Tapio Kuoppala

Surgically staged high-risk endometrial cancer: Randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy

OBJECTIVE Our purpose was to establish whether platinum-based chemotherapy combined with standard surgery and radiotherapy will improve overall and disease-free survival and lower the recurrence rate in patients with high-risk endometrial cancer. STUDY DESIGN A total of 156 patients with Stage IA-B Grade 3 (n=28), or Stage IC-IIIA Grade 1-3 (n=128) were postoperatively randomized to receive radiotherapy (56 Gy) only (Group A, n=72) or radiotherapy combined with three courses of cisplatin (50 mg/m(2)), epirubicin (60 mg/m(2)) and cyclophosphamide (500 mg/m(2)) (Group B, n=84). RESULTS The disease-specific overall five-year survival was in Group A 84.7% vs. 82.1% in Group B (p=0.148). The median disease-free survival in A was 18 (range 9-36) months and 25 (range 12-49) months in B (p=0.134), respectively. During a five-year follow-up 32 patients relapsed. Of the recurrences 5 were local and 20 distant, while 7 were combined. As calculated from the operation, the median time to recurrence was 15 (range 6-37) months in Group A, and 20 (range 8-60) months in Group B, respectively (p=0.170). Twenty-six patients died of the disease during the five-year follow-up, 11 in A and 15 in B. The patients succumbing in A lived a median 23 (range 15-44) months as compared to 37 (range 13-50) months in B (p=0.148). Chemotherapy was associated with an acceptable rate of acute toxicity. Less than 8% of the patients complained of Grade 3/4 nausea. The rate of Grade 3/4 leucopenia was at the highest at 16.6% during the third cycle but only 6.2% of the patients had Grade 3 infection. A total of 10 patients developed intestinal complications demanding surgery, 2 in Group A (2.7%) and 8 (9.5%) in Group B, respectively. CONCLUSION Adjuvant chemotherapy with cisplatin, epirubicin and cyclophosphamide failed to improve overall survival or lower the recurrence rate in patients operated on and radiated for high-risk endometrial carcinoma. Chemotherapy was associated with a low rate of acute toxicity but appeared to increase the risk of bowel complications.

Cytokine production profiles in the peritoneal fluids of patients with malignant or benign gynecologic tumors

Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. Some cytokines have been shown to have potential in the diagnosis of cancer.

Activities of antioxidant enzymes and lipid peroxidation in endometrial cancer

Antioxidant enzyme activities and lipid peroxidation were analysed in normal endometrium and endometrial cancer tissues from Finnish and Japanese patients. The catalase and glutathione peroxidase activities of normal endometrium were significantly lower in Finns than in Japanese. Lipid peroxidation was slightly higher in endometrial cancer as compared with normal endometrium both in the Finns and in the Japanese. When cancer tissues were compared with normal endometrium both in Finns and Japanese the activity of superoxide dismutase was significantly lower in cancer tissue than in normal endometrium. In Finns glutathione S-transferase activity was also lower in endometrial cancer tissue than in normal endometrium, and a similar tendency was also found in Japanese. This study suggests that endometrial cancer tissue is associated with an impaired enzymic antioxidant defence system.

Sentinel node and vulvar cancer: a series of 47 patients

Background. There is growing interest to apply the sentinel node technique in the treatment of vulvar cancer. Methods. All charts of the patients operated on for vulvar cancer at Tampere University Hospital from January 1, 2001 through June 30, 2005 were retrospectively reviewed. Demographic, clinical, and histopathological information was collected from each patient. The sentinel lymph node mapping was done intraoperatively either with a combination of the radioisotope and dye techniques (40 patients) or with the dye technique alone (7 patients). The sentinel lymph node was dissected separately for histopathological evaluation, and then a routine inguinal lymphadenectomy was performed. Results. The final FIGO surgical Stage distribution was: Stage I, 11 (23%); Stage II, 14 (30%); Stage III, 21 (45%); and Stage IV, 1 (2%). Sentinel lymph node was identified in 46 (98%) women with either one or both of the methods. In Stage I–II, the sentinel lymph node identification rate was 25/25 (100%) with the combined method. The only patient with unidentified sentinel lymph node had lymphatic spread beyond inguinal area or Stage IV disease. Eighteen of the sentinel lymph nodes (39%) were positive for tumor cells, and in 5 cases additional metastatic nodes were found. One patient with macroscopically enlarged metastatic inguinal nodes and Stage III disease had a negative sentinel lymph node. In the 25 patients with Stage I–II disease, the false‐negative rate of the sentinel lymph node method was 0/4, giving a negative predictive value of 1.00. Conclusions. A sentinel node identification rate of 98% with a false‐negative rate of 0% in the patients with Stage I–II disease is an encouraging finding.

Surgical staging, treatment, and follow-up of borderline tumors in different hospital categories: a prospective nationwide survey in Finland.

Background. Surgical treatment and staging of ovarian borderline tumors have been reported to be often suboptimal and differ considerably. We evaluated the extent of surgical treatment of these tumors in different hospital categories. Material and methods. A prospective survey performed in 1999 included 65 patients operated on for borderline ovarian tumors and covered 78% of such patients reported to the Finnish Cancer Registry. Detailed information of demographic data and surgical treatment was reported by the responsible physicians using a special questionnaire after confirmation of histopathology. Results. Fifty‐eight patients (89%) had stage I tumor, only two patients (3%) had stage II disease and five patients (8%) had stage III disease with peritoneal implants. The majority of the patients underwent bilateral salpingo‐oophorectomy (66%) and hysterectomy (58%). Unilateral salpingo‐oophorectomy was performed for 21 (32%) and omentectomy for 22 (34%) patients. Ten out of the 16 women under 40 years of age had fertility‐sparing surgery. Peritoneal biopsies were taken in 16 (25%) women and lymphadenectomy was performed for 9 (14%) patients with clinical suspicion of invasive ovarian carcinoma. Frozen section was taken in half of the patients and the histology remained the same in 72% of the final pathology reports. No clear differences of the extent of surgical treatment were detected between different hospital categories. Overall cumulative 5‐year relative survival rate was 96%. Conclusions. Bilateral salpingo‐oophorectomy and hysterectomy was performed for the majority of patients with borderline ovarian tumor. More attention should be paid to adequate staging of borderline tumors in all hospital categories.

Vitamin D and mineral metabolism in intrahepatic cholestasis of pregnancy

Serum concentrations of 25(OH)D, 24,25(OH)2D, 1,25(OH)2D, total protein, calcium, phosphorus, magnesium and alkaline phosphatase were measured in patients with intrahepatic cholestasis of pregnancy and in control subjects at the third trimester of pregnancy and at delivery. 25(OH)D levels of 40.5 +/- 21.5 nmol/l in the patient group were initially significantly (P less than 0.01) higher than the value of 26.3 +/- 9.5 nmol/l in the control group and decreased significantly (P less than 0.01) to 26.0 +/- 16.3 nmol/l at delivery. The levels of active 1,25(OH)2D and inactive 24,25(OH)2D did not alter in either group. Also the concentrations of calcium, phosphorus and magnesium remained unchanged in both groups. No significant differences in fetal vitamin D metabolites were observed between patients and controls, and the other analysed fetal parameters were similar in both groups. Cholestyramine and/or phenobarbital treatment had no influence on vitamin D metabolites. Since levels of 1,25(OH)2D and mineral parameters remained normal and a change in 25(OH)D concentrations was only transient, the clinical role of 25(OH)D variations cannot be substantial.

Can the fetus regulate its calcium uptake

Summary. To investigate the role of the fetus in vitamin D metabolism concentrations of vitamin D metabolites, 25(OH)D, 24,25(OH)2D and 1,25(OH)2D, were measured in human umbilical artery and vein. There were no differences between artery and vein in 25(OH)D and 24,25(OH)2D levels. 1,25(OH)2D concentrations were statistically significantly higher in the artery than in the vein. It has been shown in animal experiments that 1,25(OH)2D is an important factor in the maintenance of the placental calcium gradient. We suggest that the fetus actively produces 1,25(OH)2D and hence has the capacity to control its calcium influx.

Placebo-controlled study on the efficacy of the pyrimido-pyrimidine derivative RA 233 in ovarian cancer.

This prospective double-blind, multicenter study was aimed at evaluating the clinical efficacy of RA 233 (a derivative of dipyridamole) in ovarian cancer. Following primary surgery, 497 patients with ovarian cancer were treated with combination cytotoxic chemotherapy; those in clinical stage II were also treated with pelvic irradiation. The patients were randomly allocated to receive RA 233 (N = 251) or placebo (N = 246) for 2 years. The groups did not significantly differ from each other in any of the clinical, therapeutic, or histopathological variables evaluated. There were no significant differences between RA 233-treated patients and placebo-treated patients with respect to appearance of new metastases, progressive growth of malignancy, or survival of all patients, in any of the clinical stages of the disease, in radically operated patients or in nonradically operated patients, in different histopathological groups, or in different age groups. Hence, supplementation of carcinoma therapy with long-term administration of the antiplatelet drug RA 233 has no clinical benefit in this malignancy. Using Coxs multifactorial stepwise analysis, this study revealed that the clinical stage of the disease, the extent of surgery, and the histopathology of the tumor, but not the age of the patient or the use of RA 233, were significant and independent predictors of survival. With respect to the histopathology, the poor prognosis of serous and mesonephric carcinomas appeared to be independent of the other prognosis indicators.

Magnetic resonance imaging based volume estimation of ovarian tumours: use of a segmentation and 3D reformation software

The application of a new segmentation software, Anatomatic in the evaluation of volumetric measurements of ovarian tumours and the new Medimag three-dimensional (3D) software in the evaluation of 3D image representation of ovarian tumours with 1.5 T magnetic resonance imaging (MRI) is described. Our goal was to compare MRI based volumetry with operative findings at laparotomy for six consecutive patients with suspected ovarian tumours. Volumetric analysis and three dimensional image reconstructions of the tumours were obtained. At laparotomy, the tumour sizes were measured in situ, and the volumes were calculated. Using Anatomatic, reproducible tumour volumes were achieved with ease and within a reasonably fast time in patients with ovarian tumours without ascites. Medimag helped achieve realistic 3D representations of the tumours. For the four solitary tumours segmentation based volumetry and laparotomy findings agreed in three cases. In one patient with an oval shaped tumour, the segmented volume was double as compared to that estimated at laparotomy. Of the two patients with multiple tumours, both patients had significant ascites, and volumetry misinterpreted the fluid as tumour cyst fluid and markedly overestimated the tumour size. In conclusion, the MRI based segmentation volumetry and 3D image reconstructions are rapid, and reproducible methods of measuring ovarian tumours in patients without significant ascites.

Amniotic fluid 25-hydroxyvitamin D concentrations in normal and complicated pregnancy

The concentration of 25-hydroxyvitamin D (25(OH)D) was measured in 85 samples of amniotic fluid (AF) obtained near term from mothers with normal pregnancy, diabetes, pre-eclampsia or intrahepatic cholestasis of pregnancy. Significantly lower AF 25(OH)D levels were found in diabetic mothers than in the three other groups. Our results suggest that the vitamin D status of the fetoplacental unit may be somewhat impaired in diabetic pregnancy.