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S100A8 and its dimerization partner S100A9 are emerging as important chemokines in cancer. We previously reported that Smad4-negative pancreatic tumors contain fewer stromal S100A8-positive monocytes than their Smad4-positive counterparts. Here, we studied S100A8/A9-expressing cells in colorectal tumors relating their presence to clinicopathological parameters and Smad4 status. Two-dimensional gel electrophoresis (n = 12) revealed variation in the levels of S100A8 protein in colorectal cancer tumors, whereas immunohistochemical analysis (n = 313) showed variation in the numbers of stromal S100A8-positive and S100A9-positive cells. Loss of Smad4 expression was observed in 42/304 (14%) colorectal tumors and was associated with reduced numbers of S100A8-positive (P = 0.03) but not S100A9-positive stromal cells (P = 0.26). High S100A9 cell counts were associated with large tumor sizes (P = 0.0006) and poor differentiation grade (P = 0.036). However, neither S100A8 nor S100A9 cell counts predicted poor survival, except for patients with Smad4-negative tumors (P = 0.02). To address the impact of environmental S100A8/A9 chemokines on tumor cells, we examined the effects of exogenously added S100A8 and S100A9 proteins on cellular migration and proliferation of colorectal and pancreatic cancer cells. S100A8 and S100A9 enhanced migration and proliferation in Smad4-positive and Smad4-negative cancer cells. However, transient depletion of Smad4 resulted in loss of responsiveness to exogenous S100A8, but not S100A9. S100A8 and S100A9 activated Smad4 signaling as evidenced by phosphorylation of Smad2/3; blockade of the receptor for the advanced glycation end products inhibited this response. In conclusion, Smad4 loss alters the tumor’s interaction with stromal myeloid cells and the tumor cells’ response to the stromal chemokine, S100A8. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented about the new frameshift mutation in the adenomatous polyposis coli (APC) gene at exon 15 in familial adenomatous polyposis (FAP) with desmoid tumor.

The article presents a case study of a 28-year-old female with a history of left breast lumpectomy and diagnosed with desmoid fibromatosis or aggressive fibromatosis after ultrasound-guided core biopsy. Topics discussed include her clinical examination identifies swelling in right iliac fossa close to the right iliac crest, without any regional lymphadenopathy, her Immunohistochemistry detected smooth muscle actin and cytoplasmic expression of b-catenin, and treatment with radiotherapy.

Background: Acute uncomplicated diverticulitis (AUD) is common and antibiotics are the cornerstone of traditional conservative management. This approach lacks clear evidence base and studies have recently suggested that avoidance of antibiotics is a safe and efficacious way to manage AUD. The aim of this systematic review is to determine the safety and efficacy of treating AUD without antibiotics., Methods: A systematic search of Embase, Cochrane library, MEDLINE, Science Citation Index Expanded, and ClinicalTrials. gov was performed. Studies comparing antibiotics versus no antibiotics in the treatment of AUD were included. Meta-analysis was performed using the random effects model with the primary outcome measure being diverticulitis-associated complications. Secondary outcomes were readmission rate, diverticulitis recurrence, mean hospital stay, requirement for surgery and requirement for percutaneous drainage., Results: Eight studies were included involving 2469 patients; 1626 in the non-antibiotic group (NAb) and 843 in the antibiotic group (Ab). There was a higher complication rate in the Ab group however this was not significant (1.9% versus 2.6%) with a combined risk ratio (RR) of 0.63 (95% CI, 0.25 to 1.57, p=0.32). There was a shorter mean length of hospital stay in the Nab group (standard mean difference of -1.18 (95% CI, -2.34 to -0.03 p= 0.04). There was no significant difference in readmission, recurrence and surgical intervention rate or requirement for percutaneous drainage., Conclusion: Treatment of AUD without antibiotics may be feasible with outcomes that are comparable to antibiotic treatment and with potential benefits for patients and the NHS. Large scale randomised multicentre studies are needed. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies.