The role of surgery in the palliation of advanced pelvic malignancy.

Advanced pelvic malignancy, regardless of the cancer of origin, is often multivisceral and complex. The management of advanced pelvic malignancy is resource-intensive and requires multidisciplinary input. The definition of resectability is evolving with improving multimodal therapy, preoperative staging and optimisation, perioperative care, and advanced surgical techniques. Pelvic exenteration is a highly morbid procedure and has been shown to improve survival and quality of life when performed with a curative intent. Unresectable distant solid organ or lymph node metastases and an inability to achieve a clear resection margin preclude curative pelvic exenteration. Patients with advanced pelvic malignancy who are deemed palliative are mostly managed by non-operative treatment such as chemo-, radio-, immuno-, hormonal therapy, pain management and palliative care, as well as allied health and psychosocial support team. These patients may present with severe and debilitating symptoms including intractable pain, ulcerating/proliferating tumour, pelvic fistula/sepsis/bleeding, urinary and bowel obstruction/incontinence. Interventional radiological and surgical procedures such as percutaneous drainage, nephrostomy, intestinal and urinary diversion, intestinal bypass, and venting gastrostomy have an important role in symptom control and improving quality of life. Palliative pelvic exenteration should be carefully considered along with life expectancy, patient wishes and tumour characteristics. Comprehensive discussion with patient is crucial to achieve realistic expectations. These patients should not only be discussed in a multidisciplinary team meeting with palliative care input, but also be referred for a formal palliative care consultation. Tumour anatomical extent should be considered both for and against pelvic exenteration whether involving the posterior compartment i.e. sacrectomy; lateral compartment incorporating neurovascular bundle and the anterior compartment requiring pubic bone excision as all can be associated with high morbidity rates. Patient recovery may be protracted too if surgery is complicated by perineal wound or flap breakdown in cases necessitating wide perineal skin and soft tissue excision. Furthermore, evidence from quality of life and cost-effectiveness studies do not provide robust data to support pelvic exenteration with palliative intent. Whilst a relatively 'straightforward' central soft tissue pelvic exenteration may offer reasonable symptomatic relief in a patient with an acceptable life expectancy, palliative pelvic exenteration overall should only be considered in highly selected patients.

Excellent Outcomes After Extended Radical Pelvic Resection for Locally Advanced and Recurrent IBD-Associated Anorectal Cancer.

BACKGROUND: Anorectal cancer arising in IBD can be challenging to manage. There is a paucity of reports describing locally advanced and recurrent anorectal cancer in this setting. OBJECTIVE: This study aimed to describe patients who underwent extended radical pelvic resection for locally advanced and recurrent IBD-associated anorectal cancer. DESIGN: This is a retrospective review of a prospectively maintained database of extended radical pelvic resection. SETTINGS: This study was conducted at a quaternary pelvic malignancy referral center. PATIENTS: All of the patients who underwent extended radical pelvic resection for IBD-associated anorectal cancer between September 1994 and September 2019 were included. MAIN OUTCOME MEASURES: Demographic, operative, and oncologic outcomes were assessed. RESULTS: Ten patients (1.3%) were identified of 765 (6 men; median age = 51 y). The average time from the diagnosis of IBD to cancer was 23 years. Five patients had surgery for primary cancer previously. All of the patients had previous complex abdominal and perineal surgical interventions. There were 7 adenocarcinomas and 3 squamous cell carcinomas. Nine underwent pelvic exenteration and 1 rectal resection with radical vaginectomy. The median operating time, intraoperative blood loss, and blood transfusion were 698 minutes, 1.8 L, and 4.5 units. The median hospital stay was 24 days. The operative mortality and morbidity rates were 0% and 60%. At a median follow-up of 51.3 months, 7 patients remained alive and free of cancer. LIMITATIONS: This is a retrospective study of a small number of patients. CONCLUSIONS: Extended radical pelvic resection offers a potential cure for locally advanced and recurrent IBD-associated anorectal cancer with acceptable operative mortality and morbidity rates. A high index of suspicion is required to achieve early diagnosis. Multiple factors need to be considered in the multimodal treatment of such complex patients. See Video Abstract at http://links.lww.com/DCR/B418. EXCELENTES RESULTADOS DESPUS DE LA RESECCIN PLVICA RADICAL EXTENDIDA POR CNCER ANORRECTAL RECURRENTE Y LOCALMENTE AVANZADA, ASOCIADA A ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:Cáncer anorrectal surgiendo de la enfermedad inflamatoria intestinal, puede ser difícil de manejar. Hay escasez de informes que describan el cáncer anorrectal localmente avanzado y recurrente en este contexto.OBJETIVO:El estudio tiene como objetivo, describir a los pacientes que se sometieron a resección pélvica radical extendida por cáncer anorrectal recurrente y localmente avanzada, asociada con enfermedad inflamatoria intestinal.DISEÑO:Esta es una revisión retrospectiva, de una base de datos mantenida prospectivamente de resección pélvica radical extendida.AJUSTES:El estudio se realizó en un centro de referencia cuaternaria en malignidad pélvica.PACIENTES:Se incluyeron a todos los pacientes sometidos a resección pélvica radical ampliada por cáncer anorrectal, asociada a enfermedad inflamatoria intestinal entre septiembre de 1994 y septiembre de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron los resultados demográficos, quirùrgicos y oncológicos.RESULTADOS:Diez pacientes (1.3%) fueron identificados de 765 (seis masculinos; mediana de edad 51 años). El tiempo promedio desde el diagnóstico de la enfermedad inflamatoria intestinal hasta el cáncer, fue de 23 años. Cinco pacientes fueron previamente sometidos a cirugía por cáncer primario. Todos los pacientes tuvieron previamente, intervenciones quirúrgicas abdominales y perineales complejas. Hubo siete adenocarcinomas y tres carcinomas de células escamosas. Nueve se sometieron a exenteración pélvica y una a resección rectal con vaginectomía radical. La mediana del tiempo de operación, pérdida de sangre intraoperatoria y transfusión sanguínea, fueron 698 minutos, 1.8 litros y 4.5 unidades respectivamente. La mediana de la estancia hospitalaria fue de 24 días. Las tasas de mortalidad y morbilidad operatoria fueron 0% y 60% respectivamente. En una mediana de seguimiento de 51,3 meses, siete pacientes permanecieron vivos y libres de cáncer.LIMITACIONES:Es un estudio retrospectivo con número pequeño de pacientes.CONCLUSIONES:La resección pélvica radical extendida, ofrece una cura potencial para el cáncer anorrectal recurrente y localmente avanzada, asociada a0 enfermedad inflamatoria intestinal y con tasas aceptables de mortalidad y morbilidad operatoria. Se requiere un alto índice de sospecha para obtener un diagnóstico temprano. Se deben considerar múltiples factores en el tratamiento multimodal de pacientes tan complejos. Consulte Video Resumen en http://links.lww.com/DCR/B418. (Traducción-Dr Fidel Ruiz Healy).

Propensity score-matched analysis comparing laparoscopic to robotic surgery for colorectal cancer shows comparable clinical and oncological outcomes.

Robotic colorectal surgery is gaining popularity. The objective of this study was to compare clinical and cancer outcomes in propensity-score matched cohorts (PSM-1:1) undergoing colorectal cancer (CRC) surgery performed using laparoscopic or robotic surgery in a single institution. A PSM cohort comparison was performed in a tertiary referral cancer and National accredited rectal cancer surgery centre. Patients with CRC undergoing laparoscopic or robotic resection with curative intent from 2016 to 2019 (inclusive) were assessed for inclusion. Matched cohorts were selected using a 1:1 ratio. Statistical analysis was performed using SPSS, version 22. 128 patients were analysed [laparoscopic (n = 64); robotic (n = 64)]. Median age was 64 years (29-84 years). 55% (n = 70) of patients were male, 45% female (n = 58). SSI rates were slightly lower in the robotic group [10.9% (n = 7) v 12.5% (n = 8) p = 0.40]. Anastomotic leak rates were equal in both groups [5.4% (n = 3)]. All but one patient received an R0 resection in each group, median LNY was 14 in the robotic group and 12 in the laparoscopic group (p = 0.004) and no difference in disease recurrence (p = 0.465) or survival (p = 0.886) was observed. Structured introduction of a robotic colorectal programme over a 3-year period has resulted in equivalent outcomes with an established laparoscopic programme for CRC.

Lymphovascular invasion: a comprehensive appraisal in colon and rectal adenocarcinoma.

BACKGROUND: Colon and rectal adenocarcinomas differ at a multitude of levels. The association between outcome and predictor in 1 group may obscure the relationship between outcome and predictor in the other. OBJECTIVE: The current study aims to evaluate the prognostic properties of lymphovascular invasion in colon and rectal adenocarcinoma separately. MATERIALS AND METHODS (DESIGN, SETTING AND PATIENTS): A comparative retrospective analysis was undertaken to determine the prognostic properties of lymphovascular invasion in colon and rectal adenocarcinomas. Patients were classified as lymphovascular invasion positive and lymphovascular invasion negative in separate colon and rectal cancer cohorts. Within cohorts, a univariate analysis was undertaken to determine the association between lymphovascular invasion positivity and local/systemic recurrence and overall/disease-free survival. Findings were evaluated by using Kaplan-Meier estimates, log-rank analysis, and a Cox proportional hazards multivariate model. MAIN OUTCOME MEASURE: The primary outcomes measured were overall and disease-free survival. RESULTS: Five hundred twenty-seven patients were included in the analysis (379 with colon cancer and 148 with rectal cancer). On univariate analysis, lymphovascular invasion positivity was associated with adverse locoregional recurrence in colon (p = 0.002) but not rectal adenocarcinoma (p = 0.13). Conversely, lymphovascular invasion positivity was associated with adverse systemic recurrence in rectal (p = 0.002) but not colon adenocarcinoma (p = 0.35). On multivariate analysis, lymphovascular invasion positivity was an independent predictor of adverse disease-free survival in colon (p = 0.02) and rectal adenocarcinoma (p < 0.001). Regarding overall survival, lymphovascular invasion positivity was a poor prognostic indicator in rectal adenocarcinoma only (p = 0.04). LIMITATIONS AND CONCLUSIONS: In this retrospective analysis, lymphovascular invasion positivity was associated with different patterns of disease recurrence in colon and rectal cancer. Lymphovascular invasion positivity was associated with adverse overall survival in rectal cancer only.

Aerosolized intraperitoneal local anesthetic for laparoscopic surgery: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Postoperative pain remains a significant challenge following laparoscopy. Aerosolized intraperitoneal local anesthetic (AILA) is a novel method to deliver local anesthetic. The aim was to evaluate aerosolized ropivacaine in pain management following laparoscopic Nissen fundoplication (LNF) and cholecystectomy (LC). METHODS: This prospective randomized double-blinded placebo-controlled trial enrolled consecutive patients undergoing LNF and LC. The treatment group (TG) received intraperitoneal ropivacaine (5 mL 1 % Naropin(®)) at CO2 insufflation via the AeroSurge(®) aerosolizer device through the camera port. The control group (CG) received 5 mL of saline in the same manner. Postoperative shoulder tip pain at rest 6 h postoperatively was the primary study endpoint, with secondary endpoints of shoulder and abdominal pain within the first 24 h, recovery room stay, hospital stay, and postoperative analgesia use. Pain scores were collected using the Verbal Rating Score. RESULTS: Eighty-seven patients were included in the final analysis (TG n = 40, CG n = 47). There was no significant difference between CG and TG at the primary endpoint. In the LC group, AILA significantly reduced shoulder tip pain at rest at 10 (p = 0.030) and 30 min (p = 0.040) and shoulder tip pain on movement at 10 (p = 0.030) and 30 min (p = 0.037). In the LNF group, AILA significantly reduced postoperative abdominal pain at rest at 6 h (p = 0.009). AILA reduced overall incidence of shoulder tip pain in the LC group (11.8 vs. 57.9 %, p = 0.004). CONCLUSION: This study did not demonstrate a significant difference between TG and CG in the primary endpoint, pain at 6 h postoperatively.

Massive carotid artery aneurysm presenting as an oropharyngeal swelling in a young woman.

A 28-year-old woman presented to the emergency department with a 5-day history of a sore throat and a pharyngeal swelling that increased in size. The patient was previously investigated for Marfan's syndrome after episodes of bilateral spontaneous pneumothoraces but did not meet the criteria for diagnosis. Examination revealed a large pulsatile lesion in the oropharynx. CT angiography revealed an internal carotid artery aneurysm. The patient underwent a successful urgent open repair of the aneurysm with a primary arterio-arterial anastomosis without a patch. Histopathology of the aneurysmal sac revealed cystic medial degeneration.

Emergency presenting colon cancer is an independent predictor of adverse disease-free survival.

Twenty percent of colon cancers present as an emergency. However, the association between emergency presentation and disease-free survival (DFS) remains uncertain. Consecutive patients who underwent elective (CC) and emergent (eCC) resection for colon cancer were included in the analysis. Survival outcomes were compared between the 2 groups in univariate/multivariate analyses. A total of 439 patients underwent colonic resection for colon cancer during the interval 2000-2010; 97 (22.1%) presented as an emergency. eCC tumors were more often located at the splenic flexure (P = 0.017) and descending colon (P = 0.004). The eCC group displayed features of more advanced disease with a higher proportion of T4 (P = 0.009), N2 tumors (P < 0.01) and lymphovascular invasion (P< 0.01). eCC was associated with adverse locoregional recurrence (P = 0.02) and adverse DFS (P < 0.01 ) on univariate analysis. eCC remained an independent predictor of adverse locoregional recurrence (HR 1.86, 95% CI 1.50-3.30, P = 0.03) and DFS (HR 1.30, 95% CI 0.88-1.92, P = 0.05) on multivariate analysis. eCC was not associated with adverse overall survival and systemic recurrence. eCC is an independent predictor of adverse locoregional recurrence and DFS.

The effect of hysterectomy on colonoscopy completion: a systematic review and meta-analysis.

BACKGROUND: The primary aim of colonoscopy is a complete and thorough examination of the colon. There are a number of factors, however, that can potentially increase the difficulty of completing a colonoscopy. A significant proportion of women eligible for colorectal cancer screening have undergone hysterectomy. A history of hysterectomy is frequently considered to make colonoscopy more difficult, although there is no consensus in the literature. OBJECTIVE: The aim of this study is to assess the effect of hysterectomy on colonoscopy completion. DATA SOURCES: A systematic search of PubMed, Embase, and the Cochrane database identified 6 eligible studies. STUDY SELECTION: Studies that compared colonoscopy completion rates in women with a previous history of hysterectomy and women with no history of pelvic surgery were selected for review. INTERVENTION: Meta-analysis was performed by using random-effects methods. MAIN OUTCOME MEASURES: The primary outcome used was colonoscopy completion rate. The outcomes were calculated as odds ratio with 95% CI. RESULTS: A total of 5947 patients were included in the final analysis. The average hysterectomy rate was 26.3% ± 14.5%. The colonoscopy completion rate was significantly reduced in patients with a history of hysterectomy compared with those with no history of pelvic surgery (87.1% vs 95.5%) (OR, 0.28; 95% CI, 0.16-0.49; p < 0.001). Analysis of the funnel plot demonstrated nonsignificant across-study publication bias. There was significant across-study heterogeneity (Cochran Q, 19.6; p = 0.002). LIMITATIONS: The endoscopist's experience is poorly defined in some studies. Indication for colonoscopy was not provided in all cases. There is significant across-study heterogeneity. CONCLUSION: Colonoscopy completion rates appear decreased in women with a history of hysterectomy, but the available literature is heterogenous. Further studies in this area are warranted.

Total systemic ropivacaine concentrations following aerosolized intraperitoneal delivery using the AeroSurge.

STUDY OBJECTIVE: To evaluate intraperitoneal ropivacaine delivery with the AeroSurge device in the clinical setting and to evaluate the total systemic ropivacaine levels achieved following delivery of 50 mg of aerosolized ropivacaine. DESIGN: Preliminary, prospective, nonrandomized study. SETTING: Operating room of a university hospital. PATIENTS: 5 consecutive ASA physical status 1 and 2 patients undergoing elective laparoscopic Nissen fundoplication or cholecystectomy. INTERVENTION: Five mL of 1% ropivacaine was delivered through the 10 mm port using the AeroSurge device at peritoneal insufflation. MEASUREMENTS: Venous blood samples were collected and total ropivacaine concentration was determined using liquid chromatography-mass spectrometry. MAIN RESULTS: The AeroSurge device delivered ropivacaine, visible as mist within the peritoneal cavity. Peak concentration (Cmax) was attained between 10 and 30 minutes following the end of aerosolized ropivacaine delivery. At no stage did any level approach toxic levels. CONCLUSIONS: This preliminary study confirms that aerosolized intraperitoneal local anesthetic is feasible, with ropivacaine concentrations remaining within safe levels.

Mismatch repair protein expression in colorectal cancer.

INTRODUCTION: Alterations in at least six of the genes that encode proteins involved in the mismatch repair (MMR) system have been identified in either HNPCC or sporadic colon cancer. We aimed to analyse the proportion of patients with colorectal cancer with loss of immunostaining for MMR proteins in order to determine the feasibility of molecular screening for the loss of MMR proteins through the study of unselected patients with colorectal cancer. METHODS: A group of 33 patients with colorectal cancer was randomly selected from the department of surgery bio-bank to determine the expression of MMR proteins in their FFPE tumour tissues using immunohistochemistry techniques. Changes in protein expression following transfection of colorectal tissues were observed in stained cells using Olympus BX60 microscope and image analySIS software. RESULTS: Of the tissue specimens in which acceptable immunostaining was achieved, three samples showed loss of one or more of the MMR proteins. Both hMLH1 and hPMS2 proteins were not expressed in a 36 years old woman with cancer of the caecum. The expression of hMSH6 protein was undetermined in tumour tissues retrieved from a 61 years old man with cancer of the proximal colon. The third case was a 77 years old man with no documented family history of cancer, who had carcinoma of the rectum. He showed loss of hMLH1 expression in the tumour tissues. CONCLUSIONS: Our findings and the previous reports pointed out the importance of molecular screening of patients with colorectal cancer for MSI using immunohistochemistry. This strategy managed to identify mutations in patients otherwise would not have been detected.

Clinical applications of gene expression in colorectal cancer.

BACKGROUND: Despite developments in diagnosis and treatment, 20% of colorectal cancer (CRC) patients present with metastatic disease and 30% of cases recur after curative surgery. Furthermore, the molecular factors involved in prognosis and response to therapy in CRC is poorly understood. The aims of this study were to quantitatively examine the expression of target genes in colorectal cancer and to correlate their expression levels with clinico-pathological variables. METHODS: A detailed analysis of published CRC microarray data was performed to identify the most prominent genes. The selected genes were validated in fifty-two pairs of fresh colorectal tumour and associated normal tissue specimens by RQ-PCR using TaqMan(®) assays. Statistical analysis and correlation with clinicopathological data was performed using SPSS software. RESULTS: Expression levels of CXCL12 (P=0.000), CDH17 (P=0.026), MUC2 (P=0.000), L-FABP (P=0.000) and PDCD4 (P=0.000) were down regulated and IL8 (P=0.000) was upregulated in tumours compared to normal colorectal tissues. No significant differences were noted in expression of CEACAM5, CXCR4, CXCR7, TGFB1, TGFBR1 and TGFBR2. Furthermore, we found significant associations of gene expression levels and clinicopathological variables such as tumour size, grade, invasion and lymph node status. CONCLUSIONS: We identified a comprehensive list of genes with highly differential expression patterns in colorectal cancer that could serve as molecular markers to complement existing histopathological factors in diagnosis, follow up and therapeutic strategies for individualised care of patients.

Coexistent widespread small intestinal and colonic diverticular disease.

A 73-year-old woman with a history of multiple abdominal surgery and sigmoid diverticulosis presented with severe constipation refractory to conservative management. As a result, she had developed food aversion and cachexia. Patient opted for laparotomy and defunctioning ileostomy to improve quality of life. At laparotomy, extensive diverticulae involving the small and large bowels were identified. Defunctioning ileostomy was performed. The patient regained her quality of life and reinstituted normal diet. Histology revealed marked serosal fibrosis and pulsion diverticulae.

miRNA expressions in rectal cancer as predictors of response to neoadjuvant chemoradiation therapy.

INTRODUCTION: Neoadjuvant chemoradiation therapy has been shown to improve the outcome in patients with rectal cancer and is generally accepted as standard care; however, only selected patients would benefit from this treatment. We aimed to identify predictors of response to neoadjuvant chemoradiation therapy in colorectal cancer using formalin-fixed paraffin-embedded (FFPE) tissues as source of genetic materials and microarray analysis as investigation tool. METHODS: After optimization of RNA extraction methods from FFPE, microarray analysis was carried out on total RNA extracted from 12 pre-treatment FFPE rectal tissues using Megaplex pool A. Microarray data were analysed using an artificial neural network algorithm. Statistical analysis and correlation with clinicopathological data was performed using SPSS software. RESULTS: A distinct miRNA expression signature predictive of response to neoadjuvant CRT in 12 FFPE pre-treatment rectal cancer tissue samples was identified. These signatures consisted of three miRNA transcripts (miR-16, miR-590-5p and miR-153) to predict complete vs. incomplete response and two miRNA transcript (miR-519c-3p and miR-561) to predict good vs. poor response with a median accuracy of 100 %. CONCLUSION: Using microarray analysis of pretreatment FFPE rectal cancer tissues, we identified for the first time a group of miRNA predictors of response to neoadjuvant CRT. This, indeed, can lead to a significant improvement in patient selection criteria and personalized rectal cancer management.

Infliximab versus cyclosporine as rescue therapy in acute severe steroid-refractory ulcerative colitis: a systematic review and meta-analysis.

PURPOSE: Acute severe colitis affects 25 % of patients with ulcerative colitis (UC). Up to 30-40 % of these patients are resistant to intensive steroid therapy and therefore require rescue therapy to prevent emergent colectomy. Data comparing rescue therapy using infliximab and cyclosporine are limited and equivocal. This study evaluates the outcomes of UC patients receiving infliximab or cyclosporine as rescue therapy in acute severe steroid-refractory exacerbations. METHODS: Electronic databases (PubMed, EMBASE, and Cochrane database) were searched for studies directly comparing infliximab and cyclosporine in UC, and references of included studies were screened. Two independent reviewers identified relevant studies and extracted data. Meta-analyses were performed using the random effect model. Outcome measures included 3- and 12-month colectomy rates, adverse drug reactions, and postoperative complications. RESULTS: Six retrospective cohort studies describing 321 patients met the inclusion criteria. The meta-analysis did not show significant differences between infliximab and cyclosporine in the 3-month colectomy rate (odds ratio (OR) = 0.86, 95 % confidence interval (CI) = 0.31-2.41, p = 0.775), in the 12-month colectomy rate (OR = 0.60, 95 % CI = 0.19-1.89, p = 0.381), in adverse drug reactions (OR = 0.76, 95 % CI = 0.34-1.70, p = 0.508), and in postoperative complications (OR = 1.66, 95 % CI = 0.26-10.50, p = 0.591). Funnel plot revealed no publication bias. CONCLUSIONS: Infliximab and cyclosporine are comparable when used as rescue therapy in acute severe steroid-refractory UC. Randomized trials are required to further evaluate these agents.

Increased use of multidisciplinary treatment modalities adds little to the outcome of rectal cancer treated by optimal total mesorectal excision.

PURPOSE: Total mesorectal excision (TME) is the standard surgical treatment for rectal cancer. The roles of chemotherapy and radiotherapy have become more defined, accompanied by improvements in preoperative staging and histopathological assessment. We analyse our ongoing results in the light of changing patterns of treatment over consecutive time periods. METHODS: In total, 151 consecutive patients underwent potentially curative rectal excision for cancer in a single institution. Management and outcomes were compared between 1993-1999 and 2000-2007 which corresponded with the restructuring of the regional oncological services. RESULTS: We found an increase in patients treated with neoadjuvant chemoradiotherapy after 1999 (20/89 vs 1/62, p < 0.001). There was an increase in the mean number of lymph nodes examined (11.9 vs 9.4, p = 0.037). The locoregional recurrence rate was 5.3%. The rates were not significantly different between the two study periods [4/89 (4.5%) 1999-2007 vs 4/62 (6.5%) 1993-1999, p = 0.597]. There was no statistical difference in overall or disease-free survival in the time periods examined. CONCLUSIONS: Increasing use of neoadjuvant therapy and concomitant improvement in lymph node assessment did not translate into a concurrent reduction in the local recurrence, disease-free and overall survival rates. Our results demonstrate the enduring benefit of specialist training in TME in the outcome of rectal cancer surgery. This observational study suggests that low local recurrence rates are surrogate markers for improved overall and disease-free survival. Multidisciplinary team practice should be examined and made cost effective according to the individual unit's local recurrence rate in the light of this and other reports.

MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease.

PURPOSE: Colorectal cancer (CRC) is a clinically diverse disease whose molecular etiology remains poorly understood. The purpose of this study was to identify miRNA expression patterns predictive of CRC tumor status and to investigate associations between microRNA (miRNA) expression and clinicopathological parameters. METHODS: Expression profiling of 380 miRNAs was performed on 20 paired stage II tumor and normal tissues. Artificial neural network (ANN) analysis was applied to identify miRNAs predictive of tumor status. The validation of specific miRNAs was performed on 102 tissue specimens of varying stages. RESULTS: Thirty-three miRNAs were identified as differentially expressed in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p, miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease. Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced expression of miR-143 (p = 0.016) were associated with aggressive mucinous phenotype. Increased expression of miR-10b was also associated with mucinous tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b expression were observed from T1 to T4 lesions and from stage I to IV disease. CONCLUSION: Association of specific miRNAs with clinicopathological features indicates their biological relevance and highlights the power of ANN to reliably predict clinically relevant miRNA biomarkers, which it is hoped will better stratify patients to guide adjuvant therapy.

Complementary and alternative medicine use in oncology: a questionnaire survey of patients and health care professionals.

BACKGROUND: We aimed to investigate the prevalence and predictors of Complementary and Alternative Medicine (CAM) use among cancer patients and non-cancer volunteers, and to assess the knowledge of and attitudes toward CAM use in oncology among health care professionals. METHODS: This is a cross-sectional questionnaire survey conducted in a single institution in Ireland. Survey was performed in outpatient and inpatient settings involving cancer patients and non-cancer volunteers. Clinicians and allied health care professionals were asked to complete a different questionnaire. RESULTS: In 676 participants including 219 cancer patients; 301 non-cancer volunteers and 156 health care professionals, the overall prevalence of CAM use was 32.5% (29.1%, 30.9% and 39.7% respectively in the three study cohorts). Female gender (p < 0.001), younger age (p = 0.004), higher educational background (p < 0.001), higher annual household income (p = 0.001), private health insurance (p = 0.001) and non-Christian (p < 0.001) were factors associated with more likely CAM use. Multivariate analysis identified female gender (p < 0.001), non-Christian (p = 0.001) and private health insurance (p = 0.015) as independent predictors of CAM use. Most health care professionals thought they did not have adequate knowledge (58.8%) nor were up to date with the best evidence (79.2%) on CAM use in oncology. Health care professionals who used CAM were more likely to recommend it to patients (p < 0.001). CONCLUSIONS: This study demonstrates a similarly high prevalence of CAM use among oncology health care professionals, cancer and non cancer patients. Patients are more likely to disclose CAM usage if they are specifically asked. Health care professionals are interested to learn more about various CAM therapies and have poor evidence-based knowledge on specific oncology treatments. There is a need for further training to meet to the escalation of CAM use among patients and to raise awareness of potential benefits and risks associated with these therapies.

MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer.

BACKGROUND: Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. METHODS: We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. RESULTS: In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. CONCLUSIONS: Our study demonstrates that the top six most stably expressed miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) described herein should be validated as suitable reference genes in both high-throughput and lower throughput RT-qPCR colorectal miRNA studies.

Identification of endogenous control genes for normalisation of real-time quantitative PCR data in colorectal cancer.

BACKGROUND: Gene expression analysis has many applications in cancer diagnosis, prognosis and therapeutic care. Relative quantification is the most widely adopted approach whereby quantification of gene expression is normalised relative to an endogenously expressed control (EC) gene. Central to the reliable determination of gene expression is the choice of control gene. The purpose of this study was to evaluate a panel of candidate EC genes from which to identify the most stably expressed gene(s) to normalise RQ-PCR data derived from primary colorectal cancer tissue. RESULTS: The expression of thirteen candidate EC genes: B2M, HPRT, GAPDH, ACTB, PPIA, HCRT, SLC25A23, DTX3, APOC4, RTDR1, KRTAP12-3, CHRNB4 and MRPL19 were analysed in a cohort of 64 colorectal tumours and tumour associated normal specimens. CXCL12, FABP1, MUC2 and PDCD4 genes were chosen as target genes against which a comparison of the effect of each EC gene on gene expression could be determined. Data analysis using descriptive statistics, geNorm, NormFinder and qBasePlus indicated significant difference in variances between candidate EC genes. We determined that two genes were required for optimal normalisation and identified B2M and PPIA as the most stably expressed and reliable EC genes. CONCLUSION: This study identified that the combination of two EC genes (B2M and PPIA) more accurately normalised RQ-PCR data in colorectal tissue. Although these control genes might not be optimal for use in other cancer studies, the approach described herein could serve as a template for the identification of valid ECs in other cancer types.