Immunological and Clinico-Molecular Features of Tumor Border Configuration in Colorectal Cancer.

INTRODUCTION: Infiltrating tumor border configuration (ITBC) portends a poor prognosis compared with pushing tumor border configuration (PTBC) in colorectal cancer. The tumor and its surrounding immune microenvironment of tumor border configuration is not well-characterized. We aim to elucidate the differences in expression of molecular markers between the 2 groups using tissue microarray (TMA). STUDY DESIGN: Immunohistochemistry was performed on TMAs of surgical pathology specimens obtained from colorectal cancer patients consecutively operated at our institution from 2004 to 2015. TMAs were stained for immune cells (CD8, FOXP3, LAG3, PU1, CD163, and PDL1); HLA II, beta 2 microglobulin, and HC10 on tumor cells; BRAFV600E mutation; and DNA mismatch repair proteins (MMR) status. Patients who received neoadjuvant therapy were excluded. RESULTS: There were 646 tumors with ITBC and 310 tumors with PTBC. There was a significantly lower expression (p < 0.05) of immune components, namely CD8, FOXP3, LAG3, PU1, PDL1 immune cells, and Beta-2 Microglobulin on tumor cells in the tumors with ITBC compared with PTBC, except CD163 immune cells, and HC10 and HLAII on tumor cells. Tumors with ITBC were less likely to be associated with BRAFV600E mutations and deficient MMR proteins (p < 0.001). On analyzing MMR-proficient tumors separately, we could not find any difference in the expression of any molecular marker (including BRAF), except a lower expression of PDL1 immune cells in tumors with ITBC (p < 0.001). CONCLUSIONS: Colorectal tumors with ITBC are associated with a generalized low immune microenvironment and low rates of BRAFV600E mutation compared with tumors with PTBC. However, the molecular expression of tumor border configuration seems confounded by the MMR molecular signature. MMR-proficient colorectal tumors with ITBC are associated with a lower expression of only PDL1 immune cells among all immune markers examined.

A novel homozygous SLC19A2 mutation in a Portuguese patient with diabetes mellitus and thiamine-responsive megaloblastic anaemia.

Thiamine-responsive megaloblastic anaemia (TRMA) is a rare syndrome where patients present with early onset diabetes mellitus, megaloblastic anaemia and sensorineural deafness. This report describes a new case of TRMA syndrome in a female patient of Portuguese descent, born to unrelated parents. The patient was found to have a novel homozygous change R397X in exon 4 of the SLC19A2 gene, leading to a premature stop codon. The patient's diabetes and anaemia showed a good response to daily thiamine doses, reducing the daily insulin dose requirement. The report further indicates that TRMA is not only limited to consanguineous or ethnically isolated families, and should be considered as a differential diagnosis for patients presenting with suggestive clinical symptoms.

Minimally invasive surgery versus open surgery for the treatment of solid abdominal and thoracic neoplasms in children.

BACKGROUND: Minimally invasive surgery (MIS) is an accepted surgical technique for the treatment of a variety of benign diseases. Presently, the use of MIS in patients with cancer is progressing. However, the role of MIS in children with solid neoplasms is less clear than it is in adults. Although the use of diagnostic MIS to obtain biopsy specimens for pathology is accepted in paediatric surgical oncology, there is limited evidence to support the use of MIS for the resection of malignancies. This review is the second update of a previously published Cochrane review. OBJECTIVES: To ascertain differences in outcome between the minimally invasive and open surgical approaches for the treatment of solid intra-abdominal or intra-thoracic neoplasms in children. The primary outcomes of interest are OS, EFS, port-site metastases and recurrence rate; the secondary outcome of interest is surgical morbidity. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2014, Issue 1), MEDLINE/PubMed (from 1966 to February 2014) and EMBASE/Ovid (from 1980 to February 2014) to identify relevant studies. In addition, we searched reference lists of relevant articles and reviews and the conference proceedings of the International Society for Paediatric Oncology and the American Society of Clinical Oncology from 2003 to 2013. On 1 May 2014 we scanned the ISRCTN Register (on www.controlled-trials.com), the National Institutes of Health register (on www.controlled-trials.com and www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (on www.apps.who.int/trialsearch) for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing MIS to open surgery for the treatment of solid intra-thoracic or intra-abdominal neoplasms in children (aged 0 to 18 years) were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors performed the study selection independently. MAIN RESULTS: The literature search retrieved 542 references. After screening the titles and abstracts we excluded 534 references which clearly did not meet the inclusion criteria. We assessed eight full text studies for eligibility and all of these studies were excluded from the review because they were not RCTs or CCTs. These excluded studies included case series, retrospective chart reviews and retrospective cohort studies. The scanning of reference lists and conference proceedings did not identify any additional studies and no (ongoing trials) were identified by the searches of trial registries. No studies that met the inclusion criteria of this review were identified AUTHORS' CONCLUSIONS: No RCTs or CCTs evaluating MIS for the treatment of solid intra-thoracic or intra-abdominal neoplasms in children could be identified. The current evidence base informing the use of MIS in children with solid abdominal and thoracic neoplasms is based on other study designs like case reports, retrospective chart reviews and cohort studies and should be interpreted with caution. Thus there is insufficient evidence to allow any definitive conclusions regarding the use of MIS in these patients. High quality RCTs comparing MIS to open surgery are required. To accomplish this, centres specialising in MIS in children should collaborate.