Lymph node metastases are more frequent in paediatric appendiceal NET ≥1.5 cm but without impact on outcome - Data from the German MET studies.

BACKGROUND: Paediatric appendiceal neuroendocrine tumours (appNET) are very rare tumours, mostly detected incidentally by histopathological evaluation after appendectomy. Treatment recommendations are based on adult data considering high-risk NET as defined by European Neuroendocrine Tumour Society (ENETS) guidelines for completion right-sided hemicolectomy (RHC). Recent data suggest that less aggressive therapy may be justified. PROCEDURE: Analysis of children and adolescents with appNET prospectively registered with the German Malignant Endocrine Tumour (MET) studies between 1997 and 2022. RESULTS: By December 2022, 662 patients (64.7% females, 35.3% male) had been reported. Median age was 13.3 years [4.5-17.9], median duration of follow-up 2.2 years [0-10.9]. No distant metastases were reported. Tumour size was <1 cm in 63.5%, 1-2 cm in 33.2%, and >2 cm in 3.2% of patients. WHO grade 1 and 2 tumours were diagnosed in 76.9% and 23.1% of patients, respectively. Lymphovascular invasion and lymph node metastases were associated with tumour size ≥1.5 cm. 27.0% of patients presented with high-risk NET according to ENETS criteria. Of those, only 55.9% underwent secondary oncological right hemicolectomy. Neither distant metastases, nor recurrences or disease-related deaths occurred in patients with appendectomy only as well as in patients with completion RHC. Overall and event-free survival were both 100%. CONCLUSIONS: Internationally harmonized consensus recommendations on treatment of children and adolescents with appendiceal NET are urgently needed to avoid completion RHC in high-risk patients.

Use of teduglutide in adults with short bowel syndrome-associated intestinal failure.

Short bowel syndrome (SBS) is a rare gastrointestinal disorder associated with intestinal failure (SBS-IF) and poor health-related outcomes. Patients with SBS-IF are unable to absorb sufficient nutrients or fluids to maintain significantly metabolic homeostasis via oral or enteral intake alone and require long-term intravenous supplementation (IVS), consisting of partial or total parenteral nutrition, fluids, electrolytes, or a combination of these. The goal of medical and surgical treatment for patients with SBS-IF is to maximize intestinal remnant absorptive capacity so that the need for IVS support may eventually be reduced or eliminated. Daily subcutaneous administration of the glucagon-like peptide 2 analog, teduglutide, has been shown to be clinically effective in reducing IVS dependence and potentially improving the health-related quality of life of patients with SBS-IF. The management of patients with SBS-IF is complex and requires close monitoring. This narrative review discusses the use of teduglutide for patients with SBS-IF in clinical practice. The screening of patient eligibility for teduglutide treatment, initiation, monitoring of efficacy and safety of treatment, adapting or weaning off IVS, and the healthcare setting needed for SBS-IF management are described, taking into consideration data from clinical trials, observational studies, and clinical experience.

[Sustainable waste management in general surgical operations]. / Nachhaltiges Abfallmanagement bei allgemeinchirurgischen Operationen.

BACKGROUND AND OBJECTIVE OF THE STUDY: Hospitals, especially surgical departments, are among the largest producers of waste in Germany. Data on waste management in the operating room (OR) are largely lacking. The aim of this study was to assess and discuss the possibilities of reducing waste and recovering recyclable materials in general surgery against the background of current practice. METHODOLOGY: Surgical departments throughout Germany were surveyed on waste management. First, the theoretical waste separation possibilities for laparoscopic appendectomy were determined. Subsequently, a simple system for the separation of recyclables was established and practically tested in 35 operations. These were compared with 35 appendectomies without separation. RESULTS: Only 25.7% of hospitals perform waste separation. Theoretically, 20.7% of waste can be recycled, in practice up to 18.9%. Paper, cardboard and plastics, especially polyethylene terephthalate (PET) and high-density polyethylene (HDPE) were separated. This leads to a significant reduction in residual waste without extending the operation time. DISCUSSION: Separation of recyclables can contribute to more sustainable waste management in the OR. High-value recyclables can be recycled and the residual waste mass can be significantly reduced. This is possible without special effort and does not delay the processes in the OR. The opportunities for this have hardly been used in Germany to date.

Site-specific trends in gastroenteropancreatic neuroendocrine neoplasms in Bavaria, Germany.

INTRODUCTION: Neuroendocrine neoplasms (NEN) are rare and heterogeneous epithelial tumors, occurring throughout the body. For gastroenteropancreatic (GEP)-NEN, rising incidence rates were reported for the last decades, with underlying causes remaining largely unexplained. We evaluated NEN trends stratifying by their histologic subtypes. METHODS: Incident cases of GEP-NEN diagnosed between 2005 and 2019 were retrieved from the prospective, population-based Bavarian Cancer Registry. GEP-NEN were divided in their histologic subtypes, that is, neuroendocrine tumors (NET) G1, NET G2/G3, other NET versus small-cell neuroendocrine carcinoma (NEC), large-cell NEC, and other NEC. We calculated annual age-standardized incidence rates (ASIRs) per 100,000 persons for the total of GEP-NEN, NEN histologic subtypes, and tumor sites. We used an annual percentage change (APC) approach including a joinpoint analysis to investigate NEN incidence trends. RESULTS: ASIR of GEP-NEN rose from 2.2 in 2005 to 4.8 in 2019, characterized by a significant increase until 2012 (APC 2005-2012: 10.1%), followed by modest rise (APC 2012-2019: 1.5%). In the last decade, this increase was mainly driven by the rise of NET G1 and G2/G3, while incidence for NEC declined. Over the study period, ASIR increased significantly for all GEP-sites except the colon. APCs were largest for the stomach, the appendix, the pancreas, and the rectum. CONCLUSIONS: This study found a significant increase in the incidence of GEP-NET. Though this development may partially be attributable to the increased use of advanced detection techniques and changes in NEN classification, further research should also focus on the identification of NEN risk factors.

High In-Hospital Mortality in SARS-CoV-2-Infected Patients with Active Cancer Disease during Omicron Phase of the Pandemic: Insights from the CORONA Germany Study.

INTRODUCTION: SARS-CoV-2 infected patients with cancer have a worse outcome including a significant higher mortality, compared to non-cancer patients. However, limited data are available regarding in-hospital mortality during the Omicron phase of the pandemic. Therefore, the aim of the study was the comparison of mortality in patients with history of cancer and patients with active cancer disease during the different phases of the COVID-19 pandemic, focusing on the current Omicron variant of concern. METHODS: We conducted a multicenter, observational, epidemiological cohort study at 45 hospitals in Germany. Until July 20, 2022, all adult hospitalized SARS-CoV-2 positive patients were included. The primary endpoint was in-hospital mortality regarding cancer status (history of cancer and active cancer disease) and SARS-CoV-2 virus type. RESULTS: From March 11, 2020, to July 20, 2022, a total of 27,490 adult SARS-CoV-2 positive patients were included in the study. 2,578 patients (9.4%) had diagnosis of cancer, of whom 1,065 (41.3%) had history of cancer, whereas 1,513 (58.7%) had active cancer disease. Overall 3,749 out of the total of 27,490 patients (13.6%) died during the hospital stay. Patients with active cancer disease had a significantly higher mortality compared to patients without cancer diagnosis, in both phases of the pandemic (wild-type to Delta: OR 1.940 [1.646-2.285]); Omicron: 2.864 [2.354-3.486]). After adjustment to co-variables, SARS-CoV-2 infected patients with active cancer disease had the highest risk for in-hospital mortality compared to the other groups, in both phases of the pandemic. CONCLUSION: The CORONA Germany study indicates that hospitalized patients with active cancer disease are at high risk of death during a SARS-CoV-2 infection. Mortality of patients with history of cancer improved to nearly the level of non-cancer patients during Omicron phase.

Robotic operations in urgent general surgery: a systematic review.

Robotically assisted operations are the state of the art in laparoscopic general surgery. They are established predominantly for elective operations. Since laparoscopy is widely used in urgent general surgery, the significance of robotic assistance in urgent operations is of interest. Currently, there are few data on robotic-assisted operations in urgent surgery. The aim of this study was to collect and classify the existing studies. A two-stage, PRISMA-compliant literature search of PubMed and the Cochrane Library was conducted. We analyzed all articles on robotic surgery associated with urgent general surgery resp. acute surgical diseases of the abdomen. Gynecological and urological diseases so as vascular surgery, except mesenterial ischemia, were excluded. Studies and case reports/series published between 1980 and 2021 were eligible for inclusion. In addition to a descriptive synopsis, various outcome parameters were systematically recorded. Fifty-two studies of operations for acute appendicitis and cholecystitis, hernias and acute conditions of the gastrointestinal tract were included. The level of evidence is low. Surgical robots in the narrow sense and robotic camera mounts were used. All narrow-sense robots are nonautonomous systems; in 82%, the Da Vinci® system was used. The most frequently published emergency operations were urgent cholecystectomies (30 studies, 703 patients) followed by incarcerated hernias (9 studies, 199 patients). Feasibility of robotic operations was demonstrated for all indications. Neither robotic-specific problems nor extensive complication rates were reported. Various urgent operations in general surgery can be performed robotically without increased risk. The available data do not allow a final evidence-based assessment.

Long-term results of teduglutide treatment for chronic intestinal failure - Insights from a national, multi-centric patient home-care service program.

BACKGROUND & AIMS: Teduglutide is a Glucagon-like peptide-2 (GLP-2) agonist indicated for the treatment of patients with parenteral support (PS) dependent short bowel syndrome (SBS) with chronic intestinal failure (cIF). Its application is accompanied by a structured nation-wide home-care service program in Germany. We investigated care characteristics and outcome parameters in a clinical real-world observational setting. METHODS: Data generated within a therapy-accompanying home-care service program for adult SBS-cIF patients were analyzed retrospectively for patients treated up to 1 year (data cut: April 2020). RESULTS: In total, 52 teduglutide-treated patients were included by 6 German cIF centers. At teduglutide administration start, 49/52 patients were on PS, 3 of them without macronutrients. The majority of patients received individualized parenteral nutrition (PN) (n = 32/46), while 13/46 were on commercial premixed bags. PS application was done by patients themselves (37%), home-care nurses (19%), relatives (8%) or by a combination of those (16%). In patients with PS dependency at baseline and available follow-up data (n = 40-44), teduglutide treatment resulted in significantly reduced PN days, caloric needs, infusion time, and infusion volume after 6 and 12 months. After 1 year, reduction of infusion time was positively correlated with a reduction of PN calories and volume; 30 patients (68%) were responders (PS-volume reduction ≥20%), and 6 patients (14%) were completely weaned off PS. Sleep disturbances per night were significantly reduced after 3 months of treatment and stool characteristics improved in consistency and significantly in frequency, while meal frequency remained stable. CONCLUSIONS: Teduglutide treatment associated reduction in PS volume and calories was accompanied by reduced infusion days, infusion times, sleep disturbances, stable oral intake surrogates, and improved stool characteristics, all of these potential parameters for improving quality of life. Furthermore, analyzed care characteristics reflect SBS-cIF treatment as a complex, resource-intensive and demanding task for both, healthcare system and patients.

Treatment Approaches and Outcome of Patients with Neuroendocrine Neoplasia Grade 3 in German Real-World Clinical Practice.

BACKGROUND: Neuroendocrine neoplasia grade 3 (NEN G3) represents a rare and heterogeneous cancer type with a poor prognosis. The aim of our study was to analyze real-world data from the German NET Registry with a focus on therapeutic and prognostic aspects. METHODS: NEN G3 patients were identified within the German NET Registry. Demographic data and data on treatments and outcomes were retrieved. Univariate analyses were performed using the Kaplan-Meier-method. Multivariate analysis was performed using a Cox proportional hazard model. RESULTS: Of 445 included patients, 318 (71.5%) were diagnosed at stage IV. Well-differentiated morphology (NET G3) was described in 31.7%, 60% of cases were classified as neuroendocrine carcinoma (NEC), and the median Ki67 value was 50%. First-line treatment comprised chemotherapy in 43.8%, with differences in the choice of regimen with regard to NET or NEC, and surgery in 41.6% of patients. Median overall survival for the entire cohort was 31 months. Stage, performance status and Ki67 were significant prognostic factors in multivariate analysis. CONCLUSIONS: The survival data of our national registry compare favorably to population-based data, probably mainly because of a relatively low median Ki67 of 50%. Nevertheless, the best first- and second-line approaches for specific subgroups remain unclear, and an international effort to fill these gaps is needed.

The European Neuroendocrine Tumour Society registry, a tool to assess the prognosis of neuroendocrine neoplasms.

BACKGROUND: Neuroendocrine neoplasms (NENs) are rare tumours with variable clinical behaviour. Their natural history is ideally best approached in large, multicentre and multinational registries with long-term patients' follow-up. The European Neuroendocrine Tumour Society registry aims to obtain information regarding NEN outcomes and prognostic factors in a European frame. PATIENTS AND METHODS: We collected data from 7 national NEN registries (Belgium, Czech Republic, Germany, Greece, Poland, Spain, Switzerland), representing 10,102 patients. Anonymised/pseudonymised data were collected in a secured server. Descriptive statistical methods were applied, as well as Kaplan-Meier survival curves and multivariable analyses for prognostic factors of overall survival (OS). RESULTS: median age of the study population was 60 years (range: 18-102), 48% were female. Common primary tumour sites were pancreas (27%) and small intestine (21%). Stage 4 disease was found in 47% of patients, while 26/10/16% had stage 1/2/3 disease, respectively. Grading (n = 6952) was G1/2/3 in 48/37/15% of the patients, respectively. Surgery was the main treatment, provided to 71% of patients, followed by somatostatin analogues (32%), chemotherapy (20%), Peptide receptor Radionuclide Therapy (PRRT) (9%) and targeted therapies (8%). OS at 5 years was 74%, influenced by grade, stage and tissue of origin in multivariate analysis. A Ki67 cut-off value set at 55% within the G3 group allowed to separate 2 groups with a meaningful different OS. CONCLUSION: We report the first analysis of the European Neuroendocrine Tumour Society registry, comprising 10,102 patients with NEN from 7 European countries. This large cohort study describes prognostic factors for the survival of NENs throughout Europe, including primary tumour site, grade, stage and treatment.

ENETS standardized (synoptic) reporting for endoscopy in neuroendocrine tumors.

Despite efforts from various endoscopy societies, reporting in the field of endoscopy remains extremely heterogeneous. Harmonisation of clinical practice in endoscopy has been highlighted by application of many clinical practice guidelines and standards pertaining to the endoscopic procedures and reporting are underlined. The aim of the proposed "standardised reporting" is to (1) facilitate recognition of gastrointestinal neuroendocrine neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multidisciplinary team, (3) to provide a basis for a standardised endoscopic follow-up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data. The ultimate goal is to improve disease management, patient outcome and reduce the diagnostic burden on the side of the patient by ensuring the highest possible diagnostic accuracy and validity of endoscopic exams and possibly interventions.

Frailty in elderly patients with acute appendicitis.

PURPOSE: Acute appendicitis in the elderly is becoming increasingly recognized for its often severe course. For various elective and urgent operations in older patients, frailty is a risk factor for poor outcomes. However, there is a lack of data on frailty in elderly patients with acute appendicitis. METHODS: Patients over 65 years old who underwent surgery for acute appendicitis in three hospitals between January 2015 and September 2020 were assessed with the Hospital Frailty Risk Score (HFRS) and the modified Frailty Index (mFI). Outcomes of interest, including morbidity, mortality, and length of stay, were recorded. RESULTS: While frailty can be measured with both tests, the mFI has better applicability and takes significantly less time to implement compared to the HFRS (21.6 s vs. 80.3 s, p < 0.0001) while providing the same information value. Patients who exhibited frailty according to either assessment had a significantly higher rate of milder (OR 5.85/2.87, p < 0.0001/0.009) and serious (OR 4.92/3.61, p < 0.011/0.029) complications, more admissions to the intensive care unit (OR 5.16/7.36, p < 0.0001), and an almost doubled length of stay (12.7 days vs. 6.6 days, p < 0.005). Up to 31% of these patients required institutional care after discharge, which is significantly more than those without frailty (p < 0.0001). Furthermore, the mortality rate in frail patients was significantly elevated to 17%, compared to less than 1% in non-frail patients (p = 0.018). CONCLUSION: In elderly patients, frailty is a significant risk factor for negative outcomes. Frailty can be assessed more quickly and reliably with the mFI compared to the HFRS.

PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study.

BACKGROUND: A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. METHODS: In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. RESULTS: 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88-99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59-91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. CONCLUSIONS: PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.

Localization Defines Streptozotocin/5-FU Response in Primary Pancreatic Neuroendocrine Tumours.

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.

De Novo Development of Distal Jejunal and Duodenal Adenomas After 41 Months of Teduglutide Treatment in a Patient With Short-Bowel Syndrome: A Case Report.

The glucagon-like peptide-2 (GLP-2) analogue teduglutide is a medical treatment option for patients with short-bowel syndrome-associated chronic intestinal failure. Because studies in mice have shown that GLP-2 analogues may promote the growth of colonic neoplasms, surveillance colonoscopies before and during teduglutide therapy were recommended. The occurrence of small-intestinal neoplasms has not been reported so far, except for a recent report about de novo development of hamartomatous duodenal polyps. We report a case of de novo development of small-intestinal premalignant adenomatous polyps in both bulbar duodenum and distal jejunum in a patient treated with teduglutide for 41 months. Therefore, additional endoscopic surveillance of the upper gastrointestinal tract may be advised during teduglutide therapy for early detection and removal of potential small-bowel adenomas.

Efficacy and Safety of CAP7.1 as Second-Line Treatment for Advanced Biliary Tract Cancers: Data from a Randomised Phase II Study.

CAP7.1 is a novel topoisomerase II inhibitor, converted to active etoposide via carboxylesterase 2 (CES2), with signals of efficacy in treatment-refractory solid tumours. In a Phase II trial, 27 patients with advanced biliary tract cancers (BTC) were randomised 1:1 to CAP7.1 plus best supportive care (BSC), or BSC alone, with crossover to CAP7.1 upon disease progression. The primary objective was disease control rate (DCR) following 28-day cycles of CAP7.1 (200/150 mg/m2; iv), or BSC until progression. Secondary objectives included progression-free survival (PFS), time-to-treatment failure (TTF), overall survival (OS) and safety. Fourteen patients received CAP7.1 and 13 BSC. DCR favoured CAP7.1 vs. BSC (50% vs. 20%; treatment difference: 30%, 95%CI -18.44, 69.22, full analysis set [FAS]), with disease progression in 40% vs. 70%, respectively. Significantly longer median PFS was achieved for CAP7.1 vs. BSC: 66 vs. 39 days, respectively (hazard ratio [HR] 0.31; 95%CI 0.11, 0.86; p = 0.009; FAS). Similar trends were observed for TTF and OS. CES2-positive patients had longer median PFS (158 vs. 56 days) and OS (228 vs. 82 days) vs. CES2-negative patients. Adverse events were predictable, dose-dependent and consistent with those previously observed with etoposide. These efficacy and safety findings in second-line BTC warrant further clinical investigation of CAP7.1.

A review of systemic therapy in biliary tract carcinoma.

Biliary tract carcinoma (BTC) has a poor prognosis and is increasing in incidence. Although surgery, chemotherapy and other treatment modalities have improved, surgery remains the only potential curative treatment and is appropriate for only those few patients who present with localized, resectable disease. However, for the majority of patients, unresectable disease is evident at diagnosis and about 95% of patients die within 10 years, despite the majority receiving chemotherapy. Long-term survival is significantly greater for patients with resected BTC compared to those with unresectable disease. In unresected disease, life expectancy is limited, with first-line gemcitabine/cisplatin (GEM/CIS) accepted as standard of care. Currently no standard second-line regimen which provides significant improvement of clinical outcomes exists for those who present with refractory disease or who relapse after first-line treatment. Of particular importance is establishing the impact of best supportive care (BSC) as a benchmark for survival outcomes to which the impact of treatment modalities can be compared. Survival outcome often differs significantly for patients with different prognostic factor profiles even when receiving the same therapy so that it can be difficult to predict which patient subgroup might benefit most from which therapy. Therefore, the influence of prognostic factors on survival under different therapies as well as under BSC needs to be further assessed in order to arrive at truly evidence-based, best therapeutic decisions for individual patients. Encouraging new research into the genomic landscape of BTC may help to further subdivide the BTC population into molecular-genetic clusters likely to be sensitive to different targeted therapy approaches leading to further improvements in survival. Consequently, an unmet need exists not only to develop new and more effective therapies for this devastating disease, but also to integrate original research findings into a more complex, dynamic, individualized therapeutic decision model to aid clinicians in making evidence-based, best therapeutic decisions for individual patients.

Efficacy and Toxicity of 5-Fluorouracil-Oxaliplatin in Gastroenteropancreatic Neuroendocrine Neoplasms.

OBJECTIVES: The objective of this study was to investigate the efficacy and tolerability of 5-fluorouracil-oxaliplatin (FOLFOX) in advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). METHODS: Retrospective analysis of consecutive 72 advanced GEP-NENs treated with FOLFOX between 2005 and 2016 at a single German referral center for NENs was performed. We assessed treatment response by response evaluation criteria in solid tumors 1.0 criteria, progression-free survival by Kaplan-Meyer method, and risk factor analysis by Cox-regression model. RESULTS: Patients were 44.5% G1/G2, 55.5% G3, receiving a median of 7 treatment cycles (range, 2-21), and had a median of 18 months of follow-up (range, 3-111 months). Disease control was achieved in 75.0% of cases but 91.3% in the 23 patients receiving FOLFOX as first line (P = 0.04). Median progression-free survival of the overall population was 8 months. A better outcome was significantly related to treatment duration (P = 0.02) and grade of histological differentiation for G3 patients (well differentiated vs poorly differentiated, P = 0.03). Adverse events occurred in 88.8% of patients, mostly grade 1 and 2 hematotoxicity and chemotherapy-induced peripheral sensory neuropathy (84.1% and 50.0% of patients, respectively). CONCLUSIONS: Our results support FOLFOX as therapeutic option in advanced GEP-NENs with poor prognosis, either at first or further therapy line. Longer duration of therapy was associated with a more durable benefit.

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.

Teduglutide for the treatment of adults with intestinal failure associated with short bowel syndrome: pooled safety data from four clinical trials.

BACKGROUND: In multiple clinical studies, teduglutide reduced parenteral support (PS) with a consistent safety profile in adults with short bowel syndrome-associated intestinal failure (SBS-IF). The objective of this study was to assess adverse events (AEs) from a pooled data set. METHODS: Safety data from four prospective clinical trials of teduglutide in patients with SBS-IF were assimilated. AEs were evaluated in patient groups based on treatment received in each study and in populations stratified to create distinct subgroups based on aetiology, bowel anatomy and baseline PS volume requirements. RESULTS: Safety data are reported for up to 2.5 years, totalling 222 person-years exposure to teduglutide. In most patients, AEs were reported as mild or moderate in severity in all patient groups and occurred at comparable rates between patients who received teduglutide or placebo. Several common gastrointestinal AEs, including abdominal pain, nausea and abdominal distension, were reported more frequently earlier in the course of treatment, with their frequency declining over time. Fewer gastrointestinal AEs were reported in patients with vascular causes of SBS-IF and patients with most of their colon-in-continuity than in other patient subgroups. Across the patient stratification subgroups, the predominant treatment-emergent AEs for which patients receiving teduglutide had a significantly increased relative risk were abdominal distension and gastrointestinal stoma complication compared with patients receiving placebo. CONCLUSIONS: Teduglutide had a safety profile consistent with prior adult data and no new safety concerns were identified. The most frequently reported AEs were gastrointestinal in origin, consistent with the underlying disease condition and intestinotrophic actions of teduglutide. CLINICAL TRIAL REGISTRY INFORMATION: NCT00081458/EudraCT, 2004-000438-35; NCT00798967/EudraCT, 2008-006193-15; NCT00172185/EudraCT, 2004-000439-27; NCT00930644/EudraCT, 2009-011679-65.

Nonoperative Antibiotic Treatment of Appendicitis in Adults: A Survey among Clinically Active Surgeons.

BACKGROUND: As a result of well-publicized studies, the nonsurgical antibiotic therapy of uncomplicated acute appendicitis has been propagated since 2006. A final assessment regarding efficiency and long-term results is not possible; however, nonoperative therapy of acute appendicitis is actually being discussed more diversely and receives a lot of attention. It is still unknown how far this therapy has found its way into everyday clinical care. METHODS: An online questionnaire was sent to 1,400 randomly selected specialists for general/visceral surgery in Germany. Representativeness was achieved by a preselection according to the geographical origin and the care level of the hospitals. RESULTS: 14% of surgeons stated that they methodically treat appendicitis conservatively. 38.1% do so in exceptional cases, while 48.8% reject this therapy. For methodically use, sonography or computed tomography is demanded beforehand. Nonoperative therapy is performed more often in metropolitan areas and maximum-care/university hospitals. Patients' request for antibiotic therapy is an important factor for conservative treatment. The main argument against this therapy is "medical doubts." 26% of the surgeons would treat their own appendicitis conservatively. There are distinct associations between the application of conservative therapy, satisfaction with it, and expectations about future development. The response rate was 19.9%. CONCLUSION: The nonoperative antibiotic therapy of appendicitis is part of clinical practice in Germany. There are differences in preconditions as well as in the acceptance of this therapeutic option with a high proportion of general rejection.