Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile’s ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice

Afectación gastroduodenal como presentación inusual de la enfermedad de Crohn

It is relatively uncommon for Crohn’s disease to implicate the gastric and duodenal regions and occasionally it can cause pyloric stenosis, in which medical therapy may be ineffective and surgery might be required. We report two exceptional cases with prepyloric stenosis secondary to Crohn’s disease, aiming to emphasize the clinical suspicion and to describe the diagnostic imaging procedure and surgical treatments.Es relativamente infrecuente que la enfermedad de Crohs afecte al estomago y duodeno y ocasionalmente puede producir estenosis pilórica, en estas situaciones el tratamiento médico suele ser ineficaz y se requiere tratamiento quirúrgico. Se exponen dos casos clínicos excepcionales de estenosis prepilórica asociada a la enfermedad de Crohn, dirigidos a enfatizar en la sospecha clínica y describir el diagnóstico y el tratamiento quirúrgico

Application of tissue engineering in perianal Crohn´s Disease

En este trabajo se ha realizado una revisión bibliográfica de los artículos más relevantes que han sido publicados en revistas científicas de impacto durante los últimos años con el objetivo de conocer las nuevas opciones terapéuticas en el tratamiento de las complicaciones fistulosas de la Enfermedad de Crohn que repercuten de forma importante en la calidad de vida de los pacientes que la padecen. Las Terapias Avanzadas en este campo, se centran en las células madre como nuevo enfoque en el tratamiento de las fístulas perianales de los enfermos de Crohn. Dentro de la Ingeniería Tisular, el método empleado es la transferencia de células que pueden proceder de diferentes fuentes (mesenquimales o hematopoyéticas) y con diferentes formas de aplicación (local o sistémica) además de distinto origen (alogénico o autólogo). Las células madre pueden obtenerse de tejido adiposo, médula ósea o de origen hematopoyético. La forma más frecuente empleada es a partir de tejido adiposo alogénico administrándolas de forma local en el trayecto de la fístula ya que de esta manera existen menos efectos adversos y la obtención tiene menor morbimortalidad en comparación con el resto de métodos. Las células de origen hematopoyético, hasta hoy, tienen un número relativamente elevado de efectos adversos que no las convierten en una opción aceptable en el tratamiento de estas complicaciones. Actualmente, a pesar de ser una opción de tratamiento aparentemente eficaz y segura, son necesarios más estudios que impliquen mayor número de pacientes con muestras más homogéneas y con un seguimiento mayor en el tiempo.In this work we have reviewed the most relevant articles that have been published in scientific journals of great impact for the last years in order to know the new therapeutic options in the treatment of the fistulous complications in Crohn's Disease, which widely affect to the quality of life in those patients who suffer from it. Advanced Therapies in this field focus on stem cells as a new approach in the treatment of perianal fistulas of Crohn's patients. Within Tissue Engineering, the method used is the transfer of cells that can come from different sources (mesenchymal or hematopoietic) and with different ways of application (local or systemic) as well as from different origin (allogeneic or autologous). Stem cells can be obtained from adipose tissue, bone marrow or hematopoietic origin. The most frequent form used is from allogenic adipose tissue, administering them locally in the path of the fistula since, this way, there are fewer adverse effects and its obtaining has lower morbidity and mortality compared to the rest of the methods. Cells of hematopoietic origin, up to now, have a relatively high number of adverse effects that do not make them an acceptable option in the treatment of these complications. Currently, despite being an apparently effective and safe treatment, it is completely necessary to have more patients with more homogeneous samples and a longer follow-up over time

The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

Preliminary data of this work were presented by RCM and awarded at the 2009 Annual Meeting of the Spanish Society of Coloproctology (AECP) held in Barcelona.Background: We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). Methods: The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. Results: Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions: We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accuratelyFounded by the Fundación Investigación Mutua Madrileña. We are indebted to M. Expósito Ruiz for statistical support. and to J-L Marín Aznar for pathologic analysisYe

Microarray profiling of mononuclear peripheral blood cells identifies novle candidate genes related to chemoradiation response in rectal cancer

Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1–2 and downstaging being defined as responders and patients with grade 3–5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced rectal cancer. Moreover, our investigation added further evidence to the importance of mononuclear cells’ mediated response in the neoadjuvant treatment of rectal cancer.This investigation was supported by the Fundación Investigación Biomédica Mutua Madrileña. MC, CC and AB were supported by projects P08-TIC-4299 and CTS2200 of Junta de Andalucía, TIN2009-13489 of DGICT, Madrid, and GREIB PYR_2010-02 and 2010_05 of University of Granada

Firmas Génicas de respuesta al tratamiento neoadyuvante en el cáncer de recto

Tesis Univ. Granada. Departamento de Cirugía y sus Especialidade

Preventing parastomal hernias with systematic intraperitoneal specifically designed mesh

Abstract Background Parastomal hernia is a very common complication after stoma formation. Current surgical techniques for repairing parastomal hernia have unsatisfactory results. We aim to assess our preliminary experience with prophylactic mesh placement at the time of stoma formation. Methods Data were prospectively recorded. A specifically designed mesh made of polyvinyl fluoride with central conduit (Dynamesh IPST®) was fixed using an intra-peritoneal onlay technique. Safety was evaluated by means of surgical data and frequency of mesh-related complications, efficacy by the rate of parastomal hernias. Results Thirty-four patients were included in the study. Three of them died before a year of follow up (not related to the stoma), so they were excluded. The other 31 patients (11 women and 20 men) were prospectively followed up after different pathologies resulting in a permanent colostomy. Twelve months after surgery CT-Scan imaging revealed two (6.4%) parastomal hernias, one of them already clinically suspected. During the follow up, 29% of the patients (n = 9) developed another type of hernia (incisional, inguinal or both). In five patients (16.1%) a light stomal retraction of the otherwise slightly prominent ostomy was observed. Median clinical follow-up was 17.5 months (range 12–34). Conclusion Prophylactic parastomal mesh placement might be a safe and effective procedure with a potential to reduce the risk of parastomal hernia. Routine use of this technique should be further analysed

The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

Abstract Background We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). Methods The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. Results Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately.</p

Patients and tumour characteristics.

<p>CRT: Chemoradiation; Cap: Capecitabine; Capox: Capecitabine and Oxaliplatine; cTN: clinical stage, Surg: surgical technique, LAR: Low anterior resection, APR: Abdmino-perineal resection; HART: Hartmann, TRG: Tumor Regression Grade; Downst: Downstaging; Resp: response, Leuc: leucocytes (×10³×ml), Lymp: lymphocytes (%).</p