[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.

Diagnosis and treatment of small follicular thyroid carcinomas.

BACKGROUND: Follicular thyroid microcarcinomas (mFTCs) of 10 mm or less in size rarely manifest clinically and their clinical significance is controversial. This study assessed their characteristics and incidence, and analysed treatment modalities used for mFTC. METHODS: Members of the German Association of Endocrine Surgeons were asked to review patients with mFTC operated on between 1990 and 2005. RESULTS: Data for 90 patients from 26 institutions were reported. Histopathological slides were available for re-evaluation in 35 patients. Most initial diagnoses had to be revised because of incorrect size assessment or incorrect diagnosis (benign adenoma, papillary thyroid carcinoma (PTC), follicular variant of PTC). The diagnosis of mFTC was confirmed in only four patients. As a result of the incorrect histopathological diagnosis, unnecessary completion thyroidectomy and radioiodine ablation were performed in 17 and 20 patients respectively. The incidence of mFTC was calculated to be 0.12 per million population per year. CONCLUSION: mFTC is exceptionally rare. Such tumours are overdiagnosed, resulting in unnecessary treatment associated with avoidable morbidity. Histopathological re-evaluation by an experienced pathologist is recommended before embarking on further treatments when a diagnosis of mFTC is made.

Long-term follow-up of surgically treated gallbladder cancer patients.

AIMS: Palliative attempts have traditionally led treatment of gallbladder cancer but resection offers the only chance for long-term survival. This study investigates the impact of surgery with curative intent in gallbladder cancer treatment and evaluates prognostic factors for survival. METHODS: Two hundred and sixty-seven patients were admitted for surgical therapy. Sixty received resection with curative intent and form the basis of this analysis. RESULTS: R0 resection (n=45) was a highly significant independent survival predictor (P<0.001). All 5-year survivors (n=10) had tumour-free resection margins. Early T stage (P=0.017) and highly differentiated cancer (P=0.008) had a significant better outcome. Nodal spreading increased by local tumour extension and lymphatic involvement decreased patient survival (P=0.018). Patients' age (>75 years) was without influence on long-term survival. CONCLUSIONS: Long-term survival is possible both in elderly patients and in advanced cancer.

[Therapy of gallbladder carcinoma. Experience of a central hospital]. / Die Therapie des Gallenblasenkarzinoms. Eine Standortanalyse.

INTRODUCTION: There are various options for the treatment of gallbladder carcinoma; however, only radical resection offers a chance for prolonged survival. METHODS: The aim of this study was to analyze retrospectively patients suffering from gallbladder carcinoma in a central hospital in Austria. From 1986 to 1999, 77 patients were treated in this surgical department. The median age of the patients was 71.3 years. RESULTS: In 28 patients the cancer was resected and 22 persons underwent palliative surgery. An explorative laparotomy was performed in 16 patients. Eleven patients had no surgical therapy, 10 persons received gemcitabine or a combination chemotherapy regimen consisting of leucoverin, 5-fluorouracil and mitomycin C. The median survival of patients without chemotherapy following radical resection (n = 15) was 10.7 months (one patient with metastatic cancer was excluded) and for patients with tumor remaining margins (n = 8) 3.2 months (P = 0.023). Without chemotherapy the median patient survival following palliative resection (n = 17) and explorative laparotomy (n = 15) was 1.5 months and 2.1 months. The median survival without surgical therapy was 1.6 months. Chemotherapy was administered to four of the resected patients (median survival 16.5 months), in five patients following palliative surgery and in one patient after explorative laparotomy (median survival 4.3 months) (P = 0.034). In a multivariate analysis, tumor resection (P = 0.034) and tumor-free resection margins (P = 0.025) proved to be the most important determinants for patient survival. CONCLUSION: Tumor resection is the most important factor for a prolonged patient survival. Following radical resection in an early tumor stage and combining this approach with an established chemotherapy, patient survival could be increased significantly.

Phase II trial of gemcitabine, epirubicin and granulocyte colony-stimulating factor in patients with advanced pancreatic adenocarcinoma.

Although the novel cytidin analogue gemcitabine has shown superior anti-tumour activity than 5-fluorouracil in advanced pancreatic cancer, further improvements of therapeutic results are warranted. This goal might be achieved by combining gemcitabine with other active drugs. This trial evaluated the efficacy and tolerance of such a combination regimen with epirubicin and granulocyte colony-stimulating factor (G-CSF) in patients with metastatic disease. Seventy patients with metastatic pancreatic adenocarcinoma were enrolled in this multicentre trial. Patients received 4-weekly courses of a combination regimen consisting of epirubicin 60 mg m(-2) given as intravenous bolus injection on day 1, gemcitabine 1000 mg m(-2) infused over 30 min on days 1, 8 and 15, and G-CSF administered at 5 microg kg(-1) day(-1) subcutaneously from days 2-6 during each cycle. The efficacy of treatment was assessed by conventional measures, i.e. objective response, progression-free and overall survival, as well as by analysis of clinical benefit response (defined as > or = 50% reduction in pain intensity, > or = 50% reduction in daily analgesic consumption, and/or > or = 20-point improvement in Karnofsky performance status that was sustained for > or = 4 consecutive weeks). Of 66 patients evaluable for objective response, one achieved complete and 13 partial remissions, for an overall response rate of 21% (95% confidence interval (CI), 12-33%); 27 additional patients (41%) had stable and 25 (38%) increasing disease. The median time to progression was 3.8 months. Median survival was 7.8 months, and the probability of surviving beyond 12 months was 21.2%. Out of 60 patients with tumour-related symptoms, who were considered evaluable for clinical benefit response, 26 (43%) experienced significant palliation. The median time to achieve a clinical benefit response was 7 weeks, and its median duration was 22 weeks. Chemotherapy was well-tolerated with leukopenia/granulocytopenia representing the most common and dose-limiting side-effect. Gastrointestinal and other subjective toxicities were infrequent and generally rated minor. We conclude that the combination of gemcitabine, epirubicin and G-CSF seems to be an effective palliative treatment with only moderate toxic effects in patients with metastatic pancreatic adenocarcinoma. Our results in terms of objective and clinical benefit response, as well as survival seem to suggest an advantage over gemcitabine-monotherapy, though this remains to be confirmed in a randomized trial.

Two consecutive phase II studies of 5-fluorouracil/leucovorin/mitomycin C and of gemcitabine in patients with advanced biliary cancer.

INTRODUCTION: Carcinoma of the biliary system is a rare tumor entity, and patients with advanced disease face a dismal prognosis. Because of the absence of standard chemotherapy for advanced biliary carcinoma, we have performed two consecutive studies to evaluate the clinical potential of 5-fluorouracil, leucovorin and mitomycin C as well as the novel antimetabolite gemcitabine in this disease. PATIENTS AND METHODS: A total of 39 consecutive patients suffering from locally inoperable or metastatic biliary cancer were enrolled in the study between March 1994 and October 1997. Twenty patients were treated with leucovorin 200 mg/m2 and 5-FU 400 mg/m2, both given as intravenous bolus on days 1-4, and mitomycin C 8 mg/m2 on day 1 (group A). Treatment cycles were repeated every 28 days. The second cohort included 19 patients, who received gemcitabine 1200 mg/m2 on days 1, 8 and 15 with a 2-week interval before the next treatment cycle (group B). Treatment was continued for a maximum of 6 cycles in the absence of progressive disease in both groups, and endpoints of the study were responses rates, survival and toxicity. RESULTS: In group A, 5 patients (25%) had a partial response (PR), 6 additional patients (30%) had stable disease (SD) and 9 patients (45%) progressed during treatment. The median survival was 9.5 months (range, 3-14.5) with the median time to progression being 4 months (range, 3-9). In group B, 3 patients achieved a PR (16%), 4 showed SD (21%), while the remaining 12 patients had progressive disease. A median survival of 6.5 months (range, 2-11.5) was obtained, and the median time to progression was 2.5 months (range, 1-6+). Toxicity was generally mild in both treatment arms, 6 patients in group A required dose reductions, while no dose adaptation had to be performed for gemcitabine. CONCLUSION: Our data suggest that treatment of advanced biliary cancer is feasible and can be safely performed with both regimens applied in our study. While administration of gemcitabine has resulted in only mild toxicities, its exact impact on the management of advanced biliary cancer should be evaluated in a controlled trial.