Carcinoids and Capsules: A Case Series Highlighting the Utility of Capsule Endoscopy in Patients With Small Bowel Carcinoids

Background: Neuroendocine tumors (NETs) or carcinoids arise at many different sites of the gastrointestinal tract. The small intestine is the most common site for NETs. Diagnosing small bowel carcinoids remains challenging given their non-specific presentations and the overall low incidence of small bowel tumors. Video capsule endoscopy (VCE) has significanly improved our ability to detect small bowel malignancies. We explore the value of VCE in the initial workup and management of a series of small bowel carcinoid patients. Methods: We retrospectively analyzed adult patients undergoing surgical management for small bowel lesions from July 2005 to September 2015 at a tertiary care center. Patient characteristics, presenting symptomatology, diagnostic workup and surgical management were analyzed among patients with histologically confirmed small bowel carcinoid tumors. Results: Our study identified 16 patients treated surgically for small bowel carcinoids. The majority of patients (87.5%) presented with either occult gastrointestinal bleeding or anemia. Most patients (87.5%) were initially evaluated with various endoscopic and imaging modalities before all ultimately undergoing surgery. Seventy-five percent of patients had a VCE, with 83.3% (10/12) having positive findings that correlated with intraoperative findings compared to 62.5% (5/8) with computed tomography scan, 21.4% (3/14) with colonoscopy, 44% (4/9) with deep enteroscopy, and 0% (0/9) with esophagogastroduodenoscopy (EGD). Conclusions: In the absence of any contraindications, VCE is an effective endoscopic modality in the diagnostic workup of small bowel NETs. Furthermore, positive VCE findings appear to highly correlate with surgical findings, thus suggesting a valuable role for VCE in the initial surgical assessment of patients with small bowel NETs

p.(L576P) -KIT mutation in GIST: Favorable prognosis and sensitive to imatinib?

Exon 11 KIT mutations are found in a majority of gastrointestinal stromal tumors (GIST) and are usually predictive of response to imatinib, a KIT, PDGFRA and ABL inhibitor. Exon 11 mutations with poor sensitivity to imatinib and poor outcome can be observed on rare occasions, including p.(L576P). In silico and in vitro studies suggested a decreased binding affinity for imatinib in p.(L576P) KIT mutations, thereby offering an explanation for their poor outcome and poor response to standard therapy. These observations were further corroborated with anecdotal case reports of refractoriness or non-durable response to imatinib therapy. However, we describe the favorable response to imatinib and outcome in 5 p.(L576P)-KIT mutant GIST patients treated at a tertiary sarcoma referral center. The sensitivity of p.(L576P)-KIT mutations to imatinib, and the prognostic impact of this mutation need to be further evaluated in a larger cohort. Based on our observations, p.(L576P) mutated GISTs should be treated with standard first line imatinib therapy

Role of Mucosal Protrusion Angle in Discriminating between True and False Masses of the Small Bowel on Video Capsule Endoscopy

The diagnosis of small-bowel tumors is challenging due to their low incidence, nonspecific presentation, and limitations of traditional endoscopic techniques. In our study, we examined the utility of the mucosal protrusion angle in differentiating between true submucosal masses and bulges of the small bowel on video capsule endoscopy. We retrospectively reviewed video capsule endoscopies of 34 patients who had suspected small-bowel lesions between 2002 and 2017. Mucosal protrusion angles were defined as the angle between the small-bowel protruding lesion and surrounding mucosa and were measured using a protractor placed on a computer screen. We found that 25 patients were found to have true submucosal masses based on pathology and 9 patients had innocent bulges due to extrinsic compression. True submucosal masses had an average measured protrusion angle of 45.7 degrees ± 20.8 whereas innocent bulges had an average protrusion angle of 108.6 degrees ± 16.3 (p < 0.0001; unpaired t-test). Acute angle of protrusion accurately discriminated between true submucosal masses and extrinsic compression bulges on Fisher’s exact test (p = 0.0001). Our findings suggest that mucosal protrusion angle is a simple and useful tool for differentiating between true masses and innocent bulges of the small bowel

Adult Pleomorphic Rhabdomyosarcoma: A Multicentre Retrospective Study.

BACKGROUND Pleomorphic rhabdomyosarcoma (RMS) is a rare sub-type of RMS. Optimal treatment remains undefined. PATIENTS AND METHODS Between 1995 and 2014, 45 patients were diagnosed and treated in three tertiary sarcoma Centers (United Kingdom, Switzerland and Germany). Treatment characteristics and outcomes were analyzed. RESULTS The median age at diagnosis was 71.5 years (range=28.4-92.8 years). Median survival for those with localised (n=32, 71.1%) and metastatic disease (n=13, 28.9%) were 12.8 months (95% confidence interval=8.2-34.4) and 7.1 months (95% confidence interval=3.8-11.3) respectively. The relapse rate was 53.8% (four local and 10 distant relapses). In total, 14 (31.1%) patients received first line palliative chemotherapy including multi-agent paediatric chemotherapy schedules (n=3), ifosfamide-doxorubicin (n=4) and single-agent doxorubicin (n=7). Response to chemotherapy was poor (one partial remission with vincristine-actinomycin D-cyclophosphamide and six cases with stable disease). Median progression-free survival was 2.3 (range=1.2-7.3) months. CONCLUSION Pleomorphic RMS is an aggressive neoplasm mainly affecting older patients, associated with a high relapse rate, a poor and short-lived response to standard chemotherapy and an overall poor prognosis for both localised and metastatic disease

Rare Aggressive Behavior of MDM2

Dedifferentiated liposarcoma (DDL) is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, nonlipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo. DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct) liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2-amplified retroperitoneal liposarcoma

Adult soft tissue myoepithelial carcinoma: treatment outcomes and efficacy of chemotherapy.

Soft tissue myoepithelial carcinomas are a rare, malignant subgroup of myoepithelial tumours mostly arising in the extremities with equal predilection for women and men. The mainstay of management of localised disease is complete surgical resection. Despite optimal treatment, 40-45% of tumours recur. Data regarding the efficacy of systemic therapy for advanced and metastatic disease are lacking. The primary aim of this study was to evaluate the outcome of all patients with soft tissue myoepithelial carcinoma treated at a single referral centre. The secondary aim was to establish the efficacy of systemic therapies in patients with advanced disease. A retrospective review of the prospectively maintained Royal Marsden Sarcoma Unit database was performed to identify soft tissue myoepithelial carcinoma patients treated between 1996 and 2019. Patient baseline characteristics and treatment history were recorded. Response to systemic therapy was evaluated using RECIST 1.1. We identified 24 patients treated at our institution between 1996 and 2019,12 males and 12 females. Median age at presentation was 49.6 years [interquartile range (IQR) 40.5-63.3 years]. Twenty-two out of 24 patients (91.7%) underwent primary surgical resection. Nine patients (37.5%) received systemic treatment. A partial response was documented in one patient treated with doxorubicin. The median progression-free survival for first-line chemotherapy was 9.3 months. Myoepithelial carcinoma frequently recurs after complete surgical resection. Conventional chemotherapy demonstrated some activity in myoepithelial carcinoma, however, more effective systemic therapies are required and enrolment in clinical trial should be encouraged