass (n = 112). Analysis of this group of patients showed that some subgroups of patients (e.g., Stage IV disease or a total metastatic tumor load of more than 1000 g prior to debulking surgery) had a poor survival despite cytoreduction to no or less than 1 g of total residual tumor load. The complication rate was high especially in the group with unfavorable prognosis (postoperative mortality, 6%). In the period 1989-1997 (n = 173) the patients were surgically evaluated to receive primary chemotherapy (43%) or primary debulking surgery (57%). Prognostic variables were similar for both treatment periods. The actuarial crude survival was higher in the second time period (3-year crude survival of 26% +/- 4. 3 and 42% +/- 4.6 for the first and second time periods, respectively; P = 0.0001). The postoperative mortality was 0% during the second time period. From 1993 on, the decision to give neoadjuvant chemotherapy or to perform primary debulking surgery in patients with clinically obvious metastatic disease was made with the help of an open laparoscopy (n = 77). Median duration of the laparoscopy, blood loss, and hospital stay due to this procedure were 25 min, 10 ml, and 2 days. Primary and interval debulking surgery was performed in 36 and 63% of this subgroup of patients, respectively., Conclusion: In this retrospective analysis over two different time periods, crude survival was higher when treating about half of the patients with advanced ovarian carcinoma with primary chemotherapy instead of primary debulking surgery. The role of neoadjuvant chemotherapy should be evaluated in a prospective randomized study., (Copyright 1998 Academic Press.)

Prenatal diagnosis of toxoplasmosis gondii in twin pregnancies has been described twice. In both cases they were accomplished by prenatal blood sampling of the foetuses. We report the first prenatal diagnosis with a discordant result in a dizygotic pregnancy. One of the foetuses died in utero and the other was born unaffected at term.

Tumour stromal neovascularization was investigated in 114 invasive and 20 in situ carcinomas of the uterine cervix by staining representative sections with the specific endothelial marker anti CD31 (clone JC/70A, isotope IgG1). A digital image analyser was used to measure the immunoreactivity. The following parameters were determined in the 'hot spots': vessel counts, vessel perimeter and endothelial stained area (expressed per mm2). The results were correlated with clinical and histopathological data. There was no significant relationship between the histopathological findings (tumour histology, tumour differentiation, FIGO stage, presence of lymph node metastasis or lymphovascular space involvement) and the median vessel count. In a univariate analysis all angiogenesis parameters had prognostic value: a higher vascularity was associated with worse prognosis (P < 0.05). Multiple regression analysis showed that vascular permeation (P < 0.001) and the median vessel count (P = 0.005) were the most important prognostic indicators. In the future these criteria may be used for selection of patients for anti-angiogenesis therapy.

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine fetal ultrasounds showed the presence of apparently isolated bilateral club feet. Fetal karyotyping documented an interstitial deletion of the long arm of chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such deletion is associated with severe psychomotor retardation, the pregnancy was terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of this interstitial de novo deletion in all mitoses. The breakpoints on 5q were analyzed by fluorescent in situ hybridization and were localized at 5q15 and q31.1. This case illustrates the importance of fetal karyotyping in cases of isolated club feet. At autopsy, the fetus presented had minor anomalies and contractures of knee and hip joints. These clinical findings could fit the diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the fetus and that the de novo interstitial deletion occurred on the paternally inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2 gene. Clinical findings in this fetus and those of other described cases with interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

Objective: The oncoprotein bcl-2 inhibits apoptosis. The purpose of this study was to assess the expression of bcl-2 in human cervical carcinoma and to correlate this with clinicopathologic parameters., Study Design: Immunohistochemical staining for bcl-2 protein (MoAB clone 124) was performed on operative tissue specimens from 22 patients with carcinoma in situ of the cervix and from 137 patients with invasive cervical carcinoma (International Federation of Gynecology and Obstetrics stages I to IV). The immunoreactivity of bcl-2 was scored as positive (> or = 5% staining cells) or negative (< 5% staining cells)., Results: Eighty-two percent of in situ carcinomas and 61% of invasive cervical carcinomas were bcl-2 positive. Expression of bcl-2 was correlated to tumor stage (p < 0.001) and to presence of vascular (p < 0.005) or lymphatic tumor (p < 0.023) permeation. In univariate analysis there was a strong relationship between bcl-2 expression and overall survival (p < 0.001). In multivariate analysis bcl-2 expression (p < 0.001), International Federation of Gynecology and Obstetrics stage (p = 0.011), and presence of lymphatic permeation (p = 0.014) proved to be independent prognostic factors., Conclusions: Expression of bcl-2 is lost during tumor progression and is a strong prognostic parameter, suggesting that the regulation of apoptosis plays an important role in the behavior of cervical carcinomas. Better understanding of the mechanisms involved may lead to improved medical treatment strategies.

Aim: To evaluate the patterns of bcl-2 expression in early stage cervical carcinoma; to compare bcl-2 expression with clinicopathological findings; and to assess its prognostic value., Methods: Wertheim radical hysterectomy specimens from 76 patients (FIGO stages Ia-IIb) with untreated nonmetastatic invasive cervical carcinoma were studied. Expression of bcl-2 was detected immunohistochemically using a monoclonal antibody. A tumour was regarded as positive when more than 5% of the neoplastic cells exhibited bcl-2 immunoreactivity., Results: Forty eight (63%) cervical carcinomas were scored as bcl-2 positive and 28 (37%) as bcl-2 negative. Most tumours showed heterogeneous cytoplasmic staining. Bc1-2 immunoreactivity did not correlate with tumour histology, tumour stage, presence of lymph node metastases, or involvement of the lymphovascular space. The five year survival rate for patients with bc1-2 negative tumours was 34% and was 71% for patients with bc1-2 positive tumours. On multiple regression analysis (Cox proportional hazards model), bc1-2 expression and vascular permeation were independent predictors of overall survival., Conclusions: Bcl-2 expression seems to be associated with less aggressive behaviour in early stage cervical carcinoma. The transition to bcl-2 independence may play an important role in tumour progression.

Objective: Our purpose was to evaluate the effectiveness, benefits, and potential side effects of the use of the cavitational ultrasonic surgical aspirator for cytoreduction of advanced ovarian cancer., Study Design: Forty patients with stage IIC to IV ovarian carcinoma were randomized to undergo ultraradical cytoreductive surgery with (group 1, 20 patients) or without (group 2, 20 patients) the use of the CUSA 200 cavitational ultrasonic surgical aspirator (Valleylab, Boulder, Colo). Preoperative and postoperative information and follow-up data were collected prospectively and compared between both groups., Results: The amount of residual tumor after debulking surgery, the duration of the operation, and the rate of perioperative complications were comparable in both study groups. The amount of perioperative blood loss was significantly lower (1450 ml vs 1650 ml, p=0.02) in group 1. These patients had less morbidity (p<0.05), and could be discharged from the hospital significantly sooner (14 days vs 16 days, p=0.031). CA 125 levels 1 and 2 months after surgery were significantly lower in the group with cavitational ultrasonic surgical aspirator (p<0.01 and p<0.01, respectively), suggesting more successful cytoreduction. However, this is not reflected in a better disease-free or overall survival., Conclusion: Cavitational ultrasonic surgical aspirator-assisted cytoreductive surgery of advanced ovarian carcinoma is more effective in eradicating disease, reduces morbidity, and is cost beneficial.

We assessed the pharmacokinetics of aluminoxamine and ferrioxamine in dogs with sustained intermittent bile duct ligation and either normal renal function or stable chronic renal failure. A first group of male beagle dogs were given aluminoxamine and ferrioxamine, while a second group received desferrioxamine after loading them with iron and aluminum. Only minute amounts of ferrioxamine and aluminoxamine were found in the bile after administration of these compounds. The distribution volume of aluminoxamine and ferrioxamine appeared to be confined to the extracellular space and their renal excretion correlated with renal function. Administration of desferrioxamine to iron and aluminum-loaded dogs resulted in an increased biliary ferrioxamine but negligible aluminoxamine excretion. Renal clearance of the in vivo formed ferrioxamine and aluminoxamine in this group strongly correlated with renal function. Our observations indicate that biliary excretion of intravenously administered ferrioxamine and aluminoxamine is negligible even in renal failure. The data presented in this study provide indirect evidence that desferrioxamine administration to iron- and aluminum-loaded dogs results in the intra-hepatic formation of ferrioxamine which is partly excreted in the bile. Biliary excretion of aluminoxamine after desferrioxamine administration remained negligible.