Landscape of Biomarkers and Pathologic Response in Rectal Cancer: Where We Stand?

Colorectal cancer (CRC) is a neoplasm with a high prevalence worldwide, with a multimodal treatment that includes a combination of chemotherapy, radiotherapy, and surgery in locally advanced stages with acceptable pathological complete response (pCR) rates, this has improved with the introduction of total neoadjuvant therapy (TNT) reaching pCR rates up to 37% in compare with classic neoadjuvant treatment (NAT) where pCR rates of around 20-25% are achieved. However, the patient population that benefits most from this therapy has not been determined, and there is a lack of biomarkers that can predict the course of the disease. Multiple biomarkers have been studied, ranging from hematological and molecular markers by imaging technique and combinations of them, with contradictory results that prevent their use in routine clinical practice.

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue.

Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types.

Plocabulin Displays Strong Cytotoxic Activity in a Personalized Colon Cancer Patient-Derived 3D Organoid Assay.

Plocabulin is a novel microtubule-disrupting antitumor agent of marine origin that is currently undergoing phase II clinical trials. Plocabulin has potent antiproliferative and antiangiogenic actions in carcinoma cell lines and has antitumor activity in xenografted mice. Here, we used three-dimensional (3D) tumor organoids derived from three colorectal cancer (CRC) patients to study the effect of plocabulin in a personalized assay system that ensures dose dependence and high reproducibility.

Vitamin D differentially regulates colon stem cells in patient-derived normal and tumor organoids.

Intestine is a major target of vitamin D and several studies indicate an association between vitamin D deficiency and inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk and mortality. However, the putative effects of 1α,25-dihydroxyvitamin D (calcitriol), the active vitamin D metabolite, on human colonic stem cells are unknown. Here we show by immunohistochemistry and RNAscope in situ hybridization that vitamin D receptor (VDR) is unexpectedly expressed in LGR5 colon stem cells in human tissue and in normal and tumor organoid cultures generated from patient biopsies.

Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts.

The Wnt/β-catenin signalling pathway is essential for intestinal epithelium homeostasis, but its aberrant activation is a hallmark of colorectal cancer (CRC). Several studies indicate that the bioactive vitamin D metabolite 1α,25-dihydroxyvitamin D (1,25(OH)D) inhibits proliferation and promotes epithelial differentiation of colon carcinoma cells in part through antagonism of the Wnt/β-catenin pathway. It is now accepted that stromal fibroblasts are crucial in healthy and pathologic intestine: pericryptal myofibroblasts are constituents of the stem cell niche and cancer-associated fibroblasts (CAFs) contribute to CRC progression.

The human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts.

Colorectal cancer results from the malignant transformation of colonic epithelial cells. Stromal fibroblasts are the main component of the tumour microenvironment, and play an important role in the progression of this and other neoplasias. Wnt/β-catenin signalling is essential for colon homeostasis, but aberrant, constitutive activation of this pathway is a hallmark of colorectal cancer.

Vitamin D receptor expression and associated gene signature in tumour stromal fibroblasts predict clinical outcome in colorectal cancer.

Objective: Colorectal cancer (CRC) is a major health concern. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this disease. Given the strong influence of tumour stroma on cancer progression, we investigated the potential effects of the active vitamin D metabolite 1α,25-dihydroxyvitamin D (1,25(OH)D) on CRC stroma.

Negative-Pressure Therapy to Reduce the Risk of Wound Infection Following Diverting Loop Ileostomy Reversal: An Initial Study.

Objective: To evaluate if the application of a negative-pressure therapy system (Prevena Incision Management System, Kinetics Concepts Inc, [KCI] an Acelity Company, San Antonio, Texas) on ileostomy-closure surgical wounds would reduce surgical site infections (SSIs) in comparison with conventional closure and dressing.

Design: Prospective interventional pilot study.

Setting: La Paz University Hospital, tertiary care academic hospital in Madrid, Spain.

Galactomannan Downregulates the Inflammation Responses in Human Macrophages via NFκB2/p100.

We show that galactomannan, a polysaccharide consisting of a mannose backbone with galactose side groups present on the cell wall of several fungi, induces a reprogramming of the inflammatory response in human macrophages through dectin-1 receptor. The nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NFκB2)/p100 was overexpressed after galactomannan challenge. Knocking down NFκB2/p100 using small interfering RNA (siRNA) indicated that NFκB2/p100 expression is a crucial factor in the progression of the galactomannan-induced refractoriness.

Increased postoperative complications after protective ileostomy closure delay: An institutional study.

Aim: To study the morbidity and complications associated to ileostomy reversal in colorectal surgery patients, and if these are related to the time of closure.

Methods: A retrospective analysis of 93 patients, who had undergone elective ileostomy closure between 2009 and 2013 was performed. Demographic, clinical and surgical variables were reviewed for analysis.

[Doppler-guided transanal haemorrhoidal dearterialisation. An alternative treatment for haemorrhoids].

Introduction: The frequency of haemorrhoid disease and the deterioration in the quality of life in the immediate post-operative period has led to the appearance of new techniques in an attempt to obtain improve patient satisfaction.

Patients And Method: A prospective study was carried out in which 50 consecutive patients with a diagnosis of Goligher grade III haemorrhoids were intervened. To perform the haemorrhoid dearterialisation, a device called THD R was used (designed by TKC SRL and distributed by Palex Medical).