Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125).

OBJECTIVE: To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients. METHODS: From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed. RESULTS: At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2-0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). CONCLUSION: Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.

Cancer-associated serum antigen level: a novel prognostic indicator for survival in patients with recurrent ovarian carcinoma.

The aim was to examine the value of the pretherapeutic serum cancer-associated serum antigen (CASA) level as a prognostic factor for survival in patients with recurrent epithelial ovarian carcinoma. Serum levels of CASA and cancer antigen (CA)125 were prospectively determined in 70 consecutive patients with recurrent ovarian cancer before the start of second-line chemotherapy. Univariate and multivariate analyses of survival were performed. The median level of serum CASA was 6.5 U/mL (range: 0.2-1437 U/mL). Univariate analysis showed that patients with a CASA level >10.0 U/mL had significantly shorter survival than patients with CASA level < or =10.0 U/mL (P= 0.002). Using different CASA cutoff levels (6.0, 6.5, and 10.0 U/mL), multivariate Cox analyses identified CASA as an independent prognostic factor for survival at every cutoff level. The strongest prognostic function for CASA was found at a cutoff level of 10.0 U/mL (>10 vs < or =10 U/mL; hazard ratio, 2.7; 95% confidence interval, 1.6-4.7; P < 0.001). The pretreatment CA125 level was not found to be significantly associated with survival by any of the cutoffs (35, 65, 132, and 339 U/mL). A pretreatment elevated level of the tumor marker CASA is an adverse prognostic factor for survival in patients with ovarian cancer relapse.

Surgical cytoreduction in recurrent ovarian carcinoma in patients with complete response to paclitaxel-platinum.

AIM: The objective was to analyse the impact of secondary cytoreductive surgery in patients with recurrent ovarian carcinoma. METHODS: Retrospective review of 572 consecutive patients with primary ovarian carcinoma. Thirty-eight patients with intraabdominal/pelvic recurrence consisted the study group. Clinical variables affecting tumour resectability and survival were evaluated. RESULTS: Complete tumour resection was obtained in 42% of patients. A solitary tumour recurrence was independently associated with complete tumour resection (p=0.009). Median survival for patients with complete and incomplete tumour resection was 51.8 and 19.9 months. The parameter, residual tumour, was found independently correlated with survival after the relapse surgical procedure (p=0.02). However, including also the parameter, number of relapse tumour sites, in the multivariate analysis, the parameter, residual tumour, was no longer significantly associated with survival. CONCLUSIONS: Complete tumour resection following secondary cytoreductive surgery is associated with improved survival in selected groups of patients with recurrent ovarian cancer. However, other clinical factors than surgical cytoreduction are of considerable significance in determining the outcome of the salvage treatment.

Do CA125 response criteria overestimate tumour response in second-line treatment of epithelial ovarian carcinoma?

Recent studies indicate that cancer antigen 125 (CA125) response criteria tend to overestimate a tumour reduction measured by standard WHO response criteria in recurrent epithelial ovarian carcinoma. The aim of the study was to validate the recently introduced GCIG (The Gynaecological Cancer Intergroup) CA125 response criteria in predicting a tumour response measured by WHO (World Health Organization) criteria. Changes in CA125 levels (GCIG criteria) were retrospectively compared with alterations in the tumour load (WHO criteria) during second-line chemotherapy with topotecan or paclitaxel-platinum in 124 consecutive patients with recurrent or refractory disease. In patients assessable by both response criteria (n=72), the overall response rate using GCIG CA125 criteria was 57% (95% confidence interval (CI): 45-69%) and significantly higher than the response rate of 39% (95% CI: 28-51%) using WHO response criteria (P=0.045). The GCIG CA125 criteria had a sensitivity of 96% (95% CI: 82-100%), a specificity of 68% (95% CI: 52-81%) and an accuracy of 79% (95% CI: 68-88%) in predicting a response measured by WHO criteria. In conclusion, the GCIG CA125 response criteria seem to overestimate a tumour response by WHO criteria when monitoring the efficacy of second-line chemotherapy with topotecan or paclitaxel-platinum in patients with epithelial ovarian carcinoma.

Results of reinduction therapy with paclitaxel and carboplatin in recurrent epithelial ovarian cancer.

OBJECTIVE: The purpose of the study was to evaluate the treatment results and toxicity of a retreatment regimen of paclitaxel and carboplatin in patients with ovarian cancer relapse. METHODS: A retrospective analysis of 241 consecutive patients with primary epithelial ovarian cancer receiving paclitaxel and a platinum analogue as first-line treatment was performed. Relapse treatment of platinum-sensitive patients consisted of paclitaxel (175 mg/m(2)) over 3 h followed by carboplatin at an area under the concentration-time curve of 5, repeated every 3 weeks. RESULTS: Forty-three patients with relapse were treated with paclitaxel and carboplatin after a median progression-free interval from the end of first-line chemotherapy of 15.8 months (range 6.0-41.7 months). In patients with evaluable disease the overall response rate was 84% (95% CI: 68.0-93.8%). The progression-free survival and overall survival from start of relapse treatment were a median of 9.7 months (range 1.4-26.9 months) and 13.1 months (range 4.5-35.5 months), respectively. In a multivariate Cox analysis independent prognostic factors for progression-free survival after first relapse were response to relapse treatment (P = 0.002, hazard ratio = 13.9) and time to first recurrence (P = 0.016, hazard ratio = 0.167). The planned treatment was accomplished by 67% of patients. Grade 4 neutrocytopenia over 1 week was observed in 9.3% of patients. Grade 1-2 peripheral neuropathy was reported in 30% of patients. Only 1 patient had her paclitaxel dose attenuated because of grade 4 neuropathy. CONCLUSION: Retreatment with paclitaxel and carboplatin in patients with platinum-sensitive epithelial ovarian cancer relapse yielded a high response rate and encouraging progression-free survival and overall survival. Paclitaxel-carboplatin reinduction therapy is generally well tolerated and the toxicity is manageable.

Subcutaneous noradrenaline concentration increase in normal subjects during cold exposure evaluated by microdialysis.

Changes in local noradrenaline level in subcutaneous tissue were measured in four healthy males (23-33 years) during cold stimulation using a microdialysis technique. The subcutaneous dialysate noradrenaline concentration increased during cold exposure by a factor of 3.5 (P < 0.003). A correction factor due to plasma overflow of noradrenaline to subcutaneous tissue was calculated from noradrenaline infusion studies. This correction had a minimal effect on the observed increase in dialysate noradrenaline concentration and the level of significance was only slightly altered after correction for plasma overflow. The microdialysis technique in combination with a sensitive radioenzymatic noradrenaline assay may be useful to assess changes in local subcutaneous noradrenaline level in man during physiological stimulation.

Determination of local catecholamine release by microdialysis.

Release of noradrenaline in subcutaneous tissue was measured using a microdialysis technique in combination with an ultrasensitive radio-enzymatic noradrenaline assay. Experiments were performed in conscious dogs with and without tyramine added to the perfusion medium. In the absence of tyramine, the interstitial noradrenaline levels in subcutaneous tissue were similar to arterial blood concentrations provided the former were corrected for recovery. With tyramine added to the perfusion medium, noradrenaline levels in subcutaneous tissue increased tenfold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue. In four healthy males, the subcutaneous dialysate noradrenaline concentration increased during cold exposure by a factor of 3.5 (Friedman test, P < 0.003). Skin temperature decreased by an average of -12 degrees C +/- 0.6 degrees C during cold exposure. The microdialysis technique in combination with a sensitive radio-enzymatic noradrenaline assay may be useful to assess local subcutaneous noradrenaline release.

Serial human chorionic gonadotrophin determination in the diagnosis of ectopic pregnancy.

Serial human chorionic gonadotrophin (HCG) determinations were made in 21 patients with ectopic pregnancy (EUP) and in 29 patients with early intrauterine pregnancy (IUP) to examine the increase in HCG values. The median slope of the HCG rise for the patients with EUP was 116 IU/1/2 days and 4,220 IU/1/2 days in patients with IUP. The slopes were significantly different (p < 0.05). Using a discrimination limit of 980 IU/1/2 days, the predictive value of a slope below this limit was 90% in EUP compared to the control group of intrauterine pregnancies. Determination of the slope of HCG rise may be of value in early recognition of ectopic pregnancy in patients with increasing HCG levels below the ultrasonographic discriminatory zone. An international agreement on discrimination limits and unity of HCG algorithms is suggested.

Clinical evaluation of a prototype glucose electrode.

A new prototype direct reading glucose electrode working with glucose oxidase and hydrogen peroxide was preliminarily tested clinically during insulin-induced hypoglycemia in eight healthy subjects, and during hyperglycemia in five dysregulated diabetic patients. The results for 282 whole blood samples were compared to those of our routine method, which measures the glucose concentration in whole blood. The correlation was: y = 1.05.x - 0.05 mmol/L, r = 0.99. The glucose electrode measured a glucose concentration of 10.5 mmol/L +- 0.49 mmol/L (between-day imprecision) in a control serum (glucose 10.0 mmol/L). The glucose electrode supposedly responds to the activity of glucose that equals the molality (mmol glucose per kg water). The ratio of results with the glucose electrode and our routine method was lower than the expected ratio between water concentration in calibrator and whole blood, which is 1.18. A steep gradient from blood sample to glucose electrode, depending on the diffusion coefficient and hematocrit might explain the discrepancy.

Serious intestinal complication five years after insertion of a Nova-T.

This report presents a case of sigmoid perforation five years after insertion of a Nova-T. This case illustrates that serious complications of third generation IUDs may occur even after several years of intraabdominal location. An IUD, which has perforated the uterus, cannot be left in the peritoneal cavity. Therefore, removal of a perforated IUD is still a medical indication as recommended by the World Health Organization and IPPF International Medical Advisory Panel Meetings.

Noradrenaline release in skeletal muscle and in adipose tissue studied by microdialysis.

1. In adipose tissue and in skeletal muscle the extracellular noradrenaline levels were studied by microdialysis in the conscious dog and compared with the noradrenaline concentration in arterial plasma. 2. The experiments were performed with and without tyramine added to the perfusion medium, and noradrenaline was measured by a sensitive radioenzymic assay. 3. In the absence of tyramine, the interstitial noradrenaline levels in adipose tissue and skeletal muscles were similar to arterial blood concentrations, provided that the former were corrected for recovery. The recovery estimated from experiments in vitro averaged 16% at room temperature. 4. With tyramine added to the perfusates, noradrenaline levels increased 10-fold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue. 5. Our results indicate that the microdialysis technique combined with a sensitive assay for measuring noradrenaline may be applicable to the assessment of local noradrenaline release in adipose tissue and in skeletal muscle. This may be of interest, especially in adipose tissue during physiological stimulation in which sympathetic activity is difficult to evaluate by other techniques.

Effect of insulin-induced hypoglycaemia on absorption of unmodified insulin after subcutaneous or intramuscular injection.

The effect of insulin-induced hypoglycaemia on the absorption of iodine-125 labelled unmodified insulin (10 U) from thigh after subcutaneous or intramuscular injection was studied in eight immobilized, supine, normal subjects. Ultrasonic determination of the subcutaneous thickness was used to accurately localize the site for insulin injection. Insulin absorption was studied twice during hypoglycaemia or normoglycaemia in random order. Insulin absorption was similar after subcutaneous and intramuscular injections (residual activity at 5 h: SC 59.3 +/- 5.0 (+/- SE) %; IM 55.2 +/- 3.7%). Hypoglycaemia did not change the disappearance rate of iodine-125 insulin after either subcutaneous (55.0 +/- 4.4%) or intramuscular injection (52.6 +/- 5.7%), despite a plasma glucose nadir of 1.7 +/- 0.2 mmol I-1. In a controlled study under standardized conditions hypoglycaemia has no effect on insulin absorption rate.(ABSTRACT TRUNCATED AT 250 WORDS)

[The importance of early exercise therapy in the treatment of Colles' fracture. A clinically controlled study]. / Betydningen af tidlig ergoterapi ved behandling af Colles-fraktur. En klinisk kontrolleret undersøgelse.

Forty patients participated in a study of the importance of early occupational therapy for the prognosis in stable Colles' fractures. Seventeen patients were treated by an occupational therapist 1-3 days after the injury, and the need for appliances and home-care was estimated. Twenty-three patients completed the usual treatment. Five weeks after the injury, we found significantly (p less than 0.05) better function of the hand in the 17 patients with early occupational therapy. This difference in function could not be found after 13 weeks. The rate of complications was the same in the two groups. The results indicate that contact with the occupational therapist shortly after the injury is valuable in patients with stable Colles' fractures.

Knee complaints in patients with normal arthroscopic findings.

Clinical follow-up was obtained in 96 patients with knee complaints but normal arthroscopic findings (mean observation time, 10 months). About one-third had no symptoms at follow-up; in another third there was improvement; in the remaining third there were unchanged or worsened symptoms, and a clinical re-examination indicated that alterations in the soft tissues around the knee might explain the worsening. However, 10 patients in the last group had not only significant worsening of the knee symptoms but also severe complaints in other regions of the body and a psychosomatic factor was suspected. Most of the patients with symptoms at follow-up had significant wasting of the quadriceps muscles. Energetic exercises seem important even in patients with normal arthroscopic findings.