[Neuroendocrine tumours of the GI tract--data from the German NET Registry]. / Neuroendokrine Tumoren des Verdauungstrakts - Daten des deutschen NET-Registers.

BACKGROUND: Neuroendocrine tumours (NET) are rare and heterogeneous neoplasia. To obtain valid data on epidemiology, diagnostics, therapy, prognosis and risk factors is the aim of the German NET registry. PATIENTS AND METHODS: Data from 2009 histologically proven NET were collected from 35 NET centres between 1999 and 2010. Data collection has been performed prospectively since 2004. Results: Median follow-up was 34.5 months and median age at diagnosis 56.4 years. Primary tumour localisations were pancreas (34.2%), midgut (5.8%), stomach (6.5%), bowel (6.9%), duodenum (4.8%) and neuroendocrine CUP (12.6%). Synchronous metastases were seen in 46% and second malignancies in 12%. From 860 patients, 402 (46.7%) had functional tumours with the following hormone excess syndromes: carcinoid syndrome (19.1%; n = 164), persistent hyperinsulinaemic hypoglycaemia (17.7%; n = 152), Zollinger- Ellison syndrome (7.1%; n = 61), glucagonoma (0.7%; n = 15), Verner-Morrison syndrome (0.4%; n = 8) and somatostatinoma syndrome(0.1%; n = 2). Surgical therapy was performed in 78%, therapy with somatostatin receptor analogues(SSA) in 28%, peptide radioreceptor therapy (PRRT) in 19%, chemotherapy in 18% and interferon therapy in 6.5%. Only surgery was done in 47%, whereas 53% received a second therapy. General mortality rate during follow-up was 14.9%. The tumour-specific survival rates for 2, 5 and 10 years were 94, 85 and 70%. The 5-year survival is dependent on the surgical or non-surgical therapy (82 versus 61%, p < 0.001) and also on the primary tumour site (90/30% for midgut, 85/65% for pancreas, p < 0.001). Grading (G1, G2, G3) based on proliferation index Ki-67 recommended by the ENETS guidelines and WHO classification is highly correlated to the 5-year survival rate (88, 82, 33%, p < 0.001). CONCLUSION: The German NET registry provides valid multicentric data on NET in Germany. Surgical therapy is the most frequent and important therapy with good clinical outcome. In non-resectable, metastatic tumours, systemic therapies are common. Continuation and evaluation of the new WHO and TNM classifications for NET and their therapies will be a future focus of the registry.

[Diagnostics and therapy for neuroendocrine neoplasia of an unknown primary - a plea for open exploration]. / Diagnostik und Therapie bei neuroendokrinen Neoplasien mit unklarem Primarius - ein Plädoyer für die offene Exploration.

BACKGROUND: Neuroendocrine neoplasia (NEN) are a rare and heterogenous tumour entity. The subgroup with unknown primary tumour (N-CUP) seems to have a worse prognosis as resection of the primary is necessary for cure. The diagnostics and therapeutic algorithms for N-CUP in a German single centre are presented. PATIENTS/METHODS: Analysis of the surgical databank showed 35 cases of N-CUP in 261 cases with NEN from gastroenteropancreatic and lung origin over 2 decades (03/1990-03/2011). Three groups were built: K1 - primary detection after operative exploration (n = 10), K2 - unknown primary after operative exploration (n = 10) and K3 - no operative exploration for various reasons (n = 13). RESULTS: Initially 13.4 % (35/261) of patients presented as N-CUP, after intensified diagnostics 12.7 % (33/261) and after operative exploration 8.8 % (23/261) remained with unknown primary tumour. The sex ratio was 1 : 1, the median age is significantly higher in N-CUP [63.8 years (y) vs. 55.9 y, p = 0.004), the 5-year-survival is lower (58 vs. 72 %, n. s.). compared to NEN with known primary. Operative exploration was performed in 60.6 % (20/33), 30 % (6/20) of them were found to have inoperable situations, in 20 % (4/20) single site metastases were removed completely and in 50 % (10/20) a primary tumour was detected (8 × midgut, 2 × pancreas) intraoperatively. In these cases 70 % (7/10) got complete tumour resection (R0) and in 30 % (3/10) primary tumour resection with debulking of liver metastasis was done. In K3 (39.4 %, 13/33) most patients [69.2 % (9/13)] were treated with chemotherapy. The median age in K1 was significantly lower than in K3 (54.9 y vs. 68.3 y, p = 0.028), male dominance was seen in K3 (3,3 : 1, n. s.). The average Ki-67 index was 4.3, 23.8 and 53 % in K1, K2 and K3 (p < 0.0001 for K1 and K3 and p = 0.035 for K2 and K3), respectively. The death rate was 20, 30 and 76.9 % in K1, K2 and K3, respectively. CONCLUSION: Primary tumours of the midgut and pancreas are often found in the subset of well differentiated neuroendocrine CUP syndrome after open surgical exploration. A high rate of complete tumour resection and cure can be achieved in these cases. After common diagnostic tools (CT, MRI and somatostatin receptor scintigraphy), immunhistochemistry can give important hints (CDX-2 for midgut, TTF-1 for lung and thyroid) for a primary lesion. Also in single site metastasis without primary tumour detection a good clinical outcome is seen after complete resection.

[Future of endoscopic surgery--German health law and minimal access surgery in an university hospital]. / Zukunft der endoskopischen Chirurgie--GSG-Probleme der MIC in einer Universitätsklinik.

The future development of endoscopic surgery depends on a medical and economical benefit. Medical advantages are demonstrated under professional conditions of practice in a retrospective study: endoscopical repair of the groin (TEP n = 44) vs. conventional Shouldice- (n = 17) and Lichtenstein (n = 19) method, laparoscopical hemifundoplication (n = 7) vs. traditional Nissen-Rosetti procedure (n = 3) and also resection of the sigmoid (lap. n = 26) vs. open surgery (n = 12). The overall hospital stay is shortend dramatically (primary hernia of the groin 8.8 (Shouldice) and 7.4 (Lichtenstein) vs. 3.1 days (TEP); (hemi-) fundoplication 11.1 (open) vs. 5.0 days (lap.); resection of sigmoid 19.0 (open) vs.17.0 days (lap.)) At the same time quality of care is held or improved. Comparison of real cost analysis revealed a better economical result (593-970 DM lower cost for TEP, 1.256 DM lower costs for lap. hemifundoplication, and 1.918 DM in case of lap. resection of sigmoid) for minimal-access-surgery (MAS), although particular costs for the endoscopic surgical procedure are increasing up to 100%, especially at the beginning (learning curve). The German payment-system does not regard the special conditions of MAS. There is no case-related payment for MAS due to the lower overall costs. Therefore the financial result is worse than for conventional treatment.

[Quality in hospital treatment. How is it assured and who determines the guidelines?]. / Qualität in der Krankenhausbehandlung. Wie wird sie gesichert, und wer bestimmt die Richtlinien?

BACKGROUND: Internal quality control of medical performance in the interest of patient safety is not a new idea. In fact it has been implemented in varying degrees since the beginnings of medicine. ACTUAL SITUATION AND METHODS: Ever since hospitals are compelled by law to apply methods of quality assurance and external quality control, the question arises as to whether this law can achieve a concrete increase in quality of patient care or whether it rather serves to support economically motivated goals of health care policies, in the sense of an increase in efficiency of performance by physicians. Seen in the light of the overall situation of hospital care, the attempt to create mandatory quality standards is problematical. A reduction of hospital beds and a decrease in the average length of hospital stay contrasts the growing number of treated patients. This presents a problem which must be compensated for, despite cutbacks in budget and personnel. Methods of quality analysis are of the implicit as well as of the explicit type. Implicit methods are based on retrospective data analysis lacking previously set standards of comparison. These methods harbor the danger of viewer-dependent subjectivity (restricted reliability). Explicit methods are based upon comparison to previously defined standards. These methods are more objective, but often fail to give consideration to individual situations (restricted validity). The infrastructure necessary in order to sensibly apply quality control in the hospitals is not yet present in Germany. The software required in order to record and analyse data is still in a stage of development in many places. CONCLUSION: It is of importance not to leave external quality control to politicians and economists unfamiliar with the subject matter, but rather that quality control is implemented by experts in the medical field.

[Primary gastrointestinal lymphomas]. / Primäre gastrointestinale Lymphome.

From 1980 up to 1987 seven patients with primary gastrointestinal lymphoma were treated at the surgical department of the Medical University of Lübeck; six of them were women. The mean age was 73.3 years. The tumors were located in the stomach (4), the large bowel (2) and the small intestine (1), representing disease at Ann-Arbor-stage IE (5) and IIE (2). All patients underwent primary surgery, except one due to his bad general conditions. Irradiation-therapy followed in one case, chemotherapy in two cases when relapse of disease was revealed. Three patients are still alive (0.8 to 6.8 years) without evidence of recurrent lymphoma. The success of surgery as a curative treatment is closely related to the stage of disease; both are important factors influencing prognosis. Surgery is still necessary for diagnosis, tumor-staging and prevention of regional complications as bleeding or perforation, especially when conservative therapy is performed.

Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content.

Patients with medullary thyroid carcinomas (MTC) were analyzed according to age, sex, and tumor stage. In addition, the MTC were screened for the predominant histologic pattern, immunocytochemical spectrum (60 tumors), and DNA content (DNA cytophotometry and DNA flow cytometry, 25 tumors). These findings were correlated with follow-up data available for 45 of these patients. Forty-eight percent of the tumors revealed a polygonal cell pattern, whereas 22% showed spindle-cell predominance. All tumors contained cytokeratin, chromogranin A, and calcitonin (CT). Calcitonin gene-related peptide (CGRP) was present in 92%, carcinoembryonic antigen (CEA) in 77%, neuron-specific enolase (NSE) in 75%, and vimentin in 53% of cases. Positivity for neurotensin, somatostatin, neurofilaments, bombesin, and alpha human chorionic gonadotropin (a-hCG) and serotonin ranged between 3% and 27%. All MTC were negative for substance P, adrenocorticotropic hormone (ACTH), thyroglobulin (TG), or S-100 protein. Local recurrences and regional lymph node metastases revealed identical staining patterns as the primaries. Prognosis of MTC was found not to be related to histologic features (dominant architectural pattern, cellular shape, presence of amyloid deposits) or immunocytochemical pattern. Instead, survival was significantly correlated to age, sex, and stage of disease. The best prognosis was seen in women younger than 40 years and revealing an early stage of disease. DNA measurements added valuable information in assessing the prognosis of MTC.

[Metastases of the thyroid gland--morphology and clinical aspects of 25 secondary thyroid neoplasms]. / Metastasen in der Schilddrüse--Morphologie und Klinik von 25 sekundären Schilddrüsengeschwülsten.

Morphological and clinical findings in 25 secondary tumours of the thyroid are described. The most common sources of such lesions were the kidneys (32%), lung (28%) and breast (20%). In the majority of cases, thyroidectomy was performed prior to identification and treatment of the primary cancer. Conversely, among renal cell carcinomas, the metastatic lesion frequently appeared many years after resection of the primary tumour. This suggests that secondary thyroid tumours occasionally may be the only important malignant disease remaining. Hence, adequate surgical treatment may prove to be life-prolonging or life-saving.