The Role of Alternative Lymph Node Classification Systems in Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NEN): Superiority of a LODDS Scheme Over N Category in Pancreatic NEN (pNEN).

Lymph node (LN) involvement in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) has been reported to have prognostic and therapeutic implications. Numerous novel LN classifications exist; however, no comparison of their prognostic performance for GEP-NEN has been done yet. Using a nationwide cohort from the German Neuroendocrine Tumor (NET) Registry, the prognostic and discriminatory power of different LN ratio (LNR) and log odds of metastatic LN (LODDS) classifications were investigated using multivariate Cox regression and C-statistics in 671 patients with resected GEP-NEN. An increase in positive LN (pLN), LNR, and LODDS was associated with advanced tumor stages, distant metastases, and hormonal functionality. However, none of the alternative LN classifications studied showed discriminatory superiority in predicting prognosis over the currently used N category. Interestingly, in a subgroup analysis, one LODDS classification was identified that might be most appropriate for patients with pancreatic NEN (pNEN). On this basis, a nomogram was constructed to estimate the prognosis of pNEN patients after surgery. In conclusion, a more accurate classification of LN status may allow a more precise prediction of overall survival and provide the basis for individualized strategies for postoperative treatment and surveillance especially for patients with pNEN.

Pulsed-field ablation combined with ultrahigh-density mapping in patients undergoing catheter ablation for atrial fibrillation: Practical and electrophysiological considerations.

BACKGROUND: Pulsed-field ablation (PFA) yields a novel ablation technology for atrial fibrillation (AF). PFA lesions promise to be highly durable, however clinical data on lesion characteristics are still limited. OBJECTIVE: This study sought to investigate PFA lesion creation with ultrahigh-density (UHDx) mapping. METHODS: Consecutive AF patients underwent PFA-based pulmonary vein isolation (PVI) using a multispline catheter (Farwave, Farapulse Inc.). Additional ablation, including left atrial posterior wall isolation (LAPWI) and mitral isthmus ablation (MI) were performed in a subset of persistent AF patients. The extent of PFA-lesions and decrease of LA-voltage were assessed with pre- and post PFA UHDx-mapping (Orion™ catheter and Rhythmia™ 3D-mapping system, Boston Scientific). RESULTS: In 20 patients, acute PVI was achieved in 80/80 PVs, LAPW isolation in 9/9 patients, MI ablation in 2/2 (procedure time: 123 ± 21.6 min, fluoroscopy time: 19.2 ± 5.5 min). UHDx-mapping subsequent to PVI revealed early PV-reconnection in five case (5/80, 6.25%). Gaps were located at the anterior-superior PV ostia and were successfully targeted with additional PFA. Repeat UHDx mapping after PFA revealed a significant decrease of voltage along the PV ostia (1.67 ± 1.36 mV vs. 0.053 ± 0.038 mV, p < .0001) with almost no complex electrogram-fractionation at the lesion border zones. PFA-catheter visualization within the mapping system was feasible in 17/19 (84.9%) patients and adequate in 92.9% of ablation sites. CONCLUSION: For the first time illustrated by UHDx mapping, PFA creates wide antral circumferential lesions and homogenous LAPW isolation with depression of tissue voltage to a minimum. Although with a low incidence, early PV reconnection can still occur also in the setting of PFA.

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.

Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasia.

Malnutrition is a common problem in oncological diseases, influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet been studied systematically in neuroendocrine neoplasms (NEN), which, due to their growing prevalence and additional therapeutic options, provide an increasing clinical challenge to diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches, and to analyse the short- and long-term outcome of malnourished patients. A detailed subgroup analysis was also performed to define risk factors for poorer outcome. When applying malnutrition screening scores, 21-25% of the NEN patients were at risk of or demonstrated manifest malnutrition. This was confirmed by anthropometric measurements, by determination of serum surrogate parameters such as albumin as well as by bioelectrical impedance analysis (BIA), particularly phase angle α. The length of hospital stay was significantly longer in malnourished NEN patients, while long-term overall survival was highly significantly reduced. Patients with high-grade (G3) neuroendocrine carcinomas, progressive disease and undergoing chemotherapy were at particular risk of malnutrition associated with a poorer outcome. Multivariate analysis confirmed the important and highly significant role of malnutrition as an independent prognostic factor for NEN besides proliferative capacity (G3 NEC). Malnutrition is therefore an underrecognized problem in NEN patients which should systematically be diagnosed by widely available standard methods such as Nutritional Risk Screening (NRS), serum albumin assessment and BIA, and treated to improve both short- and long-term outcomes.

Pharmacological strategies to enhance adaptation in intestinal failure.

PURPOSE OF REVIEW: Intestinal failure because of more or less extensive resection of parts of the small and large intestine (short bowel syndrome) results from the reduction of absorptive surface of the remaining intestine and frequently results in dependence on parenteral nutrition. Parenteral nutrition, although lifesaving, is associated with short and long-term complications as well as with reduced quality of life and overall survival. RECENT FINDINGS: Pharmacological enhancement of the physiological intestinal adaptive response by subcutaneous application of the glucagon-like peptide 2 analogue teduglutide results in an improved, hyperadaptive response. This is reflected by decreased parenteral calorie and fluid requirements, decreased parenteral nutrition infusion days per week including complete weaning off parenteral nutrition with complete oral autonomy, improved quality of life, and metabolic and nutritional stability. SUMMARY: The advent of teduglutide as an authority-approved specific medication for intestinal failure in parenteral nutrition-dependent short bowel syndrome offers an effective and beneficial treatment for these patients. As a result, patients are more stable whether for medical or further surgical management including intestinal transplantation. Long-term efficacy and safety still have to be proven.

Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome.

INTRODUCTION: The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. METHODS: Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. RESULTS: The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. CONCLUSIONS: Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide.

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.

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.

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.

Assessing Non-Invasive Liver Function in Patients with Intestinal Failure Receiving Total Parenteral Nutrition-Results from the Prospective PNLiver Trial.

Abstract: Liver abnormalities in intestinal failure (IF) patients receiving parenteral nutrition (PN) can progress undetected by standard laboratory tests to intestinal failure associated liver disease (IFALD). The aim of this longitudinal study is to evaluate the ability of non-invasive liver function tests to assess liver function following the initiation of PN. Twenty adult patients with IF were prospectively included at PN initiation and received scheduled follow-up assessments after 6, 12, and 24 months between 2014 and 2019. Each visit included liver assessment (LiMAx [Liver Maximum Capacity] test, ICG [indocyanine green] test, FibroScan), laboratory tests (standard laboratory test, NAFLD [non-alcoholic fatty liver disease] score, FIB-4 [fibrosis-4] score), nutritional status (bioelectrical impedance analysis, indirect calorimetry), and quality of life assessment. The patients were categorized post-hoc based on their continuous need for PN into a reduced parenteral nutrition (RPN) group and a stable parenteral nutrition (SPN) group. While the SPN group (n = 9) had significantly shorter small bowel length and poorer nutritional status at baseline compared to the RPN group (n = 11), no difference in liver function was observed between the distinct groups. Over time, liver function determined by LiMAx did continuously decrease from baseline to 24 months in the SPN group but remained stable in the RPN group. This decrease in liver function assessed with LiMAx in the SPN group preceded deterioration of all other investigated liver function tests during the study period. Our results suggest that the liver function over time is primarily determined by the degree of intestinal failure. Furthermore, the LiMAx test appeared more sensitive in detecting early changes in liver function in comparison to other liver function tests.

Oral intake and plasma citrulline predict quality of life in patients with intestinal failure.

OBJECTIVE: Chronic intestinal failure (cIF) is a rare medical condition usually treated by long-term parenteral nutrition (PN). Owing to disease-associated symptoms and treatment-specific complications, patients with cIF commonly present with reduced quality of life (QoL) compared with healthy controls. The aim of this study was to identify factors associated with QoL in patients with cIF. METHODS: Ninety adult patients with cIF receiving PN were included in an observational study between 2014 and 2017. QoL based on the novel Short Bowel Syndrome-Quality of Life (SBS-QoL) scale and the Short-Form 36 (SF-36) health survey and nutritional status, liver function, and standard blood chemistry were assessed in every study patient. Univariate and multivariable regressions were conducted to determine independent predictors of QoL. RESULTS: Oral food intake and plasma citrulline were the two independent variables associated with the SBS-QoL subscale 1 (R2 = 0.240) and subscale 2 (R2 = 0.235). Oral intake (ß = -43.909, P = 0.015) and citrulline (ß = -0.952, P = 0.003) were also significantly associated with the SBS-QoL sum scale (R2 = 0.209). The results of SF-36 health survey were significantly associated with both SBS-QoL subscale 1 (P <0.001) and subscale 2 (P <0.001) and the SBS-QoL sum scale (P <0.001). CONCLUSIONS: Citrulline and oral intake are predictors of QoL in patients with cIF. Although citrulline appears to be good screening tool, oral food ingestion should be considered as key goal in patients with cIF.

Determinants of Quality of Life in Patients With Intestinal Failure Receiving Long-Term Parenteral Nutrition Using the SF-36 Questionnaire: A German Single-Center Prospective Observational Study.

BACKGROUND: Parenteral nutrition (PN) is a life-sustaining therapy for patients with chronic intestinal failure (IF) but inevitably has an impact on patients' quality of life (QoL). The purpose of this study was to examine multiple aspects of QoL by utilizing the standardized Short Form 36 (SF-36) health survey. METHODS: Between 2014 and 2017, a total of 90 adult patients with IF who were receiving PN were prospectively enrolled in an observational study. All subjects underwent nutrition status assessment, liver assessment, blood tests, and QoL assessment based on the SF-36. Univariate and multivariable analyses were performed to identify determinants of 8 domains and 2 summary scales of the SF-36. RESULTS: Analysis of the SF-36 questionnaire data showed that QoL was significantly worse compared with the general German population across all categories. Multivariable analysis revealed that bioelectrical impedance analysis of phase angle (1/10 categories), stoma/fistula (4/10 categories), oral intake (4/10 categories), infusions per week (1/10 categories), duration of PN (1/10 categories), citrulline (4/10 categories), and hemoglobin levels (1/10 categories) are independent risk factors affecting QoL. CONCLUSION: This study uses the largest cohort of IF patients assessed by the standardized SF-36 questionnaire to comprehensively analyze QoL. Presence of oral intake, presence of ostomy, and citrulline levels were independently correlated with 4 of 10 categories of the SF-36. These results indicate that to improve QoL for IF patients, clinical care should focus on addressing the social and emotional value of oral intake, educational interventions, early stoma closure, and application of new targeted therapies.

Advanced liver function assessment in patients with intestinal failure on long-term parenteral nutrition.

BACKGROUND & AIMS: Intestinal failure associated liver disease (IFALD) is one of the leading complications and causes of deaths in adult patients receiving home parenteral nutrition for chronic intestinal failure (CIF). Early diagnosis of IFALD is key to alleviate the progression of hepatic dysfunction. The aim of this study was to evaluate the capability of noninvasive liver function tests. METHODS: 90 adult patients with CIF receiving long-term home parenteral nutrition were included in a prospective cross-sectional study at our department between 2014 and 2017. All participants underwent dynamic liver function assessment (maximum liver function capacity [LiMAx] test, indocyanine green [ICG] test), transient elastography (FibroScan), blood tests and comprehensive nutritional status assessment. Univariate and multivariable analysis were performed to identify predictors of liver function. RESULTS: LiMAx, ICG test, and FibroScan highly correlated with standard liver function tests. Multivariable analysis identified intact ileum (B = 520.895; p = 0.010), digestive anatomy type 3 (B = 75.612; p = 0.025), citrulline level (B = 3.428; p = 0.040), parenteral olive oil intake (B = -0.570; p = 0.043), and oral intake (B = 182.227; p = 0.040) as independent risk factors affecting liver function determined by LiMAx test. ICG test and FibroScan showed no correlation with gastrointestinal and nutrition-related parameters. CONCLUSION: The LiMAx test is significantly associated with widely accepted risk factors for IFALD by multivariable analysis, whereas ICG test and FibroScan failed to show significant correlations. Liver function assessment by LiMAx test may therefore have the potential to detect alterations in liver function and identify patients at risk for the development of IFALD. Longitudinal studies are needed to investigate the impact of liver function determined by LiMAx test on long-term outcome in patients with CIF.

[Intestinal Rehabilitation in Short Bowel Syndrome and Chronic Intestinal Failure]. / Intestinale Rehabilitation bei Kurzdarmsyndrom und chronischem Darmversagen.

Patients with severely orally decompensated malsaborption due to surgical rescetion suffer from short bowel syndrome (SBS). The resultant decrease in intestinal surface area after rescetion of parts of the intestines leads to chronic functional intestinal insufficiency or even complete failure (cIF) which requires parenteral fluid and nutrient restoration for establishment of metabolc stability. Since the introduction of glucagon-like peptide (GLP)-2 analogues such as teduglutide functional rehabilitation of the remaining gastrointestinal tract has become a causal treatment option. Teduglutide functionally and effectively enhances intestinal absorption of fluid as well micro- and macronutrients allowing a reduction of parenteral nutrition and/or volume with even complete weaning off in some patients. This results increased metabolic stability, oral autonomy, quality of life and putatively less complications.

Malnutrition predicts long-term survival in hospitalized patients with gastroenterological and hepatological diseases.

BACKGROUND & AIMS: Malnutrition is a common problem in hospitalized patients, influencing treatment outcomes, length of hospital stay, quality of life and overall survival. However, the association of nutritional status parameters with long-term mortality has not yet been studied systematically in gastroenterological-hepatological patients. The present study aimed to assess the association between nutritional status parameters as characterized by Nutritional Risk Screening (NRS), anthropometry, serum transferrin, bioelectrical impedance analysis (BIA) and long-term overall survival in hospitalized gastroenterological-hepatological patients. METHODS: Nutritional status was assessed in 644 gastroenterological-hepatological patients by NRS score. In addition, body mass index (BMI) and serum transferrin were determined and BIA was performed. Mid-upper arm circumference (MUAC) and triceps skinfold thickness (TST) were measured. Patients were followed for a mean period of 67 months (mean 54.8, range 0-107 months). RESULTS: During malnutrition screening, 475 (73.8%) patients were diagnosed as sufficiently nourished by NRS (NRS 0-2), while an increased risk of malnutrition was found in 169 (26.2%) patients (NRS≤3). Malnutrition was significantly associated with less favourable results for BMI (p < 0.001), serum transferrin (p < 0.001), BIA (p < 0.001), MUAC (p < 0.001) and TST (p < 0.05). Overall 5-year survival rates (YSR) were much shorter in malnourished patients whether with (5-YSR: 43.9%) or without (73.6%) malignancy. Overall 5-year survival rates (YSR) were much shorter in malnourished patients whether with (5-YSR: 43.9%) or without (73.6%) malignancy. By the multivariable analysis the NRS ≥3 and, phase angle (PhA) over the 5th percentile or over the mean of the cohort were found to be associated with long-term survival. CONCLUSIONS: Malnutrition is highly prevalent in hospitalized gastroenterological-hepatological patients and is associated with distinct clinical diagnoses. In the present study we demonstrated that malnutrition characterized by the NRS, anthropometry, serum transferrin and BIA, not only predicts short-term but also significantly poor long-term outcome in these patients.

Experience with teduglutide treatment for short bowel syndrome in clinical practice.

BACKGROUND & AIMS: Teduglutide, a glucagon-like peptide 2 (GLP-2) analog, is an approved medication specific for short bowel syndrome patients with chronic intestinal failure (SBS-IF). Due to its intestinotrophic properties, it improves intestinal absorption of fluids and nutrients, which was shown to reduce the need for parenteral support in clinical trials. The present report aims to describe the experience of teduglutide's effects in routine medical care with focus on clinical and nutritional effects. METHODS: Data of adult SBS-IF patients, treated with teduglutide between Sept. 2014 and May 2017 within a structured multidisciplinary program to enhance intestinal rehabilitation, were analyzed retrospectively from a single university medical center. RESULTS: In total, 27 patients were treated with teduglutide. Parenteral nutrition independency was achieved in 4/19 (21%) patients analyzed, with two remaining on intravenous fluids. A clinically significant reduction of parenteral volume was observed in 15/19 patients (79%) with onset between 1 and 45 weeks. Significant parenteral support reductions were observed, ranging from about -20% in patients treated for 3 months to about -45% in patients treated for 2 years. This was accompanied by an increase in parenteral nutrition-free days. We also report on a clinically relevant and significant effect of teduglutide-mediated improvement of stool frequency and consistency. Furthermore, nutritional status subgroup analysis revealed long-term stability in body weight, albumin levels and body composition albeit parenteral support reduction. Structural effects of teduglutide treatment were observed on small intestinal mucosa with significantly increased villus height, crypt depth and plasma citrulline levels. CONCLUSIONS: Teduglutide can be applied to anatomically and clinically heterogeneous SBS-IF patients and results in an adaptive response with variable time and effect range in routine medical care. Teduglutide-induced functional and structural changes bring on a gradual reduction of parenteral support at no cost to body composition and suggest an improved intestinal function with compensatory effect on nutritional status.

A score derived from routine biochemical parameters increases the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms.

BACKGROUND: Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs. METHODS: This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs. RESULTS: CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713-0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430). CONCLUSIONS: CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.

Management of follow-up of neuroendocrine neoplasias.

Neuroendocrine neoplasias (NEN) comprise heterogeneous epithelial neoplasms with a large variety of clinical presentations, treatment options and outcomes. Since potentially all NEN bear malignant potential it is important for long-term clinical management and improvement of outcome to decide on successful and oncologically and economically meaningful follow-up strategies. Evidence-based outcome data validating specific follow-up strategies are, however, not available to date and thus outcome data, known prognostic factors and clinical experience guide the decisions on follow-up regimens. The review summarizes general recommendations as well as specific considerations based on tumor entities, clinicopathological tumor characteristics and clinical experience. Follow-up shall serve the patient to improve outcome, benefit from more effective therapies and suffer less from unnecessary and/or toxic therapeutic interventions and finally preserve or gain a good quality of life.