Belgian guidelines for pathology reporting of neuroendocrine neoplasms of the pancreaticobiliary and gastrointestinal tract.

Since neuroendocrine neoplasms are rare tumors, registration of patient data in national and multinational registries is recommended. Indeed, this will facilitate multicenter studies on the epidemiology, efficacy and safety of diagnostic and therapeutic strategies for well-differentiated neuroendocrine tumors as well as for neuroendocrine carcinomas. In Belgium, data on patient and tumor characteristics of all newly diagnosed malignancies have been collected in the Belgian Cancer Registry since 2004 including anonymized full pathological reports. The Digestive Neuroendocrine Tumor (DNET) registry collects information on classification, staging, diagnostic tools and treatment in a prospective national online database. However, the terminology, classification and staging systems of neuroendocrine neoplasms have changed repeatedly over the past 20 years as a result of a better understanding of these rare tumors, by joining forces internationally. These frequent changes make it very difficult to exchange data or perform retrospective analyses. For optimal decision making, for a clear understanding and to allow reclassification according to the latest staging system, several items need to be described in the pathology report. This paper provides an overview of the essential items in reporting neuroendocrine neoplasms of the pancreaticobiliary and gastrointestinal tract.

Real-world first-line treatment of patients with BRAFV600E-mutant metastatic colorectal cancer: the CAPSTAN CRC study.

BACKGROUND: BRAFV600E mutations occur in 8%-12% of metastatic colorectal cancer (mCRC) cases and are associated with poor survival. European guidelines recommend combination (doublet or triplet) chemotherapy plus bevacizumab in first line. However, an unmet need remains for more effective treatments for these patients. PATIENTS AND METHODS: CAPSTAN CRC is a European, retrospective, multicenter, observational study evaluating real-world treatment practices for patients with BRAFV600E-mutant mCRC treated between 1 January 2016 and 31 January 2020. The primary objective was to describe first-line treatment patterns. Secondary objectives included describing baseline demographics, mutational testing procedures, treatment effectiveness, and safety. RESULTS: In total, 255 patients (median age 66.0 years; 58.4% female) with BRAFV600E-mutant unresectable mCRC from seven countries were included. Most had right-sided tumors (52.5%) and presented with synchronous disease at diagnosis (66.4%). Chemotherapy plus targeted therapy (68.7%) was preferred at first line over chemotherapy alone (31.3%). The main first-line treatments were FOLFOX plus bevacizumab (27.1%) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) with/without bevacizumab (27.1%/19.2%). Median duration of first-line treatment was 4.9 months. Overall, 52.5% received second-line treatment. Across all first-line regimens, progression-free survival (PFS) and overall survival were 6.0 [95% confidence interval (CI) 5.3-6.7] months and 12.9 (95% CI 11.6-14.1) months, respectively. Triplet plus targeted therapy was associated with more adverse events (75.0%) compared with triplet chemotherapy alone (50.0%) and doublet chemotherapy alone (36.1%). Multivariate analysis identified low body mass index and presence of three or more metastatic sites as significant prognostic factors for PFS. CONCLUSIONS: This study is, to date, the largest real-world analysis of patients with BRAFV600E-mutant mCRC, providing valuable insights into routine first-line treatment practices for these patients. The data highlight the intrinsic aggressiveness of this disease subgroup, confirming results from previous real-world studies and clinical trials, and stressing the urgent need for more effective treatment options in this setting.

Another gastrointestinal lesion amendable for ablation.

A 79-year-old patient, with a history of redoendoscopic ampullectomy (low grade dysplasia), was referred to our hospital with cholestatic liver function abnormalities and dilation of the common bile duct. Diagnostic endoscopic ultrasound (EUS) was performed (Figure 1, left), as well as upper gastrointestinal endoscopy (Figure 1, right). What is the final diagnosis and which treatment would you propose?

Lessons learned about appendiceal neuroendocrine neoplasms from data analysis of the Belgian Cancer Registry 2010-2015.

BACKGROUND AND STUDY AIMS: Appendiceal neuroendocrine neo-plasms (aNENs) are a diverse group of malignant neoplasms of varying biological behavior for which information about manage-ment and outcome is sparse, with the majority of available studies being retrospective, including only a limited number of patients, and therefore not necessarily reflecting the reality in the community. In the present study clinical, epidemiological and pathological data of appendiceal neuroendocrine neoplasms in Belgium is provided and compared with current literature. METHODS: A population-based study was conducted by linking data of the Belgian Cancer Registry with medical procedures in the Belgian Health Insurance database for patients diagnosed with aNEN between 2010 and 2015. RESULTS: We found an aNEN incidence of 0.97/100.000 person years in Belgium. Neuroendocrine carcinoma of the appendix are rare. Most appendiceal neuroendocrine tumors (aNETs) are small G1 tumors. Positive lymph nodes are often found in tumors larger than 2cm, especially aNET G2. CONCLUSION: A rapid uptake of changing classifications was seen in the community. However, systematic reporting of risk factors for small aNEN can still be improved and should be stimulated. In 9% of cases, reclassifications had to be made, pointing out that in a retrospective analysis, original pathological reports should be checked for specific parameters, before reliable conclusions can be drawn.

Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method.

BACKGROUND AND STUDY AIMS: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel. PATIENTS AND METHODS: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. RESULTS: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). CONCLUSIONS: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance.

Single-centre experience on use of videocapsule endoscopy for obscure gastrointestinal bleeding in 120 consecutive patients.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) has become first choice for evaluation of the small bowel in case of obscure gastrointestinal bleeding (OGIB). The influence of clinical factors on CE diagnostic yield remains controversial and little is known about the exact impact of CE on management and outcome. We aimed to identify the ideal candidates for CE examination in daily practice by reviewing our own data and the available literature. PATIENTS AND METHODS: We retrospectively analyzed data of 120 consecutive patients with OGIB (33 overt - 87 occult) that underwent CE in a single centre. RESULTS: Complete evaluation of the small bowel was achieved in 82.5%, with only one case of capsule retention. The overall diagnostic yield was 47.5% and no difference was noted in the overt versus the occult group. Only the presence of cardiovascular comorbidity was associated with a statistically significant increase in diagnostic yield (p = 0,041). Arterio-venous malformation (AVM) was diagnosed most frequently in 68.4% of positive studies. Specific management alterations were made in 22 patients (18.3%) following CE, mostly guided by a positive result (91%) (p = 0,0001). CONCLUSION: In daily practice it remains very difficult to predict pathology detection rate on CE as well as to estimate the impact on further management and outcome in the individual patient. Diagnostic yield is significantly higher in patients with cardiovascular comorbidity than in those without.