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Simple Summary: Neuroendocrine neoplasms (NENs) of unknown primary (NEN-UPs) encompass a small group within all diagnosed NENs. As a result, diagnostic work-up and the therapy algorithm are not standardized. In this study we consecutively analyzed a cohort of 113 patients, initially diagnosed as NEN-UPs. After extensive diagnostic work-up, in 11.5% (13 patients) a primary tumor site could be identified. Our study revealed that an extensive diagnostic work-up, in particular somatostatin receptor (SSTR)-PET, is associated with a better clinical outcome. Our study proposes that a detailed diagnostic investigation and the identification of a primary tumor site can provide the rationale for a tumor-specific therapy, contributing to a prolonged survival in NEN-UPs. Neuroendocrine neoplasms (NENs) represent a rare and heterogenous group of tumors with predominantly gastroenteropancreatic or pulmonary origin. Despite numerous diagnostic efforts, the primary tumor site remains unknown in up to 20% of the patients diagnosed with NEN. In this subgroup of NEN patients, a standard diagnostic algorithm has not yet been integrated into clinical routine. Of note, an undetermined primary tumor site in NENs is associated with an impaired clinical outcome by at least "formally" limiting treatment options exclusively approved for NENs of a certain histological origin. In this retrospective study, a patient cohort of 113 patients initially diagnosed with NEN of unknown primary (NEN-UP) was analyzed. In 13 patients (11.5%) a primary tumor site could be identified subsequently, amongst others, by performing somatostatin receptor (SSTR)-PET-based imaging, which was irrespective of the initial clinical or demographic features. Diagnostic work-up and therapeutic regimens did not differ significantly between patients with an identified or unidentified primary tumor site; only a detailed immunohistochemical assessment providing additional information on the tumor origin proved to be significantly associated with the detection of a primary tumor site. Our study revealed that a profound diagnostic work-up, particularly including SSTR-PET-based imaging, leads to additional treatment options, finally resulting in significantly improved clinical outcomes for patients with NEN-UPs. [ABSTRACT FROM AUTHOR]

Simple Summary: The choice of the surgical and therapeutic approach for patients suffering from neuroendocrine liver metastases (NELM) plays a central role in the therapeutic strategy. Whilst debulking surgery is widely accepted as an alternative approach for eligible patients, its prognostic influence remains a point of discussion. With the advent of minimally invasive liver surgery (MILS), its applicability for the treatment of neuroendocrine tumors has scarcely been described. Here, we aimed to investigate different surgical strategies in the multimodal treatment of NELM, including minimally invasive approaches. Tumor debulking showed comparable survival outcomes to curative intended liver surgery, and MILS was not inferior to open liver surgery in terms of survival rates and as such should be recommended also in patients with NELM. 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. [ABSTRACT FROM AUTHOR]

Introduction: Incidence of pancreatic neuroendocrine tumours (pNETs) is on the rise. The only curative treatment is surgical resection in localized or oligo-metastatic disease. However, patients may present with locally advanced or unresectable primary tumours. So far, no conversion therapy to achieve resectability has been established, which is partly due to lack of data on primary tumour response to therapies. Here, we specifically evaluate the primary tumour response to streptozocin/5-FU in a large cohort of metastatic pNET patients. Methods: Five ENETS centres in Germany contributed 84 patients to the study cohort for retrospective analysis. Results: Overall response rate (ORR) in primary tumours was 34% and disease control rate (DCR) 88%. ORR was different in metastases at 44% and DCR at 70%. Partial remission in primary tumours was more frequent among those located in pancreatic tail than that in pancreatic head (49% vs. 14%, p = 0.03). Correspondingly, metastases from tumours originating from pancreatic tail responded more frequently than metastases originating from pancreatic head (88.5% vs. 41.7%, p = 0.005). The median PFS of the primary tumours was longer than that in metastases (31 months vs. 16 months; p = 0.04). Considerable downsizing of the primary tumour was rare and occurred primarily in tumours located in the pancreatic tail. Conclusion: STZ/5-FU can achieve disease stabilization in a high proportion of metastatic pNET patients. In the majority of cases however it does not induce substantial downsizing of the primary tumour, thus possibly limiting its potential as conversion chemotherapy. Furthermore, the difference in response rate observed between different primary tumour locations warrants further exploration. [ABSTRACT FROM AUTHOR]

Introduction: Patient surveys of disease burden on daily living rarely explore the impact that patient information sources can have on optimizing care. Methods: To identify unmet needs/possible solutions for information and support to address the physical, emotional, and informational challenges that patients living with neuroendocrine tumors (NETs) may have, an online survey was conducted among patients recruited by the Carcinoid Cancer Foundation (US), Netzwerk Neuroendokrine Tumoren (NeT) e.V. (Germany), and Association de Patients porteurs de Tumeurs Endocrines Diverses (France); these organizations approved the survey questions. Results: Between August 2015 and November 2015, 741 online surveys were completed in France (n = 73), Germany (n = 240), and the US (n = 428) during a 6-week period. Over 65% of patients were diagnosed ≤ 5 years ago. Across the three countries, multiple symptoms were experienced before diagnosis. These symptoms were consistent with those of functional tumors, most commonly diarrhea (40–47%) and flushing (12–45%). The most common emotion upon diagnosis was anxiety (20–67%). The greatest physical challenges for patients living with NETs included fatigue (26–66%), diarrhea (22–48%), pain/discomfort (13–40%), and sleep disturbance (16–35%), despite cancer management. Information sources classed as "very useful" included patient-association websites, disease awareness websites, and journals; "patients-like-me" case studies were most favored (43–67%) for future use as sources of information. Conclusion: Patients with NETs face negative emotions and multiple physical challenges that require psychological support/coping strategies, and they seek reliable, personally relevant, easily understood information, including that from interactions with other patients. Plain Language Summary: Plain language summary available for this article. [ABSTRACT FROM AUTHOR]

Background Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. Methods A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan–Meier curves and uni-variate log rank test Cox models. Findings Median overall survival of all patients was 59 (95% confidence interval [CI] 49–68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83–5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79–5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41–12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18–0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9–46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71–4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow and kidney function higher than grade III occurred in 0.2–1.5% of patients. Interpretation These results indicate that peptide receptor radionuclide therapy is a highly effective therapy for patients with low to intermediate grade neuroendocrine neoplasms with minor adverse events. [ABSTRACT FROM AUTHOR]

Background Nonmelanoma skin cancer ( NMSC) is the most common cancer in Germany, but detailed information on survival is lacking. Objectives To provide survival estimates for female and male patients with basal cell carcinoma ( BCC), squamous cell carcinoma ( SCC), sarcoma, adenocarcinoma and Merkel cell carcinoma. Further subgroup analyses were carried out by age, tumour stage and body site. Methods In total 459 640 patients diagnosed with NMSC in 1997-2011 were included from population-based cancer registers, covering a population of 33 million inhabitants. Age-standardized absolute and relative 5-year and 10-year survival were calculated using period analysis. Results The absolute and relative 5-year survival were 87·1% and 102·9% for BCC, 77·6% and 93·6% for SCC, 82·1% and 96·0% for sarcoma, 71·4% and 85·7% for adenocarcinoma and 60·0% and 70·7% for Merkel cell carcinoma, respectively. Higher age, female sex and advanced stage were associated with lower survival. Conclusions A comprehensive overview of NMSC survival in Germany is provided. The differences between the NMSC subtypes require a more differentiated consideration of patient survival. The survival advantage of patients with BCC may be related to health-promoting factors related to the BCC diagnosis, such as changes to a healthier lifestyle. [ABSTRACT FROM AUTHOR]

The article presents information on the actual practice of melanoma follow-up and treatment in Germany. In 2008, approximately 17,800 cutaneous invasive melanomas and 5,000 melanomas in situ were discovered in 2008 in the country, and instance trends demonstrate a threefold growth over the last 30 years.

Background. Interpretation of small intestinal neuroendocrine tumours (NETs) by Ga-68 DOTATOC PET/CT can be difficult. The potential benefit of arterial hyperperfusion for the detection of NETs was evaluated. Methods. Between 2006 and 2009, 320 consecutive Ga-68 DOTATOC PET/CT examinations, performed for NETs, revealed 40 lesions suggesting intestinal NETs in 25 patients. Two groups of lesions were distinguished: epigastric lesions evaluable in the arterial and venous CT scan (Group 1) and hypogastrial lesions evaluable in the venous CT scan only (Group 2). Lesions were jointly rated by two radiologists and a nuclear medicine physician. Maximum standard uptake values (SUVmax) of lesions and background were assessed. The reference standard was histology (available for 28 lesions) or follow-up (for a mean of 22.9 months). Results. PET detected all suspicious lesions but was false positive in 3 lesions. In Group 1 the arterial scan performed significantly better than the venous scan (p = 0.008). Diagnostic performance was better in Group 1 than in Group 2 (p < 0.001). SUVmax of true positive lesions were significantly higher than background SUVmax (p < 0.001) and SUVmax of false positive lesions (p = 0.005). Conclusions. The arterial phase of multiphase Ga-68 DOTATOC PET/CT might improve the localization of intestinal NETs and, thereby, improve the overall diagnostic accuracy of this modality in the assessment of intestinal NETs by adding information about lesion perfusion not available when only venous CT is performed [ABSTRACT FROM AUTHOR]

Poorly differentiated head and neck neuroendocrine neoplasms are very rare. Surgical resection alone is insufficient to control the disease because of the high incidence of metastases. However, due to the lack of randomised clinical trials, treatment recommendations for this cancer vary considerably and are based on a limited number of small retrospective studies. We performed a retrospective analysis of all patients treated at our institution between 2003 and 2011. We assessed the stage of disease, type of therapy, toxicity, treatment response, time to progression and overall survival for all cases. Ten patients received combined modality treatment with chemotherapy in addition to surgery or radiation or both. According to Response Evaluation Criteria In Solid Tumours (RECIST) criteria, six of nine evaluable patients achieved complete remission and three patients had a partial remission. The mean duration of response was 358 days, with a range from 141 to 1080 days. The overall 1-year survival rate was 88%; however, only approximately 50% of patients were alive after 2 years. Multimodality treatment concepts induce high initial remission rates in poorly differentiated neuroendocrine head and neck carcinomas. However, the time to relapse is usually short, and therefore long-term prognosis of this rare head and neck tumour remains poor. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine neoplasms are categorized as neuroendocrine tumors and neuroendocrine carcinomas. Until now, cancer registry reporting of pancreatic cancers does not include a stratification by these two subgroups. We studied the incidence and survival of pancreatic cancer with a special focus on pancreatic neuroendocrine neoplasms., Methods: We analyzed data from the population-based cancer registries of North Rhine-Westphalia (NRW) and Saarland (SL), Germany, of the years 2009-2018. We included primary malignant pancreatic tumors and report morphology-specific age-standardized (World Standard population) incidence rates for ages 0-79 years and age-standardized relative survival (period approach, ICSS standard). All analyses were restricted to non-death certificate only cases., Results: We analyzed 23,037 patients with a newly diagnosed primary pancreatic cancer. Among morphologically specified cancers, adenocarcinoma (92 %) and neuroendocrine neoplasms (7 %) were the most common morphologies. The age-standardized incidence rates of adenocarcinoma, neuroendocrine tumors and neuroendocrine carcinomas were 4.0-5.5 (in NRW and SL), 0.1-0.3, and 0.1-0.3 per 100,000 person-years, respectively. Neuroendocrine tumors had the highest age-standardized 5-year relative survival with 75.5 % (standard error, SE 2.3) in NRW and 90.6 % (SE 10.2) in SL followed by neuroendocrine carcinomas (NRW: 30.0 %, SE 3.1; SL: 32.3 %, SE 8.7) and adenocarcinomas (NRW: 11.3 %, SE 0.4; SL: 10.2 %, SE 1.5)., Discussion: The distinction between neuroendocrine tumors and neuroendocrine carcinomas by the WHO divides neuroendocrine neoplasms into two prognostically clearly distinct subgroups that should be separately analyzed in terms of survival. The first year after diagnosis of pancreatic cancer is the most critical year in terms of survival., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT), a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs) in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61% and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell-cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs. [ABSTRACT FROM AUTHOR]

The article discusses the highlights of the Third Global Workshop on Melanoma in Berlin, Germany on November 18, 2009. Among the topics discussed were recent advances in the field of melanoma, which included the impact of an increased molecular understanding of its genesis, heterogeneity and progression on patient therapy. Participants also discussed the implications of recent data on adjuvant therapy for advanced melanoma.

Background Late recurrent melanoma (MM) is rare. Objective In the present study, we analysed the frequency of late recurrent MM in south-eastern Germany. Patients and methods In our centre, 2314 MM patients were documented (1972–2001). A total of 1881 patients in stage I or II (AJCC) with a follow-up of ≥10 years were selected and screened for late recurrence (≥10 years after diagnosis). Results Twenty patients were identified (1.1%), 13 women and 7 men, median age 44 years (age range 30–74 years). Nineteen suffered from cutaneous MM and one had a uveal MM (excluded from further analysis). The primary cutaneous MM occurred on the trunk (6), on the upper limb/shoulder (4), or on the lower limb (9). MM type was superficial spreading (13), nodular (2), acrolentiginous (1), lentigo maligna-type (1) or unclassified (2). Tumour thickness varied from 0.33 mm to 9.5 mm (median 2.0 mm). Ulceration was seen in four, and spontaneous regression in two MM patients. Invasiveness into blood or lymphatic vessels occurred in seven MM patients. The largest period from primary diagnosis to recurrence was 25.1 years with a median of 13.9 years. Metastatic spread was loco-regional (12 patients) or distant (7). Four patients were survivors and three of these had in-transit metastases only. Overall survival was 14.7 ± 6.6 years. Statistical analysis could not identify factors significantly associated with late recurrence. Conclusions Late recurrence is a clinical sign of melanoma dormancy. We conclude that late recurrences argue for a lifelong follow-up of melanoma patients. [ABSTRACT FROM AUTHOR]

Abstract: Merkel cell carcinoma is a rare cutaneous neoplasm in older adults that has a high propensity for nodal metastases and local recurrence, has poor prognosis, and in the last few years has increased in incidence. We retrospectively review our experience of the surgical treatment of Merkel cell carcinoma of the face in 10 patients (9 women and 1 man) between 1993 and 2007. Follow-up ranged from 5 to 132 months (mean 38.8, median 29). Relapse-free survival for all patients was 47% at 2 years. We support the need for complete excision with wide 2–3cm margins throughout all tumour stages although this might be limited when it affects the face. We also recommend radiotherapy for patients with disease that is stage II and above; the value of adjuvant radiotherapy is outlined in many studies. Therapeutic functional neck dissection should be done in cases of nodal disease. The role of chemotherapy is still not clear, and it has not been used in our department. [Copyright &y& Elsevier]

Aims: Clinical experience with neuroendocrine tumors (NETs) is difficult to acquire because they are rare and heterogeneous. The impact of guidelines on the care for NETs is not known. The German NET Registry compiled information for Germany pertaining to three questions: who provides care for NET patients; does the care comply with proposed guidelines, and are the results comparable to those described in the literature? Patients and Methods: Between 2004 and 2007 data on 1,263 patients from 21 centers were compiled in a dedicated database. Results: Tumor location, age and sex compared well with published data. Most patients were cared for in centers with more than 100 (47.9%) or between 20 and 99 patients (46.1%). Imaging (magnetic resonance tomography, computer tomography, ultrasound) was available for 79% of the patients, specific laboratory tests for 67%, somatostatin receptor scintigraphy for 56%, and pathology findings for 79%. High-quality pathology reports were rare (2%). Sufficient documentation was mostly found in large centers. Surgery was the first-line therapy in 70.9%, while medical therapy was the second-line therapy in 45.7% of the patients. Median follow-up was 2.8 (0.4–6.4) and median overall survival was 2.5 (0.34–6.3) years. Conclusions: Most patients were referred to large specialized centers. Those centers adhered best to published guidelines for NETs. However, there are still significant deficiencies in the documentation of diagnostic results, mainly with regard to pathology reports. Therapeutic strategies were comparable between centers. The data provide a basis for future studies assessing improvements in documentation, diagnosis and treatment of NET. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

CONTEXT: Adrenal and extra-adrenal phaeochromocytoma are chromaffin cell-derived tumours that are discovered due to classical symptom triad with headache, sweating and palpitations combined with persistent or paroxysmal hypertension. However, an increasing proportion of phaeochromocytoma seems to be discovered incidentally upon abdominal imaging. OBJECTIVE: To specify the exact circumstances of discovery of adrenal and extra-adrenal phaeochromocytoma. DESIGN AND PATIENTS: Four German endocrine centres participated in this retrospective study. Medical records of 201 patients with adrenal and extra-adrenal phaeochromocytoma who were diagnosed between 1973 and 2007 were analyzed. RESULTS: The typical triad of symptoms was found only in 10% of cases. Ten percent of patients presented were without clinical symptoms and 6.1% were normotensive. Documented blood pressure peaks occurred in 44.1% of cases. In 24 patients (12.2%), phaeochromocytoma was malignant. Before 1985, <10% of cases were incidentally discovered, whereas thereafter the frequency was >25% (29.4% of the total study population). Patients with incidentally detected phaeochromocytoma were significantly older (53.1±1.9 vs 47.0±1.3 years; P<0.05) and often had less blood pressure peaks (37.0 vs 70.7%; P<0.001) than patients in whom the diagnosis was suspected on clinical grounds. Of phaeochromocytomas 94.4% were intra-adrenal tumours, of which 12.9% were bilateral. Bilateral tumours were significantly smaller than unilateral tumours (36.6±14.7 vs 52.5±34.3 mm; P<0.05), whereas extra-adrenal tumours had a mean diameter of 52.6±28.7 mm. CONCLUSIONS: Owing to better availability and accessibility of imaging procedures, the number of incidentally discovered phaeochromocytoma is increasing and reaches nearly 30% in our study population. Every adrenal incidentaloma should be investigated for the presence of phaeochromocytoma. [ABSTRACT FROM AUTHOR]

We report a case of a 52-year-old woman with a palpable recurrent metastasis of a neuroendocrine carcinoma to the upper outer quadrant of the right breast. For the treatment of this lesion, MR-guided laser-induced thermotherapy was performed with a cooled power laser system (Nd:YAG-Laser). An open 0.2-T MR unit was used for the monitoring of the laser energy delivery to the breast; thus, a thermosensitive fast low-angle shot 2D sequence for MR thermometry was used, so the ablation of the tumor and the increase of laser-induced necrosis could be interactively visualized with the repetitive use of this sequence. The postinterventional MR control exams 1 day and 4 months after laser-induced thermotherapy at the 1.5-T MR unit (Magnetom Symphony Quantum, Siemens, Erlangen, Germany) verified the complete ablation of the tumor without any signs of residual or relapsing tumor. [ABSTRACT FROM AUTHOR]

The article focuses on an erythrophoroma in ornamental carp, Cyprinus carpio L. The culture of ornamental carp or koi, Cyprinus carpio L., has been practiced in Japan for centuries and has been more recently initiated in the United States, Germany, and other countries. The fish are reared primarily for sale to hobbyists who display them in garden pools and at competitive shows. Both colour and colour pattern are fundamental determinants of the value of individual fish. Pigment cell tumors or chromophoromas of fishes include erythrophoroma, xanthophoroma, melanoma and guanophoroma, of which inelanonias are the most common.

The relationship between cutaneous malignant melanoma (MM) and possible risk factors was assessed in a case-controlled study. Two hundred patients and 200 non-melanoma controls of German origin matched for age and sex were interviewed and examined for pigmented moles and pigmentation characteristics. In patients with MM significantly more melanocytic nevi ≥ 2 mm (MCN) were found (mean, 53 MCN) compared to control cases (mean, 18 MCN). For persons with > 60 MCN the relative risk (RR) for developing MM increased 15 times compared to s 10 MCN. Additional independent markers for an increased risk were presence of atypical MCN (RR = 7 vs. none) found in 45% of patients and in 5% of the control group, moderate to large numbers of actinic lentigines (RR = 6.2 vs. none), and lack of tanning as well as a tendency to sunburn (skin type I; RR = 2.2 vs. skin type IV) No significant correlation was found between the relative risk for MM and hair color, eye color, duration of free time sun exposure and number of sunburns. Individuals with permanent outdoor profession and sun exposure, however, showed a clearly increased relative risk for developing MM. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine tumors grade 3 (NET G3) are a newly defined subgroup of neuroendocrine neoplasms. They do not respond well to platinum + etoposide-based chemotherapy. The alternative suggested options have not been analyzed in untreated NET G3 patients so far, therefore the optimal treatment strategy for these tumors is unclear. In our analysis we showed that FOLFOX is the most active regimen holding the highest chance of tumor shrinkage, whereas temozolomide/capecitabine is the most effective, leading to the most durable tumor control. Well-differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications. Commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Suggested alternative treatment protocols have not been studied in first-line therapy of NET G3 so far. We performed a retrospective analysis of patients with NET G3 in the databases of 3 German cancer centers. Out of 142 patients, 136 patients received palliative first-line therapy: overall response rate (ORR) was 35.1% for PE (n = 37), 56.4% for FOLFOX (n = 39), 27.3% for temozolomide/capecitabine (TEM/CAP) (n = 22), 45.0% for streptozotocin/5-fluorouracil (STZ/5-FU) (n = 20), and 16.7% for other (n = 18). Median progression-free survival (PFS) for PE was 6.9 months. Compared to PE, PFS in the other treatment groups was 6.9 months for FOLFOX (p = 0.333), 12.0 months for TEM/CAP (p = 0.093), 4.8 months for STZ/5-FU (p = 0.919), and 14.1 months for other (p = 0.014). In a univariate setting, all non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 months; p = 0.049) which could not be confirmed in a multivariate analysis. In conclusion, NET G3 with FOLFOX showed the highest ORR, and with TEM/CAP showed the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this tumor entity is needed. [ABSTRACT FROM AUTHOR]

Polyps occur significantly less frequently in the upper gastrointestinal tract compared to the lower gastrointestinal tract. They are usually incidental findings at esophagogastroduodenoscopy. A distinction is made between epithelial lesions and subepithelial tumors. Endoscopic screening is not recommended in Germany (exception: hereditary risk groups). Polyps are sometimes symptomatic, generally in the case of advanced tumor size. In this case, or in the case of potential for malignant transformation, resection is necessary and can usually be performed endoscopically. Surgical resections are rarely necessary. Epithelial lesions are removed by means of endoscopic mucosal resection (EMR). For subepithelial tumors, advanced procedures such as endoscopic submucosal dissection (ESD), submucosal tunneling endoscopic resection (STER), or endoscopic full-thickness resection are available. These procedures should primarily be performed at centers with appropriate expertise. Endoscopic follow-up is primarily determined by the tumor entity and the resection status.

Introduction: Neuroendocrine tumors (NET) of the rectum are a rare subgroup of NETs with mostly favorable prognosis. Some, however, tend to have a poorer outcome. Aim(s): Analysis of potential prognostic factors among rectal NETs and correlation with overall survival using the large multicentric cohort of the German NET Registry. Materials and methods: The German NET Registry (G-NET-Reg) collects data from histologically proven NETs diagnosed since 1999 from 35 centers in Germany. Histopathological parameters and clinical data, as well as information on overall and NET-specific outcome of solely rectal NETs, were obtained and statistically analyzed with regard to prognosis. Results: Of 2,358 NETs within the G-NET-Reg, 111 had a rectal primary. Median age at initial diagnosis was 57 years. Twenty-four percent had metastasis at initial diagnosis (extensive disease, ED), while 76% did not (limited disease, LD). In over 60% of cases, local endoscopic resection was the initial therapy. Status of metastasis at initial diagnosis (LD v. ED), ENETS Grading (G1/G2 v. G3) and WHO 2000/10 classification (WDET/WDEC v. PDEC, NET-G1/G2 v. NEC-G3) were each significantly able to stratify prognosis (p<0.001). In LD, however, outcome of G1- and G2-NETs did not differ while G3-NETs were associated with poorer prognosis (G1/G2 v. G3 p<0.001). Conclusion: Outcome of rectal NETs is mainly auspicious. Important prognostic factors are status of metastasis at initial diagnosis, ENETS-Grading and WHO-classification of 2000 and 2010. [ABSTRACT FROM AUTHOR]

Malignant melanoma (MM) is currently the fastest increasing malignancy and constitutes a major public health burden. The number of common naevi (CN) is known to be related to the MM risk and may serve as a marker in epidemiological studies. For the KORA, Cooperative Health Research in the region of Augsburg, Germany, Survey 2000, a random sample stratified by age and gender of the adult population of the city of Augsburg was drawn. CN are frequent in the adult general population and their number depends on demographic, body metric, and genetic factors as well as parameters of an individual ultraviolet exposure.