Transanal mesorectal excision: early outcomes in Australia and New Zealand.

BACKGROUND: Transanal total mesorectal excision (taTME) aims to overcome some of the technical challenges faced when operating on mid and low rectal cancers. Specimen quality has been confirmed previously, but recent concerns have been raised about oncological safety. This multicentre prospective study aimed to evaluate the safety of taTME among early adopters in Australia and New Zealand. METHODS: Data from all consecutive patients who had taTME for rectal cancer from July 2014 to February 2020 at six tertiary referral centres in Australasia were recorded and analysed. RESULTS: A total of 308 patients of median age of 64 years underwent taTME. Some 75.6 per cent of patients were men, and the median BMI was 26.8 kg/m2. The median distance of tumour from anal verge was 7 cm. Neoadjuvant chemoradiotherapy was administered to 57.8 per cent of patients. The anastomotic leak rate was 8.1 per cent and there was no mortality within 30 days of surgery. Pathological examination found a complete mesorectum in 295 patients (95.8 per cent), a near-complete mesorectum in seven patients (2.3 per cent), and an incomplete mesorectum in six patients (1.9 per cent). The circumferential resection margin and distal resection margin was involved in nine patients (2.9 per cent), and two patients (0.6 per cent) respectively. Over a median follow-up of 22 months, the local recurrence rate was 1.9 per cent and median time to local recurrence was 30.5 months. CONCLUSION: This study showed that, with appropriate training and supervision, skilled minimally invasive rectal cancer surgeons can perform taTME with similar pathological and oncological results to open and laparoscopic surgery.

International validation of a risk prediction algorithm for patients with malignant colorectal polyps.

AIM: The optimal management strategy for patients with endoscopically resected malignant colorectal polyps (MCP) has yet to be defined. The aim of this study was to validate a published decision-making tool, termed the Scottish Polyp Cancer Study (SPOCS) algorithm, on a large international population. METHODS: The SPOCS algorithm allocates patients to risk groups based on just two variables: the polyp resection margin and the presence of lymphovascular invasion (LVI). The risk groups are termed low (clear margin, LVI absent), medium (clear margin, LVI present) or high (involved/non-assessable margin). The International Polyp Cancer Collaborative was formed to validate the algorithm on data from Australia, Denmark, UK and New Zealand. RESULTS: In total, 1423 patients were included in the final dataset. 680/1423 (47.8%) underwent surgical resection and 108/680 (15.9%) had residual disease (luminal disease 8.8%, lymph node metastases 8.8%). The SPOCS algorithm classified 602 patients as low risk (in which 1.5% had residual disease), 198 patients as medium risk (in which 7.1% had residual disease) and 484 as high risk (in which 14.5% had residual disease) (P < 0.001, χ2 test). Receiver operating characteristic curve analysis demonstrated good accuracy of the algorithm in predicting residual disease (area under the curve 0.732, 95% CI 0.687-0.778, P < 0.001). When patients were designated as low risk, the negative predictive value was 98.5%. CONCLUSION: The SPOCS algorithm can be used to predict the risk of residual disease in patients with endoscopically resected MCPs. Surgery can be safely avoided in patients who have a clear margin of excision and no evidence of LVI.

Multivariate Statistical and Multiproxy Constraints on Earthquake-Triggered Sediment Remobilization Processes in the Central Japan Trench.

Understanding the impact of earthquakes on subaqueous environments is key for submarine paleoseismological investigations seeking to provide long-term records of past earthquakes. For this purpose, event deposits (e.g., turbidites) are, among others, identified and stratigraphically correlated over broad areas to test for synchronous occurrence of gravity flows. Hence, detailed spatiotemporal petrographic and geochemical fingerprints of such deposits are required to advance the knowledge about sediment source and the underlying remobilization processes induced by past earthquakes. In this study, we develop for the first time in paleoseismology a multivariate statistical approach using X-ray fluorescence core scanning, magnetic susceptibility, and wet bulk density data that allow to test, confirm, and enhance the previous visual and lithostratigraphic correlation across two isolated basins in the central Japan Trench. The statistical correlation is further confirmed by petrographic heavy grain analysis of the turbidites and additionally combined with our novel erosion model based on previously reported bulk organic carbon 14C dates. We find surficial sediment remobilization, a process whereby strong seismic shaking remobilizes the uppermost few centimeters of surficial slope sediment, to be a predominant remobilization process, which partly initiates deeper sediment remobilization downslope during strong earthquakes at the Japan Trench. These findings shed new light on source-to-sink transport processes in hadal trenches during earthquakes and help to assess the completeness of the turbidite paleoseismic record. Our results further suggest that shallow-buried tephra on the slope might significantly influence sediment remobilization and the geochemical and petrographic fingerprints of the resulting event deposits.

Anal squamous intraepithelial lesions: an update and proposed management algorithm.

The term anal squamous intraepithelial lesion (ASIL) is used to describe premalignant change of anal squamous cells that precede the development of squamous cell carcinoma. Pathophysiology is driven by the human papilloma virus (HPV), and progression and regression of ASIL being well described, with 12% of high-grade lesions progressing to invasive cancer within 5 years. Vaccination against HPV is effective for primary prevention. Management consists of identification and treatment of high-grade lesions to prevent progression to squamous cell carcinoma. Management of established ASIL aims to avoid the progression to invasive cancer and maintain fecal continence. A combination of surveillance, excision, ablative, or topical therapies is used to achieve this. The aim of the present study was to review the contemporary evidence about ASIL and to suggest a management algorithm.

Mineralogical control on the fate of continentally derived organic matter in the ocean.

First-order relationships between organic matter content and mineral surface area have been widely reported and are implicated in stabilization and long-term preservation of organic matter. However, the nature and stability of organomineral interactions and their connection with mineralogical composition have remained uncertain. In this study, we find that continentally derived organic matter of pedogenic origin is stripped from smectite mineral surfaces upon discharge, dispersal, and sedimentation in distal ocean settings. In contrast, organic matter sourced from ancient rocks that is tightly associated with mica and chlorite endures in the marine realm. These results imply that the persistence of continentally derived organic matter in ocean sediments is controlled to a first order by phyllosilicate mineralogy.

Prognostic factors and patterns of failure after surgery for T4 rectal cancer in the beyond total mesorectal excision era.

BACKGROUND: Despite advances in the rates of total mesorectal excision (TME) for rectal cancer surgery, decreased local recurrence rates and increased 5-year survival, there still exists large variation in the quality of treatment received. Up to 30 per cent of rectal cancers are locally advanced at presentation and approximately 5-10 per cent still breach the mesorectal plane and invade adjacent structures despite neoadjuvant therapy. With the evolution of extended resections for rectal cancers beyond the TME plane, proponents advocate that these resections should be performed only in specialist centres. The aim was to assess the prognostic factors and patterns of failure after beyond TME surgery for T4 rectal cancers. METHODS: Data were collected from prospective databases at three high-volume institutions specializing in beyond TME surgery for T4 rectal cancers between 1990 and 2013. The primary outcome measures were overall survival, local recurrence and patterns of first failure. RESULTS: Three hundred and sixty patients were identified. The negative resection margin (R0) rate was 82·8 per cent (298 patients) and the local recurrence rate was 12·5 per cent (45 patients). The type of surgical procedure (Hartmann's: hazard ratio (HR) 4·49, 95 per cent c.i. 1·99 to 10·14; P = 0·002) and lymphovascular invasion (HR 2·02, 1·08 to 3·77; P = 0·032) were independent predictors of local recurrence. The 5-year overall survival rate for all patients was 61 (95 per cent c.i. 55 to 67) per cent. The 5-year cumulative incidence of first failure was 8 per cent for local recurrence, 6 per cent for local and distant disease, and 18 per cent for distant disease. CONCLUSION: This study has demonstrated that a coordinated approach in specialist centres for beyond TME surgery can offer good oncological and long-term survival in patients with T4 rectal cancers.

ANTECEDENTES: A pesar de las mejoras en los porcentajes de extirpación total del mesorrecto (total mesorectal excision, TME) en la cirugía de cáncer de recto, la disminución de los porcentajes de recidiva local y el aumento de la supervivencia a 5 años, todavía existe una gran variabilidad en la calidad del tratamiento recibido. Hasta el 30% de los cánceres de recto están localmente avanzados en el momento del diagnóstico y aproximadamente el 5-10% sobrepasarán el plano mesorrectal e invadirán las estructuras adyacentes a pesar del tratamiento neoadyuvante. Con la evolución de las resecciones ampliadas para los cánceres de recto que sobrepasan el plano de la TME, los defensores recomiendan que estas resecciones solo se realicen en centros especializados. El objetivo fue evaluar los factores pronósticos y los patrones de recidiva después de la cirugía ampliada más allá de la TME para los cánceres de recto T4. MÉTODOS: Los datos se recogieron a partir de bases de datos prospectivas de tres instituciones de alto volumen especializadas en resecciones ampliadas más allá de la TME para el cáncer de recto T4 entre 1990 y 2013. Los criterios de valoración principal fueron la supervivencia global, la recidiva local y los patrones de la primera recidiva. RESULTADOS: Se identificaron 360 pacientes. El margen de resección fue negativo (R0) en el 82,8% (n = 298) y el porcentaje de recidiva local fue de 12,5% (n = 45). El tipo de cirugía realizada (Hartmann: cociente de riesgos instantáneos, hazard ratio, HR 4,49; i.c. del 95%: 1,99-10,14; P = 0,002) y la invasión linfovascular (HR 2,02; i.c. del 95%: 1,08-3,77; P = 0,032) fueron factores predictivos independientes de recidiva local. La supervivencia global a 5 años para todos los pacientes fue del 61% (i.c. del 95%: 55-67). La incidencia acumulada a los 5 años de la primera recidiva fue de 8% para la recidiva local, 6% para la recidiva local y a distancia, y 18% para la recidiva a distancia. CONCLUSIÓN: Este estudio demuestra que un abordaje coordinado en centros especializados para cirugía más allá de la TME puede ofrecer una buena supervivencia oncológica y a largo plazo en pacientes con cáncer de recto T4.

Sulphuric acid-mediated weathering on Taiwan buffers geological atmospheric carbon sinks.

The chemical composition of the Gaoping River in Taiwan reflects the weathering of both silicate and carbonate rocks found in its metasedimentary catchment. Major dissolved ion chemistry and radiocarbon signatures of dissolved inorganic carbon (DIC) reveal the importance of pyrite-derived sulphuric acid weathering on silicates and carbonates. Two-thirds of the dissolved load of the Gaoping River derives from sulphuric acid-mediated weathering of rocks within its catchment. This is reflected in the lowest reported signatures DI14C for a small mountainous river (43 to 71 percent modern carbon), with rock-derived carbonate constituting a 14C-free DIC source. Using an inverse modelling approach integrating riverine major dissolved ion chemistry and DI14C, we provide quantitative constraints of mineral weathering pathways and calculate atmospheric CO2 fluxes resulting from the erosion of the Taiwan orogeny over geological timescales. The results reveal that weathering on Taiwan releases 0.31 ± 0.12 MtC/yr, which is offset by burial of terrestrial biospheric organic carbon in offshore sediments. The latter tips the balance with respect to the total CO2 budget of Taiwan such that the overall system acts as a net sink, with 0.24 ± 0.13 MtC/yr of atmospheric CO2 consumed over geological timescales.

Megathrust earthquake drives drastic organic carbon supply to the hadal trench.

The giant 2011 Tohoku-oki earthquake has been inferred to remobilise fine-grained, young surface sediment enriched in organic matter from the slope into the >7 km deep Japan Trench. Yet, this hypothesis and assessment of its significance for the carbon cycle has been hindered by limited data density and resolution in the hadal zone. Here we combine new high-resolution bathymetry data with sub-bottom profiler images and sediment cores taken during 2012-2016 in order to map for the first time the spatial extent of the earthquake-triggered event deposit along the hadal Japan Trench. We quantify a sediment volume of ~0.2 km3 deposited from spatially-widespread remobilisation of young surficial seafloor slope sediments triggered by the 2011 earthquake and its aftershock sequence. The mapped volume and organic carbon content in sediment cores encompassing the 2011 event reveals that this single tectonic event delivered >1 Tg of organic carbon to the hadal trench. This carbon supply is comparable to high carbon fluxes described for other Earth system processes, shedding new light on the impact of large earthquakes on long-term carbon cycling in the deep-sea.

Compound-Specific Radiocarbon Analysis by Elemental Analyzer-Accelerator Mass Spectrometry: Precision and Limitations.

We examine instrumental and methodological capabilities for microscale (10-50 µg of C) radiocarbon analysis of individual compounds in the context of paleoclimate and paleoceanography applications, for which relatively high-precision measurements are required. An extensive suite of data for 14C-free and modern reference materials processed using different methods and acquired using an elemental-analyzer-accelerator-mass-spectrometry (EA-AMS) instrumental setup at ETH Zurich was compiled to assess the reproducibility of specific isolation procedures. In order to determine the precision, accuracy, and reproducibility of measurements on processed compounds, we explore the results of both reference materials and three classes of compounds (fatty acids, alkenones, and amino acids) extracted from sediment samples. We utilize a MATLAB code developed to systematically evaluate constant-contamination-model parameters, which in turn can be applied to measurements of unknown process samples. This approach is computationally reliable and can be used for any blank assessment of small-size radiocarbon samples. Our results show that a conservative lower estimate of the sample sizes required to produce relatively high-precision 14C data (i.e., with acceptable errors of <5% on final 14C ages) and high reproducibility in old samples (i.e., F14C ≈ 0.1) using current isolation methods are 50 and 30 µg of C for alkenones and fatty acids, respectively. Moreover, when the F14C is >0.5, a precision of 2% can be achieved for alkenone and fatty acid samples containing ≥15 and 10 µg of C, respectively.

Population-based study demonstrating an increase in colorectal cancer in young patients.

BACKGROUND: New Zealand has among the highest rates of colorectal cancer in the world and is an unscreened population. The aim of this study was to determine the trends in incidence and tumour location in the New Zealand population before the introduction of national colorectal cancer screening. METHODS: Data were obtained from the national cancer registry and linked to population data from 1995 to 2012. Incidence rates for colorectal cancer by sex, age (less than 50 years, 50-79 years, 80 years or more) and location (proximal colon, distal colon and rectum) were assessed by linear regression. RESULTS: Among patients aged under 50 years, the incidence of distal colonic cancer in men increased by 14 per cent per decade (incidence rate ratio (IRR 1·14), 95 per cent c.i. 1·00 to 1·30; P = 0·042); the incidence of rectal cancer in men increased by 18 per cent (IRR 1·18, 1·06 to 1·32; P = 0·002) and that in women by 13 per cent (IRR 1·13, 1·02 to 1·26; P = 0·023). In those aged 50-79 years, there was a reduction in incidence per decade of proximal, distal and rectal cancers in both sexes. In the group aged 80 years and over, proximal cancer incidence per decade increased by 19 per cent in women (IRR 1·19, 1·13 to 1·26; P < 0·001) and by 25 per cent in men (IRR 1·25, 1·18 to 1·32; P < 0·001); among women, the incidence of distal colonic cancer decreased by 8 per cent (IRR 0·92, 0·86 to 0·98); P = 0·012), as did that of rectal cancer (IRR 0·92, 0·86 to 0·97; P = 0·005). CONCLUSION: The increasing incidence of rectal cancer among younger patients needs to be considered when implementing screening strategies.

The long-term outcome of anti-TNF alpha therapy in perianal Crohn's disease.

BACKGROUND: The aim of the present study was to evaluate the long-term outcomes of anti-tumour necrosis factor alpha therapy in perianal Crohn's disease and identify factors predicting response to treatment. METHODS: Data from hospital clinical records and coding databases were retrospectively reviewed from a tertiary care hospital in Christchurch, New Zealand. The study included 75 adult patients with perianal Crohn's disease commenced on anti-tumour necrosis factor alpha therapy from January 2000 to December 2012. Response to treatment was determined from records relating to clinical evaluation, magnetic resonance imaging follow-up and whether further surgical intervention was required. RESULTS: 73% (55) of all patients and 38 of the 57 (67%) patients with perianal fistulas responded to anti-tumour necrosis factor alpha therapy. Patients with complex fistulas were less likely to improve as compared to patients without fistulising disease. Five of the 57 (13%) patients with perianal fistulas demonstrated complete healing on clinical evaluation; however, magnetic resonance imaging confirmed complete healing in only two. Patients that had taken antibiotics and those that had previously required abscess drainage were less likely to respond to treatment [relative risk (RR) = 0.707 and 0.615, respectively; p = 0.03, p = 0.0001]. Responders were less likely to require follow-up surgery (RR = 0.658, p = 0.014) including ileostomy or proctectomy. CONCLUSIONS: Although anti-tumour necrosis factor alpha tends to improve symptoms of perianal Crohn's disease, in the long term, it rarely achieves complete healing. Perianal fistulising disease, a history of perianal abscess and antibiotic treatment are predictors of poor response to therapy.

Impact of restenting for recurrent colonic obstruction due to tumour ingrowth.

BACKGROUND: Endoscopic stenting is used to palliate malignant large bowel obstruction. A proportion of patients will develop recurrent obstruction due to tumour ingrowth and require reintervention. This study aimed to assess the outcome (clinical success and complication rates) of endoscopic reintervention compared with surgical intervention in patients with stent obstruction due to tumour ingrowth. METHODS: This was an observational study using data from a database of patients who underwent palliative colonic stenting between January 1998 and March 2017 at Christchurch Public Hospital. RESULTS: A total of 190 patients underwent colonic stent insertion, for palliation in 182 cases. Reintervention was performed in 55 (30·2 per cent). Thirty-one patients (17·0 per cent) developed obstruction within the stent at a median of 4·6 (i.q.r. 2·3-7·7) months after the procedure. Of these, 21 had endoscopic restenting and ten underwent surgery. Restenting had technical and clinical success rates of 100 per cent, and involved a significantly shorter length of stay compared with surgery (median 2 (i.q.r. 1-4) versus 11 (6-19) days respectively; P = 0·006). Seven of the 21 patients in the restented group underwent a third palliative intervention. The overall stoma rate in the restented group was significantly lower than that in the surgical group (4 of 21 versus 10 of 10; P < 0·001). There was no difference in complications or survival between the two groups. CONCLUSION: Among palliative patients who develop malignant stent obstruction, endoscopic restenting had a high chance of technical success. It resulted in a shorter hospital stay and lower stoma rate than those seen after surgery.

Meta-analysis of prophylactic mesh to prevent parastomal hernia.

BACKGROUND: Rates of parastomal hernia following stoma formation remain high. Previous systematic reviews suggested that prophylactic mesh reduces the rate of parastomal hernia; however, a larger trial has recently called this into question. The aim was to determine whether mesh placed at the time of primary stoma creation prevents parastomal hernia. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL were searched using medical subject headings for parastomal hernia, mesh and prevention. Reference lists of identified studies, clinicaltrials.gov and the WHO International Clinical Trials Registry were also searched. All randomized clinical trials were included. Two authors extracted data from each study independently using a purpose-designed sheet. Risk of bias was assessed by a tool based on that developed by Cochrane. RESULTS: Ten randomized trials were identified among 150 studies screened. In total 649 patients were included in the analysis (324 received mesh). Overall the rates of parastomal hernia were 53 of 324 (16·4 per cent) in the mesh group and 119 of 325 (36·6 per cent) in the non-mesh group (odds ratio 0·24, 95 per cent c.i. 0·12 to 0·50; P < 0·001). Mesh reduced the rate of parastomal hernia repair by 65 (95 per cent c.i. 28 to 85) per cent (P = 0·02). There were no differences in rates of parastomal infection, stomal stenosis or necrosis. Mesh type and position, and study quality did not have an independent effect on this relationship. CONCLUSION: Mesh placed prophylactically at the time of stoma creation reduced the rate of parastomal hernia, without an increase in mesh-related complications.

Cohort study of mesenteric panniculitis and its relationship to malignancy.

BACKGROUND: Mesenteric panniculitis (MP) is a rare condition that historically has been associated with the presence of malignancy. Paraneoplastic phenomena in general regress with cure and in most cases with treatment of the cancer. This study was undertaken to determine whether MP regressed with cancer treatment and cure. METHODS: This was a retrospective review of a database of all patients with MP confirmed on CT between 2003 and August 2015 at Christchurch Hospital. Patients were categorized as having malignant or non-malignant disease, and follow-up scans were assessed for remission of MP. Patients with malignancy were further categorized as having malignancy cured or not cured. RESULTS: A total of 308 patients were identified with possible MP; 135 were excluded as radiological appearances were not typical of MP (43 patients) or there was no follow-up CT (92). Of 173 patients (131 men) included, 75 (43·4 per cent) were diagnosed with malignancy. Follow-up imaging showed that 33 patients (19·1 per cent) had remission of MP, whereas 140 (80·9 per cent) had no remission. There was no difference in the rates of MP remission in the malignancy versus no malignancy groups (P = 1·000), or between groups in which malignancy was cured or not cured (P = 0·572). Nor was there any difference in the rates of MP remission in malignancy cured versus no malignancy groups (P = 0·524). CONCLUSION: MP does not behave like a paraneoplastic phenomenon. The association with malignancy is most likely an epiphenomenon of the many CT images acquired for staging of cancer.

Disability in Restorative Proctocolectomy Recipients Measured using the Inflammatory Bowel Disease Disability Index.

BACKGROUND AND AIMS: The inflammatory bowel disease [IBD] disability index [IBD-DI], which measures IBD-associated disability, has been validated on IBD patients but not those who have had restorative proctocolectomy with ileal pouch-anal anastomosis [RP with IPAA]. This study aimed to utilize the IBD-DI in RP with IPAA recipients and compare ulcerative colitis [UC]-indicated RP with IPAA patients to medically treated UC patients. METHODS: This study was population based. Demographic, indication, complication and direct cost data were collected via medical records while disability, quality of life [QoL] and indirect costs were measured using questionnaires and structured interviews. De-identified raw data about medically treated UC patients were provided by a previous study for comparison. RESULTS: In total there were 136 RP with IPAA patients [mean 11.5 years of follow up]. Eighty-four completed the IBD-DI and 80 completed the IBD questionnaire [IBDQ]. The IBDQ and IBD-DI were highly correlated [r = 0.84, p < 0.01]. Worse QoL and disability were found in those who had their position affected at work [both p < 0.01] and those who had more than 100 days off work in the last year [p < 0.01 for QoL and p = 0.012 for disability]. Lower QoL and disability scores were associated with higher indirect and total costs [p < 0.01]. UC patients treated with RP with IPAA had less disability than medically treated UC patients [p = 0.04]. CONCLUSIONS: Disability in RP with IPAA recipients can be measured using the IBD-DI. Perioperative complications and high costs of care are associated with higher levels of disability. Disability of RP with IPAA recipients was lower than that of medically managed UC patients.

Salvage surgery in patients with recurrent or residual squamous cell carcinoma of the anus.

INTRODUCTION: Anal squamous cell cancers are uncommon, and primary treatment is radical chemoradiotherapy. The role of radical surgery is in salvage of patients with residual and recurrent disease. The primary aim of the study is to determine how often such salvage surgery is required, while the secondary aim is to determine which features indicate salvage surgery may be required and to determine the outcome of salvage surgery. METHODS: A prospective database was analysed of all patients with anal cancer over an 18 year period (Dec 1996-Jan 2015). The records of patients requiring salvage surgery were reviewed. RESULTS: 203 Patients were identified with anal cancers, of which 180 had squamous cell anal carcinoma. 112 Female (median age 59.4, range 33-92) 68 male (median age 63.8 range 36-87). Of these 27 patients (15%) required salvage surgery. 23 Patients had a R0 resection. 18 Patients had an extended resection (16 R0) while 9 had a routine APR (7 R0). The 30-day post-operative mortality rate was 0%. The overall 5 year survival was 78%, not significantly different from those not requiring salvage surgery (p = 0.23). Age, gender, AJCC stage, T stage, radiation therapy alone, were not predicators of the need for salvage surgery. CONCLUSIONS: Salvage surgery is uncommonly required. Extended surgery beyond routine APR is often required to obtain an R0 resection. Excellent patient survival can be achieved in highly selected cases. There were no identifiable clinical predictors of those needing salvage surgery, and consideration should be given to explore molecular and genetic factors.

Translating colorectal cancer genetics into clinically useful biomarkers.

Colorectal cancer (CRC) is a major health problem worldwide accounting for over a million deaths annually. While many patients with Stage II and III CRC can be cured with combinations of surgery, radiotherapy and chemotherapy, this is morbid costly treatment and a significant proportion will suffer recurrence and eventually die of CRC. Increased understanding of the molecular pathogenesis of CRC has the potential to identify high risk patients and target therapy more appropriately. Despite increased understanding of the molecular events underlying CRC development, established molecular techniques have only produced a limited number of biomarkers suitable for use in routine clinical practice to predict risk, prognosis and response to treatment. Recent rapid technological developments, however, have made genomic sequencing of CRC more economical and efficient, creating potential for the discovery of genetic biomarkers that have greater diagnostic, prognostic and therapeutic capabilities for the management of CRC. This paper reviews the current understanding of the molecular pathogenesis of CRC, and summarizes molecular biomarkers that surgeons will encounter in current clinical use as well as those under development in clinical and preclinical trials. New molecular technologies are reviewed together with their potential impact on the understanding of the molecular pathogenesis of CRC and their potential clinical utility in classification, diagnosis, prognosis and targeting of therapy.

Progress in the management of retrorectal tumours.

AIM: Tumours in the retrorectal space are rare and pathologically heterogeneous. The roles of imaging and preoperative biopsy, nonoperative management and the indications for surgical resection are controversial. This study investigated a series of retrorectal tumours treated in a single institution with the aim of producing a modern improved management algorithm. METHOD: A retrospective analysis was conducted of the management of all retrorectal lesions identified between 1998 and 2013 from a radiology database search. Patient demographics, presenting symptoms, imaging, biopsy, management and the results were recorded. Descriptive statistics were used and Kaplan-Meier survival analysis was performed. RESULTS: Sixty-nine patients with a confirmed retrorectal tumour were identified. The median age was 50 (36-67 interquartile range) and 42 (56%) were female. Twenty (29%) of the tumours were malignant: 4 of 41 cystic lesions were malignant (12.9%) vs. 16 of 28 solid (or heterogeneous) lesions (57.1%) (P < 0.0001). Imaging demonstrated a 95% sensitivity and 64% specificity for differentiating benign from malignant tumours. Magnetic resonance imaging (MRI) was significantly better at distinguishing between benign and malignant tumours than computed tomography (94% vs. 64%, P = 0.03). Percutaneous biopsy was performed in 16 patients and only 27 underwent resection. There was no evidence of local recurrence associated with biopsy. Solid lesions were associated with a nonsignificant decreased overall survival (P = 0.348). CONCLUSION: This study demonstrated that MRI should be the investigation of choice for retrorectal lesions. Biopsy of solid lesions is safe and useful for guiding neoadjuvant and surgical therapy. Cystic lesions without suspicious radiological features can be followed by serial imaging without resection.