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PTEN (phosphatase and tensin homologue deleted from chromosome 10) is a well established tumor suppressor gene, which was cloned to chromosome 10q23. PTEN plays an important role in controlling cell growth, apoptosis, cell adhesion, and cell migration. In various studies, a genetic change as well as loss of PTEN expression by different carcinomas has been described. To date, the role of PTEN as a differentiation marker for neuroendocrine tumors (NET) and for the loss of PTEN expression is still unknown. It is assumed that loss of PTEN expression is important for tumor progression of NETs. We hypothesize that PTEN might be used as a new prognostic marker. We report 38 patients with a NET of the pancreas. Tumor tissues were surgically resected, fixed in formalin, and embedded in paraffin. PTEN expression was evaluated by immunohistochemistry and was correlated with several clinical and pathological parameters of each individual tumor. After evaluation of our immunohistochemistry data using a modified Remmele Score, a widely accepted method for categorizing staining results for reports and statistical evaluation, staining results of PTEN expression were correlated with the clinical and pathological parameters of each individual tumor. Our data demonstrates a significant difference in survival with existence of lymph node or distant metastases. Negative patients show a significant better survival compared with positive patients. Furthermore, we show a significant difference between PTEN expression and WHO or TNM classification. Taken together, our data shows a positive correlation between WHO classification and the new TNM classification of NETs, and loss of PTEN expression as well as survival. These results strongly implicate that PTEN might be helpful as a new prognostic factor.

Rectovaginal fistuale (RVF) are a serious and disabling problem for the patients and a surgical challenge for the treating physicians. The most common causes of RVF are postoperative complications, inflammatory bowel disease, complications of radiotherapy, obstetric complications, and neoplasia. Therapeutic options are diverse and results often unsatisfactory. This article presents the treatment of patients with rectovaginal fistulae in the general surgery department of University Hospital in Duesseldorf, Germany. The therapeutic strategy for treatment of RVF is divided according to aetiology, localisation, and comorbidity. A diverting ileostomy is particularly useful if acute inflammation exists. Secondary repair may then be a better option. An initial approach with a local repair by preanal repair is justified in low RVF. For failures muscle flaps are promising.

Surgical therapy of incidentally postoperative diagnosed small sporadic medullary thyroid cancer (MTC) is discussed controversially. In principle completion thyroidectomy with neck dissection and regulary tumor follow-up are under discussion. A total of 277 patients with MTC were treated between 1986 and 2004. In 22 cases diagnosis of a small (pT1 or pT2) sporadic MTC was incidental and only postoperatively confirmed. Normally total thyroidectomy with neck dissection is standard surgical therapy of a known MTC. Because of postoperative incidental diagnosis in all 22 cases surgical therapy was less then total thyroidectomy. Mutation analysis of RET Proto-Oncogen and familial history were negative in all cases. All patients were systematically followed-up in defined intervals by calcitonin, pentagastrin stimulation test, carcinoembryonic antigen and ultrasound. Median follow-up is 6.2 years (range: 2-13 years) and although a hemithyroidectomy or less was performed all 22 patients are cured by the MTC. We conclude that completion thyroidectomy and neck dissection are not mandatory in such patients, if the tumor is completely resected and genetic background is excluded. Indispensably a systematic long term follow-up of at least 10 years, better a life-long, is mandatory.

Ghrelin is a novel gastrointestinal-brain hormone that was first described by Kojima et al. as a growth-hormone-releasing peptide. It can be isolated and purified from different tissues. Evidence of antiproliferative effects in neoplastic cells (binding to normal and neoplastic tissues) supports the hypothesis that ghrelin also plays an important role in endocrine regulation. Whether ghrelin may be involved in formation of neuroendocrine tumours (NET) of the gastrointestinal tract (GIT) in cases of MEN-1 is under discussion. Over the last sixteen years, 227 patients with GIT NET were treated at our institution. Mutations of the menin gene were identified in twelve patients. Eleven of these tumours (islet cell tumours) were localized in the pancreas and one in the stomach. Tissues from these tumours were resected, fixed in formalin and embedded in paraffin. Sections were examined by immunohistochemistry with a primary antibody for ghrelin. Three out of twelve NET in MEN-1 patients (25%) showed ghrelin expression by immunohistochemistry. Comparison between ghrelin-positive and ghrelin-negative tumours regarding biological activity, morphological aspects and clinicopathological parameters shows no substantial differences. The reported incidence of ghrelin expression in NET of the gastrointestinal tract by MEN-1 was not seen in our patients. Whether or not ghrelin has an influence on neuroendocrine tumour development related to deficient menin-genes is unknown.

Objective: Rectovaginal fistulae (RVF) are a serious and debilitating problem for patients and a challenge for the treating surgeons. We present our experiences in the surgical treatment of these patients. Methods: Study population consisted of 22 consecutive patients (range 26-70 years) with RVF treated in our department between 2003 and 2009. 13 RVF were observed after colorectal or gynaecological surgery, 3 occurred after radiotherapy, 2 due to tumour infiltration, 4 because of local inflammation (3x diverticultis, 1x ulcus simplex recti). The RVF was classified in all patients before treatment as either 'low' or 'high'. Results: Local procedures (transvaginal excision, preanal repair) as initial treatment were performed in 9 patients with low fistula. In 13 cases with high fistula an abdominal approach was performed to close the fistula. A recurrence was observed in 8/22 cases (36%), which were treated by a gracilis flap (n=2), a bulbospongiosus composite (n=1), a second abdominal approach (n=4), and a re-local excision (n=1). Ultimatively, in 19 cases the defect healed but in 3 patients the RVF persisted. Conclusions: Most important predictor of healing/failure is etiology followed by localization and recurrence of the RVF. Local (preanal, transvaginal) procedures are suitable for low RVF, whereas abdominal surgery is necessary in high RVF. In recurrent RVF, muscle flaps are promising procedures. Hintergrund: Rektovaginale Fisteln (RVF) stellen für betroffene Patientinnen ein schwerwiegendes psychosoziales Problem dar und bedeuten für den Chirurgen eine komplexe therapeutische Herausforderung. Wir berichten über unsere Erfahrung in der chirurgischen Therapie dieser Patientinnen.Methoden: Wir berichten über 22 Patientinnen (26-70 Jahre) mit RVF, die zwischen 2003 und 2009 in unserer Klinik behandelt wurden. 13 RVF wurden nach colorektaler oder gynäkologischer Operation festgestellt. 3 als postaktinische Folgeschäden, 2 durch Karzinominfiltrationen und 4 durch entzündliche Veränderung aufgetreten (3x Divertikulitis, 1x ulcus simplex recti). Die RVF wurden in tiefe und hohe Fistel unterteilt.Ergebnisse: Initiale Therapie zum Fistelverschluss war bei 9 Pat. durch lokale Exzision/preanal repair, bei 13 Pat. durch einen transabdominellen Zugang. Eine Rezidivfistel war in 8/22 (36%) Fällen nachweisbar. Dann wurde definitiver Fistelverschluss erreicht: 1x lokale Exzision, 4x transabdominell, 2x Gracilis-Plastik, 1x M. bulbospongiosus composite. In 19 Fällen kam es zur Ausheilung des Defektes, bei drei Patientinnen besteht eine Persistenz der RVF.Schlussfolgerungen: Die Ätiologie einer RVF hat den größten Einfluss auf die Heilungsrate gefolgt von der Lokalisation und dem Rezidiv. Bei tief liegenden Fisteln empfehlen wir zunächst ein lokales Vorgehen wie beispielsweise preanal repair und Fistelexzision. Transabdominelles Vorgehen bietet sich bei hoch liegenden Fisteln an. Bei RVF-Rezidiven ist an die Interposition eines Muskelschwenklappens (z.B. Gracilis-Plastik) zu denken.

Mature cystic teratomas are often found in gonadal sites, but are very rarely located extragonadally, for example, in retroperitoneum, mediastinum, central nervous system, lung, or liver. In the literature, only 10 cases of cystic teratoma originating from the diaphragm have been reported. Here, we report for the first time a metachronous occurrence of a benign mature cystic teratoma in the left diaphragm together with a serotonin-producing neuroendocrine tumor of the ileum. The 51-year-old, female patient received a partial resection of the ileum due to a neuroendocrine tumor (pT3N1M0) 4 years ago. Furthermore, she was operated for a benign cystadenoma of the right ovary 3 years ago. In her past medical history, she had an appendectomy in her childhood and a subtotal thyroidectomy 10 years ago. To our knowledge, this is the first report describing the metachronous occurrence of benign mature cystic teratoma in the diaphragm and a highly differentiated neuroendocrine tumor of the ileum. The possible coincidence of both diseases is discussed.

Here we tested whether global histone modifications predict survival in organic hyperinsulinism and whether global histone modification pattern can be used to distinguish benign from malignant primary insulinoma. A tissue microarray (TMA) was built, using samples from 63 patients with organic hyperinsulinism. The TMA was classified according to the WHO classification of 2004 [WHO 1A: benign insulinoma (wdPET); WHO 1B: unknown behavior (wdPETub); WHO 2/3: malignant insulinoma (wdPEC/pdPEC)]. The TMA consisted of tissue cores from islands of Langerhans, primary insulinomas, lymph node metastases, and hepatic metastases. Immunohistochemistry was performed on consecutive TMA slides with antibodies against H3K9Ac, H3K18Ac, H4K12Ac, H3K4diMe, and H4R3diMe. The Remmele immunoreactive scoring system was used to classify the staining. The IHC staining results were correlated to the WHO-classification of 2004 as well as to clinical follow-up data (mean: 107 months; range: 1-312 months). A nuclear staining pattern was observed for all antibodies directed against histone H3 and H4 acetylation/methylation sites. We observed significant differences in the distribution of the medians across all investigated tissue types (H3K9Ac, p=0.004; H3K18Ac, p=0.001; H4K12Ac, p=0.006; H4R3diMe, p=0.002) except for H3K4diMe (p=0.183). Correlation of the histone modification with the WHO-classification and clinical follow-up data, showed in the dichotomized groups ["low" (score 0-3), "moderate" (4-7) vs. "high" (≥8)] that patients with lower H3K18Ac levels ("low + moderate") had a significantly decreased relapse-free survival vs. patients with high H3K18Ac levels (p=0.038). The WHO classification and age were also of significant prognostic impact upon univariate analysis. A backwards Cox proportional hazards model revealed the independent prognostic effekt of H3K18Ac levels. Our data revealed low K18 acetylation levels of histone H3 as independent prognostic factor in organic hyperinsulinism. This result warrants validation with independent data sets of organic hyperinsulinism, but is in line with several previous studies in different cancer entities. The broad applicability of this potential biomarker might lead to standardized diagnostic tests in near future and may help to manage insulinoma patients more effectively.

Introduction: Surgical treatment of Graves' disease has changed over the last decade from Dunhills operation to total thyroidectomy as the standard operative procedure. Materials and methods: Prospective analysis of 207 patients (81% female, 19% male)having been operated between 2000[for full text, please go to the a.m. URL], 128. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Das Auftreten einer bronchovaskulären Fistel ist eine seltene Komplikation, die im Rahmen von bronchoplastischen Eingriffen bei Lungentumoren auftreten kann. Wir stellen den seltenen Fall einer angiobronchialen Fistel nach Portimplantation bei einem 62 jährigen Patienten vor und[for full text, please go to the a.m. URL], 128. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Hämoglobin-Glutamer 200 (HbG200; Oxyglobin®, Biopure Corp.) ist eine kommerziell erhältliche zellfreie Hämoglobinlösung, die wie kürzlich gezeigt eine Induktion der Hämoxygenase (HO)-1 in der Leber bewirkt (JSR 2008;150:243-254). Ziel dieser Studie war [for full text, please go to the a.m. URL], 127. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: CD133+ und CD34+ Zellen werden nach Leberresektion peripher mobilisiert. CD133 KMSZen haben in eigener Erfahrung das Potential zur Förderung klinischer Leberregeneration. Hepatocyte Growth Factor (HGF) zeigt, wenn präklinisch nasal appliziert oder klinisch überexpremiert,[for full text, please go to the a.m. URL], 127. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Insulinome als häufigste Tumorentität endokriner Pankreastumoren sind durch die Whipple Trias (rezidivierenden Hypoglykämien (BZ< 50 mg/dl); neuroglykopenische Symptome; Besserung durch Kohlenhydrataufnahme) gekennzeichnet. Laborchemisch beweisend sind pathologische[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Doppeladenome sind die ungewöhnlichste und umstrittenste Entität beim primären Hyperparathyreoidismus (pHPT). Sie sind neben den Mehrdrüsenerkrankungen, die alle vier Drüsen befallen, hauptverantwortlich für unbefriedigende Resultate nach dem Ersteingriff. [for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Beim Zufallsbefund eines papillären Mikrokarzinoms (< 1 cm) ist eine Nachoperation und Radiojodtherapie gemäß Leitlinien nur selten indiziert. Die Frage ist, ob bei dieser Tumorgröße eine Radiojodtherapie indiziert ist, wenn eine Thyreoidektomie vorangegangen[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Das Nebennierenrindenkarzinom ist eine seltene maligne Erkrankung mit einer sehr schlechten Prognose. Die Inzidenz liegt bei 2 Fällen auf 1 Millionen Einwohner. Es macht 0,2% aller malignen Tumore und 0,2% aller krebsbedingten Todesfälle aus. Die klinische Präsentation[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Die Fallvorstellung vereint drei interessante Fakten bei einer Patientin:Bei der Patientin hat ein „Giant Insulinoma“ von 15 cm Größe bei Vorliegen einer multiplen endokrinen Neoplasie vom Typ 1 (MEN 1) zu einer so genannten Skip Metastierung in die Lunge geführt.[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: In der antikörper-basierten Tumortherapie stellt das Zelladhäsionsmolekül EpCAM eine wichtige Zielstruktur dar. Um zu prüfen, ob es sich bei EpCAM um ein attraktives Ziel zur molekularen Therapie des Ösophagus-Plattenepithelkarzinoms handelt, haben wir die Expression[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Die Ösophagusperforation ist eine Verletzung, die trotz chirurgischer Therapie zu einer lebensbedrohlichen Mediastinitis und Sepsis führen kann. Die Möglichkeit eines endoskopischen Verschlusses des Defekts hat sich in der Vergangenheit mangels Verfügbarkeit sicherer [for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Typischerweise metastasieren neuroendokrine Tumoren (NET) des Pankreas in die Leber. Für den Chirurgen stellt sich die Frage, ob ein Sicherheitsabstand in der neuroendokrinen Leberchirurgie zu fordern ist, da der Einfluß des Sicherheitsabstandes auf die Rezidivhäufigkeit und[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie