Mindfulness and fear of hypoglycaemia in parents of children with Type 1 diabetes: results from Diabetes MILES Youth - The Netherlands.

AIMS: To identify the sociodemographic and clinical correlates of fear of hypoglycaemia among parents of children (aged 4-18 years) with Type 1 diabetes and to examine the relationships between parental fear of hypoglycaemia, mindfulness and mindful parenting. METHODS: Sociodemographic, self-reported clinical and psychological data were extracted from the cross-sectional Diabetes MILES Youth - The Netherlands dataset. Questionnaires included the Hypoglycaemia Fear Survey - Parent Worry (parental fear of hypoglycaemia), the Freiburg Mindfulness Inventory - Short version (mindfulness) and the Interpersonal Mindfulness in Parenting Scale (mindful parenting). RESULTS: A total of 421 parents (359 mothers) participated. Hierarchical linear regression analyses showed that greater parental fear of hypoglycaemia was related to younger parental age, low educational level, non-Dutch nationality, more frequent blood glucose monitoring, and less general mindfulness. Adding mindful parenting to the model negated the previous contribution of general mindfulness. In this model, lower mindful parenting was related to greater parental fear of hypoglycaemia. In particular, parents with an increased ability to be less judgemental of themselves as parents and less reactive to emotions within parenting interactions reported less fear of hypoglycaemia. In total, 21% of the variance in parental fear of hypoglycaemia was explained. CONCLUSION: Parental fear of hypoglycaemia was associated largely with parental characteristics, including non-modifiable sociodemographics (i.e. age, education, nationality) and modifiable psychological factors (i.e. mindful parenting). These findings suggest that it is important to further explore mindfulness-based interventions for parents to reduce fear of hypoglycaemia next to interventions to reduce hypoglycaemia.

Kinetic modeling and efficacy of intraperitoneal paclitaxel combined with intravenous cyclophosphamide and carboplatin as first-line treatment in ovarian cancer.

OBJECTIVE: The purpose of this study was to determine the efficacy, tolerability, and pharmacokinetics of intraperitoneal (ip) paclitaxel combined with intravenous (iv) carboplatin and cyclophosphamide. PATIENTS AND METHODS: Twenty-five newly diagnosed patients with Stage IC-IV epithelial ovarian cancer received ip paclitaxel with iv carboplatin and cyclophosphamide as a first-line treatment. Paclitaxel pharmacokinetics was determined during the first cycle on day 1 or 8. RESULTS: This regimen was well tolerated, as abdominal pain and hematological toxicities were minor, while neurotoxicity grade I/II was reported in only 20% and myalgia in 24% of patients and were fully reversible. After treatment 13 of 18 (72%) of the patients had no evidence of disease. At a median follow-up of 30 months patients with residual disease after surgery (n = 10) had a median progression-free survival (PSF) of 13 months; for the optimally debulked group (n = 15) the actuarial PFS was 60% at 48 months. The elimination of paclitaxel from the peritoneal cavity and plasma followed first-order kinetics and was not influenced by adding carboplatin with cyclophosphamide. CONCLUSION: This regimen was well tolerated, with minimal hematologic or neurotoxicity, and allowed the application of a triple-drug schedule without compromising dose intensity. To judge its efficacy, comparison with a standard iv paclitaxel-based schedule should be performed in a formal phase III study.

A phase I and pharmacokinetic study of intraperitoneal topotecan.

PURPOSE: To evaluate the feasibility and pharmacology of intraperitoneal (IP) topotecan. PATIENTS AND METHODS: Fifteen patients with recurrent ovarian cancer in a phase I trial were treated with escalating IP topotecan doses (5-30 mg/m(2)) for pharmacokinetic analysis. RESULTS: Dose limiting toxicity (DLT) was acute hypotension, chills and fever at the 30 mg/m(2) dose level. Haematological toxicity and abdominal pain were mild for all dose levels studied. PHARMACOKINETICS: Peak plasma levels of total topotecan were reached at 2.7 +/- 1.1 h after IP instillation. The apparent V(ss) was 69.9 +/- 25.4 L/m(2), plasma clearance 13.4 +/- 2.5 L/h/m(2) and plasma T1/2 3.7 +/- 1.3 h. The plasma AUC was correlated with the dose (R = 0.95, P < 0.01). The plasma AUC ratio of lactone versus total topotecan (lactone + carboxy-forms) increased with the dose from 16% to 55%, (R = 0.84, P < 0.01). Peritoneal total topotecan was cleared from the peritoneal cavity at 0.4 +/- 0.3 L/h.m(2) with a T1/2 = 2.7 +/- 1.7 h. The mean peritoneal/plasma AUC ratio for total topotecan was 54 +/- 34. CONCLUSION: A substantial dose of topotecan can be delivered by the IP route, achieving cytotoxic plasma levels of topotecan, with acceptable toxicity. The recommended dose for further phase II trials is 20 mg/m(2) IP, which enables combination with active doses of other cytotoxic drugs, in view of its limited myelotoxicity when given by this route.

Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer.

PURPOSE: To investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients. PATIENTS AND METHODS: Follow-up data were evaluated in patients with early-stage squamous cell cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy. Routine serum SCC-ag determination was performed at each follow-up visit. RESULTS: Recurrent disease occurred in 35 (16%) of 225 patients and was preceded or accompanied by serum SCC-ag elevation 26 times (sensitivity, 74%). In five (14%) of these 35 patients, elevated serum SCC-ag was the first measured clinical indicator. Desite salvage therapy, all five patients died of disease. In the other 31 patients (21 with serum SCC-ag elevation), either symptoms and/or positive signs led to recurrence detection. Median survival time after recurrence was worse (9 months; range, 2 to 112+) for patients with an elevated serum SCC-ag value at recurrence in comparison with patients with normal serum SCC-ag values (20 months; range, 4 to 96; P <.01). In 23 of the 190 patients without recurrences, serum SCC-ag values became falsely elevated. In 16 of these 23 patients, the repeat sample after 6 weeks showed a normal SCC-ag, and in seven patients benign (especially skin) disorders were found. CONCLUSION: Serum SCC-ag analysis results in earlier recurrence detection in a small proportion (14%) of patients but did not contribute to better survival. As long as treatment possibilities for recurrent cervical cancer patients are not improved, serum SCC-ag analysis should not be carried out in routine follow-up.

Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of the vulva.

PURPOSE: To determine the diagnostic accuracy of the sentinel lymph node procedure in patients with squamous cell carcinoma of the vulva and to investigate whether step sectioning and immunohistochemistry of sentinel lymph nodes increase the sensitivity for detection of metastases. PATIENTS AND METHODS: Between July 1996 and July 1999, 59 patients with primary vulvar cancer were entered onto a two-center prospective study. All patients underwent sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with technetium-99m-labeled nanocolloid and intraoperative blue dye). Radical excision of the primary tumor with uni- or bilateral inguinofemoral lymphadenectomy was performed subsequently. Sentinel lymph nodes and lymphadenectomy specimens were sent for histopathologic examination separately. Sentinel lymph nodes, negative at the time of routine pathologic examination, were re-examined with step sectioning and immunohistochemistry. RESULTS: In 59 patients, 107 inguinofemoral lymphadenectomies were performed (11 unilateral and 48 bilateral). All sentinel lymph nodes, as observed on preoperative lymphoscintigram, were identified successfully intraoperatively. Routine histopathologic examination showed lymph node metastases in 27 groins, all of which were detected by the sentinel lymph node procedure. The negative predictive value for a negative sentinel lymph node was 100% (97.5% confidence interval [CI], 95% to 100%). Step sectioning and immunohistochemistry showed four additional metastases in 102 sentinel lymph nodes (4%; 95% CI, 1% to 9%) that were negative at the time of routine histopathologic examination. CONCLUSION: Sentinel lymph node procedure with the combined technique is highly accurate in predicting the inguinofemoral lymph node status in patients with early-stage vulvar cancer. Future trials should focus on the safe clinical implementation of the sentinel lymph node procedure in these patients. Step sectioning and immunohistochemistry slightly increase the sensitivity of detecting metastases in sentinel lymph nodes and should be included in these trials.

Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors.

OBJECTIVES: The goals of this study were to analyze preoperative serum levels of CA 125, carcinoembryonic antigen (CEA), and CA 19-9 in patients with borderline ovarian tumors and to investigate if routine assessment of these markers in follow-up may lead to earlier detection of recurrence. METHODS: For patient identification a database was used, in which data from all patients treated for gynecologic malignancies in the Department of Gynecologic Oncology, University Hospital Groningen, The Netherlands, are compiled. Between 1982 and 1997, 44 patients with borderline ovarian tumors were identified. Clinical data and serum CA-125 and CEA levels were retrieved from the database. CA 19-9 levels were determined in retrospect in available stored preoperative (24 patients) and follow-up (43 patients) serum samples. RESULTS: Preoperative CA 125 levels were elevated in 8 of 33 (24%), CEA levels in 3 of 32 (9%), and CA 19-9 levels in 11 of 24 (46%) cases. In patients with mucinous tumors preoperative CA 19-9 was more frequently elevated (8/14, 57%) than CA 125 (3/20, 15%) (P = 0.02) or CEA (2/18, 11%) (P = 0.02). Complete follow-up serum CA 125, CEA, and CA 19-9 levels were available for 43 of 44 patients. Median follow-up was 84 months (range, 22-204). During follow-up two patients (5%) had recurrent disease. In one patient CA 125 became elevated at the time of recurrence; in the other patient (in retrospect) the CA 19-9 level did not return to normal after surgery, but kept rising, preceding clinical symptoms of recurrence for 13 months. CONCLUSIONS: If one chooses to use serum markers in follow-up of mucinous borderline ovarian tumors CA 19-9 should be included. Measurement of serum tumor markers in the follow-up of patients with borderline ovarian tumors may lead to earlier detection of recurrence in only a very small proportion of patients, while the clinical value of earlier detection of recurrence remains to be established.

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.

The clinical value of squamous cell carcinoma antigen in cancer of the uterine cervix.

A review is given of the clinical use and interpretation of serum tumor marker levels during the treatment of patients with cancer of the uterine cervix. Pretreatment serum squamous cell carcinoma (SCC) antigen provides a new prognostic factor in early stage squamous cell carcinoma of the uterine cervix. Elevated serum values of SCC antigen at the time of diagnosis of stage IB and IIA cervical cancer indicate a 3 x increased risk of tumor recurrence, independent of tumor diameter, grade or the presence of lymph node metastases. High pretreatment SCC antigen levels could therefore be used to select 'high-risk' patients for adjuvant therapy. Measurement of the serum SCC antigen levels provides a means of monitoring the effect of therapy. During the postoperative follow-up of patients with localized cancer of the uterine cervix the measurement of SCC antigen can lead to the early detection of recurrent disease when curative therapy is still an option. The profile of serum SCC antigen parallels the response to radiotherapy and provides a way of evaluating the effectiveness of chemotherapy. Serial measurements after surgery and during radio- and chemotherapy demonstrate that SCC antigen is a more sensitive marker for recognizing tumor progression or recurrence than CYFRA-21.1, TPS or CEA. When following up patients with a pure adenocarcinoma of the cervix measurements of serum CA 125 and CEA are preferred over SCC antigen measurements.

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.

The value of cancer antigen 125 (CA 125) during treatment and follow-up of patients with ovarian cancer.

Although the nature of the cancer antigen 125 leaves many questions unanswered, the use of serum measurements as a means to assess the response to surgery and chemotherapy in ovarian cancer is now well documented. Good prognostic significance is attributed to a rapid decline in cancer antigen 125 levels after chemotherapy in patients with advanced ovarian cancer. Pre-operative serum cancer antigen 125 levels may successfully discriminate benign from malignant adnexal masses in postmenopausal women, but in women in their reproductive years the specificity is low. In stage I ovarian cancer patients, high preoperative cancer antigen 125 levels are reported to lead to a sixfold increase in the risk of dying from the disease. Low expectations on the specificity and outcome of cancer antigen 125-based screening of asymptomatic women are contradicted by the first results of screening programmes for postmenopausal women. Large, randomized, controlled studies will assess if survival can be improved by early detection of ovarian cancer. Experimental immunotherapy by activation of the idiotypic network directed against cancer antigen 125 may offer new possibilities to prolong survival in advanced ovarian cancer.

Concurrent chemo- and radiotherapy in patients with locally advanced carcinoma of the cervix.

BACKGROUND: The feasibility of concurrent chemotherapy and radiotherapy for advanced primary carcinoma of the cervix was evaluated and the results were compared to historical controls. PATIENTS AND METHODS: In a single institution study, patients (n = 74) with primary cervical carcinoma received 3 cycles carboplatin/5-fluorouracil concurrent with radiotherapy followed by salvage hysterectomy (group I). Treatment results were compared with those of a historical control group (n = 39) (group II), treated similarly but without chemotherapy. RESULTS: In group I median follow-up is 28 months (12-68+) and in group II 23 months (14-90+ months). The 5-year overall survival, progression-free survival and local recurrence free survival for group I and II are, respectively, 69% versus 38% (P < 0.003), 67% versus 38% (P < 0.005) and 84% versus 43% (P < 0.0001). Two patients in each group developed posttreatment enteritis. CONCLUSIONS: Radiotherapy with concurrent carboplatin and 5-fluorouracil resulted in a better overall survival, disease free survival and local disease free survival compared to historical controls. The toxicity of this schedule did not exceed that of radiation alone in historical controls.

Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma.

PURPOSE: To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors. PATIENTS AND METHODS: Sera from 653 women treated for squamous cervical cancer between 1978 and 1994 were analyzed for the presence of SCC-ag and related to clinicopathologic characteristics and patient outcome using univariate and multivariate analyses. RESULTS: Increased pretreatment SCC-ag levels correlated strongly with unfavorable clinicopathologic characteristics (International Federation of Gynecology and Obstetrics [FIGO] stages IB to IV [P < or = .00005]; stages IB and IIA: tumor size [P = .0236], deep stromal infiltration [P = .00009], and lymph node metastasis [P = .0001]). After multivariate analysis, elevated pretreatment serum SCC-ag levels (P = .001), lesion size (P = .043), and vascular invasion by tumor cells (P = .001) were independent predictors for the presence of lymph node metastases. In Cox regression analysis, controlling for SCC-ag, lesion size, grade, vascular invasion, depth of stromal infiltration, and lymph node status only the initial SCC-ag level had a significant independent effect on survival (P = .0152). Even in node-negative patients, the risk of recurrence was three times higher if the SCC-ag level was elevated before therapy. CONCLUSION: The determination of pretreatment serum SCC-ag level provides a new prognostic factor in early-stage disease, particularly in patients with small tumor size. In future trials to assess the value of new treatment strategies, pretreatment serum SCC-ag levels can be used to help identify patients with a poor prognosis.

Cell biological markers of drug resistance in ovarian carcinoma.

The aim of the study is to review the mechanisms of resistance to four classes of drugs that are widely used in ovarian carcinoma: platinum (cisplatin/carboplatin) compounds, classical alkylating agents (cyclophosphamide/melphalan), natural drugs (doxorubicin), and "new drugs" (taxol and taxotere). Both platinum and classical alkylating agents mediate their cytotoxicity by the formation of drug-DNA adducts, resulting in DNA damage. Therefore, drug resistance mechanisms are (in part) comparable. In ovarian carcinoma cell lines increased repair of DNA damage and increased detoxification by binding of drugs to glutathione, possibly catalyzed by glutathione S-transferases, have been identified as the most prominent resistance mechanisms to these drugs. Studies on the role of DNA repair mechanisms and glutathione in human ovarian carcinoma are hampered by the complexity of enzyme systems involved in DNA repair and intratumor heterogeneity for glutathione. Resistance to doxorubicin appears to be mediated by enhanced efflux from the cell by increased expression of membrane glycoproteins acting as a drug efflux pump, such as P-glycoprotein. Resistance to doxorubicin can also be due to quantitative and/or qualitative changes in the nuclear target of doxorubicin, topisomerase (Topo) II. Finally, resistance to taxol may be mediated by enhanced expression of P-glycoprotein, while presumed other mechanisms such as alterations in tubulin structure, the cellular "target" of taxol, and changes in polymerization of tubulin are still largely unresolved. Several ways to modulate the reviewed resistance mechanisms are also described. In conclusion, this review shows that many cell biological factors may be involved in drug resistance. The relevance of the identification of most of these factors in ovarian carcinoma patients however remains to be established.

Recombinant human interleukin-3 to dose-intensify carboplatin and cyclophosphamide chemotherapy in epithelial ovarian cancer: a phase I trial.

PURPOSE: To define the optimal dose of recombinant human interleukin-3 (rhIL-3) required to intensify the dose of carboplatin and cyclophosphamide for advanced epithelial ovarian cancer. PATIENTS AND METHODS: Seventeen patients were treated on day 1 with carboplatin (dose adjusted for creatinine clearance: range, 257 to 385 mg/m2; median, 300 mg/m2) and cyclophosphamide (750 mg/m2). rhIL-3 5 micrograms/kg/d (n = 10) or 10 micrograms/kg/d (n = 7) was administered subcutaneously (SC) on days 2 through 11. Carboplatin dose was escalated if no postponement of cycles 1 to 3 had occurred. RESULTS: A 3-week interval was achieved in 62% of cycles and a 4-week interval in 81%, with no difference between the rhIL-3 doses. A neutrophil nadir less than 0.5 x 10(9)/L occurred in 35% of the cycles at 5 micrograms/kg/d and in 52% at 10 micrograms/kg/d of rhIL-3 (nonsignificant difference). The mean platelet nadir in cycle 1 was 173 +/- 78 x 10(9)/L at 5 micrograms/kg/d and 340 +/- 152 x 10(9)/L at 10 micrograms/kg/d of rhIL-3 (P < .05), with a faster recovery of platelets at 10 micrograms/kg/d (P < .05). Progressive myelotoxicity occurred for leukocytes and platelets at both rhIL-3 doses and required chemotherapy postponement in later cycles. The planned six cycles were completed by 41% of patients. Fever (> or = 38.5 degrees C) occurred in 38% of cycles at 5 micrograms/kg/d and in 97% at 10 micrograms/kg/d (P < .0005); headache and myalgias occurred in 30% and 44%, respectively. After two cycles, diffuse erythema, facial edema, and urticaria were observed in two patients at 5 micrograms/kg/d and in five patients at 10 micrograms/kg/d of rhIL-3. This resolved after discontinuation of rhIL-3 and administration of corticosteroids and antihistamines. CONCLUSION: A dose of 5 micrograms/kg/d of rhIL-3 proved to be optimal to intensify the carboplatin and cyclophosphamide regimen. It permitted the administration of carboplatin and cyclophosphamide combination therapy every 3 weeks in 62% of cycles.

Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas.

PURPOSE: To determine the prognostic value of immunostaining of P-glycoprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. PATIENTS AND METHODS: Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival. RESULTS: P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately. CONCLUSION: Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy.

Phase II study of high-dose megestrol acetate in patients with advanced ovarian carcinoma.

The EORTC Gynaecological Cancer Cooperative Group conducted a phase II study of high dose oral megestrol acetate: 800 mg/day for 1 month followed by 400 mg/day as maintenance treatment, in heavily pretreated patients with ovarian cancer. Of 72 patients included in this study, 54 were fully evaluable for response and toxicity. The response rate was low with only 1 patient having a partial response, 9 patients with stable disease and 44 patients with progressive disease. The toxicity profile was low. However, 1 patient died after 2 months of treatment, and in 3 patients thrombo-embolic events occurred. Weight gain varied in 20 of the 61 patients from 0.5 to 16 kg. This study does not suggest that the overall 10% benefit from hormonal therapy for chemotherapy refractory ovarian cancer will improve by increasing the dose.

Total pelvic exenteration: a justified procedure.

Twenty patients with advanced primary or locally recurrent pelvic tumours treated by total pelvic exenteration are described. There wer no operative or postoperative deaths. The most frequent postoperative complications appeared to be related to previous irradiation. Four patients developed non-fatal intestinal complications within 30 days of operation that required further surgery. After a mean follow-up of 19 months the crude 2-year survival rate was 40 per cent. This procedure is judged to be useful in a selected group of patients.

Cancer-associated antigen CA 195 in patients with mucinous ovarian tumours: a comparative analysis with CEA, TATI and CA 125 in serum specimens and cyst fluids.

The CA 195 levels in ovarian cyst fluids from malignant mucinous tumours (median 2,300,000 U/ml) were significantly higher than the levels in benign mucinous tumours and malignant non-mucinous tumours (medians of 26,800 and 1,700 U/ml, respectively, p = 0.039 and 0.011). Also, the carcinoembryonic antigen (CEA) and tumour-associated trypsin inhibitor (TATI) levels in cyst fluid from mucinous tumours were much higher than those in non-mucinous tumours. Pretreatment serum CA 195 levels were found to be elevated (> 10.5 U/ml) in 72% of the patients with malignant mucinous tumours (n = 25), compared with 35% in malignant non-mucinous tumours and 28% in benign mucinous tumours. The positivity rate shown for serum CA 195 in malignant mucinous tumours was higher than that measured for serum TATI, CA 125 or CEA (60, 53 and 42%, respectively). Measurement of serum CA 195 can be valuable in the clinical management of patients with mucinous ovarian cancer.