Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors.

PURPOSE: Neuroendocrine tumors of the small intestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3-20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading. METHODS: Demographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively. RESULTS: A total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3-9%) and G2 high (Ki67 10-20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases. CONCLUSION: Lymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.

[Differentiated Strategies for the Therapy of Liver Metastases in Gastro-entero-pancreatic Neuroendocrine Neoplasia]. / Differenzierte Therapiestrategie bei Lebermetastasen gastro-entero-pankreatischer Neuroendokriner Neoplasien.

Neuroendocrine neoplasias comprise a heterogenous group of malignant tumours, mostly arising from the gastro-entero-pancreatic system (GEP). Most of these tumours develop from the small intestine and pancreas and the liver is the predominant site for distant metastases. Patients may be asymptomatic for a long time and liver metastases are frequently diagnosed by chance or during operations for bowel obstruction, for example, during emergency surgery. The only curative therapy consists in complete removal of primary and metastases. In case of metastatic disease, various treatment modalities need to be discussed in interdisciplinary tumour boards comprised of specialists from gastroenterology, (liver-)surgery, radiology, nuclear medicine, radiotherapy, pathology and endocrinology. By combining different therapies, even patients with progressive disease may reach long-term overall survival with good quality of life. The most important factors for decisions on therapy are individual factors like tumour grading, hormonal functionality, type of metastases and evolution of the disease. Adequate treatment of liver metastases comprises various surgical strategies as well as locally ablative radiological interventions and nuclear medical therapies, in complement to systemic treatments.

Long-term outcome of surgical resection in patients with gastroenteropancreatic neuroendocrine neoplasia: results from a German nation-wide multi-centric registry.

BACKGROUND: Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy. MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999-2012). It focuses on patients without distant metastases (limited disease, LD, stage I-IIIB). RESULTS: Data of 2239 patients with NEN were recorded. Median age was 59 years, the gender ratio was 1:1.3 (f:m). A total of 986 patients (44%) had LD, and the 5-year survival rate (5 years) was 77% for all and 90% for patients with LD. A total of 1635 patients (73%) received a surgical therapy (1st to 6th line); the 5 and 10 ysr were 83/65% after and 59/35% without surgery for all patients (p < .001). The resection margins in the LD patients were 76%, 16%, and 3% for R0, R1 and R2, respectively. The 10 ysr was 84%, 59% and 42% for R0, R1 and R2 resections, respectively (p = .021 R0/R1, p < .001 R0/R2). The R0 resection rate was 75% for G1/G2 NET and 67% for G3 NEC. CONCLUSION: The rate of complete tumour resection (R0) in LD is independent of tumour grading, and R0 resection is the key determinant of long-term survival, as demonstrated by the 10 ysr. of 84%. All NEN patients with limited disease should be considered for operation, if possible, as the best 10-year survival is shown after an R0 resection.

Curative and palliative surgery in patients with neuroendocrine tumors of the gastro-entero-pancreatic (GEP) tract.

The incidence of neuroendocrine tumors (NET) increases with age. Lately, the diagnosis of NET was mainly caused by early detection of small NET (<1 cm) in the rectum and stomach, which are depicted by chance during routine and prophylactic endoscopy. Also in patients with large and metastatic pancreatic and intestinal tumors thorough pathologic investigation with use of different immunohistologic markers discovers more neuroendocrine tumors with low differentiation grade (G2-G3) and more neuroendocrine carcinomas (NEC), nowadays, than in former times. While gastric and rectal NET are discovered as small (<1 cm in diameter) and mainly highly differentiated tumors, demonstrating lymph node metastases in less than 10% of the patients, the majority of pancreatic and small bowel NET have already metastasized at the time of diagnosis. This is of clinical importance, since tumor stage and differentiation grade not only influence prognosis but also surgical procedure and may define whether a combination of surgery with systemic biologic therapy, chemotherapy or local cytoreductive procedures may be used. The indication for surgery and the preferred surgical procedure will have to consider personal risk factors of each patient (i.e. general health, additional illnesses, etc.) and tumor specific factors (i.e. tumor stage, grade of differentiation, functional activity, mass and variety of loco regional as well as distant metastases etc.). Together they define, whether radical curative or only palliative surgery can be applied. Altogether surgery is the only cure for locally advanced NET and helps to increase quality of life and overall survival in many patients with metastatic neuroendocrine tumors. The question of cure versus palliative therapy sometimes only can be answered with time, however. Many different aspects and various questions concerning the indication and extent of surgery and the best therapeutic procedure are still unanswered. Therefore, a close multidisciplinary cooperation of colleagues involved in biochemical and localization diagnostics and those active in various treatment areas is warranted to search for the optimal strategy in each individual patient. How far genetic screening impacts survival remains to be seen. Since surgeons do have a central role in the treatment of NET patients, they have to understand the need for integration into such an interdisciplinary team.

Measurement of Basal Serum Calcitonin for the Diagnosis of Medullary Thyroid Cancer.

Calcitonin (CT), a tumor marker for medullary thyroid cancer (MTC), can be stimulated with pentagastrin or calcium. Because of the unavailability of pentagastrin, basal CT measurement is frequently used for the preoperative diagnosis of MTC. The aim of the study was to define basal serum calcitonin (bCT) cut-off thresholds for diagnosing MTC. Within a retrospective analysis, 114 patients (51 males) were included fulfilling the criteria of an increased preoperative bCT level (>10 pg/ml) and the criteria of an available postoperative histology analysis. Based on a ROC plot analysis, the cut-off values for the diagnosis of MTC vs. non-malignancy (C cell hyperplasia and goiter) were identified. The most precise bCT thresholds for the identification of MTC were ≥46 pg/ml for males (sensitivity: 93.6%, specificity: 95.0%, PPV: 97%, NPV: 90%) and ≥35 pg/ml for females (sensitivity: 87.3%, specificity: 87.5%, PPV: 98%, NPV: 50%). Using these cut-offs, only 6% of male patients were not identified of having MTC, whereas 5% were false positive (having instead C cell hyperplasia). In females, the discrepancy was higher since 13% of female MTC patients were false negative by using the cut-off of ≥35 pg/ml, and 13% had false positive results (suffering from C cell hyperplasia). Gender-specific bCT cut-offs for the identification of MTC vs. C cell hyperplasia and non-malignancy were defined, which can be used in clinical routine. In female patients, however, the accuracy is much lower compared to males.

Total Parathyroidectomy With Routine Thymectomy and Autotransplantation Versus Total Parathyroidectomy Alone for Secondary Hyperparathyroidism: Results of a Nonconfirmatory Multicenter Prospective Randomized Controlled Pilot Trial.

OBJECTIVE: This randomized controlled multicenter pilot trial was conducted to find robust estimates for the rates of recurrence of 2 surgical strategies for secondary hyperparathyroidism (SHPT) within 36 months of follow-up. BACKGROUND: SHPT is a frequent consequence of chronic renal failure. Total parathyroidectomy with autotransplantation (TPTX+AT) and subtotal parathyroidectomy (SPTX) are the standard surgical procedures. Total parathyroidectomy alone (TPTX) might be a good alternative, as morbidity and recurrence rates are low according to small-scale retrospective studies. METHODS: The trial was performed as a nonconfirmatory randomized controlled pilot trial with 100 patients on long-term dialysis with otherwise uncontrollable SHPT to generate data on the rate of recurrent disease within a 3-year follow-up period after TPTX or TPTX+AT. Parathyroid hormone (PTH) and calcium levels, recurrent or persistent hyperparathyroidism, parathyroid reoperations, morbidity, and mortality were evaluated during a 3-year follow-up. RESULTS: A total of 52 patients underwent TPTX and 48 TPTX+AT. Patient characteristics, preoperative baseline data, duration of surgery (02:29 vs 02:47 hrs, P = 0.17) and mean hospital stay (10 ± 7.1 vs 8 ± 3.7 days, P = 0.11) did not differ significantly. Persistent SHPT developed in 1 TPTX and 2 TPTX+AT patients. None of the TPTX patients required delayed parathyroid AT to treat permanent hypoparathyroidism. Serum-calcium values were similar (2.1 ± 0.3 vs 2.1 ± 0.2, P = 0.95) whereas PTH rose by time in the TPTX+AT group and was significantly higher at the end of follow-up when compared with the TPTX group (31.7 ± 43.6 vs 98.2 ± 156.8, P = 0.02). Recurrent SHPT developed in 4 TPTX+AT and none of the TPTX patients. CONCLUSIONS: TPTX+AT and TPTX seem to be safe and equally effective for the treatment of otherwise uncontrollable SHPT. TPTX seems to suppress PTH more effectively and showed no recurrences after 3 years. The hypothesis that TPTX is superior to TPTX+AT referring to the rate of recurrent SHPT has to be tested in a large-scale confirmatory trial. Nevertheless, TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of SHPT.

Evaluation of malignant parathyroid tumours in two European cohorts of patients with sporadic primary hyperparathyroidism.

PURPOSE: Parathyroid carcinoma (PC) is remarkable for its rare occurrence and challenging diagnostics. PC accounts for 0.1-5 % cases of primary hyperparathyroidism (PHPT). The differentiation from benign tumours is difficult even by morphological criteria. To address these issues, we assessed the PC frequency in two separate European PHPT cohorts and evaluated the demographic, clinical, morphological and molecular background. METHODS: A retrospective study was carried out, using continuously maintained database (2005-2014) of PHPT patients from two tertiary referral university hospitals in Europe. The demographic, clinical data and frequency of PC among surgically treated PHPT was detected. Immunohistochemistry (IHC) was performed to detect parafibromin, representing protein product of HRPT2 gene and proliferation marker Ki-67. RESULTS: Both PHPT cohorts were characterised by close mean age values (58.6 and 58.0 years) and female predominance. The frequency of PC differed significantly between the cohorts: 2.1 vs. 0.3 %; p = 0.004. PC was characterised by invariable complete loss of parafibromin contrasting with parathyroid adenomas. The proliferation fraction was similar in both PC cohorts (10.6 and 11.0 %). PC showed significantly higher proliferation fraction than typical parathyroid adenomas (1.6 %), atypical adenomas (1.6 %) or adenomas featuring focal loss of parafibromin (2.2 %). CONCLUSIONS: PC frequency can range significantly between the two European cohorts. The differences can be attributable to selection bias of patients referred for surgery and are not caused by discordant definition of malignant parathyroid histology. Diffuse loss of parafibromin and increased proliferation fraction by Ki-67 are valuable adjuncts in PC diagnostics due to significant differences with various clinical and morphological subtypes of adenoma.

Resection of Ileoinguinal and Ileohypogastric Nerves Combined with Gluing in Modified Lichtenstein Repair.

We conducted a cohort trial to investigate the relevance of resection of the ilioinguinal and iliohypogastric nerves in combination with mesh fixation with BioGlue™ (CryoLife® Inc., Kennsaw, Georgia) in modified Lichtenstein repair to the development of chronic pain and hernia recurrence.1 In all, 430 patients underwent Lichtenstein repair. In 247 patients the mesh was fixed by means of glue, and in 183 patients it was fixed with conventional sutures. In all cases the inguinal nerves N. ilioinguinalis and N. iliohypogastricus were located and resected after identification to prevent nerve reaction to the mesh. The pain intensity was measured with a numeric analogous scale (NAS) 24 hours after surgery. All complications were recorded with a follow-up of up to 5 years. There was a significantly lower pain intensity level in the gluing group compared with the suture group 24 hours after surgery (0.016 t test). The level was 3.8±2.4 in bilateral hernia and 3.3±2.1 in unilateral hernia in the gluing group. It was 4.7±3.3 in unilateral and 3.7±2.2 in bilateral hernia in the suture group. The cut-suture time was lower in the gluing group. There were no severe pain syndromes (NAS≥4) in the gluing group and only 1.1% in the suture group. There was a higher incidence of non-bacterial wound infections in the gluing group (3.6%) than in the suture group (1.1%). The rate of recurrence after 5 years amounted to 2.0% in the gluing group and 2.2% in the suture group. The technique of using BioGlue™ for mesh fixation combined with systematic nerve dissection reduces acute and chronic postoperative pain after modified Lichtenstein repair. Only 2 of 430 patients suffered from severe chronic pain. Combined gluing and systematic resection of the inguinal nerves is more comfortable than standard Lichtenstein repair.

Functional long-term results after rectal cancer surgery--technique of the athermal mesorectal excision.

PURPOSE: The total mesorectal excision (TME), embedded in a multimodal therapeutic concept, is accepted as the standard therapy of the advanced adenocarcinoma of the middle and lower thirds. The thermal damages of the autonomous nerves in the little pelvis caused by dissection devices remains a large problem. For our patients, we use water-jet dissection (WJD)-aided TME with the intention to minimise the rate of bladder and sexual function disorders. METHODS: From October 2001 until June 2010, we recorded 125 patients with an adenocarcinoma of the middle and lower third of the rectum. Ninety deep anterior rectum resections and 35 abdominoperineal rectum extirpations by WJD were performed. Of the patients, 27.2 % received neoadjuvant radiochemotherapy. Bladder and sexual function disorders were assessed by International Prostate Symptom Score and International Index of Erectile Function. RESULTS: The median follow-up period was 46 (2-117) months. Considering a local recurrence rate of 9.6 %, the tumour-specific 5-year survival of the entire collective was 75.4 %. Long-term bladder function disorders showed in 6.0 % (4/64) and sexual function disorders in 25.0 % (9/36) of the male patients in the course of time. CONCLUSION: The specific advantage of the WJD technique is not only the facilitated dissection between the mesorectal fascia and the surrounding nervous structures in the little pelvis but also a completely athermal TME. The rate of bladder and sexual function disorders is an excellent result compared to that of international centres. Due to the size of the patient collective and the retrospective character of the study, further studies are necessary to validate the presented results.

Postoperative vocal cord dysfunction despite normal intraoperative neuromonitoring: an unexpected complication with the risk of bilateral palsy.

BACKGROUND: Intraoperative neuromonitoring (IONM) has become standard practice in thyroid surgery for many surgeons. It reduces the risk of vocal cord palsy in high-risk patients and has led to two-stage operations to prevent bilateral palsies. The specificity of detecting nerve injuries is not 100 %, leading to patients with vocal cord dysfunction (VCD) despite regular neuromonitoring (false-negative IONM). We aimed to evaluate possible risk factors for this phenomenon and its importance regarding bilateral palsies. METHODS: We performed a retrospective analysis of all patients with false-negative IONM. RESULTS: A total of 2152 patients (3426 nerves at risk) underwent surgery for benign disease between January 2008 and October 2010. Sensitivity for predicting VCD was 85.4 % and specificity 99.0 %. The positive predictive value was 68.0 % and the negative predictive value 99.6 %. We were not able to identify risk factors for false-negative IONM. We found four patients with delayed occurrence of VCD after regular IONM (1-8 weeks). We registered two patients with bilateral VCD after false negative IONM on the first side of bilateral resections (2/7) and four patients with bilateral palsy after correct IONM (4/1256). The relative risk for bilateral VCD between patients with false-negative IONM on the primary resection side and patients with correct IONM was 89.7. CONCLUSIONS: Although seldom, false-negative IONM is of clinical importance as it bears a high risk of bilateral VCD if it occurs on the first side of a bilateral resection. It can also have a latent occurrence after surgery.

Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine.

For the histopathological work-up of resected neuroendocrine tumors of the small intestine (siNET), the determination of lymphatic (LI), microvascular (VI) and perineural (PnI) invasion is recommended. Their association with poorer prognosis has already been demonstrated in many tumor entities. However, the influence of LI, VI and PnI in siNET has not been sufficiently described yet. A retrospective analysis of all patients treated for siNET at the ENETS Center of Excellence Charité-Universitätsmedizin Berlin, from 2010 to 2020 was performed (n = 510). Patients who did not undergo primary resection or had G3 tumors were excluded. In the entire cohort (n = 161), patients with LI, VI and PnI status had more distant metastases (48.0% vs. 71.4%, p = 0.005; 47.1% vs. 84.4%, p < 0.001; 34.2% vs. 84.7%, p < 0.001) and had lower rates of curative surgery (58.0% vs. 21.0%, p < 0.001; 48.3% vs. 16.7%, p < 0.001; 68.4% vs. 14.3%, p < 0.001). Progression-free survival was significantly reduced in patients with LI, VI or PnI compared to patients without. This was also demonstrated in patients who underwent curative surgery. Lymphatic, vascular and perineural invasion were associated with disease progression and recurrence in patients with siNET, and these should therefore be included in postoperative treatment considerations.

Cinacalcet effects on the perioperative course of patients with secondary hyperparathyroidism.

PURPOSE: Since its registration in 2004, the calcimimetic agent cinacalcet has been established as an alternative treatment for secondary hyperparathyroidism (SHPT). Working by allosteric activation of the calcium-sensing receptor, cinacalcet can lower parathyroid hormone (PTH) and calcium (Ca) in patients with SHPT. The influence of calcimimetics on the perioperative course has been unclear so far. METHODS: We retrospectively analyzed the data of patients with primary operation for SHPT between 2004 and 2011, comparing the perioperative course of patients with and without preoperative cinacalcet treatment. RESULTS: Fifty-six patients had cinacalcet therapy, and 54 patients had no calcimimetic medication prior to surgery. Gender, age, hemodialysis, and medical treatment were similar in both groups. Also, PTH levels were similar preoperatively and postoperatively (preoperative, 1,249 ± 676 vs. 1,196 ± 601 pg/ml; postoperative, 86 ± 220 vs. 62 ± 91 pg/ml). Patients with cinacalcet preoperatively had significant lower Ca levels preoperatively (2.49 ± 0.25 vs. 2.61 ± 0.24 mmol/l) and postoperatively (1.75 ± 0.37 vs. 1.86 ± 0.35 mmol/l) and had a higher rate of oral Ca substitution postoperatively (93 vs. 74 %). The risk for postoperative persistent disease was slightly higher in these patients compared to those without preoperative cinacalcet therapy (5 vs. 0 %, not significant). CONCLUSIONS: In our experience, cinacalcet did not alter the perioperative course in SHPT patients.

IONM-guided goiter surgery leading to two-stage thyroidectomy--indication and results.

PURPOSE: Intraoperative neuromonitoring (IONM) in thyroid surgery allows for changing the operative strategy during bilateral procedures to avoid bilateral recurrent laryngeal nerve palsy (RLNP). While this strategy is comprehendible for the surgeon, the question remains, whether it is always necessary. METHODS: Two thousand five hundred forty-six patients underwent surgery with IONM between January 2008 and October 2010 (4,012 nerves at risk). We performed a retrospective review of all patients after thyroid surgery. In 98 cases, signal loss occurred on the primary side. Of these patients, 64 required bilateral surgery. We proceeded with the contralateral surgery in 24 cases. Forty operations were ended unilaterally. The second operation was performed on 18 patients in total, 16 after confirmation of primarily intact (n = 8) or recovered vocal cord function (n = 8) and twice under persisting dysfunction. Patient satisfaction was evaluated using a five-point scale. RESULTS: We have shown a significant difference (p = 0.017) in the rate of bilateral RLNP when signal loss on the primary side resulted in termination of the procedure compared to continuation. Our evaluation of patient satisfaction did not show a significant difference when comparing the two-stage operation to other procedures. CONCLUSIONS: We have shown a significant difference in the rate of bilateral RLNP when comparing termination and continuation of a bilateral procedure after primary IONM signal loss. We strongly recommend a two-stage thyroidectomy after signal loss on the primary side of resection in benign bilateral goiter surgery.

German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors.

INTRODUCTION: Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages. METHODS: The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization. RESULTS: The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases. CONCLUSION: These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.

[Surgery of hyperparathyroidism]. / Chirurgie des Hyperparathyreoidismus.

The surgical removal of diseased parathyroid glands is the only curative treatment for primary and secondary hyperparathyroidism. Before an intervention, the confirmed diagnosis and an accurate localization are decisive for selection of the appropriate procedure. After appropriate localization diagnostics, a focussed intervention is possible for primary hyperparathyroidism, whereby every intervention must be controlled by intraoperative monitoring of parathyroid hormone. Reoperations or multiple glandular disease necessitate a differentiated approach with appropriate prior diagnostics.

[Special features of the diagnostics and treatment of hereditary primary hyperparathyroidism]. / Besonderheiten in Diagnostik und Therapie des hereditären primären Hyperparathyreoidismus.

Between 2% and 10% of patients with primary hyperparathyroidism (pHPT) are diagnosed with hereditary forms of primary hyperparathyroidism (hpHPT). They are more prevalent in younger patients before the age of 40 years, in patients with persistence or recurrence of pHPT and pHPT patients with multi-glandular disease (MGD). The various forms of hpHPT diseases can be classified into four syndromes, i.e., hpHPT associated with diseases of other organ systems, and four diseases that are confined to the parathyroid glands. Approximately 40% of patients with hpHPT suffer from multiple endocrine neoplasia type 1 (MEN-1) or show germline mutations of the MEN­1 gene. Currently, germline mutations that lead to a specific diagnosis in patients with hpHPT have currently been described in 13 different genes, which enables a clear diagnosis of the disease; however, a clear genotype-phenotype correlation does not exist, even though the complete loss of a coded protein (e.g. due to frame-shift mutations in the calcium sensing receptor, CASR) often leads to more severe clinical consequences than merely a reduced function of the protein (e.g. due to point mutation). As the various hpHPT diseases require different treatment approaches, which do not correspond to that of sporadic pHPT, a clear definition of the specific form of hpHPT must always be strived for. Therefore, before surgery of a pHPT with clinical, imaging or biochemical suspicion of hpHPT, genetic proof or exclusion of hpHPT is necessary. The differentiated treatment approach for hpHTP can only be defined by taking the clinical and diagnostic results of all the abovenamed findings into account.

Surgical Approach to Liver Metastases in GEP-NET in a Tertiary Reference Center.

Indications for liver resection in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) vary from liver resection with curative intent to tumor debulking or tissue sampling for histopathological characterization. With increasing expertise, the number of minimally invasive liver surgeries (MILS) in GEP-NET patients has increased. However, the influence on the oncological outcome has hardly been described. The clinicopathological data of patients who underwent liver resection for hepatic metastases of GEP-NET at the Department of Surgery, Charité-Universitätsmedizin Berlin, were analyzed. Propensity score matching (PSM) was performed to compare MILS with open liver surgery (OLS). In total, 22 patients underwent liver surgery with curative intent, and 30 debulking surgeries were analyzed. Disease-free survival (DFS) was longer than progression-free survival (PFS) (10 vs. 24 months), whereas overall survival (OS) did not differ significantly (p = 0.588). Thirty-nine (75%) liver resections were performed as OLS, and thirteen (25%) as MILS. After PSM, a shorter length of hospital stay was found for the MILS group (14 vs. 10 d, p = 0.034), while neither DFS/PFS nor OS differed significantly. Both curative intended and cytoreductive resection of hepatic GEP-NET metastases achieved excellent outcomes. MILS led to a reduced length of hospital, while preserving a good oncological outcome.

German Association of Endocrine Surgeons practice guidelines for the surgical treatment of benign thyroid disease.

INTRODUCTION: Benign thyroid disorders are among the most common diseases in Germany, affecting around 15 million people and leading to more than 100,000 thyroid surgeries per year. Since the first German guidelines for the surgical treatment of benign goiter were published in 1998, abundant new information has become available, significantly shifting surgical strategy towards more radical interventions. Additionally, minimally invasive techniques have been developed and gained wide usage. These circumstances demanded a revision of the guidelines. METHODS: Based on a review of relevant recent guidelines from other groups and additional literature, unpublished data, and clinical experience, the German Association of Endocrine Surgeons formulated new recommendations on the surgical treatment of benign thyroid diseases. These guidelines were developed through a formal expert consensus process and in collaboration with the German societies of Nuclear Medicine, Endocrinology, Pathology, and Phoniatrics & Pedaudiology as well as two patient organizations. Consensus was achieved through several moderated conferences of surgical experts and representatives of the collaborating medical societies and patient organizations. RESULTS: The revised guidelines for the surgical treatment of benign thyroid diseases include recommendations regarding the preoperative assessment necessary to determine when surgery is indicated. Recommendations regarding the extent of resection, surgical techniques, and perioperative management are also given in order to optimize patient outcomes. CONCLUSIONS: Evidence-based recommendations for the surgical treatment of benign thyroid diseases have been created to aid the surgeon and to support optimal patient care, based on current knowledge. These recommendations comply with the Association of the Scientific Medical Societies in Germany requirements for S2k guidelines.

Evaluation of Biocompatibility of Alloplastic Materials: Development of a Tissue Culture In Vitro Test System.

Optimized biocompatibility is a major requirement for alloplastic materials currently applied in surgical approaches for hernia, incontinence, and prolapse situations. Tissue ingrowth/adherence and formation of connective tissue seem to have important influence in mesh incorporation at the implant site. In an in vitro approach we randomly investigated 7 different mesh types currently used in surgeries with various indications with regard to their adherence performance. Using a tissue culture approach, meshes were incubated with tissue representative of fibroblasts, muscle cells, and endothelial cells originating from 10 different patients. After 6 weeks, the meshes were assessed microscopically and a ranking of their adherence performance was established. Tissue culture was successful in 100% of the probes. We did not remark on interindividual differences concerning the growth and adherence performance after incubation with the different meshes in the investigated 10 patients. The ranking was consistent in all patients. In this test system, PVDF Dynamesh® (FEG Textiltechnik, Aachen, Germany) was the mesh with the best growth-in score. The test system was feasible and reproducible. Pore size seems to be a predictor of adherence performance. The test system may be a helpful tool for further investigations, and the predictive value should be assessed in further in vitro and in vivo experiments.