On verification of hyperthermia treatment planning for cervical carcinoma patients.

PURPOSE: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SAR(calc)) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (DeltaT(meas)) after a short power pulse was measured, which is proportional to SAR(meas). The SAR(calc) along the catheter tracks was extracted from the calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS: The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/- 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R approximately 0.85-0.93) when thermal contact was good, but much weaker (R approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.

Squamous cell carcinoma of the vulva with bulky positive groin nodes-nodal debulking versus full groin dissection prior to radiation therapy.

Patients with clinical palpable involved groin lymph nodes and squamous cell cancer of the vulva are frequently treated by a full inguinal-femoral lymph node dissection followed by adjuvant radiotherapy to the groins and pelvis. Theoretically, less radical surgery for the groin such as nodal debulking, where only the macroscopically involved nodes are resected, allowing radiotherapy to treat any remaining microscopic disease may potentially decrease morbidity without compromising survival The objective of this retrospective study was to compare the groin recurrence rate and survival (disease specific and overall survival) of patients with clinically involved groin nodes and squamous cell carcinoma of the vulva treated either by a full inguino-femoral lymphadenectomy or by a nodal debulking followed by radiotherapy. Forty patients from three separate databases who met these criteria were identified. Patients were treated either by a full inguino-femoral lymphadenectomy or by a debulking of the clinically involved inguinal lymph nodes. All patients received adjuvant radiotherapy to the groins. In these two groups, there was no difference in groin recurrence rate expressed as groin recurrence-free survival (P= 0.247). In a univariate analysis, both overall and disease-free survival were better in the group of patients treated by nodal debulking. However, in a multivariate analysis, other variables such as extracapsular growth were independent predictors for survival while the method of surgical dissection for the groin had no independent significant impact on survival.

Partial urethral resection in the surgical treatment of vulvar cancer does not have a significant impact on urinary continence. A confirmation of an authority-based opinion.

Partial resection of the urethra is sometimes necessary in the surgical treatment of locally advanced vulvar cancer. In this study, the frequency of urinary incontinence after partial urethral resection was compared with that of patients who were treated without partial resection of the urethra. Eighteen patients with vulvar cancer encroaching or infiltrating the urethra, treated by a radical vulvectomy and partial urethrectomy, were compared with 17 patients treated by vulvectomy without partial removal of the urethra. Data on urinary incontinence pre- and postoperatively from both groups were retrospectively collected from the patient files. A questionnaire on urinary incontinence was sent to a subset of patients from both groups in order to get information on the current micturation pattern. In four out of 18 patients (22%) with a partial urethrectomy, incontinence was reported, versus two out of 17 patients (12%) in the control group (P= 0.860). Eight patients in the study group and 12 in the control group are currently alive, and all responded to the questionnaire. Two (25%) in the study group and three (25%) in the control group reported to have current symptoms of urinary incontinence. This retrospective study shows that partial resection of 1-1.5 cm of the distal urethra in addition to a radical local excision for vulvar cancer does not result in a significant increase in the frequency of urinary incontinence, compared with vulvar cancer patients without partial urethrectomy.

Phase II study of carboplatin and whole body hyperthermia (WBH) in recurrent and metastatic cervical cancer.

OBJECTIVE: Hyperthermia enhances carboplatin cytotoxicity preclinically, and clinical studies have shown radiant heat Whole Body Hyperthermia (WBH) to be safe. In this study, the efficacy and toxicity of the combination of 41.8 degrees C WBH and carboplatin in recurrent and/or metastatic cervical cancer were explored. METHODS: Recurrent and/or metastatic cervical cancer patients were treated with 41.8 degrees C WBH and concurrent carboplatin, cycled every 28 days (max. 6 cycles). RESULTS: Twenty-one of 25 participants were evaluable for response: one complete remission, six partial responses, stable disease in nine patients and progression in five, leading to a response rate of 33%. Three of four evaluable chemotherapy pre-treated patients progressed, while this was seen in only 2 of 17 chemotherapy-naive patients. The median survival is 7.8 months (range 1.3 to 43+) and no patients were lost to follow up. Grades 3/4 toxicities were common: leukopenia in 35%, thrombopenia in 61% and anemia in 22% of all treatments. Excessive, partly reversible renal toxicity was seen in two patients (grades 3 and 4). CONCLUSION: The efficacy of WBH and carboplatin in recurrent and/or metastatic cervical cancer seems comparable to that of other palliative chemotherapy regimens in this disease. The considerable toxicity, though largely manageable, includes unexpected and severe unacceptable renal toxicity. This regimen seems less suitable for palliative care.

Squamous cell cancer of the vulva with occult lymph node metastases in the groin: the impact of surgical technique on recurrence pattern and survival.

OBJECTIVE: The triple incision technique is an established surgical method of management for early vulvar cancer. There is only limited data available on the efficacy of this form of treatment for patients with occult inguinofemoral lymph node metastases. It was the objective of this study to obtain more insight into the efficacy of this treatment compared with the en bloc resection, when utilized in surgical pathological advanced disease. METHODS: A retrospective review was performed in patients with vulvar cancer in the presence of occult inguinofemoral lymph node metastases. Tumor diameter, extracapsular nodal spread, FIGO stage, number of positive lymph nodes, and type of treatment were analyzed in relation to recurrence pattern and survival in both univariate and multivariate analyses. RESULTS: There was no significant impact of surgical technique on disease-specific and overall survival. When corrected for other prognostic variables in a multivariate analysis, the type of surgical treatment was an independent predictor for vulvar recurrence (HR 0.10, 95% CI 0.02-0.44, P = 0.002) but not for inguinal/pelvic recurrence. CONCLUSION: The type of surgical technique did not influence disease-specific and overall survival in patients with occult inguinofemoral lymph node metastases. The triple incision technique is an independent poor prognostic variable for vulvar recurrence.

Sarcoma in association with multimodality management of vulvar cancer: two case reports.

BACKGROUND: Radiation-induced or -associated sarcoma is a rare event which has been well described in the literature. However, this entity has been infrequently described in association with genital tract malignancies. To our knowledge it has never been described in association with the management of vulvar cancer. CASES: . Two different cases of sarcoma developing after primary management for vulvar cancer are presented, the first being a case of angiosarcoma developing in the lower abdominal wall 36 months after initial therapy and the second a case of fibrosarcoma developing on the vulva 7 years after multimodality treatment. CONCLUSION: Radiation-associated sarcoma after treatment for vulvar carcinoma is a rare event. A multimodality treatment of carcinoma of the vulva should not be withheld because of fear of sarcomagenesis.

A limited role for adjuvant radiotherapy after the Wertheim/Okabayashi radical hysterectomy for cervical cancer confined to the cervix.

BACKGROUND: The indications for radiotherapy after radical hysterectomy for early stage cervical cancer are changing. In the past only tumor outside the cervix was considered an indication for radiotherapy. Today adjuvant radiotherapy is also considered for an "intermediate-risk" group with tumor confined to the cervix but poor prognostic primary tumor parameters such as large tumor diameter, vascular space invasion, and deep stromal penetration. OBJECTIVE: The aims of this study were to determine the risk of isolated pelvic recurrences in an intermediate-risk group (GOG Study No. 92) and to analyze whether this group will theoretically benefit from adjuvant pelvic radiotherapy. PATIENTS AND METHODS: A retrospective analysis was performed on 271 patients with early cervical cancer treated by a radical hysterectomy in a uniform fashion in one institute. Radiotherapy was administered only when tumor was found outside the cervix. Tumor diameter, capillary lymphatic space invasion, and depth of stromal penetration were assessed in all patients. Recurrence pattern, disease-specific survival, and recurrence-free interval were determined in the intermediate-risk group and compared with the remaining patients of the group with tumor confined to the cervix. RESULTS: A significant difference in disease-specific survival (89% versus 97%, P < 0.03) and 5-year recurrence-free interval (86% versus 95%, P < 0.02) was noted in the intermediate-risk group (n = 56) compared with the total group with tumor confined to the cervix. Three patients in the intermediate-risk group died of disease with a pelvic recurrence. Two of these patients had a combined pelvic and distant recurrence. CONCLUSION: Our retrospective results fail to support a survival benefit of extending indications for adjuvant radiotherapy other than postive nodes, parametrial extension, and positive margins.

Multiple organ dysfunction syndrome induced by whole-body hyperthermia and polychemotherapy in a patient with disseminated leiomyosarcoma of the uterus.

OBJECTIVE: Whole-body hyperthermia (WBH) in combination with chemotherapy is a relatively new promising treatment modality for patients with cancer. The objective of this report is to present the development of an acute systemic inflammatory response syndrome (SIRS) with multiple organ dysfunction syndrome (MODS) following WBH in combination with chemotherapy. Although WBH can also induce cytokine production, MODS has not been described before in association with WBH. DESIGN: Case report. The patient was treated with WBH (core temperature 41.8 degrees C using a radiant heat device (Aquatherm) ) in combination with polychemotherapy (ifosfamide, carboplatin and etoposide (ICE) ) in the context of a clinical trial for metastatic sarcomas. SETTING: Department of medical oncology and intensive care unit of a university hospital. PATIENT: A 58-year-old Caucasian woman treated for disseminated leiomyosarcoma of the uterus, who developed SIRS with brain dysfunction, hypotension, respiratory failure and renal dysfunction following WBH/ICE. INTERVENTIONS: She was successfully treated in the intensive care unit by mechanical ventilation, inotropics and antibiotics. MEASUREMENTS AND RESULTS: There was a remarkable recovery within 2 days: she regained full conciousness, could be extubated, inotropic support was stopped and creatinine levels returned to pre-treatment levels. All cultures remained sterile. After almost complete recovery, 5 days later a second episode of fever during neutropenia occurred and, despite antibiotic treatment, she died of Bacteroides distasonis sepsis. CONCLUSION: WBH should be added as a new cause to the already known list of physical-chemical insults which can result in MODS.

[Hyperthermia in combination with chemotherapy in gynecological cancers]. / Hyperthermie in combinatie met chemotherapie bij gynaecologische tumoren.

Hyperthermia in combination with chemotherapy has a strong biological rationale based on thermal enhancement of cytotoxicity and partial circumvention of resistance. Weekly locoregional hyperthermia in combination with cisplatin is an effective treatment (response rate: 52%) for patients with a recurrence of a previously irradiated carcinoma of the uterine cervix. A comparative trial versus cisplatin alone was recently started. Hyperthermic intraperitoneal chemotherapy is aimed at situations after optimal cytoreductive surgery in patients with carcinomatous peritonitis. The warmth enhances the penetration of the oncolytic agent. Whole-body hyperthermia using the Aquatherm apparatus in combination with chemotherapy is feasible: results in patients with metastatic sarcomas are promising. Trials with whole-body hyperthermia are in progress in patients with platinum refractory ovarian cancer and in patients with a metastatic carcinoma of the uterine cervix.

Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on exclusion of invasion and on relief of symptoms.

van Beurden M, van der Vange N, ten Kate FJW, de Craen AJM, Schilthuis MS, Lammes FB. Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on exclusion of invasion and on relief of symptoms. Int J Gynecol Cancer 1998; 8: 73-77. A study was undertaken to determine the effectiveness of extensive and restricted surgery for vulvar intraepithelial neoplasia (VIN) 3. All consecutive patients with VIN 3 admitted to a tertiary referral hospital were included. The main outcome measures were relief and recurrence of symptoms and progression to invasive disease in patients with VIN 3 after extensive or restricted surgery. Of every vulvoscopic visible lesion a biopsy was taken to establish extent and grade of VIN and to rule out invasive carcinoma. Patients with unifocal VIN 3 underwent extensive surgery. Patients with multifocal VIN 3 underwent extensive or restricted surgery or an expectant management was adopted, depending on the existence of symptoms and the presence of invasive vulvar carcinoma. Forty-seven patients were evaluated. Eighty-three percent of patients had a long history of symptoms. Eight patients (17%) had unifocal VIN 3. In 9% of the patients a superficially invasive vulvar carcinoma was found, ie with a depth of invasion of 1 mm or less. Only 20% of the extensively operated patients had free surgical margins. There was recurrence of symptoms in all of the extensively operated patients, in contrast to a 26% persistence or recurrence rate of symptoms in the restrictedly operated patients. In patients with multifocal VIN 3 who underwent restricted surgery, young age of the patient (P = 0.02) and large extension of VIN 3 (P = 0.02) were significant factors in predicting persistence or recurrence of symptoms. Only once was a superficially invasive vulvar carcinoma diagnosed during follow-up, and this was in an extensively operated patient. Vulvoscopically directed biopsies in VIN 3 are a safe method to exclude invasive disease. Restricted surgery is effective in relieving symptoms in multifocal VIN 3.

Recurrent cervical carcinoma after radical hysterectomy: an analysis of clinical aspects and prognosis.

Samlal RAK, van der Velden J, van Eerden T, Schilthuis MS, Gonzalez Gonzalez D, Lammes FB. Recurrent cervical carcinoma after radical hysterectomy: an analysis of clinical aspects and prognosis. Int J Gynecol Cancer 1998; 8: 78-84. The purpose of the present study was to evaluate the clinical aspects and prognosis of patients with tumor recurrence in surgically treated stage IB and IIA cervical carcinoma patients. Two hundred and seventy-one stage IB and IIA cervical carcinoma patients underwent a Wertheim Okabayashi radical hysterectomy with pelvic lymphadenectomy. The median follow-up time was 60 months. Recurrence occurred in 27 patients (10%): 14 had a pelvic recurrence and 13, and extrapelvic recurrence. The site of recurrence was influenced by various pathological factors as well as by the primary treatment mode. 77% of recurrences were detected within three years after primary treatment. The median recurrence-free interval in patients with a pelvic recurrence was significantly shorter than in patients with an extrapelvic recurrence (14 months vs. 17 months, P = 0.03). The mortality rate of the group of patients with recurrent disease was 85% (23/27). Patients with a pelvic central recurrence had a significantly better outcome than did patients whose recurrences were located at the pelvic sidewall. Two patients with a pulmonary recurrence were treated with surgery and show no evidence of disease after 4 and 8 years respectively, of follow-up. The overall detection rate of recurrent disease by routine follow-up was only 36%. However, asymptomatic patients had a significantly better prognosis when compared with symptomatic patients. Therefore, we recommend frequent follow-up visits during the first 3 years after primary treatment to detect recurrence in an early stage.

Surgical pathologic factors that predict recurrence in stage IB and IIA cervical carcinoma patients with negative pelvic lymph nodes.

BACKGROUND: The purpose of this analysis was to identify pathologic risk factors for recurrence and patterns of recurrence in patients with International Federation of Gynecology and Obstetrics Stage IB and IIA cervical carcinoma and negative pelvic lymph nodes after radical hysterectomy. METHODS: During the period 1982-1991, 271 clinically staged patients with Stage IB or IIA cervical carcinoma underwent a Wertheim-Okabayashi radical hysterectomy with pelvic lymph node dissection. The study group was composed of 196 lymph node negative patients. Pathology slides were reviewed and multivariate analysis performed to identify independent prognostic factors. RESULTS: The recurrence rate in the study group was 7.7%. In multivariate analysis, the following factors were identified as independent risk factors for recurrence: adenocarcinoma (P = 0.003), depth of invasion as a fraction of tumor penetration of the cervical stroma (P = 0.01), and an extensive stromal inflammatory cell infiltrate (P = 0.04). Based on these factors, the following risk groups were identified: a low risk group (N = 140, 5-year disease free interval [DFI] = 97%) and a high risk group (N = 55, 5-year DFI = 81%). An evaluation of the recurrence patterns for these patients showed a predominance of pelvic recurrences. CONCLUSIONS: This study showed that among patients with Stage IB and IIA cervical carcinoma and negative pelvic lymph nodes, a subset with a significant risk for recurrence could be identified. Because the majority of recurrences in the lymph node negative group were pelvic recurrences, the value of adjuvant radiotherapy as a treatment for selected lymph node negative patients should be evaluated in a prospective study.

Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix.

BACKGROUND: The biologic rationale for combining cisplatin with locoregional hyperthermia (HT) relates to the potentiating effect of HT on cisplatin cytotoxicity. METHODS: Patients with recurrent cervical carcinoma, who had a pelvic recurrence after radiotherapy, were treated with weekly cycles of locoregional HT (using the 70-megahertz, 4 antenna-phased array system for 1 hour and cisplatin, 50 mg/m2 intravenously [i.v.], for a maximum of 12 cycles.) RESULTS: Twenty-three patients were entered in this study. A total of 169 cycles were given. Responses were observed in 12 of 23 patients, a response rate of 52% (95% confidence interval, 31-73%). Salvage surgery became possible in 3 of 12 responding patients, whose tumors were previously considered unresectable. The median duration of response was 9.5+ months, the median overall survival was 8+ months, and the 1-year survival was 42%. No correlation was found between treatment outcome and clinical parameters such as age, weight, performance status, and histology. Thermal parameters such as T20, T50, and T90 were higher in responding patients, but were not significantly different from nonresponding patients. Overall toxicity was moderate. Subcutaneous fatty necrosis due to HT occurred in 10% of the cycles, whereas 2 patients developed skin burns. Squamous cell carcinoma antigen proved to be a valuable tool for the evaluation of response and detection of progression. CONCLUSIONS: Weekly locoregional HT and cisplatin, 50 mg/ m2 i.v., for a maximum of 12 cycles was effective treatment in patients with a previously irradiated recurrent carcinoma of the uterine cervix.

Identification of high-risk groups among node-positive patients with stage IB and IIA cervical carcinoma.

The purpose of the present study was to identify a subset of high-risk patients among surgically treated node-positive patients with stage IB and IIA cervical carcinoma. From 1982 through 1991, 334 patients underwent radical hysterectomy for FIGO stage IB and IIA cervical carcinoma. In 68 patients pathological analysis of the surgical specimen revealed positive pelvic nodes. In this group, a Cox proportional hazard analysis was performed to examine the prognostic significance of clinicopathological variables. Only for adenocarcinoma (P = 0.002) and parametrium infiltration (P = 0.003) was evidence of an association with prognosis found. Based on these two factors, patients with positive pelvic nodes were categorized into a low-risk group (squamous cell carcinoma without parametrium infiltration, N = 33) and a high-risk group (squamous cell carcinoma with parametrium infiltration or adenocarcinoma, N = 34). The 5-year disease-specific survival in the low-risk group was 94% compared with 60% in the high-risk group (P = 0.003). For patients in the high-risk group, there is an urgent need for alternative adjuvant treatment to improve outcome.

Influence of diagnostic conization on surgical morbidity and survival in patients undergoing radical hysterectomy for stage IB and IIA cervical carcinoma.

The purpose of this retrospective study was to investigate whether diagnostic conization influenced surgical morbidity of a subsequent radical hysterectomy in patients with early cervical carcinoma. Furthermore, the impact of an irradical conization on nodal metastases and prognosis was analysed. Included were 271 patients with stage IB and IIA cervical carcinoma who underwent an Okabayashi radical hysterectomy between 1982 and 1991. There were 68 patients who underwent conization prior to radical hysterectomy. The conization-radical hysterectomy interval was approximately six weeks. Surgical morbidity in patients with a previous conization was not significantly different from that in patients without a previous conization. Survival was also not significantly different between these groups (95% vs. 91%, p = 0.23). Multivariate analysis showed that an irradical conization was not associated with an increased risk for nodal metastases or a poorer prognosis. We suggest that in early cervical carcinoma, a diagnostic conization does not adversely affect early morbidity of a following radical hysterectomy. An irradical conization does not seem to influence prognosis.

Feasibility, toxicity, and preliminary results of weekly loco-regional hyperthermia and cisplatin in patients with previously irradiated recurrent cervical carcinoma or locally advanced bladder cancer.

PURPOSE: The biological rationale for combining locoregional hyperthermia (HT) with cisplatin (CDDP) is the potentiating effect of HT on CDDP uptake and cytotoxicity. Feasibility, toxicity, and preliminary results of a clinical trial of weekly loco-regional HT in combination with cisplatin are described in this article. METHODS AND MATERIALS: Patients with previously irradiated unresectable local recurrent cervical carcinoma or locally advanced bladder carcinoma were treated with weekly cycles of locoregional HT (70 MHz four antenna phased array system) for 1 h and CDDP 50 mg/m(2) IV for a maximum of 12 courses. RESULTS: Fourteen patients, 10 patients with recurrent cervical carcinoma and 4 with locally advanced bladder carcinoma, were entered in this study. A total of 100 cycles were given. Overall toxicity was acceptable; Grade 3 (WHO) toxicity (gastrointestinal, hematological, and neurotoxicity) was observed in 5 out of 14 patients. No Grade 4 toxicity was seen. Subcutaneously fatty necrosis due to HT occurred in 11% of the cycles, while two patients developed skin burns. Two out of 10 patients with recurrent cervical carcinoma were not evaluable for response. Four out of eight evaluable cervical carcinoma patients responded (two pathologic complete responses, one pathologic confirmed partial response, one partial response): response rate 50% (95% confidence interval 15.7-84.3%). Salvage surgery became possible in three out of four responding patients, whose tumors were previously considered unresectable. Two out of the four evaluable patients with locally advanced bladder carcinoma responded (two partial responses). CONCLUSIONS: Weekly loco-regional HT and CDDP 50 mg/m(2)/week for a maximum of 12 courses is feasible with an acceptable toxicity, which seems not to be enhanced by the addition of loco-regional HT. The encouraging preliminary results of this treatment schedule warrant further study, especially in patients with previously irradiated recurrent cervical carcinomas.

Intestinal obstruction in patients with advanced ovarian cancer.

A retrospective analysis of the management of intestinal obstruction in 31 patients with advanced ovarian carcinoma is described. Between 1981 and 1992 31 patients developed intestinal obstruction after their initial treatment. Nineteen patients underwent surgery, while the remaining 12 were treated conservatively. Careful evaluation with contrast studies of both the small intestine and colon is recommended to improve the prediction of site(s) of obstruction, and may reduce the number of unsuccessful operative procedures. Fifteen of the surgically treated patients survived for a period of 60 days or more. The majority, 13, were discharged to their homes after an average hospital stay of 24 days. Major postoperative complications occurred in three of the 19 patients. There was no surgical-related mortality. Two patients died within 30 days postoperatively (urosepsis and advanced tumor). While the median survival in the 19 surgical treated patients was 109 days (range 15-775), the conservatively treated 12 patients survived for a mean of 37 days (range 6-260). Surgical management of intestinal obstruction in selected cases is feasible and improves quality of life substantially.

Serum CA 125 levels in epithelial ovarian cancer: relation with findings at second-look operations and their role in the detection of tumour recurrence.

Pre-operative serum CA 125 levels were elevated (greater than 35 U/ml) in 44 of 46 (96%) patients with epithelial ovarian cancer. Their serum CA 125 levels ranged from 36 to 8670 U/ml and a correlation with tumour stage was found. Also, during progressive disease, 49 of 53 patients showed elevated levels. At the time of second-look operations, elevated serum CA 125 levels indicated the presence of tumour. However, the presence of small tumour residues (less than 2 cm) and of microscopically detectable tumour in biopsies were not associated with raised CA 125 levels, only a few patients (2 of 13 and 2 of 17, respectively) showed levels higher than 35 U/ml before the second-look operation. Rising levels preceded the clinical discovery of a relapse in 15 of the 22 patients with a median lead time of 3.5 months (1-17 months), and in three patients rising levels were found at the time the tumour recurrence was detected. It is concluded that CA 125, despite its general usefulness, is unable to detect tumour nodules of less than 2 cm in size, but it proved to be a sensitive and early indicator of tumour recurrence and progression.

Analysis of renal structural and functional features in two rat strains with a different susceptibility to glomerular sclerosis.

Individual differences in susceptibility to the development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) after loss of renal mass were studied in two rat strains. Male Wistar rats, and most other rat strains, were found to develop FSGHS associated with proteinuria with ageing, a process which could be accelerated by unilateral nephrectomy (UN). In male PVG/c rats, however, a complete resistance to the development of FSGHS was found even at 1 year after UN. The Wistar rat was found to have a lower number of nephrons per kidney and to differ from the PVG/c rat in its response to UN: Wistar rats showed an increase of whole kidney glomerular filtration rate and renal plasma flow in the remaining kidney with expansion of glomerular volume and with increased mesangial deposition of circulating macromolecules. In the PVG/c rat, UN led to a comparable proportional increase in glomerular filtration rate and renal plasma flow in the remaining kidney. However, in contrast to the Wistar rat neither glomerular hypertrophy nor enhanced mesangial macromolecular accumulation were observed after UN. Although the precise mechanisms underlying these effects are not identified, the current data support the "mesangial overloading" concept of FSGHS in which a local enhanced mesangial accumulation of circulating macromolecular material is thought to initiate the development of the sclerotic glomerular lesions. Moreover, to our knowledge this is the first description of a rat strain showing complete resistance to the development of FSGHS after UN. This PVG/c strain therefore seems to be a useful laboratory animal in comparison to other rat strains to further study the renal adaptation process after kidney ablation.

Mesangial function and glomerular sclerosis in rats after unilateral nephrectomy.

To investigate the possible relationship between disturbance of mesangial function and segmental localization of glomerular sclerosis, five uninephrectomized male Wistar rats and five sham-operated controls received colloidal carbon intravenously. At 4 months 8.4 +/- 2.5% of the glomeruli of the nephrectomized rats showed focal sclerosis. Glomeruli of nephrectomized rats contained significantly more carbon than glomeruli of controls. Glomeruli with focal sclerosis contained significantly more carbon than normal glomeruli in the same kidneys with a preferential tracer localization within the lesions. In another experiment carbon injections were given before surgery. At 4 months 12.6 +/- 4.1% of the glomeruli of the nephrectomized rats showed focal sclerosis, an incidence not significantly different from that of the first experiment. Glomerular carbon content was equal in experimental and control rats and no preferential localization of the tracer within the lesions was found. From these results we conclude that the preferential localization of carbon in the glomerular lesions in rats nephrectomized before injection of carbon is caused by the increased delivery of tracer shortly after injection to those glomerular areas where sclerosis will develop at a later time. The development of focal sclerosis may be related to the local deposition of harmful substances from the circulation.