Faculty Bibliography

The purpose of this systematic review was to compare the diagnostic ability of blood markers for colorectal cancer (CRC). A systematic review of the literature for diagnostic blood markers for primary human colorectal cancer over the last 5 years was performed. The primary outcome was to assess the diagnostic ability of these markers in diagnosing colorectal cancer. The secondary outcome was to see whether the marker was compared to other markers. The tertiary outcome was to assess diagnostic ability in early versus late CRC, including stage IV disease. We identified 51 studies (29 prospective, 14 retrospective, and 8 meta-analyses). The markers were divided in broadly four groups: nucleic acids (RNA/DNA/messenger RNA/microRNAs), cytokines, antibodies, and proteins. The most promising circulating markers identified among the nucleid acids were NEAT_v2 non-coding RNA, SDC2 methylated DNA, and SEPT9 methylated DNA. The most promising cytokine to detect CRC was interleukin 8, and the most promising circulating proteins were CA11-19 glycoprotein and DC-SIGN/DC-SIGNR. Sensitivities of these markers for detecting primary colorectal carcinoma ranged from 70 to 98% and specificities from 84 to 98.7%. The best studied blood marker was SEPT9 methylated DNA, which showed great variability with sensitivities ranging from 48.2 to 95.6% and specificities from 80 to 98.9%, making its clinical applicability challenging. If combined with fecal immunochemical test (FIT), the sensitivity improved from 78 to 94% in detecting CRC. Methylated SEPT9, methylated SDC2, and -SIGN/DC-SIGNR protein had better sensitivity and specificity than CEA or CA 19-9. With the exception of SEPT9 which is currently being implemented as a screening test for CRC all other markers lacked reproducibility and standardization and were studied in relatively small population samples.

A comparison between NCCN, ESMO and JSCCR Guidelines is presented, concerning the treatment of rectal cancer, with an analysis and discussion of their discrepancies. Differences indicate areas for research.

BACKGROUND:This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas. METHODS:Patients undergoing elective surgical resection for CRC were recruited at St. Mary's Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy. RESULTS:Twenty-eight patients were recruited (12 males, median age 71, range 35-89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC's 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy. CONCLUSION:REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer.

OBJECTIVE:The aim of this study was to assess resection margin status and its impact on survival after abdominoperineal excision and pelvic exenteration for primary or recurrent rectal cancer. SUMMARY OF BACKGROUND DATA:Resection margin is important to guide therapy and to evaluate patient prognosis. METHODS:A meta-analysis was performed to assess the impact of resection margin status on survival, and a regression analysis to analyze positive resection margin rates reported in the literature. RESULTS:The analysis included 111 studies reporting on 19,607 participants after abdominoperineal excision, and 30 studies reporting on 1326 participants after pelvic exenteration. The positive resection margin rates for abdominoperineal excision were 14.7% and 24.0% for pelvic exenteration. The overall survival and disease-free survival rates were significantly worse for patients with positive compared with negative resection margins after abdominoperineal excision [hazard ratio (HR) 2.64, P < 0.01; HR 3.70, P < 0.01, respectively] and after pelvic exenteration (HR 2.23, P < 0.01; HR 2.93, P < 0.01, respectively). For patients undergoing abdominoperineal excision with positive resection margins, the reported tumor sites were 57% anterior, 15% posterior, 10% left or right lateral, 8% circumferential, 10% unspecified. A significant decrease in positive resection margin rates was identified over time for abdominoperineal excision. Although positive resection margin rates did not significantly change with the size of the study, some small size studies reported higher than expected positive resection margin rates. CONCLUSIONS:Resection margin status influences survival and a multidisciplinary approach in experienced centers may result in reduced positive resection margins. For advanced anterior rectal cancer, posterior pelvic exenteration instead of abdominoperineal excision may improve resection margins.

AIM/OBJECTIVE:There is wide disparity in the care of patients with multivisceral involvement of rectal cancer. The results are presented of treatment of advanced and recurrent colorectal cancer from a centre where a dedicated multidisciplinary team (MDT) is central to the management. METHOD/METHODS:All consecutive MDT referrals between 2010 and 2014 were examined. Analysis was undertaken of the referral pathway, site, selection process, management decision, R0 resection rate, mortality/morbidity/Clavien-Dindo (CD) classification of morbidity, length of stay (LOS) and improvement of quality of life. RESULTS:There were 954 referrals. These included locally advanced primary rectal cancer (LAPRC b-TME) (39.0%), rectal recurrence (RR) (22.0%), locally advanced primary colon cancer (LAPCC T3c/d-T4) (21.1%), colon cancer recurrence (CR) (12.4%), locally advanced primary anal cancer (LAPAC-failure of CRT/T3c/d-T4) (3.0%) and anal cancer recurrence (AR) (2.2%). Among these patients 271 operations were performed, 212 primary and 59 for recurrence. These included 16 sacrectomies, 134 total pelvic exenterations and 121 other multi-visceral exenterative procedures. An R0 resection (no microscopic margin involvement) was achieved in 94.4% and R1 (microscopic margin involvement) in 5.1%. In LAPRC b-TME the R0 rate was 96.1% and for RR it was 79%. The LOS varied from 13.3 to 19.9 days. RR operations had the highest morbidity (CD 1-2, 33.3%) and LAPRC operations had the highest rate of CD 3-4 complications (18.4%). Most (39.6%) of the referred patients were from other UK hospitals. CONCLUSION/CONCLUSIONS:Advanced colorectal cancer can be successfully treated in a dedicated referral centre, achieving R0 resection in over 90% with low morbidity and mortality. Implementation of a standardized referral pathway is encouraged.

BACKGROUND:Rectal cancer involving at least one adjacent organ (mrT4b) requires multi-visceral resection to achieve clear resection margin (R0). Performing pelvic compartment preservation according to the tumour response has not been considered. This study assesses the impact of changing the surgical strategy according to tumour response in rectal cancer mrT4b. METHODS:Patients with non-metastatic T4b rectal cancer at two tertiary referral centres between 2008 and 2013 were grouped as "Responders" ypT0-3abNx versus "Non-responders" ypT3cd-4Nx and divided into three surgical procedures: total mesorectal excision (TME), extended-TME (eTME) and beyond-TME (b-TME). End-points were circumferential resection margin, postoperative morbidity, definitive stoma formation, 3-years local recurrence (3y-LR) and 3-years disease-free survival (3y-DFS) according to both tumours' response and surgical procedures. RESULTS:Among 883 patients with rectal cancer, 101 were included. Responders had a higher rate of induction chemotherapy (59.7% vs. 38.2%; p = 0.04). Morbidity and definitive stoma formation were significantly higher in Non-responders. R0 was not impacted by either the tumour response or the surgical procedures. The 3y-LR was lower in Responders (14%) compared to Non Responders (32%) (HR 1.6; 95% CI: 1.02-2.59; p = 0.041), and was two-fold higher in e-TME compared to b-TME in Non-responders, whereas no difference was found in Responders. The 3y-DFS was higher in Responders irrespective to the surgery (71% vs. 47%; p = 0.07). CONCLUSION/CONCLUSIONS:In Responders, TME or e-TME are technically and oncollogically feasible and should be considered in preferrence to b-TME. In Non-responders, allowing for high rates of morbidity and local recurrence in patients with e-TME, b-TME procedures should be preferred.

BACKGROUND:Few cases of pouch-related cancers have been reported in ulcerative colitis (UC), and squamous cell carcinoma (SCC) is very rare. METHOD/METHODS:A systematic review of the literature was performed to identify all unequivocal cases of pouch-related SCC in UC patients. RESULTS:Eight cases of SCC developing after ileal pouch-anal anastomosis (IPAA) have been observed since 1978. Two arose from the pouch mucosa and 6 from below. The pooled cumulative incidence of SCC is below 0.06% after IPAA. Many patients had neoplasia on the preoperative specimen, but squamous metaplasia of the pouch or anorectal mucosa may have an important role in SCC. These patients are rarely offered chemoradiation therapy and the outcome is poor. Selected patients with SCC located close to the pouch outlet can be treated with chemoradiation prior to consideration of surgery and salvage their pouch. A chemoradiation regimen is suggested to avoid pouch excision in these patients. CONCLUSIONS:SCC is rare after pouch surgery but associated with extremely poor survival. Very low SCC can be managed with chemoradiation treatment, preserving the pouch and avoiding surgery, even in older patients. The role of pouch metaplasia, surveillance frequency, and treatment modalities after IPAA need further studying.

The aim of this study was to identify the mode of presentation and incidence of colorectal cancer in pregnancy (CRC-p), assess the outcomes of the mother and foetus according to gestational age, treatment delivered and cancer features and location. A systematic review of the literature was carried out to identify studies reporting on CRC-p and pooled analysis of the reported data. Seventy-nine papers reporting on 119 patients with unequivocal CRC-p were included. The calculated pooled risk is 0.002% and age at diagnosis has decreased over time. The median age at diagnosis was 32 (range, 17-46) years. Twelve per cent, 41 and 47% of CRC-p were diagnosed during the first, second and third trimester. The CRC-p site was the colon in 53.4% of cases, the rectum in 44% and multiple sites in 2.6%. Bleeding occurred in 47% of patients, abdominal pain in 37.6%, constipation in 14.1%, obstruction in 9.4% and perforation in 2.4%. Out of 82 patients whose treatment was described, 9.8% received chemotherapy during pregnancy. None of their newborns developed permanent disability, one developed hypothyroidism and 72% of newborns were alive. Vaginal delivery was possible in 60% of cases. Anterior resection was performed in 30% of patients and abdominoperineal excision of the rectum in 14.9%. Five patients had either synchronous (60%) or metachronous liver resection (40%). The median survival in these patients was 42 (0-120) months. Fifty-five per cent of patients were alive at the last available follow-up. The median survival of the mother was 36 (0-360) months. Patients with rectal cancer had longer survival compared with patients with colon cancer (P=0.0072). CRC-p is rare, leading to symptoms being overlooked, and diagnosis made at advanced stages. Cases described in the literature include patients who had cancer before pregnancy or developed it after delivery. Survival has not increased over time and the management of these patients requires collaboration between specialties and active interaction with the patients.