Rajaventhan Srirajaskanthan

A multimodal approach to the management of neuroendocrine tumour liver metastases

Neuroendocrine tumours (NETs) are often indolent malignancies that commonly present with metastatic disease in the liver. Surgical, locoregional, and systemic treatment modalities are reviewed. A multidisciplinary approach to patient care is suggested to ensure all therapeutic options explored.

Rectal neuroendocrine tumor

RECTAL NEUROENDOCRINE TUMORS (NET, still commonly known as carcinoids) are being diagnosed increasingly frequently as a result of increased colonic investigations and, probably an increase in incidence. Commonly, these tumors are either removed as part of a snare polypectomy without prior histology, or the lesion is biopsied and neuroendocrine tumor diagnosed prior to a decision on the best method of removal. With higher grades and stages of rectal NET, it is clear that surgical excision of the rectum and clearance of pelvic nodes is required. For the more common small G1 rectal NET <20 mm, there is still debate regarding the best method of removal. The current methods of endoscopic removal are simple polypectomy for pedunculated lesions, endoscopic mucosal resection (EMR, single or dual channel), endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM). In addition, some of these can be carried out in sequence for inadequate resection margins. In the current issue of the Journal, Joon Han Jeon et al. report a retrospective analysis of 66 patients over a 4-year period. All had G1 well-differentiated rectal NET. Staging by computed tomography (CT) imaging revealed one case of lymphovascular invasion in the TEM group but no cases of distant metastasis. EUS was performed preoperatively and confirmed no submucosal involvement. Most tumors (85.7%) were ≤10 mm in diameter and all were resected either by single-channel EMR, ESD or TEM. Tumors <10 mm were common in all groups (EMR 86.2%, ESD 91.3%, TEM 78.6%). No significant difference in baseline characteristics among these groups was noted although maximal tumor size resected by each method was not explicitly stated. All tumors were completely removed macroscopically. ESD achieved significantly higher complete microscopic resection rates than EMR (82.6% and 65.5%, respectively) whereas TEM achieved 100% completion (significance not stated for TEM compared to ESD). Operating times and duration of hospitalization were significantly greater for TEM compared to ESD and EMR. The ESD group also had significantly more cases of bleeding and other common complications compared to the EMR group. There were no cases of endoscopic perforation. With regards to clinical outcome, 21.2% (14/66) of patients had R1 resections, of which three out of the 10 followed up had additional resections (four patients lost to follow up). Unfortunately, the tumor size of R1 resections has not been stated. Four R1 resections were in the ESD group (one had additional TEM) and 10 in the EMR group (one had additional ESD and one had additional TEM). None of the additional procedures showed any residual tumor cells. Follow up was carried out using colonoscopy and CT imaging. There were no cases of local recurrence or distant metastasis seen during a median follow-up period of 21.5 ± 13.5 months. For those with endoscopic R1 resections, disease recurrence or metastasis was not detected after a median follow up of 22.4 ± 16.7 months irrespective of the resection method. Many of the patients in the above-mentioned study by Joon Han Jeon et al. (this issue of the Journal) had similar characteristics to those in a study by Sung et al. that included a total of 77 patients from the same center between 2000 and 2010. All lesions were G1 or G2 without lymphovascular invasion or distant metastasis. A similar proportion of patients had tumors <10 mm in size (81.8%) and maximal tumor size was 16 mm. Dual-channel EMR for 3–8-mm tumors and argon plasma coagulation post-resection was used on a case-by-case basis. Similarly, the R1 resection rate was 24.7% (19/77), of which six patients had additional treatment (31.6%). In comparison, there was no statistical difference between ESD and EMR for rates of histological complete resection. Mean follow up was also similar (27.2 months). Long-term follow up of residual disease detected local recurrence in only one patient after 56 months, which was treated successfully by EMR. The use of primary EMR for superficial colorectal NET has increased, coinciding with an increased reporting incidence of remnant or locally recurrent disease. Jeon et al. demonstrated a potential role for salvage EMR with cap in tumors <15 mm in size, without muscle invasion or distant and nodal metastasis after a failed en-bloc excision with primary EMR or polypectomy (n = 35). The results are encouraging with 1-year follow up with colonoscopy and CT all negative for local or systemic recurrence. Current European Neuroendocrine Tumor Society (ENETS) guidelines recommend endoscopic resection for localized G1 rectal NET <10 mm with a low risk of metastatic disease. If resection is incomplete, annual surveillance is considered adequate. The outcome of tumors between 10 and 20 mm is less clear. The metastatic risk is considered to be between 10 and 15%. In general, G1 tumors <20 mm with

Tumour Staging: Ileum

Ileal neuroendocrine tumours are one of the most common gastro-enteropancreatic neuroendocrine tumours (GEP-NETs), making up to 28% of all GEP-NETs. Small bowel NETs are the most common type of small bowel tumour; 45% of these lesions occur in the distal ileum. Small bowel neuroendocrine tumours commonly present in the sixth to seventh decade; however, they can occur at any time of life. In up to 30% of cases, these lesions are multiple, with some case series reporting this to be as high as 40%. When diagnosed, ileal NETs are frequently larger than 2 cm and have spread to regional lymph nodes.

Incidence and prevalence of neuroendocrine tumours in England

Introduction Historically the incidence and prevalence of neuroendocrine tumours (NETs) has been difficult to establish due to issues with disease coding and data collection. Studies by Ellis et al in 2006 estimated the incidence of gastroenteropancreatic neuroendocrine tumours (GEP NETs) to be 1.3 per 100,000 per year (incidence hereafter given as cases per 100,000). However, the SEER USA data suggests a four-fold higher incidence, and prevalence of 35 per 100,000. This study aimed to identify the incidence and prevalence of NETs over a ten-year period utilising the Public Health England (PHE) population-based cancer registry. Materials and methods Age-standardised incidence rates and prevalence from the 1st January 1995 to 31st March 2016 were calculated using data from the PHE National Cancer Registration and Analysis Service (NCRAS) database. Results In 2015, the age-standardised incidence rate for NETs in England (excluding small and large cell neuroendocrine carcinomas, SCLC and LCNEC respectively) was 8.84, 8.37 in males [95% CI, 8.02-8.72] and 9.30 in females [95% CI, 8.91-9.71] and; rising from 3.9 in 2001, with an average yearly increase of 0.39 cases. The incidence of SCLC was 7.72 and LCNECs was 0.44. The cohort was 90.1% White, 2.6% Asian, 1.8% Black, 1.4% other and 4.0% ethnicity unknown. The most common primary tumour sites were: 20.2% colorectal, 19.5% lung, 14.1% small intestinal, 9.6% pancreatic, 6.9% skin, and 5.3% stomach. The stage breakdown was 23.3% stage I, 11.7% stage II, 14.2% stage III, 25.9% stage IV and 24.8% stage unknown in the 91.3% of the tumours with a histological confirmation from a primary, the remaining 8.7% were unknown primaries at diagnosis. The prevalence was 19,268 (34.9 per 100 000), 8,743 males and 10,525 females. Conclusion This study has clearly demonstrated that incidence of NETs in England is significantly higher than previously reported. The data demonstrate similar incidence and prevalence rates to those reported in the SEER database. Importantly, it highlights that colorectal and lung NETs are the most common primary sites.