Pelvic exenteration for vulvar cancer: Postoperative morbidity and oncologic outcome - A single center retrospective analysis.

BACKGROUND: Pelvic exenteration may be the only curative treatment for some patients with primary advanced or recurrent vulvar cancer but is associated with high morbidity. This study evaluated the clinical outcome of patients treated at a centralized service in Norway. METHODOLOGY: This retrospective study included patients treated with pelvic exenteration for primary locally advanced or recurrent vulvar cancer between 1996 and 2019 at Oslo University Hospital, Norway. Complications were coded according to the contracted Accordion classification. Relapse free survival (RFS), cancer specific survival (CSS) and overall survival (OS) were estimated with the Kaplan Meier method. RESULTS: The 30 patients were followed for a median of 4.94 years (95%CI: 3.37-NR). Exenteration due to primary vulvar cancer was carried out in 16 (53%) patients, 14 (47%) had recurrent vulvar cancer. Free histopathological margins were achieved in 28 (93%) patients. The 90 days morbidity for grade 3 complications was 63%, predominantly wound/surgical flap infections, 7% had no complications. 90 days mortality was 3%. Five-year RFS was 26% (95% CI 8-48%), OS was 50% (95%CI: 29-69%) and CSS was 64% (95% CI 43-79%). There was no significant difference in survival between patients with primary vs recurrent disease. The 3-year CSS for patients with negative lymph nodes and positive lymph nodes was 70% (95% CI 47-84%) and 30% (95% CI 1-72%), respectively. CONCLUSIONS: Acceptable oncologic outcomes after pelvic exenteration for primary and recurrent vulvar cancer can be achieved if surgery is centralized. Careful patient selection is imperative due to significant postoperative morbidity and considerable risk of relapse.

A prognostic nomogram to predict overall survival in patients with platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Patients with platinum-sensitive recurrent ovarian cancer have variable prognosis and survival. We extend previous work on prediction of progression-free survival by developing a nomogram to predict overall survival (OS) in these patients treated with platinum-based chemotherapy. PATIENTS AND METHODS: The nomogram was developed using data from the CAELYX in Platinum-Sensitive Ovarian Patients (CALYPSO) trial. Multivariate proportional hazards models were generated based on pre-treatment characteristics to develop a nomogram that classifies patient prognosis based on OS outcome. We also developed two simpler models with fewer variables and conducted model validations in independent datasets from AGO-OVAR Study 2.5 and ICON 4. We compare the performance of the nomogram with the simpler models by examining the differences in the C-statistics and net reclassification index (NRI). RESULTS: The nomogram included six significant predictors: interval from last platinum chemotherapy, performance status, size of the largest tumour, CA-125, haemoglobin and the number of organ sites of metastasis (C-statistic 0.67; 95% confidence interval 0.65-0.69). Among the CALPYSO patients, the median OS for good, intermediate and poor prognosis groups was 56.2, 31.0 and 20.8 months, respectively. When CA-125 was not included in the model, the C-statistics were 0.65 (CALYPSO) and 0.64 (AGO-OVAR 2.5). A simpler model (interval from last platinum chemotherapy, performance status and CA-125) produced a significant decrease of the C-statistic (0.63) and NRI (26.4%, P < 0.0001). CONCLUSIONS: This nomogram with six pre-treatment characteristics improves OS prediction in patients with platinum-sensitive ovarian cancer and is superior to models with fewer prognostic factors or platinum chemotherapy free interval alone. With independent validation, this nomogram could potentially be useful for improved stratification of patients in clinical trials and also for counselling patients.

Inhibition of phytohaemagglutinin-induced lymphoproliferation by soluble annexin II in sera from patients with renal cell carcinoma.

Annexin II (AII) is a member of a family of glycoproteins which bind negatively charged phospholipids in a calcium-dependent manner. Annexins are membrane-associated proteins, expressed both in normal and malignant cells, but have also been detected as soluble molecules in serum and other body fluids. Because of their adhesive properties, it has been suggested that annexins play a role in the metastatic process. An ELISA was established for quantification of soluble AII. Within-run variation was 5.2-10.4% and run-to-run variation 12.4-15.6%. Soluble AII was detected in all sera studies. A strongly positive serum was arbitrarily given the value 100 AII units and used as reference serum. The mean level in sera from 20 normal blood donors was 49 (SE 5.6) AII units. Sera from peripheral blood of five patients with renal cell carcinoma and sera from blood obtained from the renal vein of the same patients contained 47 (SE 20) and 83 (SE 28) AII units, respectively. In two patients, AII levels were increased in renal vein serum as compared with peripheral blood serum. Interestingly, in both cases, and in none of the three remaining cases, phytohaemagglutinin-stimulated lymphoproliferation was suppressed by renal vein serum as compared with peripheral blood serum. Affinity absorption of AII from the renal vein sera with increased AII levels strongly reduced their immunosuppressive activity. Addition of affinity-purified AII to cell cultures suppressed lymphoproliferation. These data show that the level of AII is markedly increased in renal vein sera from some patients with renal cell carcinoma, suggesting that AII may be locally released in vivo. The study also demonstrates an immunosuppressive effect of soluble AII in vitro. We speculate that soluble AII released by the tumour has immunosuppressive properties. This study identifies soluble AII as a novel immunosuppressive factor in sera from patients with renal cell carcinoma. A further study including a larger number of patients is currently in progress, in order to investigate the pathological significance of this finding.

Suppression of mitogen-induced lymphoproliferation by soluble IgG Fc receptors in retroplacental serum in normal human pregnancy.

A competitive ELISA was used to quantify soluble IgG Fc receptors (FcR) in retroplacental serum (RPS) and peripheral serum (PS) from 10 women after uncomplicated full-term deliveries. The RPS contained significantly higher amounts of soluble FcR than did PS from the same individuals. RPS suppressed phytohaemagglutinin-stimulated lymphoproliferation as compared with PS, and a positive correlation (r = 0.66) was found between the degree of suppression and the difference in soluble FcR level between RPS and PS. Absorption of sera with Sepharose 4B coupled with heat-aggregated IgG strongly reduced the immunosuppressive activity, whereas absorption with Sepharose coupled with IgG F(ab')2 fragments did not. When IgG-binding material was eluted from Sepharose beads and added to cell cultures, the immunosuppressive activity was restored. The data indicate that soluble FcR at physiological levels have immunosuppressive properties. FcR-mediated immunosuppression may be of importance for maintenance of local immunosuppression during pregnancy.

Demonstration of Fc gamma receptors in human endometrium.

Cryostat sections of human endometrium bound sheep erythrocytes (E) sensitized with rabbit IgG antibody (A), (EA). Unsensitized E were not bound. Native, heat-aggregated IgG and Fc fragments of IgG inhibited the binding of EA, whereas IgM, IgA and F(ab')2 fragments of IgG did not. The data indicate the presence of receptors for the Fc part of IgG (FcR). Using immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP and monoclonal antibodies (mAbs), FcR were located to the glandular epithelial and endothelial cells, macrophages and predecidual cells of the stroma. These structures were also stained by mAbs against all three FcR classes and a 40-kD low affinity placental FcR. Preliminary results indicate that the expression of FcR varies during different stages of the menstrual cycle. FcR in the endometrium may play a rôle in local immunoregulation necessary for nidation and development of the blastocyst.

Pregnancy outcome in Norway after Chernobyl.

Pregnancy outcome has been studied in terms of legal abortions, early spontaneous abortions and total number of pregnancies (in an ad hoc study covering 6 counties) as well as various perinatal health problems (on the basis of routinely recorded data for epidemiological surveillance from the Medical Birth Registry of Norway). Apparently, no effects were observed in terms of an increased occurrence of legal abortions, while spontaneous abortions increased from 7.2% of all pregnancies during the last 12 months before the accident to 8.3% after the accident [corrected]. At the same time, the total number of pregnancies somewhat decreased. Based on monthly measurements in each municipality of external and internal (food-based) doses, dose-response associations were assessed for a number of perinatal health problems. No associations were observed.

PIP: The effects of Chernobyl on pregnancy outcome were investigated in Norway in terms of legal abortions, early spontaneous abortions, total pregnancies, and perinatal health problems (cataracts, microcephaly, low birth weight, and perinatal mortality). The epidemiological results showed that there were no serious gross changes in pregnancy outcome in Norway after Chernobyl in 1986. Anxiety may have led to the temporary decrease in pregnancies. The statistically significant difference in spontaneous abortions between 19867 and 1987, particularly in the months following Chernobyl, may be related but causation cannot be determined based on the present data; i.e., dietary changes due to anxiety may also be related. Further analyses will be conducted with data spanning 5 years after Chernobyl. The Central Bureau of Statistics provided data on legal abortions as reported by hospitals to county medical officers. Spontaneous abortions (16 weeks) are based on ad hoc notifications from hospitals in 5 counties: Aust-Agder, Hordaland, Oppland, Troms, and Trondelag. Compulsory notification of births is recorded in the Medial birth Registry and includes congenital malformations and other perinatal health problems. The National Institute of Radiation Hygiene recorded data after the accident on indoor gamma rates, radiocesium (Cs 134) soil samples, and municipality specific average food-based dose equivalents of Cs 134 and 137 in meat and meat supplies. The total external and internal dose is provided for May 1986-April 1989. Food-based doses remained at an elevated level for an extended period of time. Infant exposure was considered form the 2nd month of gestation. Legal abortions, induced or spontaneous, were not impacted by Chernobyl, but the effect may have been delayed to the 3rd or 4th quarter with a 1.0% increase. However, at Haukeland Hospital in Bergen, the highest abortion rates were 19.1% in 1985-86 and 19.2% in 1986-87. Pregnancies temporarily decreased in the 3rd and 4th quarters following the accident in a period usually reflecting annual increases. Cataract occurrences increased the year after the accident with 8 observed and 3.8 expected, but the P value was insignificant (P=.74). Microcephaly followed a similar pattern. Birth 2500 gms had observed values of 2726 vs. 2639.2 expected, an insignificant P value of .99. Observed perinatal deaths of 634 were less than the 718.8 expected.