Making the case for multipurpose prevention technologies: the socio-epidemiological rationale.

This paper summarises the public health rationale for multipurpose prevention technologies (MPTs) by examining recent epidemiological data and trends in sexual and reproductive health indicators. MPTs are products that combine protection against unintended pregnancy, HIV and other sexually transmitted infections. The successful introduction of new woman-controlled MPTs provides a compelling response to the multiple sexual and reproductive health risks that women face worldwide.

The species sensitivity distribution approach compared to a microcosm study: a case study with the fungicide fluazinam.

We assessed the sensitivity of freshwater organisms (invertebrates and algae) to the fungicide Shirlan (active ingredient fluazinam) in single-species laboratory tests and in microcosms. Species sensitivity distribution (SSD) curves were constructed by means of acute toxicity data for 14 invertebrate species, since algae were much less sensitive. The EC(10)-based SSD gave a median HC(5) value of 0.6microgL(-1) and a 90% confidence interval of 0.1-1.9 microgL(-1). The EC(50)-based SSD gave a median HC(5) value of 3.9 microgL(-1) (90% confidence interval: 0.9-9.9 microgL(-1)). The microcosms were treated four times with Shirlan (concentration range: 0.4-250 microgL(-1)). Responses of the microcosm communities were followed. The 2 microgL(-1) treatment was the no-observed-effect concentration (NOEC(microcosm)). The 10 microgL(-1) treatment resulted in short-term effects on a few zooplankton taxa. Clear effects were observed at 50 and 250 microgL(-1). The responses in the microcosms were in line with the toxicity data for the tested lab species. The median EC(10)-based HC(5) and the lower limit EC(50)-based HC(5) were lower, and the median EC(50)-based HC(5) was slightly higher than the NOEC(microcosm). This is consistent with other studies that compared SSDs with responses in model ecosystems that received repeated applications of pesticides.

Gonadotropins and female sex steroid hormones in cyst fluid and serum from patients with ovarian tumors.

The objective of the present study was to determine the concentrations of LH, FSH, 17beta-estradiol and progesterone in ovarian cyst fluid and serum from patients with benign and malignant ovarian tumors and to assess the correlation of the gonadotropin and female sex steroid hormone concentrations with menopausal and tumor status. Ovarian cyst fluid and blood samples were prospectively collected from 103 patients with ovarian tumors. Seventy-four of the patients had benign ovarian tumors while 29 patients had malignant ovarian tumors. Malignant ovarian tumors showed significantly higher LH and FSH cyst fluid concentrations compared to concentrations from patients with benign tumors. Within the malignant subset, LH and FSH concentrations correlated with increasing FIGO stage and grade. Furthermore, LH and FSH cyst fluid concentrations showed strong correlations (r > 0.62) with serum concentrations in case of malignant tumors, especially in postmenopausal women, but not in case of benign tumors. The highest gonadotropin concentrations were observed in cyst fluid from malignant ovarian tumors. The most probable explanation for this is an increased vascular permeability within the cysts. Supportive evidence for such an increased vascular permeability is our previous finding of significantly higher VEGF concentrations in cyst fluid from malignant ovarian tumors. The possibility of ectopic production of LH and FSH by malignant ovarian tissue cannot completely be ruled out.

P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy.

P-glycoprotein (P-gp) expression and DNA topoisomerase (Topo) II are important variables in multidrug resistant tumor cell lines. The aim of this study was to evaluate P-gp expression and Topo I and II activity in benign and malignant epithelial ovarian tumors. P-gp expression was analyzed immunohistochemically in cryostat sections of fresh tumor specimens. In the same specimens Topo I and II activity were measured by, respectively, relaxation of supercoiled plasmid pBR322 DNA and decatenation of kinetoplast DNA. P-gp expression (range, 5-100% positive staining cells) was found in 3 of 6 cystadenomas, 0 of 2 borderline tumors, 15 of 21 untreated ovarian cancers, and 8 of 13 platinum/cyclophosphamide treated ovarian cancers. Median Topo I and II activity were elevated in malignant ovarian tumors compared to benign and borderline tumors. No difference was found between median Topo I activity in untreated ovarian cancer and platinum/cyclophosphamide treated ovarian cancer. High Topo II activity (greater than or equal to 8 x 10(2) units/mg protein) was more frequent in untreated compared to platinum/cyclophosphamide treated samples. Respectively, 8- and 16-fold differences in Topo I and II activity were found in the malignant tumors. Topo II activity in malignant tumors correlated with Topo I activity (r = 0.36, P less than 0.05) and the tumor volume index (r = 0.35, P less than 0.05). However, this last weak correlation cannot explain the 16-fold differences in Topo II activity in malignant tumors. Mitotic index and P-gp expression did not correlate with Topo I or II activity. A large variability in P-gp expression and Topo I and II activity was observed in patients with ovarian cancer.

Quantitative and qualitative aspects of topoisomerase I and II alpha and beta in untreated and platinum/cyclophosphamide treated malignant ovarian tumors.

Quantitative and qualitative aspects of topoisomerase (Topo) I and II were studied in 17 malignant ovarian tumors [eight untreated and nine after platinum/cyclophosphamide (Pt/Cy) chemotherapy]. Median Topo II catalytic activity was lower (P < 0.05) in tumors after Pt/Cy chemotherapy in comparison to untreated tumors, while no differences were found for Topo I catalytic activity in tumors before and after chemotherapy, as was also found in a previous study (Van der Zee et al. Cancer Res., 51: 5915-5920, 1991). Teniposide (VM-26)-induced cleavable complex formation correlated (r = 0.60; P < 0.05) with Topo II activity, while Topo II decatenation activity was equally but incompletely inhibited by VM-26 in all tumors. No differences were found in Topo II cleavage site patterns in plasmid BR322 DNA for all tumors using an indirect end-labeling procedure. Cleavable complex formation of Topo I by camptothecin (Cpt) did not correlate with Topo I catalytic activity, while Topo I catalytic activity could equally and completely be inhibited by Cpt. By Western blotting, Topo II alpha protein expression was detected in four of eight untreated tumors and three of nine tumors after Pt/Cy chemotherapy, whereas in all tumors a M(r) 150,000 degradation product of Topo II beta was detected. Topo I protein was detected in all tumors at varying levels, but the protein levels did not correlate with Topo I catalytic activity or cleavable complex formation by Cpt. Our study shows that Topo I and II, isolated from human malignant tumors, can be stimulated by Cpt and VM-26, respectively, to induce DNA cleavage, which suggests that topoisomerases are real targets for chemotherapy in patients with ovarian cancer. From in vitro data from the literature it appears that the cleavable complex assay reflects both quantitative and qualitative changes as well as changes in the phosphorylation state of Topo I and II. In combination with the feasibility of the cleavable complex assay for Topo I and II in human malignant tumors, which was found in the present study, it appears that at present the determination of cleavable complex formation by tumors seems to be the most promising parameter of Topo I or II expression in human tumors to be related to response to Topo I- or II-targeted chemotherapy.

Early detection of breast and ovarian cancer in families with BRCA mutations.

Women at risk of breast and ovarian cancer due to a genetic predisposition may opt for preventive surgery or surveillance. The aim of this study was to determine the effectiveness of surveillance in families with a BRCA mutation. Sixty-eight BRCA-families underwent surveillance using annual mammography, transvaginal ultrasound, and estimation of CA125. Two hundred and two women had at least one breast examination, and 138 at least one examination of the ovaries. After a mean follow-up of 33 months, breast cancer was detected in 21 women, four with lymph node metastases. After a mean follow-up of 37 months, six advanced ovarian cancers were detected. The percentage of metastatic breast cancers in the current study appeared to be acceptable. However, because these women have a high-risk of developing breast cancer, they still have a substantial risk of developing metastatic disease under surveillance. Surveillance for ovarian cancer was not effective.

A phase I-II study with intraperitoneal cisplatin plus systemic etoposide in patients with minimal residual ovarian cancer.

In patients with residual ovarian cancer after standard platinum-based induction, dose intensification was achieved by intraperitoneal administration of cisplatin 90 mg/m2 with intravenous Na thiosulphate and increasing dosages of etoposide. 40 patients entered the study, 4 on 200 mg/m2, 6 on 400 mg/m2, 22 on 600 mg/m2 and 8 on 800 mg/m2 etoposide. The optimal dose for etoposide was 600 mg/m2. 29 patients on the two highest dose steps were evaluable for response. 14 patients reached a complete remission, which was surgically confirmed in 6. All these patients initially had tumour residuals smaller than 1 cm. 3 patients had a partial response, 4 had stable disease and 8 progressed. At a maximal follow-up of 2 years (median 12 months), median time to progression was 12 months and median overall survival was 14 months. Of the 14 patients with complete remission, 2 relapsed at 9 and 11 months. Apart from a rash, in 4 of 22 patients at 600 mg/m2 and in 5 of 8 at 800 mg/m2 etoposide, the main toxicity was leukopenia grade 3-4 in 58% of cycles on 600 and in 76% at 800 mg/m2 etoposide. Leukopenic fever, however, occurred only three times; thrombocytopenia was rare. Cycles had to be delayed sporadically and the etoposide dose was reduced in 9% of all cycles at 600 and in 11% at 800 mg/m2. Intraperitoneal instillation of cisplatin gave no peritoneal symptoms. Intraperitoneal cisplatin with intravenous etoposide was tolerable and effective for patients with small tumour residuals after induction for stage III ovarian cancer.

Phase II study of intraperitoneal cisplatin plus systemic etoposide as second-line treatment in patients with small volume residual ovarian cancer.

The efficacy and toxicity of intraperitoneal (i.p.) cisplatin plus systemic etoposide were studied in 36 patients with small (< 2 cm) residual i.p. ovarian cancer after achieving a partial response to platinum-based, first-line chemotherapy. Treatment comprised 90 mg/m2 i.p. cisplatin with intravenous (i.v.) sodium thiosulphate (day 1) and 600-800 mg/m2 i.v. etoposide (days 1 and 2), every 4 weeks for four to six cycles. 7 patients achieved a pathological complete response (pCR), one a pathological partial response and 16 were clinically stable without evidence of disease. After a median follow-up of 13 months, the median progression-free survival (PFS) was 11 months (95% confidence interval 7-16 months). The actuarial PFS at 24 months is 22% (95% confidence interval 8-36%). Three of six relapses after achieving a pCR (50%) were sited i.p., and 9 of 14 other patients with disease progression (64%) had an i.p. relapse, indicating insufficient local efficacy. There was no renal toxicity, but grade 3-4 leucopenia occurred in 63% and grade 3-4 thrombocytopenia in 8% of cycles, while nausea, vomiting and complete alopecia were common. Although side-effects were acceptable, the efficacy of treatment with i.p. cisplatin plus i.v. etoposide is limited.

AgarCyto: a novel cell-processing method for multiple molecular diagnostic analyses of the uterine cervix.

In diagnostic cytology, it has been advocated that molecular techniques will improve cytopathological diagnosis and may predict clinical course. Ancillary molecular techniques, however, can be applied only if a sufficient number of preparations are made from a single cell sample. We have developed the AgarCyto cell block procedure for multiple molecular diagnostic analyses on a single scraping from the uterine cervix. The optimized protocol includes primary fixation and transport in ethanol/carbowax, secondary fixation in Unifix, and embedding in 2% agarose and then in paraffin according to a standard protocol for biopsies. More than 20 microscopic specimens were produced from a single AgarCyto cell block, and standard laboratory protocols have been successfully applied for H&E staining, immunohistochemistry for Ki-67 and p53, and in situ hybridization for the centromere of human chromosome 1 and human papilloma virus Type 16. In addition, single AgarCyto sections yielded sufficient input DNA for specific HPV detection and typing by LiPA-PCR, and the protocol includes an option for DNA image cytometry. The AgarCyto cell block protocol is an excellent tool for inventory studies of diagnostic and potentially prognostic molecular markers of cervical cancer.

Sentinel lymph node identification with technetium-99m-labeled nanocolloid in squamous cell cancer of the vulva.

UNLABELLED: In patients with early-stage squamous cell cancer of the vulva, inguinofemoral lymphadenectomy is performed primarily as a diagnostic procedure. The morbidity of this procedure, however, is not negligible. The aim of this study was to evaluate the feasibility of minimally invasive detection of the sentinel inguinofemoral lymph node (SILN) and to investigate whether the histopathology of the SILNs is representative of that of the other non-SILNs. METHODS: Patients with early-stage squamous cell cancer of the vulva, planned for resection of the primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, were eligible for the study. Technetium-99m-labeled nanocolloid was injected intradermally at four locations around the tumor the day before operation. Images were recorded immediately and after 2.5 hr using a gamma camera. SILN locations were marked on the overlying groin skin. The next day, during general anesthesia, blue patent dye was injected intradermally at the same locations around the tumor. During the operation SILNs were identified at the place indicated using a handheld gamma-detection probe. It was noted if SILNs were found by the probe, by blue dye or by both techniques. After resection of the SILNs, a standard inguinofemoral lymphadenectomy was performed. The results of histopathology of the SILNs were compared with those of the non-SILNs. RESULTS: The procedure was well tolerated by 10 of 11 patients. One patient, initially agreeing to participate, refused the injection of tracer because of fear of pain. In all 10 patients, identification of the SILNs was successful. The mean time for identification was 11 min. Identification of SILNs was primarily performed using the hand probe in all patients, whereas in 10 of 18 removed SILNs afferent lymph channels were also blue stained (56%). In 8 patients, pathologic examination showed no metastatic disease in both SILNs and non-SILNs, whereas in 2 patients metastases in the SILNs (one and two metastatic lymph nodes, respectively), as well as in other non-SILNs, were found. CONCLUSION: This study shows that identification of SILNs in squamous cell cancer of the vulva is feasible with preoperatively administered 99mTc-labeled nanocolloid. Intraoperatively administered blue dye was only useful for confirmation of identification with nanocolloid. To date, no false-negative SILNs have been found, but expansion of the study is necessary to determine the possible clinical application of this new diagnostic technique.

Analysis of cryolesions in the uterine cervix: application techniques, extension, and failures.

Although cryosurgery is regularly used for treatment of cervical intraepithelial neoplasia (CIN), there are few data concerning freeze technique and attendant extension of the cryolesion. This study evaluated how to create cryolesions extensive enough to eradicate the CIN lesion completely. The way the extension of the cryolesion was influenced by type of probe, anatomical position in the cervix, shape of the external os, and freeze time was analyzed. Furthermore, we examined whether localization of the cryolesions corresponded with the CIN III location. Cryosurgery was applied to the cervix of 64 women the day before hysterectomy was performed for benign disease. Four types of probes were tested and freezing was done with a double freeze cycle. After extirpation of the uterus, slides were cut at the 3-, 6-, 9-, and 12-o'clock positions. With a computerized graphic tablet, the depth and linear extension of the cryolesion were measured morphometrically. After short freeze times, it appeared that an adequate lesion was present in only 67.4% of the slides. The large cone probe gave the best results; the small flat cervix probe the worst. At the 3- and 9-o'clock positions, a significantly higher percentage of inadequate lesions was found (60.8 and 65.3%, respectively). This proved to be due primarily to the extensive vascular supply at those positions. Longer freeze times gave an excellent result within all slides, even at the 3- and 9-o'clock positions. The topographic position of the cryolesion corresponded completely in all cases with that of the CIN III lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Minimum extension and appropriate topographic position of tissue destruction for treatment of cervical intraepithelial neoplasia.

Minimum extension and topographic position of tissue destruction for treatment of cervical intraepithelial neoplasia (CIN) is determined by the extension and the localization of the pathologic epithelium. In 65 cone specimens, we studied the depth of CIN II crypt involvement and the linear extent and topographic position of the CIN III lesions. The topographic position of the CIN III lesion was related to a reference point R, the most caudal point of the ectocervix. The mean maximum depth of CIN III crypt involvement appeared to be 1.6 +/- 1.0 mm, and the mean linear extent of the CIN III lesion was 7.4 +/- 3.7 mm. The distal border of the CIN III lesion was located at a mean distance of 8.2 +/- 4.4 mm from the reference point R, and the proximal border at a mean distance of 13.3 +/- 3.7 mm. Taking the mean + 2 SD values as directives (97.7% of the population) suggests that in almost all patients, the depth of crypt involvement did not exceed 3.6 mm; the linear extent of the CIN III did not exceed 14.8 mm. Furthermore, this implies that in almost all patients, the CIN III lesion was located between 0.6 mm distally (mean - 2 SD) and 20.7 mm proximally (mean + 2 SD) from the reference point R. Based on these results, we conclude that minimum local tissue destruction for treatment of CIN should have a depth of 4 mm over a distance of 15 mm, and should be localized at least between 1 mm distally and 21 mm proximally from the most caudal point of the ectocervix.

Detection, prevalence, and prognosis of asymptomatic carcinoma of the cervix.

Between 1979-1986, 82 of 407 patients (20%) treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis. Sixteen (20%) of these 82 patients had stage IA, 60 (73%) had stage IB, and six (7%) had stage IIA disease. Asymptomatic patients represented 16 of 23 (70%) of stage IA, 60 of 196 (31%) of stage IB, and six of 77 (8%) of stage IIA. In the Netherlands, population screening for cervical carcinoma is conducted on women aged 35-55 years. To examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups, we studied the patients referred to our department. Among the patients younger than 35 years with cervical carcinoma, 20 of 70 (29%) were asymptomatic with disease detected by incidental screening, whereas eight of 177 (5%) in the group 55 years or older had been detected by incidental screening. In the age category 35-55 years, 54 of 160 (34%) were asymptomatic. Patients aged 35-55 years had undergone population screening or incidental screening. In the patients 55 years or older, asymptomatic disease was significantly less prevalent than in younger patients. Only one of the 66 asymptomatic patients in stage IB or higher suffered tumor recurrence. Among symptomatic patients, 25 of 136 (18%) with stage IB and 17 of 71 (24%) with stage IIA had tumor recurrence. Despite the favorable prognosis of patients with asymptomatic carcinoma, asymptomatic presentation could not be shown to be a significant prognostic factor, as were tumor diameter and lymph node status.

Jessner's lymphocytic infiltration of the skin. A clinical study of 100 patients.

Jessner's lymphocytic infiltration of the skin is a well-known but poorly understood disorder. Some doubt still exists about whether it is a single entity or a heterogeneous group that can pass into polymorphous light eruption, discoid lupus erythematosus, or even malignant lymphoma. Therefore, a large number of patients with lymphocytic infiltration of the skin (N = 100; 46 male, 54 female) were examined to elucidate these questions. We conclude that lymphocytic infiltration of the skin is a single entity. Progression into polymorphous light eruption, discoid lupus erythematosus, or lymphoma was not observed. However, this study shows that lymphocytic infiltration of the skin and polymorphous light eruption cases occur simultaneously in 1 patient. In this study the cases of 10 patients with this combination are reported. An effective but harmless therapy is yet unknown. Intermittent use of topical steroids can be useful but is not effective in many patients.

Clinical value of components of the plasminogen activation system in ovarian cyst fluid.

BACKGROUND: The aim of this study was to analyze the concentrations of different components of the plasminogen activation system in cyst fluid from malignant, borderline and benign ovarian tumors and to compare these results with clinicopathological characteristics (FIGO staging, histological grading, residual tumor, ascites, tumor recurrence and disease-free survival). MATERIALS AND METHODS: One hundred and seven cyst fluid samples were enrolled from 25 malignant, 12 borderline and 70 benign ovarian tumors. Determination of uPA, tPA, PAI-1, PAI-2, uPA:PAI-1 complex and tPA:PAI-1 complex was performed by specific double determinant ELISAs based on the concept described previously by Grebenschikov et al. With these ELISAs both complexes of the activators (uPA, tPA) with their inhibitor (PAI-1) can be measured as a separate component. RESULTS: Significant differences were found in median cyst fluid concentrations of uPA, PAI-1, uPA:PAI-1 and tPA:PAI-1 from malignant, borderline and benign ovarian tumors, with the highest levels in malignant ovarian tumors. Cystic endometriosis seems to be a special entity within the benign subclass. To achieve better discrimination between malignant and benign cases we introduced a new malignancy index: ([uPA:PAI-1]+[tPA:PAI-1])x [PAI-1]. The area under a Receiver Operating Characteristic (ROC) curve amounted to 0.80. Significantly higher concentrations were found in FIGO stages II-III-IV compared with stage I for uPA (p<0.05), tPA (p<0.05), uPA:PAI-1 (p<0.01) and tPA:PAI-1 (p<0.05). CONCLUSION: Concentrations of plasminogen activation system markers in cyst fluid from ovarian tumors are related to histological subtype. The most significant components are uPA, PAI-1 and the complexes uPA:PAI-1, tPA:PAI-1. The prognostic value of the components seems to be limited but might be important in detecting high-risk borderline or low stage patients.

The "boom and bust phenomenon": the hopes, dreams, and broken promises of the contraceptive revolution.

The "boom and bust phenomenon" is a pattern that has emerged in the development, introduction, and delivery of a number of significant new contraceptive products in the United States. When a new contraceptive product is introduced with great promise and publicity, it usually experiences a "boom" during which sales, demand, and expectations are high. This boom is often followed by a "bust" phase during which a product does not live up to expectations, initial excitement falls off, and a drop in sales and use ensues. The boom and bust phenomenon goes to the heart of what some have referred to as the failed promise of the contraception revolution by creating obstacles to significant expansion of contraceptive choice in the United States. Case studies of oral contraceptives, intrauterine devices, and Norplant(R) are used to illustrate the boom and bust phenomenon and the effect it has had in shaping the direction of advances in contraceptive technology.

PIP: The ¿boom and bust phenomenon¿ is a pattern that has emerged in the development, introduction, and delivery of many contraceptive products over the last several decades in the US. When a new contraceptive product is introduced with great promise and publicity, it experiences a ¿boom¿ phase during which sales, demand and expectations for the product are high. A ¿bust¿ phase usually follows this boom, during which a product does not appear to live up to expectations, initial excitement falls off, and a drop in sales and use ensues. The boom and bust phenomenon goes through the heart of what some have referred to as the failed promise of the contraception revolution by creating obstacles to significant expansion of contraceptive use in the US. In the paper, a number of forces that have influenced the use trends and public perceptions of 3 modern methods of contraception; namely, oral contraceptives, intrauterine devices, and Norplant are examined to illustrate how the boom and the bust cycle unfolds in the US contraceptive market and what impact this phenomenon has had in shaping the advances in contraceptive technology.

Symptomatology, localization and treatment of recurrent cervical carcinoma.

In a group of 367 women treated for invasive carcinoma of the cervix tumor recurrence was discovered at an asymptomatic stage in 16 (23%) patients. The tumor recurrence was localized to the pelvis in 29 (41%) cases, in the vaginal wall in 3 (4%) cases, and 39 (55%) patients had distant metastases (with or without recurrent tumor in the pelvis). Curative treatment (surgery, n = 2; radiotherapy, n = 8) was applied in 5/29 (17%) patients whose recurrent disease was confined to the pelvis, in all 3 patients with vaginal recurrence and in 2/39 (5%) of the patients with distant metastases. Permanent remission (follow-up > 36 months) was observed in 2 patients with vaginal recurrence and in one with central recurrence. Temporary complete remission (mean 22 months, range 12-30 months) was observed in 3 patients (2 with central recurrence and one with vaginal recurrence). In 20 (69%) of the patients with central or locoregional recurrence, the primary treatment had been so radical (including adjuvant postoperative or full radiotherapy) that surgical treatment or radiotherapy of the recurrence was not considered possible or worthwhile; moreover, 4 of the patients were older than 80 years of age. In retrospect, exenterative treatment could have been considered in 14 patients (< 70 years) and based on 50% operability, could have led to a cure in 2 to 4 patients with tumor recurrence in the pelvis without distant metastases. Chemotherapy was applied to 10 patients, one of whom went into complete remission of lung metastases (follow-up 108 months).

Low complication rate during intraperitoneal therapy through a totally implanted peritoneal access port in patients with ovarian cancer.

Fifty-three patients with histologically proven ovarian cancer were treated with intraperitoneally administered cisplatin or human recombinant interferon-alpha through a totally implanted peritoneal access port. A total of 281 treatment courses were given. No complications related to surgical implantation of the port were seen. Infectious complications, intra-abdominal problems or subcutaneous drug extravasation did not occur. In two patients the number of treatment courses was limited due to inflow obstruction. A totally implanted peritoneal access port proves to be a reliable route for the intraperitoneal treatment of patients with ovarian cancer. The strict aseptic technique we used contributes to its safety by preventing intra-abdominal infections.

Carboplatin with cyclophosphamide in patients with advanced ovarian cancer: an efficacy and quality-adjusted survival analysis.

The efficacy and toxicity of a combination of carboplatin and cyclophosphamide (CC) were studied in a group of 76 patients with advanced ovarian cancer. Progression-free (PFS) and overall survival were compared with a historical group of 65 patients treated with CAP-5 (cyclophosphamide, adriamycin, cisplatin). Subjective toxicity was compared by the measurement of TWiST, the Time Without Symptoms of Disease or Treatment. Of 75 evaluable patients treated with CC, 18 (24%) had a pathologically complete remission (pCR), and 31 (41%) a partial remission (PR). CC led to leukopenia grade III in 38% and grade IV in 3% of 421 treatment cycles. Thrombocytopenia grade III was seen after 7% and grade IV after 2% of cycles. Treatment delay occurred in 11.5% and dose reduction in 21% of cycles. Nephro- or neurotoxicity did not occur. After a median follow-up of 18 months, the median PFS was 24 months and the overall survival was 25 months. Median duration of TWiST was 22 versus 10 months after CAP-5 (P < 0.01). Compared with historical controls, treatment with CC is equivalent to CAP-5. It is free of nephro- and neurotoxicity, but is more myelosuppressive. Quality of life, measured by TWiST, is significantly better during CC. As a consequence of its equivalent efficacy, but lower subjective toxicity, carboplatin should replace cisplatin in treating patients with advanced ovarian cancer.

Noninvasive detection of inguinofemoral lymph node metastases in squamous cell cancer of the vulva by L-

In the majority of patients with early stage squamous cell cancer (SCC) of the vulva, an inguinofemoral lymphadenectomy is performed (in retrospect) for diagnostic reasons: exclusion of inguinofemoral lymph node metastases. The morbidity of this procedure, however, is significant. The aim of the present study was to evaluate noninvasive detection of inguinofemoral lymph node metastases by positron emission tomography (PET) using L-[1-11C]-tyrosine (TYR) as tracer. In patients with SCC of the vulva, scheduled for resection of the primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, results of preoperative palpation of the groins and TYR-PET imaging were compared with histopathology. PET imaging was performed using two different methods. In a first group (n = 16), nonattenuation corrected 'whole body' scans were performed, and in a second group (n = 9), attenuation corrected static emission scans. Sensitivity, specificity, accuracy, and positive and negative predictive value for palpation were 62%, 89%, 82%, 67%, and 87% per groin. Sensitivity, specificity, accuracy, and positive and negative predictive value for TYR-PET were calculated for the two methodologies separately and overall. There were no significant differences. Overall values were 53%, 95%, 94%, 33%, and 98% per lymph node and 75%, 62%, 65%, 41% and 88% per groin. Detection of inguinofemoral lymph node metastases by TYR-PET is not superior to palpation. Neither palpation nor TYR-PET is able to adequately predict or exclude presence of inguinofemoral lymph node metastases in patients with SCC of the vulva.