Towards the molecular environment of the phosphotyrosine phosphatase PTP-BL: Aiming at a moving target.

Contains fulltext : mmubn000001_447981951.pdf (publisher's version ) (Closed access)RU Radboud Universiteit Nijmegen, 6 januari 2006Promotor : Wieringa, B. Co-promotor : Hendriks, W.J.A.J.167 p

First case of vaginal radical trachelectomy in a pregnant patient.

Contains fulltext : 70234.pdf (publisher's version ) (Closed access)Women who present with cervical carcinoma during pregnancy pose for us a clinical problem. In general, three treatment options exist: (i) radical hysterectomy with termination of pregnancy, (ii) a planned delay, or (iii) chemotherapy until lung maturation has occurred, both followed by a radical hysterectomy. Vaginal radical trachelectomy is an alternative approach to preserve the pregnancy. We report on a woman with a stage IBI cervical carcinoma, diagnosed at 16 weeks of gestation treated with vaginal radical trachelectomy. At a gestational age of 36 weeks, a cesarean section was performed, followed by radical hysterectomy. Follow-up of 9 months is uneventful for both the mother and the child. The vaginal radical trachelectomy is a new approach in the treatment of cervical carcinoma during pregnancy

Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy as Fertility-Preserving Treatment for Patients with FIGO 2018 Stage 1B2 Cervical Cancer

BACKGROUND: Standard treatment for International Federation of Gynecology and Obstetrics (FIGO) 2018 stage 1B2 cervical cancer (i.e., tumor size between 2 and 4 cm) is a radical hysterectomy (RH) with pelvic lymph node dissection (PLND). We evaluated the oncological and fertility outcomes treatment in patients receiving a fertility-sparing alternative consisting of neoadjuvant chemotherapy (NACT) followed by vaginal radical trachelectomy (VRT). METHODS: Patients with stage 1B2 cervical cancer who wished to preserve fertility were included from September 2009 to September 2018. NACT consisted of 6-week cycles of cisplatin or carboplatin with paclitaxel. If tumor size decreased to 2 cm or smaller, NACT was followed by a robot-assisted PLND and VRT. RESULTS: Eighteen patients were included. Median follow-up time was 49.7 months (range 11.4-110.8). Median tumor size was 32 mm (range 22-40 mm). Complete remission after NACT occurred in seven women. Four women had a poor response on NACT. Three underwent RH with PLND; one received chemoradiation after PLND instead of VRT because of positive lymph nodes. The remaining 14 patients received VRT 3-4 weeks after NACT. Four recurrences occurred: three after NACT and VRT and one after NACT and RH. Median time to recurrence was 20.8 months (range 17.0-105.7). Three recurrences occurred in women with adenocarcinoma with lymph vascular space invasion (LVSI). In four women fertility could not be preserved. To date, four women had six pregnancies, including three live births born at term, two first trimester miscarriages, and one currently ongoing pregnancy. CONCLUSION: NACT and VRT in women with stage 1B2 cervical cancer showed promising results. In 78% fertility was preserved. However, patients with poor response on NACT and with adenocarcinoma and/or LVSI were possibly at risk for recurrence. Long-term results in relation to fertility and oncological outcome are needed to corroborate these findings. IMPLICATIONS FOR PRACTICE: Standard treatment for women with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage 1B2 cervical cancer (tumor size 2-4 cm) is a radical hysterectomy and pelvic lymph node dissection (PLND). However, many of these women are young and wish to preserve fertility. Data on fertility-sparing treatment options are sparse, but neoadjuvant chemotherapy followed by a vaginal radical trachelectomy and PLND could be an alternative. Since 2009 we performed an observational cohort study in which 18 women opted for this treatment in our center. In 14 women fertility could be preserved. In four patients the tumor recurred. In four women six pregnancies occurred. After careful selection this treatment could be a good fertility-sparing treatment option

Self-reported distress in patients with ovarian cancer: is it related to disease status?

Item does not contain fulltextOBJECTIVE: Patients with epithelial ovarian cancer have a poor prognosis and often undergo intensive treatment. These patients are therefore at risk for experiencing distress and reduced quality of life. The aim of this study was to explore the self-reported distress severity, experienced problems, and quality of life in relation to their disease status. METHODS: This cross-sectional study was conducted in 2011 at a University Medical Center. Women with ovarian cancer (n = 273), both during and after treatment, were asked by mail to fill in self-report questionnaires. Distress was measured using with the Distress Thermometer (DT), Hospital Anxiety and Depression Scale, and Impact of Event Scale. Problems and quality of life were assessed with the problem list of the DT, and European Organization for Research and Treatment of Cancer Quality of Life C-30 and OV28. RESULTS: The questionnaire data of 104 patients were analyzed. Screening with the DT revealed distress in 32% [mean (SD), 3.1 (2.6)]. Distress was found with the Hospital Anxiety and Depression Scale in 14% [8.6 (5.9)] and with the Impact of Event Scale in 18% of the patients [17.5 (15.5)]. No significant differences were found in distress severity and self-reported problems between patients with and without recurrence. In both groups, the problems fatigue, condition, and neuropathy were most reported. Patients with distress (DT >/= 5) experienced significantly worse functioning, more problems, and lower quality of life than patients without distress (P < 0.01). CONCLUSIONS: This study showed that disease status in patients with ovarian cancer seems to have no influence on distress, quality of life, and the problems encountered. However, distressed patients experienced more problems, with physical and emotional functioning, and had lower quality of life. The problems fatigue, physical condition, and neuropathy are the most prevailing

Fluctuations in prevalence of cervical human papillomavirus in women frequently sampled during a single menstrual cycle.

In the last few years much attention has been focused on the implementation of human papillomavirus detection in population based screening programmes to identify women at risk for cervical cancer. Short-term fluctuations in prevalence of human papillomavirus were investigated within a single menstrual cycle. The highest prevalence was found at the follicular phase (55%), whereas the cumulative prevalence was 75%

Case-mix adjustment to compare hospital performances regarding complications after cytoreductive surgery for ovarian cancer: a nationwide population-based study.

OBJECTIVE: Complication rates after cytoreductive surgery are important quality indicators for hospitals that treat patients with advanced-stage ovarian cancer. Case-mix factors are patient and tumor characteristics that may influence hospital outcomes such as the complication rates. Currently, no case-mix adjustment model exists for complications after cytoreductive surgery; therefore, it is unclear whether hospitals are being compared correctly. This study aims to develop the first case-mix adjustment model for complications after surgery for advanced-stage ovarian cancer, enabling an accurate comparison between hospitals. METHODS: This population-based study included all patients undergoing cytoreductive surgery for advanced-stage ovarian cancer registered in the Netherlands in 2017-2019. Case-mix variables were identified and assessed using logistic regressions. The primary outcome was the composite outcome measure 'complicated course'. Patients had a complicated course when at least one of the following criteria were met: (1) any complication combined with a prolonged length of hospital stay; (2) complication requiring reintervention; (3) any complication with a prolonged length of stay in the intensive care unit; or (4) 30-day mortality or in-hospital mortality during admission following surgery. Inter-hospital variation was analyzed using univariable and multivariable logistic regressions and visualized using funnel plots. RESULTS: A total of 1822 patients were included, of which 10.7% (n=195) had a complicated course. Comorbidity and tumor stage had a significant impact on complicated course rates in multivariable logistic regression. Inter-hospital variation was not significant for case-mix factors. Complicated course rates ranged between 2.2% and 29.1%, and case-mix adjusted observed/expected ratios ranged from 0.20 to 2.67 between hospitals. Three hospitals performed outside the confidence intervals for complicated course rates. These hospitals remained outliers after case-mix adjustment. CONCLUSION: There is variation between hospitals regarding complicated course rates after cytoreductive surgery for ovarian cancer in the Netherlands. While comorbidity and tumor stage significantly affected the complicated course rates, adjusting for case-mix factors did not significantly affect hospital outcomes. The limited impact of case-mix adjustment could be a result of the Dutch centralized healthcare model

Mullerian precursor lesions in serous ovarian cancer patients: using the SEE-Fim and SEE-End protocol

Contains fulltext : 137482.pdf (publisher's version ) (Closed access)Serous ovarian cancer is suggested to develop from epithelium embryologically derived from the Mullerian ducts. The aim of the current study is to thoroughly, analyze the epithelium derived from the Mullerian ducts (cervix, endometrium and fallopian tubes) in serous ovarian cancer patients. Sixty women diagnosed with serous ovarian carcinoma were included in this multicentre, observational study. Tissues were embedded completely for histological assessment, in accordance with the SEE-Fim and SEE-End protocol (Sectioning and Extensively Examining of the Fimbriated end; and-Endometrium), and prevalence of cervical, as well as endometrial and tubal pathology was analyzed. In 31 (52%) cases, a pathologic lesion was identified, and in 16 (27%) of these cases coexistence of pathologic lesions. In 1 case, severe dysplasia was found in the cervix, in 9 (15%) cases endometrial intraepithelial carcinoma, in 19 (32%) cases atypical hyperplasia, and in 23 (43%) cases serous tubal intraepithelial carcinoma. Serous tubal intraepithelial carcinoma was seen significantly more often concurrent with endometrial atypical hyperplasia or endometrial intraepithelial carcinoma than with benign endometrium (64 vs 28%; P=0.01). To conclude, histological assessment of epithelium derived from Mullerian ducts of serous ovarian cancer patients resulted in the identification of endometrial intraepithelial carcinoma, serous tubal intraepithelial carcinoma and/or endometrial atypical hyperplasia in more than half of cases. Coexistence of these pathologic lesions was common, and might represent an effect of field carcinogenesis or tumor implantation of migrating cells

Long-term follow-up after large-loop excision of the transformation zone: evaluation of 22 years treatment of high-grade cervical intraepithelial neoplasia.

Contains fulltext : 50691.pdf (publisher's version ) (Closed access)Early treatment of cervical intraepithelial neoplasia (CIN) significantly reduces the risk of invasive cancerous progression. Residual and recurrent high-grade CIN should be detected and retreated in an early phase. Therefore, a postsurgery cytologic follow-up protocol was introduced at 3, 6, 9, and 12 months and yearly thereafter for 5 years. The aim of this study is to evaluate the long-term experience in treating high-grade CIN using large-loop excision of the transformation zone (LLETZ). Additionally, the long-term follow-up in this study gains the opportunity to document the pattern of disease recurrence beyond 5 years. The average follow-up of the 1696 women included in this study was 6.5 years. Overall, 8.5% of the patients who underwent LLETZ showed a high-grade repetitive CIN and three patients had invasive carcinoma. Eighty percent of those lesions were probably residual, whereas 20% of all high-grade repetitive lesions appeared more than 2 years after initial surgery and were considered recurrent lesions. Half of the recurrent lesions occurred more than 5 years after LLETZ