人子宫内膜癌裸鼠模型的建立及其生物学特性的研究

目的 为子宫内膜癌的体内实验及临床研究提供动物实验模型。方法 将人子宫内膜癌手术切除标本移植于BALB／C（nu/nu)裸鼠皮下,传代移植成功后进行鼠间传代。结果 共进行了14例手术标本移植,原代移植成功率为42．9％,自第5代以后,移植瘤的传代成功率均达到100．0％。至2001年5月,共有5株移植瘤传至48－63代,连续传代的移植瘤仍保持原癌组织病理形态特点及人类肿瘤染色体的特点。在传代过程中,裸鼠模型SL－1、SL－2、SL－3的DNA倍体和DNA指数均无明显变化,而SL-4、SL－5随着传代次数的增加,DNA倍体和DNA指数均发生明显变化。5个移植瘤模型雌激素受体（ER）、孕激素受体（PR）表达均为阴性;p53蛋白表达：SL－3、SL－5阴性,SL－1弱阳性,SL－2、SL－4强阳性;P16表达：SL－1、SL－4、SL－5阴性,SL-3阳性,SL－2强阳性;c-erbB－2表达：SL-3、SL-5阴性,SL－2弱阳性,SL－1、SL－4强阳性。结论 人子宫内膜癌手术标本经48－63代传代,成功建立了5株人子宫内膜癌裸鼠皮下移植瘤模型,为开展人类子宫内膜癌的体内实验及临床研究,提供了理想的动物模型。     

Transperitoneal laparoscopical iliac lymphadenectomy for treatment of malignant melanoma

Background: Current treatment for melanoma of the lower limb includes excision of the primary tumor with ilioinguinal lymphadenectomy in the case of lymph node metastases. The standard surgical approach includes sectioning of the inguinal ligament to gain access to the iliac nodes. More recently, some authors have reported that extraperitoneal laparoscopically assisted ilioinguinal lymphadenectomy for the treatment of malignant melanoma is feasible and less aggressive than standard open surgery. So far, no publications have described transperitoneal laparoscopic iliac lymphadenectomy (TPLND). Methods: From November 2001 to June 2002, 13 patients with ilioinguinal node melanoma metastases underwent TPLND (stage IIIA in 1 case, IIIB in 5 cases, IIIC in 4 cases, and IV in 3 cases). Results: In all 13 cases, the TPLND and groin dissection was performed correctly. Operative time, intra- and postoperative complications, number of lymph nodes retrieved, immediate morbidity, hospital stay, and feasibility of TPLND were evaluated. Conclusions: This study was conducted to evaluate the feasibility and the preliminary results of TPLND used to manage malignant melanoma of the lower limb. This approach has many advantages over the traditional procedure: less surgical trauma, no incision of the abdominal muscles or the inguinal ligament, and less postoperative pain. Moreover, as compared with extraperitoneal laparoscopically assisted ilioinguinal lymphoadenectomy, it provides an improved view of the operative area, dissection zone, and surrounding structures. Further research is needed to confirm these preliminary results regarding the potential applications of this method for treating malignant metastasis to the lower limb.     

Validation studies of drug exposures in pregnant women

The aim of these studies was to check the quality of data collection concerning drug use during pregnancy in the Hungarian Case-Control Surveillance of Congenital Abnormalities from four different aspects. (a) The parents of non-respondent cases were visited at home to collect data, but the Ethics Committee did not allow collection of comparable data from non-respondent control women. Thus only 200 selected non-respondent controls were visited at home and questioned about drug use as part of a validation study. There was no difference in the distribution and occurrence of frequently used drugs between the respondent and non-respondent control groups. (b) Data collection was compared between the usual method of the Case-Control Surveillance and personal interview in case with congenital limb deficiencies. In general, the two methods produced similar results with respect to drug use, but the personal interview revealed a higher use of unintended contraceptive pills while the use of antenatal care logbooks in the Case-Control Surveillance showed a higher use of drugs to prevent threatened abortion and preterm delivery. (c) A check of source and completeness of drug exposure showed that about one-quarter of the drugs used during pregnancy were not recorded in the Case-Control Surveillance, and the proportion of lack of recall was about 23%. A small group of women (2.4%) did not use prescribed drugs due to the suspected teratogenic risk. (d) The teratogenic labelling of drugs deters pregnant patients from the use of prescribed drugs, or at least shortens the duration of drug intake. Thus the evaluation of drug use on the basis of medically recorded prescribed drugs and/or usual recommendations produces a bias thus it is necessary to complete it with information from the patients.     

Economic evaluation of human papillomavirus screening in Germany

Cytology-based screening programs for cervical cancer have been effective in reducing cancer incidence and preventing premature deaths worldwide. However, there is concern about the relatively low sensitivity of current screening procedures. Although the causal association between infection with certain high-risk types of human papilloma virus (HPV) and the development of cervical cancer has been clearly established, testing for the major risk factor is not part of current screening practice. We created a tree decision model over time to evaluate different policy choices for implementing a population-based screening program. Results of the economic analysis indicate that testing with any implemented HPV DNA testing (stand alone or in combination with the Papanicolaou smear) is superior to cytology and measures presently in use. Additional costs per life-years gained cannot be reported because the HPV branches had fewer discounted overall costs (€222 million vs. €82 and €76 million, respectively), and they saved more life years (19,599 vs. 19,163 and 903, respectively) then the smear alternative. Any HPV DNA testing is preferable over the current state of the art performed in Germany. This is true not only for economic reasons but also for life-years gained. Therefore HPV DNA testing must become an essential component to back up the relatively weak sensitivity of the standard procedure.     

Carcinoma of the cervical stump. The radiumhemmet series 1959-1987. Treatment and prognosis

BACKGROUND: The purpose of this retrospective study is to evaluate the longterm prognosis for cervical stump cancer compared to matched controls with cancer in an intact uterus. METHODS: From 1959 to 1987, 145 patients were treated for an infiltrating carcinoma of the cervical stump at Radiumhemmet representing 2.2% of all cervical cancers. Three control cases to each case were selected from the cohort of cervical carcinoma cases - matched to year of treatment, stage, histology and age (plus, minus 2 years). Actuarial survival was calculated for cases and controls. Survival differences were analyzed with the Kaplan-Meier technique. The age distribution for cases ranged between 36 and 84 years with a mean age of 60.6 years. The mean age for the control series is 9 years of age (range 35-86 years). Among the cases 87.6% were squamous cell carcinoma and 12.4% were adenocarcinomas. Treatment of carcinoma of the uterine stump at Radiumhemmet followed the same modality as was practised for ordinary cervical cancer cases i.e. two brachyradium applications with 3 weeks interval followed by external irradiation. The dose of irradiation from the intracavitary application given to the stump cancers was lower than that given to comparable cases of the common cervical cases. RESULTS: No evidence was found of poorer longterm prognosis for radiologically treated squamous cell carcinoma of the uterine stump compared to that of the ordinary cervical carcinomas. Stump cancers of the adenocarcinoma type had a worse prognosis than adenocarcinomas in an intact uterus (p<0.07) and also compared with stump cancers of the squamous epithelial type (p=0.05). The complication rate was higher for the stump cancer cases compared with that for cervical cancers in intact uterus. The mean time interval from subtotal hysterectomy to the stump cancer diagnosis was 17.6 years with a range from 1 to 46 years. CONCLUSIONS: Recent discussions argue for a better sexual function after subtotal hysterectomy. Our study gave no convincing argument in terms of poorer prognosis for radiologically treated carcinoma of the uterine stump compared to that of the total cervical cancer series. It is thus necessary to weigh the possible gains with subtotal hysterectomy against the relatively low risk to fall victim of a stump cancer. Complications following surgery, as well as possible physiologic and sexual functions of the cervix, should be taken into account.     

Lymph node recurrence following stage IA vulvar carcinoma: two cases and a short overview of literature

Stage IA vulvar carcinoma is not supposed to metastasize to the lymph nodes. Therefore, it is assumed that these lesions can be safely treated by less aggressive methods than macroinvasive carcinomas. However, in this case report, two patients are described who had vulvar lesions with a depth of invasion of less than 1 mm and developed lymph node metastases in the groin despite radical wide local excision of their lesions. Both the patients underwent lymphadenectomy and received postoperative radiation therapy on the groins. Neither of the two patients died of vulvar carcinoma. Thus, we conclude that vigilance for the occurrence of lymph node metastases remains necessary after radical, local excision in stage IA vulvar cancer. However, this case report also shows that adequate treatment of groin node metastases can result in a very good long-term survival.     

Endometriosis – a decade later – still an enigmatic disease. What is the new in the diagnosis and treatment?

Abstract

Endometriosis is a common disease in women of reproduction age. It causes pain and difficulty in getting pregnant. However the exact causes of infertility associated with endometriosis still remain controversial. The treatment of endometriosis consists of medical treatment of pain as well as medical and surgical treatment of infertility caused by endometriosis and assisted reproduction techniques. Since the treatment of endometriosis is often connected with diminishing ovarian reserve, the techniques for ovarian tissue preservation and oocyte and embryo freezing are used to maintain the ability for childbearing.     

Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting

Dexamethasone (20 mg) or its equivalent in combination with 5-HT3 antagonists appears to be the gold-standard dose for antiemetic prophylaxis. Additional to concerns about the use of corticosteroids with respect to enhanced tumour growth or impaired killing of the tumour cells, there is evidence that high-dosage dexamethasone impairs the control of delayed nausea and emesis, whereas lower doses appear more beneficial. To come closer to the most adequate dose, we started a prospective, single-blind, randomized trial investigating additional dosage of 8 or 20 mg dexamethasone to tropisetron (Navoban), a 5-HT3 receptor antagonist, in cis-platinum-containing chemotherapy. After an interim analysis of 121 courses of chemotherapy in 69 patients, we have been unable to detect major differences between both treatment alternatives. High-dose dexamethasone (20 mg) had no advantage over medium-dose dexamethasone with respect to objective and subjective parameters of acute and delayed nausea and vomiting. In relation to concerns about the use of corticosteroids in non-haematological cancer chemotherapy, we suggest that 8 mg or its equivalent should be used in combination with 5-HT3 antagonists until further research proves otherwise.     

Effect of cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer

BACKGROUND AND OBJECTIVES: The value of secondary cytoreductive surgery is still controversial, especially in patients with recurrent epithelial ovarian cancer. In this retrospective study, we investigated the effect on survival of secondary cytoreduction for recurrent disease and variables influencing redebulking surgical outcome. METHODS: Between 1986 and 1997, 60 patients who received primary cytoreductive surgery and platinum-based chemotherapy for stage III and IV epithelial ovarian cancer experienced disease recurrence at least 6 months after completion of primary therapy, and secondary surgical cytoreduction was performed. The optimal residual disease cutoff was 1.0 cm. The Cox proportional regression model and Logistic stepwise regression were used in statistical processing of the data. RESULTS: The median progression-free interval between the two operations was 13 months (range, 6-56 months). Optimal secondary cytoreduction was achieved in 23 patients (38.33%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimally cytoreduced, with an estimated median survival in the optimal group of 19 months vs. 8 months in the suboptimal group (chi(2) = 22.04, P = 0.0000). Prognosis of survival for individuals with progression-free interval >12 months was better than that of those with the interval 1.0 cm after primary operation should be considered prudently.