Alan Askari

Forty-Year Analysis of Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis: An Updated Overview.

Objectives:This study provides an overview of the largest and longest-running colonoscopic surveillance program for colorectal cancer (CRC) in patients with long-standing ulcerative colitis (UC).Methods:Data were obtained from medical records, endoscopy, and histology reports. Primary end points were defined as death, colectomy, withdrawal from surveillance, or censor date (1 January 2013).Results:A total of 1,375 UC patients were followed up for 15,234 patient-years (median, 11 years per patient). CRC was detected in 72 patients (incidence rate (IR), 4.7 per 1,000 patient-years). Time-trend analysis revealed that although there was significant decrease in incidence of colectomy performed for dysplasia (linear regression, R=−0.43; P=0.007), IR of advanced CRC and interval CRC have steadily decreased over past four decades (Pearson’s correlation, −0.99; P=0.01 for both trends). The IR of early CRC has increased 2.5-fold in the current decade compared with past decade (χ2, P=0.045); however, its 10-year survival rate was high (79.6%). The IR of dysplasia has similarly increased (χ2, P=0.01), potentially attributable to the recent use of chromoendoscopy that was twice more effective at detecting dysplasia compared with white-light endoscopy (χ2, P<0.001). CRCs were frequently accompanied by synchronous CRC or spatially distinct dysplasia (37.5%). Finally, the risk of CRC was not significantly different between “indefinite” or low-grade dysplasia (log-rank, P=0.78).Conclusions:Colonoscopic surveillance may have a significant role in reducing the risk of advanced and interval CRC while allowing more patients to retain their colon for longer. Given the ongoing risk of early CRC, patients with any grade of dysplasia who are managed endoscopically should be monitored closely with advanced techniques.

Is right-sided colon cancer different to left-sided colorectal cancer? – A systematic review

Colorectal cancer (CRC) exhibits differences in incidence, pathogenesis, molecular pathways and outcome depending on the location of the tumor. This review focuses on the latest developments in epidemiological and scientific studies, which have enhanced our understanding on the underlying genetic and immunological differences between the proximal (right-sided) colon and the distal (left-sided) colorectum. The different ways in which environmental risk factors influence the pathogenesis of CRC depending on its location and the variations in surgical and oncological outcomes are also discussed in this review. In the current era of personalized medicine, we aim to reiterate the importance of tumor location in management of CRC and the implication on future clinical and scientific research.

A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival after curative elective colorectal cancer surgery.

Objective:This study aims to determine the role of the neutrophil to lymphocyte ratio (NLR) as a prognostic marker for patients with nonmetastatic colorectal cancer undergoing curative resection. Background:An NLR reflects a systematic inflammatory response, with some evidence suggesting that an elevated preoperative NLR of more than 5.0 is associated with poorer survival in patients with colorectal cancer. Methods:Data from 506 consecutive patients with a diagnosis of nonmetastatic colorectal adenocarcinoma undergoing surgical resection between 2006 and 2011 were included. Receiver operating characteristic curve analysis was used to identify the optimal value for NLR in relation to disease-free and overall survival. Univariate and multivariate Cox regression models were used to determine the role of NLR after stratification by several clinicopathological factors. Patients were followed by a standardized protocol until February 2013. Results:Median follow-up was 45 months [interquartile range, 21–65]. Multivariate Cox regression analysis identified an NLR of more than 3 as an independent prognostic factor for disease-free survival (odds ratio = 2.41; 95% confidence interval = 1.12–5.15; P = 0.024) but not for overall survival (odds ratio = 1.23; 95% confidence interval = 0.80–1.90; P = 0.347). A high NLR was significantly associated with older age, higher T and N stages, the presence of microvascular invasion, low preoperative albumin levels, and higher ASA (American Society of Anesthesiologists) status of the patient. Conclusions:For patients with colorectal cancer, a preoperative NLR of more than 3.0 may be an independent prognostic factor for disease-free survival. Considering this in addition to well-established prognostic variables may improve the processes of identifying patients at higher risk of recurrence who would benefit from adjuvant therapies or more frequent surveillance, thereby providing more personalized cancer care.

Low-Grade Dysplasia in Ulcerative Colitis: Risk Factors for Developing High-Grade Dysplasia or Colorectal Cancer

OBJECTIVES:The aim of this study was to identify risk factors associated with development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD).METHODS:Patients with histologically confirmed extensive UC, who were diagnosed with LGD between 1993 and 2012 at St Mark’s Hospital, were identified and followed up to 1 July 2013. Demographic, endoscopic, and histological data were collected and correlated with the development of HGD or CRC.RESULTS:A total of 172 patients were followed for a median of 48 months from the date of initial LGD diagnosis (interquartile range (IQR), 15–87 months). Overall, 33 patients developed HGD or CRC (19.1% of study population; 20 CRCs) during study period. Multivariate Cox proportional hazard analysis revealed that macroscopically non-polypoid (hazard ratio (HR), 8.6; 95% confidence interval (CI), 3.0–24.8; P<0.001) or invisible (HR, 4.1; 95% CI, 1.3–13.4; P=0.02) dysplasia, dysplastic lesions ≥1 cm in size (HR, 3.8; 95% CI, 1.5–13.4; P=0.01), and a previous history of “indefinite for dysplasia” (HR, 2.8; 95% CI, 1.2–6.5; P=0.01) were significant contributory factors for HGD or CRC development. Multifocal dysplasia (HR, 3.9; 95% CI, 1.9–7.8; P<0.001), metachronous dysplasia (HR, 3.5; 95% CI, 1.6–7.5; P=0.001), or a colonic stricture (HR, 7.4; 95% CI, 2.5–22.1; P<0.001) showed only univariate correlation to development of HGD or CRC.CONCLUSIONS:Lesions that are non-polypoid or endoscopically invisible, large (≥1 cm), or preceded by indefinite dysplasia are independent risk factors for developing HGD or CRC in UC patients diagnosed with LGD.

Management and Outcomes of Esophageal Perforation: A National Study of 2,564 Patients in England.

OBJECTIVES:Traditionally esophageal perforation is a rare clinical emergency that confers a high rate of mortality and major morbidity. The objective of this study was to establish the annual rate and mortality from esophageal perforation and determine the effect of hospital volume on clinical outcomes.METHODS:Hospital Episode Statistics database was used for the identification of patients admitted to hospitals within England with esophageal perforation between 2001 and 2012. The influence of hospital volume and treatment approach upon clinical outcomes was analyzed using multivariable analysis to control for patient age and medical comorbidities that may influence outcome.RESULTS:Over the 12-year study period 2,564 patients with esophageal perforation were treated at 158 hospitals. The 30- and 90-day mortality rates were 30.0 and 38.8%, respectively. Esophageal perforation etiology was spontaneous in 81.9% and iatrogenic in 5.9% of cases. There was a significant increase in the percentage of patients managed supportively and a reduction in surgical management over time. Furthermore there were significant reductions in 30-day (36.6% to 24.9%; P<0.001) and 90-day mortality (44.1% to 35.4%; P=0.006) over the 12-year study period. Important patient demographics associated with 30- and 90-day mortality included age ≥70 years, preoperative congestive cardiac failure, ischemic heart, liver, and renal disease. High hospital volume was associated with significant reductions in 30- (odds ratio (OR)=0.68; P=0.001) and 90-day mortality (OR=0.69; P=0.001). In a subset analysis of patients undergoing endoscopic intervention, hospital volume was identified as an important factor associated with mortality.CONCLUSIONS:This study provides evidence for the centralization of management of esophageal perforation to high volume centers with appropriate multi-disciplinary infrastructure to treat these complex patients.

National proficiency‐gain curves for minimally invasive gastrointestinal cancer surgery

Minimal access surgery for gastrointestinal cancer has short‐term benefits but is associated with a proficiency‐gain curve. The aim of this study was to define national proficiency‐gain curves for minimal access colorectal and oesophagogastric surgery, and to determine the impact on clinical outcomes.

Oncological outcomes of local excision compared with radical surgery after neoadjuvant chemoradiotherapy for rectal cancer: a systematic review and meta-analysis

BackgroundLow rectal cancer is conventionally managed with neoadjuvant chemoradiotherapy (CRT) followed by radical surgery (RS). In patients who refuse a stoma or are unfit for RS, an alternative approach may be the use of pre-op CRT and local excision (LE) where tumours are responsive. The aim of this systematic review is to determine whether differences exist in local recurrence (LR), overall survival (OS) and disease-free (DFS) survival between patients treated with CRT + LE and CRT + RS.MethodsA literature search was performed using MEDLINE/PubMed/Ovid databases and Google Scholar between 1946 and 2013. Studies comparing outcome following LE and RS post-CRT were included. A pooled analysis was carried out using the Mantel-Haenszel statistical (random effects) model to identify differences in LR, OS and DFS between CRT + LE and CRT + RS.ResultsEight studies were suitable for pooled analyses of LR whereas five and four studies were analysed for OS and DFS, respectively. When RS was used as the reference group, LR rate was higher in the LE group. However, this was non-significant (odds ratio (OR) 1.29, confidence interval (CI) 0.72–2.31, p = 0.40). Similarly, no difference was observed in 10-year OS (OR 0.96, CI 0.38–2.43, p = 0.93) or 5-year DFS (OR 1.04, CI 0.61–1.76, p = 0.89). There was evidence of publication bias in studies used for DFS. Subgroup analysis of above outcomes in T3/any N stage cancers showed no difference in LE versus RS.ConclusionIn the current evidence synthesis, there was no statistical difference in the LR, OS and DFS rates observed between patients treated with LE and RS for rectal cancer post-CRT. LE post-CRT may represent a viable alternative to RS for some patients wishing to avoid RS. However, further randomised studies are required to confirm these results.

A systematic review and meta-analysis of the diagnostic accuracy of pyruvate kinase M2 isoenzymatic assay in diagnosing colorectal cancer

BackgroundScreening programmes exist in many countries for colorectal cancer. In recent years, there has been a drive for a non-invasive screening marker of higher sensitivity and specificity. Stool-based pyruvate kinase isoenzyme M2 (M2-PK) is one such biomarker under investigation. The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy, sensitivity and specificity of M2-PK as a screening tool in colorectal cancer.MethodsA literature search of Ovid Medline, EMBASE and Google Scholar was carried out. The search strategy was restricted to human subjects and studies published in English. Data on sensitivity and specificity were extracted and pooled. Statistical analysis was conducted using summary receiver operating characteristic (SROC) curve methodology.ResultsA total of eight studies were suitable for data synthesis and analysis. Our analysis showed a pooled sensitivity and specificity for M2-PK to be 79% (CI 73%–83%) and 80% (CI 73%–86%), respectively. The accuracy of M2-PK was 0.85(0.82–0.88).ConclusionFaecal M2-PK assay has a relatively good sensitivity and specificity and high accuracy for screening colorectal cancer.

Bilateral transcutaneous tibial nerve stimulation for chronic constipation.

Chronic constipation is difficult to treat when symptoms are intractable. Colonic propulsion may be altered by distal neuromodulation but this is conventionally delivered percutaneously. Transcutaneous tibial nerve stimulation is noninvasive and cheap: this study aimed to assess its efficacy in chronic constipation.

The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review

CD40 is a co-stimulatory molecule belonging to the tumor necrosis factor superfamily and is essential in activation of dendritic cells. Dendritic cells (DCs) are antigen-presenting cells capable of initiating cytotoxic T-lymphocyte immune response against cancer cells. However, there are few studies on the characterization of DCs in cancer, specifically their expression of CD40, despite its implication in cancer immunotherapy. We reviewed available data on the expression of CD40 on DCs in various cancers, and its implications for cancer immunotherapy. A systematic review on CD40 expression on DCs in cancer was performed with reference to preferred reporting items for systematic reviews and meta-analyses (PRISMA). Studies that satisfied the inclusion and exclusion criteria were 21 out of 927. Variations in type and status of the cancers, source of DCs and methodology for detecting CD40 expression amongst the studies resulted in contrasting results. DCs generally expressed low CD40 in tumor infiltrating DCs (tiDCs), in DCs derived by in vitro culture from blood monocytes using cytokine stimulation (MoDCs) and in DCs exposed in vitro to tumor cells lines; the studies suggested that CD40 expression in DCs is impaired in cancer particularly in metastatic disease. However, DCs identified in fresh peripheral blood mononuclear cells (PBMC) expressed higher numbers of CD40 positive cells in some cancer patients, which could be due to tumor-derived factors leading to partially-stimulated DCs. The results provide evidence that some cancer patients may show partial systemic DC activation and expression of increased CD40 in response to the presence of tumor but that such activity may become abortive in the presence of factors produced by the tumor. This review has thus identified key papers on CD40 expression on DCs in various cancers and discusses the limitations and contrasting results of these studies in relation to variations in methodology. The results highlight the need for further studies on the role of CD40-CD40 ligand pathway to inform cancer treatment.