Middle ear adenomatous neuroendocrine tumours (MEANTs) are rare, unpredictable tumours. Although most MEANTs are characterized by a benign biological behaviour and indolent growth pattern, some... Show moreMiddle ear adenomatous neuroendocrine tumours (MEANTs) are rare, unpredictable tumours. Although most MEANTs are characterized by a benign biological behaviour and indolent growth pattern, some studies have reported locally invasive and metastastic disease. Currently, the optimal management strategy for MEANTs remains subject of debate. The aim of this study is to review the literature on MEANTs with focus on its clinical characteristics, treatment strategies and outcome. A systematic review was conducted using PubMed, Embase and Cochrane databases. A total of 111 studies comprising 198 patients with MEANT were included. Treatment modalities comprised surgery (90%), surgery with adjuvant radiotherapy (9%) and palliative (chemo)radiotherapy in (1%). Local recurrence was observed in 25% of the patients and 7% of the patients developed metastasis, over a median period of 5.7 years (range 7 months - 32 years). Twelve of 13 patients (92%) who developed metastases had a local recurrence. Four patients (2%) died of MEANT: three due to distant metastases and one due to extensive local recurrence. Reliable histopathologic predictors of outcome could not be identified. These findings indicate that the clinical presentations of MEANT vary substantially, the overall recurrence rate is considerable and initial local tumour control is paramount. Because of the unpredictable clinical course, prolonged follow-up is warranted. Show less
Background In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is... Show moreBackground In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. Methods Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. Discussion This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for theen blocresection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. Show less
Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal... Show moreTotal mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. Therefore the aim of this thesis was to identify molecular differences between rectal tumors of different stages, using gene expression profiling and genomic analysis. First protocols and data analysis algorithms for a new type of SNP array were developed. These studies showed that reliable LOH and copy number changes could be obtained from both frozen and paraffin embedded material. Consequently SNP arrays were used to type groups of TEM and TME treated samples. Five genomic events were found which could make a clear discrimination between adenomas and carcinomas. Early carcinomas treated by TEM, which were not recognized preoperatively as carcinomas, showed already carcinoma-associated aberrations. Analysis of tree core biopsies per patient showed a large degree of intra- tumor heterogeneity; although a good correlation was obtained between the biopsy with the largest number of aberrations and its corresponding tumor fraction. Gene expression array analysis was performed on the same samples as the SNP array series. A high concordance between chromosomal aberrations and changes in gene expression was observed. Finally a clinical application of these data is discussed in the preoperative staging of rectal tumours. Show less
