[EUROCRINE®: adrenal surgery 2015-2019- surprising initial results]. / EUROCRINE®: Nebennierenoperationen 2015 bis 2019 ­ überraschende erste Ergebnisse.

BACKGROUND: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries-or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)-and to assess the adherence to current international treatment guidelines. METHODS: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019. RESULTS: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands. CONCLUSION: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.

Long-term results of transanal endoscopic microsurgery after endoscopic polypectomy of malignant rectal adenoma.

BACKGROUND: There is no consensus on the treatment and prognosis of malignant rectal polyps. The aim of the present study was to determine the role of transanal endoscopic microsurgery (TEM) after endoscopic complete polypectomy of malignant rectal adenomas with long-term follow-up. METHODS: Of 105 patients with pT1 rectal carcinoma in 32 patients TEM followed complete endoscopic polypectomy while 73 had primary TEM. Local recurrence (LR), distant metastasis, overall and cancer-specific survival were determined by the Kaplan-Meier method. RESULTS: Median follow-up was 9.1 years. In 32 patients with TEM following complete polypectomy no residual cancer was found. LR occurred in 3/28 (11%) patients with low-risk carcinoma (pT1 G1/2/X, L0/X, R0) and in 1/4 (25%) with high-risk carcinoma (pT1 G3/4 or L1). After primary TEM with complete resection (minimal distance >1 mm) LR occurred in 6/60 (10%) with low-risk carcinoma. After incomplete TEM resection (minimal distance ≤1 mm) LR occurred in 3/8 (38%) patients with low-risk and in 1/5 (20%) patients with high-risk carcinoma. Grading was the only significant risk factor for LR after endoscopic polypectomy followed by TEM (p = 0.002). At all outcomes did not differ between postpolypectomy TEM and primary TEM. CONCLUSIONS: Patients with malignant rectal polyps removed by endoscopic polypectomy have a substantial risk of LR even if TEM of polyp site is cancer free. Risk of LR depends on tumor characteristics. In low-risk carcinoma long-term follow-up is necessary. The high LR rate in patients with high-risk rectal carcinoma restricts the use of TEM alone.

[Single Centre Study: Results of Transanal Endoscopic Microsurgery of Rectal Tumors since 2003 vs. Results of Endoscopic Submucosal Dissection Reported in the Literature]. / Single-Center-Studie: Ergebnisse der transanalen endoskopischen Abtragung von Rektumtumoren seit 2003 vs. literaturbasierten Ergebnissen der endoskopischen Submukosaresektion.

BACKGROUND: Due to the variety of methods for local ablation of sessile rectal polyps and low-risk T1 rectal cancer, a retrospective study by transanal local excision, the endoscopic microsurgery (TEM) was performed. The results of the TEM were compared with literature-based results of endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: 174 patients who had received a TEM during the period from March 2003 to October 2011 for a removal of a rectal polyp or low risk cancer were included in the study. The evaluation included the en bloc and R0 resection rate, duration of surgery, the postoperative hospitalisation, postoperative complications and recurrence rate. RESULTS: The en bloc-resection rate was 87.5 % (152 of 174) and the R0 resection was achieved in 84.5 % (147 of 174) of the cases. The average surgery duration was 33 (5-121) min, with an average specimen size of 4 (1.2-13) cm. The average postoperative length of stay included 5 (1-15) d. The postoperative complication rate was 3 % (4 of 174) and the recurrence rate was 4 % (7 of 174) with an average follow-up of 36 (6-108) months. CONCLUSION: Compared to the Japanese results of ESD in the rectum based on literature results, we show equal or better results for the TEM. Compared to the European results of the ESD, the results of the TEM show advantages in terms of higher en bloc and R0 resection rates, shorter intervention times also with larger specimen sizes and a lower postoperative complication rate.

Neuroendocrine tumour, mucinous adenocarcinoma and signet-ring cell carcinoma of the appendix: three cases and review of literature.

Appendiceal neoplasms are relatively common tumours. Although these tumours are often associated with signs and symptoms of acute appendicitis, most appendiceal neoplasms are clinically silent. Appendiceal neoplasms are found in 0.7 to 1.4 per cent of all appendectomy specimens. The classification of these tumours is still confusing and precise treatment methods for these neoplasms remain unclear. First choice therapy of these neoplasms is still a surgical treatment and the type of operative procedure is determined by histology and metatstatic risk. Here, we report three cases of appendiceal neoplasms and make a short review of literature.

The value of 3.0Tesla diffusion-weighted MRI for pelvic nodal staging in patients with early stage cervical cancer.

OBJECTIVE: The purpose of this study is to investigate the diagnostic accuracy of 3.0Tesla (3T) diffusion-weighted magnetic resonance imaging (MRI) in addition to conventional MRI for the detection of lymphadenopathy in patients with early stage cervical cancer compared to histopathological evaluation of the systematically removed pelvic lymph nodes as reference standard. METHODS: 68 fédération internationale de gynécologie obstétrique (FIGO) stage Ia2 to IIb cervical cancer patients were included. Sensitivity and specificity rates for two experienced observers were computed for the detection of lymphatic metastasis. Reproducibility of conventional MRI was tested by kappa statistics. The variables included in the analysis were: size of the long axis, short axis, ratio short to long axis and apparent diffusion coefficient (ADC). RESULTS: Nine patients had 15 positive pelvic nodes at histopathological examination. The sensitivity and specificity of lymphatic metastasis detection by predefined conventional MRI characteristics was 33% (95% Confidence Interval (CI) 3-64) and 83% (95% CI 74-93) on patient level, and 33% (95% CI 7-60) and 97% (95% CI 95-99) on regional level respectively for observer 1. For observer 2 the sensitivity was 33% (95% CI 3-64) and the specificity 93% (95% CI 87-100) on patient level, and 25% (95% CI 1-50) and 98% (95% CI 97-100) on regional level, respectively. The kappa-value for reproducibility of metastasis detection on regional level was 0.50. The short axis diameter showed the highest diagnostic accuracy (area under the curve (AUC)=0.81 95% CI 0.70-0.91); ADC did not improve diagnostic accuracy (AUC=0.83 95% CI 0.73-0.93). CONCLUSIONS: Diffusion-weighted MRI did not result in additional diagnostic value compared to conventional MRI.

Papanicolaou's nebular cells are related to HPV infection and HSIL.

Metaplastic cells with nebular cytoplasmic changes in the cervical smear are classified in the Dutch coding system for cervical screening as KOPAC O8 cells. Since these nebulated cells are already documented by Papanicolaou, we refer to these cells as Papanicolaou's nebular cells. We examined the simultaneous presence of these characteristic metaplastic cells and high-grade squamous intraepithelial lesion (HSIL) in a population-based data base from January 1991 and December 1996. The odds ratio (OR) of nebular cells concurring with HSIL increases with age. For the age cohort 30 years, the OR was 7.8 with a 95% confidence interval (CI) of 4.4-13.9. For the age cohort 60 years, the OR was 35.3 with a 95% CI of 7.8-159.2. Aiming to determine the nature of these nebular metaplastic cells, we performed Chlamydia and HPV PCR on 587 and 1,483 smears, respectively. With an OR of 0.9 [0.3-2.4] it is unlikely that Chlamydia plays a role in the appearance of these nebular cells in the smear. This study shows that with an OR of 5.9 [1.7-21.3] HPV is not only related to large koilocytosis but also to a nebular change of small metaplastic cells. This study reports that nebular changes of small metaplastic cells are related to cervical cancer and to HPV infection.

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

PURPOSE: To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes. MATERIALS AND METHODS: Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically. RESULTS: The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5-7 mm(3) at baseline to 25 mm(3) at day 14, while the control node remained 5 mm(3). The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%-32%), but this decrease was also seen in reactive nodes. CONCLUSION: Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values.

Limiting diffusion coefficients of ionic liquids in water and methanol: a combined experimental and molecular dynamics study.

Mutual diffusion coefficients D(12) of the ionic liquids 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C(2)MIM][NTf(2)]) and [C(4)MIM][NTf(2)] in highly diluted solutions of water and methanol have been measured at different temperatures between 288 K and 313 K using the Taylor dispersion technique. Tracer diffusion coefficients of the two cations [C(2)MIM](+) and [C(4)MIM](+) as well as the anion [NTf(2)](-) in these solutions have been obtained by molecular dynamics (MD) simulations. For our simulations we used well established force fields for the solvents water and methanol and a recently developed force field for imidazolium-based ionic liquid [C(n)MIM][NTf(2)]. Mutual diffusion coefficients D(12) have been calculated from the tracer diffusion coefficients using the Nernst-Hartley equation strictly valid only at low ionic concentration. The agreement between the diffusion coefficients reported in the literature, the experimental data obtained in this work and the MD results is excellent.

Observer variation of magnetic resonance imaging and diffusion weighted imaging in pelvic lymph node detection.

AIM: Conventional MRI and the recently developed diffusion weighted imaging (DWI) technique both are being used for the detection of pelvic lymph node metastasis in gynaecologic cancers. Little is known about the reproducibility of DWI. This study assesses the reproducibility of pelvic lymph node detection by conventional MRI and DWI. MATERIALS AND METHODS: 17 patients with gynaecological malignancies eligible for curative surgery were selected as population of interest. They had undergone preoperative conventional MRI and DWI on a 3.0T MR scanner. All images were evaluated by two experienced radiologists. Inter- and intra-observer agreements were assessed, and whether lymph node size and region were related to reproducibility. Differences were tested by Chi-square statistics. RESULTS: The reproducibility ranged between 42% and 65% for the two observers and for the two imaging tests, conventional MRI and DWI. Higher percentages of agreement were found for larger lymph nodes, i.e. for long as well as short axis diameter exceeding 5mm. Also, agreement was better for lymph nodes in the external iliac region and the obturator region compared to detection of lymph nodes in the common iliac area. Results for the newer technique, DWI, were comparable to the results of the more conventional MRI sequences. CONCLUSION: Reproducibility of MRI and DWI in the detection of pelvic lymph nodes in patients with a gynaecological malignancy was similar. For lymph nodes exceeding 5mm in both long and short axis diameter the agreement was considerably better than for smaller nodes.

The role of hypoxia inducible factor-1alpha in gynecological cancer.

Understanding the mechanisms of carcinogenesis and progression of gynecological tumors is important as these insights might lead to improved diagnostic tools for the pathologist, improved prediction of prognosis, response to therapy, and eventually better biology-based disease management, thereby improving prognosis and quality of life for the individual patient. Hypoxia is an important event in carcinogenesis because it renders a more aggressive phenotype with increased invasiveness and proliferation, formation of metastases and poorer survival. Although selecting patients with hypoxic tumors may therefore be clinically important, there is no consensus as to the method best suited for routine assessment of hypoxia. One of the potential tumor hypoxia markers is hypoxia inducible factor 1 (HIF-1). HIF-1 is the key cellular survival protein under hypoxia, and is associated with tumor progression and metastasis in various solid tumors. In this review, we show that in gynecological cancers, HIF-1A is emerging as an important factor in carcinogenesis, and that overexpression of HIF-1A and its target genes CA9 and SLC2A1 seems associated with shorter progression free- and overall survival. Since hypoxia and HIF-1A expression are associated with treatment failure, targeting HIF-1A could be an attractive therapeutic strategy with the potential for disrupting multiple pathways crucial for tumor growth. Currently, HIF-1A inhibitors are being studied in clinical trials in recurrent ovarian- and cervical cancer, and trials in other gynecological cancers are expected.

Expression of E-selectin and vascular cell adhesion molecule-1 in so-called 'negative' appendices: first results to support the pathological diagnosis in borderline cases.

BACKGROUND: Since the rate of histologically 'negative' appendices still ranges between 15 and 20%, appendicitis in 'borderline' cases remains a challenging disease. As previously described, cell adhesion molecule expression correlates with different stages of appendicitis. Therefore, it was of interest to determine whether the 'negative' appendix correlated with the absence of E-selectin or vascular cell adhesion molecule-1 (VCAM-1). METHODS: Nineteen grossly normal appendices from a series of 120 appendectomy specimens from patients with suspected appendicitis were analysed in frozen sections for the expression of E-selectin and VCAM-1. As control, 5 normal appendices were stained. RESULTS: This study showed a coexpression of E-selectin and VCAM-1 in endothelial cells in early and recurrent appendicitis. In patients with symptoms for less than 6 h, only E-selectin was detected. Cases with fibrosis and luminal obliteration were only positive for VCAM-1. In cases of early appendicitis with symptoms of less than 6 h duration, a discordance between histological and immunohistochemical results was found. CONCLUSIONS: This report indicates that E-selectin and VCAM-1 expression could be useful parameters in the diagnosis of appendicitis in borderline cases.

Trends in inflammatory status of the vaginal flora as established in the Dutch national screening program for cervical cancer over the last decade.

OBJECTIVE: To describe recent trends in the prevalence of cytologic patterns of the vaginal flora (koilocytosis, Trichomonas, dys-bacteriosis, Candida, Gardnerella, Actinomyces, Chlamydia trachomatis) over the last decade. STUDY DESIGN: From 1996 to 2005 > 500,000 cervical smears were screened in the context of the Dutch national screening program on a 5-year basis. Data from the first screening period were compared with those of the second screening period. RESULTS: Prevalences differed from 34.8 for dysbacteriosis to 0.2 for C trachomatis. Bacterial imbalance (dysbacteriosis, unequivocal Gardnerella and Trichomonas) showed a decline in all age groups. Cases of human papillomavirus (HPV)-related koilocytosis have dramatically increased among young women (30 and 35 years). CONCLUSION: Bacterial imbalance of the vaginal flora has significantly decreased during the past decade in all age cohorts. Campaigns on consciousness of vaginal hygiene might have contributed to this amazing effect. We ought to be concerned about the increase in HPV-related koilocytosis.

Detection of lymph node metastases by gadolinium-enhanced magnetic resonance imaging: systematic review and meta-analysis.

BACKGROUND: Gadolinium-based contrast agents are used with magnetic resonance imaging (MRI) to highlight tumor vascularity in organs. They are also widely used for primary tumor visualization. We conducted a systematic review and meta-analysis of the existing evidence of the accuracy of gadolinium-enhanced MRI for staging lymph node metastases. METHODS: We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for studies published in English or German from January 1, 1988, to January 1, 2008, that assessed the diagnostic accuracy of gadolinium-enhanced MRI in the evaluation of lymphatic metastases compared with histopathologic examination as the reference test. Based on a priori-defined clinical considerations, we studied three subgroups of studies: those that used a single malignancy criterion and those that used multiple malignancy criteria with or without contrast highlighting. Summaries of MRI sensitivity and specificity for detecting lymph node metastases were calculated using a bivariate regression model. All statistical tests were two-sided. RESULTS: The literature search yielded 43 full-text papers that were considered for inclusion in the meta-analysis. We performed quantitative pooled analyses on the 32 studies that provided data on patient-level diagnosis. The weighted estimates of sensitivity and specificity for all studies combined were 0.72 (95% confidence interval [CI] = 0.66 to 0.79) and 0.87 (95% CI = 0.82 to 0.91). Estimates of sensitivity and specificity were essentially unchanged for studies that used a single malignancy criterion (0.71 [95% CI = 0.61 to 0.79] and 0.88 [95% CI = 0.80 to 0.93], respectively; n = 11 studies) or multiple malignancy criteria without contrast enhancement (0.70 [95% CI = 0.58 to 0.79] and 0.86 [95% CI = 0.68 to 0.94], respectively; n = 6 studies). The sensitivity increased to 0.84 (95% CI = 0.70 to 0.92), with a specificity of 0.82 (95% CI = 0.72 to 0.89) for the nine studies that incorporated contrast enhancement in their multiple malignancy criteria. Six studies did not define the malignancy criteria they used. CONCLUSIONS: The overall accuracy of gadolinium-enhanced magnetic resonance imaging for the detection of nodal metastases is moderate. Incorporating contrast enhancement in the malignancy criteria substantially improves the accuracy of this diagnostic test.

Inflammatory events as detected in cervical smears and squamous intraepithelial lesions.

The Dutch cytological coding system, KOPAC, enables to code for eight inflammatory events, that is koilocytosis (related to human papillomavirus (HPV)), Trichomonas, dysbacteriosis [related to bacterial vaginosis (BV)], Candida, Gardnerella, Actinomyces, Chlamydia, and non-specific inflammation (leucocytosis). This study presents an analysis of 1,008,879 smears. Of each smear, the age of the woman and the reason for smear taking (screening or indication) was available. The cytoscores (per mille) for these codes were calculated. For the screening smears, the cytoscores were for koilocytosis (HPV) 2.6, for Trichomonas vaginalis 1.9, for dysbacteriosis 31.4, for Candida albicans 9.8, for Gardnerella vaginalis 0.7, for Actinomyces 6.9, for Chlamydia 0.8, and for non-specific inflammatory changes 66.4. For the calculation of the Odds Ratio (OR), normal smears were used as a reference. The cytoscores for Chlamydia and Gardnerella covaried with high grade SIL (HSIL), with an OR of 7 and 12, respectively. In addition, the OR for Trichomonas vaginalis, for dysbacteriosis, and for leucocytosis proved to be significantly high in the indication smears. This study provides an oversight of HSIL and the full range of cervical infections as detected by cytology, proving that this infectious byproduct of screening can be very valuable.

The impact of hospital type on the efficacy of chemotherapy treatment in ovarian cancer patients.

OBJECTIVE: The hospital type affects the surgical outcomes of ovarian cancer patients. In the present study, we wanted to investigate the effect of hospital type on chemotherapy efficacy. METHODS: Data were collected from 1077 ovarian cancer patients treated from 1996 to 2003 in a random sample of 18 Dutch hospitals. Hospitals were categorized by the number of medical oncologists working in a hospital and additionally by chemotherapy volume (< or =100, 101-200, or >200 patients yearly) and ovarian cancer patient-volume (< or =6, 7-12, >12 yearly). The outcomes were the proportions of patients achieving complete remission, recurrence rates, and disease-free and overall survival. Data were analyzed using multivariable logistic regression (complete remission and recurrence) and Cox regression (survival). RESULTS: Data of 761 of the 777 patients who received chemotherapy could be analyzed. Hospital type did not affect the complete remission rates, recurrence rates, or the disease-free survival. Overall survival was better in hospitals with 2 or more medical oncologists and in hospitals with a high ovarian cancer patient-volume (hazard ratios both 0.8 (95% confidence interval=0.7-1.0)). CONCLUSIONS: Thus, hospital type did not influence the outcomes of first-line chemotherapy in ovarian cancer patients. However, overall survival was better in hospitals with 2 or more medical oncologists and in hospitals with a high ovarian cancer patient-volume, suggesting differences in second-line chemotherapy.

Gardnerella infection as distinguished from cervical dysbacteriosis: the advantageous spin-off of cervical screening.

OBJECTIVE: To evaluate cytologic diagnoses of dysbacteriosis and Gardnerella infection and to obtain insight into the diagnostic problems of Gardnerella. STUDY DESIGN: One hundred randomly selected samples of each of 3 diagnostic series were rescreened by 2 pathologists, resulting in 2 rescreening diagnoses and a consensus diagnosis. A smear was considered unequivocal when the original O code and the O code of the consensus diagnoses were equal and discordant when the flora diagnoses of the 2 pathologists differed. RESULTS: Discordance was highest in the dysbacteriotic series (20%) and lowest in the healthy group (4%). Unequivocal diagnoses were established in 65% of the dysbacteriotic smears, 80% of the Gardnerella smears and 93% of the healthy smears. Misclassification of Gardnerella occurred in the presence of clusters of bacteria mixed with spermatozoa. CONCLUSION: Blue mountain cells in Gardnerella infection can be identified unequivocally in cervical smears. Because of the clinical importance of treating Gardnerella, such advantageous spin-offs of cervical screening should be exploited.

Lymph node detection by MRI before and after a systematic pelvic lymphadenectomy.

OBJECTIVE: Pelvic lymphadenectomy is considered the gold standard to diagnose and possibly treat lymphatic metastases in gynaecological cancer patients. The aim of this study is to evaluate whether all presurgical MRI detected lymph nodes were removed during the systematic pelvic lymph node dissection (PLND) in cervical cancer patients. METHODS: 21 consecutive cervical cancer patients who were scheduled to undergo a PLND were evaluated by a MRI scan prior to surgery and 6 weeks afterwards. All patients had tumour metastasis negative lymph nodes at histopathological examination. RESULTS: On average, 10 pelvic lymph nodes (range 5-17) per patient were detected by presurgical MRI. Postsurgical MRI scans showed that on average 1 (range 0-3) pelvic node per patient was not removed by surgery. In total, 14% of the presurgical MR detected nodes were not removed by surgery (31/225). Approximately half of all lymph nodes that remained after surgery were located in the obturator region. In spite of the remaining nodes, surgery and histopathological examination did detect more nodes than MRI: on average 21 lymph nodes per patient (range 9-59) were removed. Another 2 lymph nodes (range 0-6 per patient) were judged to be newly developed after surgery. CONCLUSION: Although surgery was able to remove many more lymph nodes than those detected by presurgical MRI, 14% of presurgical MRI detected lymph nodes were not removed by PLND. The value of MRI prior to surgery for the detection of pathological lymph nodes is a subject of further research.

Specialized and high-volume care leads to better outcomes of ovarian cancer treatment in the Netherlands.

OBJECTIVE: We investigated the influence of hospital and gynecologist level of specialization and volume on surgical results and on survival of ovarian cancer patients. METHODS: Data were collected from 1077 ovarian cancer patients treated from 1996 to 2003 in a random sample of 18 Dutch hospitals. Hospitals and gynecologists were classified according to specialization (general, semi-specialized or specialized) and by volume (12 cases/year). Outcomes were percentage of adequately staged and optimally debulked patients and length of overall survival. Data were analyzed using multivariable logistic regression (surgical results) and Cox regression (survival). RESULTS: The level of specialization and the volume of hospitals and of gynecologists were strongly related to the proportion of adequately staged patients (adjusted odds ratio (OR) specialized hospitals 3.9 (95% confidence interval (CI) 2.0-7.6); specialized gynecologists 9.5 (95% CI 4.7-19)). Patients with stage III disease had a higher chance of optimal debulking when treated in specialized hospitals (adjusted OR 1.7 (95% CI 1.1-2.7)) or by high volume gynecologists (adjusted OR 2.8 (95% CI 1.4-5.7)). Overall survival was best in patients treated in specialized hospitals and by high-volume gynecologists. CONCLUSION: The specialization level of hospitals and the surgical volume of gynecologists positively influence outcomes of surgery and survival. Concentration of ovarian cancer care thus seems warranted.

Is centralization of ovarian cancer care warranted? A cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of tertiary referral care for ovarian cancer patients in the Netherlands. METHODS: We collected clinical and registry data on 1077 newly diagnosed ovarian cancer patients treated from 1996-2003 in a random sample of Dutch hospitals. Decision modelling was used to compare the cost-effectiveness of treatment in general hospitals, semi-specialized hospitals, and tertiary care centers. The actual direct medical costs of ovarian cancer treatment were evaluated. Long-term outcomes in terms of costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained were estimated. To assess uncertainty, multivariable sensitivity analyses and scenario analyses were performed. RESULTS: Treatment of ovarian cancer patients in semi-specialized hospitals costs on average euro882 more than in general hospitals (95% confidence interval -720 to 2462) and yields 0.12 additional QALYs (95% CI 0.02 to 0.22), resulting in an incremental cost-effectiveness ratio (ICER) of euro7135. Patients treated in tertiary care centers incurred again higher costs (euro10,591, 95% CI 8757 to 12,480) and also higher QALYs (0.10, 95% CI 0 to 0.21), resulting in an ICER of euro102,642 compared to semi-specialized hospitals. If the optimal debulking rate in tertiary care centers would increase to 70%, costs could drop below euro30,000 per QALY. CONCLUSION: Current treatment of ovarian cancer patients in semi-specialized hospital settings is a cost-effective strategy, while treatment in tertiary care centers becomes only cost-effective when better surgical results would be achieved.

[Indications for conventional adrenalectomy]. / Indikationen zur konventionellen Adrenalektomie.

INTRODUCTION: Conventional adrenalectomy still plays an important role, even in the era of minimally invasive endocrine surgery. It was the aim of our study to analyse the indications for conventional adrenalectomy in our own patients since the introduction of the minimally invasive technique in the year 1994 - laparoscopically and retroperitoneoscopically. PATIENTS AND METHODS: Between January 1994 and September 2006, a total of 412 adrenalectomies were performed in 380 patients. Out of these, 106 operations (25.7 %) were carried out conventionally in 98 patients, and 306 operations (74.3 %) endoscopically in 282 patients. RESULTS: Indications for conventional adrenalectomy were - as compared with the minimally invasive procedure - significantly more frequent adrenocortical carcinomas (ACC), especially in the context of multivisceral resections, as well as adrenal metastases (synchronous and metachronous). In contrast, adrenal Cushing's disease (including 19 patients with bilateral tumours), pheochromocytoma, incidentaloma and Conn's syndrome constituted a more frequent indication for minimally invasive adrenalectomy. Conventionally operated adrenal pathologies with on average 6.0 (range: 1.2-19.0) cm diameter were significantly larger than the endoscopically removed tumours with on average 3.3 (range: 0.2-9.2) cm diameter (p < 0.0001). The side localisation and the frequency of bilateral adrenal tumours did not differ significantly in the two groups. CONCLUSION: Since the establishment of the minimally invasive technique in 1994, conventional adrenalectomy has been selected for 26 % of all resected adrenal pathologies at our clinic and, therefore, still plays an important role even in the era of laparoscopic surgery. The benefit of the laparoscopic procedure in the case of malignant pheochromocytoma, adrenocortical carcinoma, and isolated adrenal metastases at a locally confined stage is still unclear and requires prospective, randomised studies.