Chemotherapeutic drug sensitivity of primary cultures of epithelial ovarian cancer cells from patients in relation to tumour characteristics and therapeutic outcome.

BACKGROUND: A number of chemotherapeutic drugs are active in epithelial ovarian cancer (EOC) but so far choice of drugs for treatment is mostly empirically based. Testing of drug activity in tumour cells from patients might provide a rationale for a more individualised approach for drug selection. MATERIAL AND METHODS: Sensitivity of EOC to chemotherapeutic drugs was analysed in 125 tumour samples from 112 patients using a short-term primary culture assay based on the concept of total cell kill. Sensitivity was related to tumour histology, treatment status and clinical tumour response. RESULTS: For most EOC standard drugs serous high grade and clear cell EOC were the most sensitive subtypes and the mucinous tumours the most resistant subtype. Docetaxel, however, tended to show the opposite pattern. Samples from previously treated patients tended to be more resistant than those from treatment naïve patients. The activity of cisplatin correlated with that of other drugs with the exception of docetaxel. Tumour samples from two sites in the same patient at the same occasion showed similar cisplatin sensitivity in contrast to samples taken at different occasions. Samples from patients responding in the clinic to treatment were more sensitive to most drugs than samples from non-responding patients. At the individual patient level, drug sensitivity in vitro compared with clinical response showed sensitivities and specificities in the 83-100% and 55-83% ranges, respectively. CONCLUSIONS: Assessment of EOC tumour cell drug sensitivity in vitro provides clinically relevant and potentially useful information for the optimisation of drug treatment.

Immunoreactivity against Goblet cells in patients with inflammatory bowel disease.

BACKGROUND: A number of autoantibodies have been reported in inflammatory bowel disease (IBD). The aim of this study was to investigate to what extent sera from patients with IBD contain autoantibodies directed against normal human gastrointestinal mucosa. METHODS: Samples of sera from 50 patients with IBD and 50 healthy subjects were used for immunostaining of normal and affected human gastrointestinal tissues. RESULTS: Eighty-four percent of the sera from IBD patients showed immunoreactivity against goblet cells in the appendix compared with 8% of the sera from healthy subjects. Goblet cell reactivity of IBD patient sera varied between regions in the gastrointestinal tract. Sera from healthy subjects only reacted with goblet cells in the appendix. In the colon and the appendix, goblet cell reactivity of IBD sera was generally weak at the base of the crypts and gradually increased toward the lumen. Three IBD sera samples reacted with gastrin cells in the antrum. In colon biopsies from patients with ulcerative colitis, immunoreactivity against the remaining goblet cells showed an inverse correlation with inflammatory activity. CONCLUSIONS: These findings suggest that immunoreactivity against goblet cells may be of central importance in the pathogenesis of IBD. Identification of goblet cell antigens could lead to a better understanding of IBD and provide a new diagnostic tool.

The role of maternal age and episiotomy in the risk of anal sphincter tears during childbirth.

BACKGROUND: Many women who experience anal sphincter tear will suffer from anal incontinence. The most important tool to avoid this is to recognise the obstetric risk factors involved and thereby prevent injury. AIMS: The aim of this study was to analyse and evaluate the risk factors of anal sphincter tear during delivery. METHODS: Of a total of 57,943 vaginal deliveries, we identified 565 women with partial or total rupture of the anal sphincter and compared these women with 565 controls without sphincter tear with respect to possible risk factors. RESULTS: Several factors were significantly associated with sphincter tears, including nulliparity, birthweight, instrumental delivery, episiotomy, malpresentation, maternal age and epidural analgesia. The importance of these variables was further confirmed in a stepwise logistic regression analysis. Age was found to be a significant risk factor only when the birthweight was less than 4000 g. Episiotomy more than doubled the risk of sphincter tear when delivery was non-instrumental. CONCLUSION: There are several independent risk factors that should be considered when making decisions regarding delivery mode. Maternal age and episiotomy in non-instrumental delivery are two of these.