Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

The incidence of early onset colorectal cancer in Aotearoa New Zealand: 2000-2020.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC), diagnosed before age 50, has been rising in many countries in the past few decades. This study aims to evaluate this trend in Aotearoa New Zealand and assess its impact on Maori. METHODS: Crude incidence and age-standardized incidence of colorectal cancer (CRC) was analyzed from all new cases from the Aotearoa New Zealand national cancer registry for the period 2000-2020. Trends were estimated by sex, ethnicity, age group and location of cancer and projections made to 2040. RESULTS: Between 2000 and 2020, there were a total of 56,761 cases of CRC diagnosed in Aotearoa New Zealand, 3,702 of these being EOCRC, with age-standardized incidence decreasing significantly (P = 8.2 × 10- 80) from 61.0 to 47.3 cases per 100,000. EOCRC incidence increased on average by 26% per decade (incidence rate ratio (IRR) 1.26, p = < 0.0001) at all sites (proximal colon, distal colon and rectum), while the incidence in those aged 50-79 years decreased on average by 18% per decade (IRR 0.82, p = < 0.0005), again across all sites. There was no significant average change in CRC incidence in those over 80 years. In Maori, there was no significant change in age-standardized incidence. There was however a significant increase in crude incidence rates (IRR 1.28, p = < 0.0005) driven by significant increases in EOCRC (IRR1.36, p = < 0.0005). By 2040, we predict the incidence of EOCRC will have risen from 8.00 to 14.9 per 100,000 (6.33 to 10.00 per 100,000 in Maori). However, due to the aging population an estimated 43.0% of all CRC cases will be diagnosed in those over 80 years of age (45.9% over 70 years of age in Maori). CONCLUSION: The age-standardized incidence of CRC from 2000 to 2020 decreased in Aotearoa New Zealand, but not for Maori. The incidence of EOCRC over the same period continues to rise, and at a faster rate in Maori. However, with the ageing of the population in Aotearoa New Zealand, and for Maori, CRC in the elderly will continue to dominate case numbers.

Identifying important microbial and genomic biomarkers for differentiating right- versus left-sided colorectal cancer using random forest models.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease, with subtypes that have different clinical behaviours and subsequent prognoses. There is a growing body of evidence suggesting that right-sided colorectal cancer (RCC) and left-sided colorectal cancer (LCC) also differ in treatment success and patient outcomes. Biomarkers that differentiate between RCC and LCC are not well-established. Here, we apply random forest (RF) machine learning methods to identify genomic or microbial biomarkers that differentiate RCC and LCC. METHODS: RNA-seq expression data for 58,677 coding and non-coding human genes and count data for 28,557 human unmapped reads were obtained from 308 patient CRC tumour samples. We created three RF models for datasets of human genes-only, microbes-only, and genes-and-microbes combined. We used a permutation test to identify features of significant importance. Finally, we used differential expression (DE) and paired Wilcoxon-rank sum tests to associate features with a particular side. RESULTS: RF model accuracy scores were 90%, 70%, and 87% with area under curve (AUC) of 0.9, 0.76, and 0.89 for the human genomic, microbial, and combined feature sets, respectively. 15 features were identified as significant in the model of genes-only, 54 microbes in the model of microbes-only, and 28 genes and 18 microbes in the model with genes-and-microbes combined. PRAC1 expression was the most important feature for differentiating RCC and LCC in the genes-only model, with HOXB13, SPAG16, HOXC4, and RNLS also playing a role. Ruminococcus gnavus and Clostridium acetireducens were the most important in the microbial-only model. MYOM3, HOXC4, Coprococcus eutactus, PRAC1, lncRNA AC012531.25, Ruminococcus gnavus, RNLS, HOXC6, SPAG16 and Fusobacterium nucleatum were most important in the combined model. CONCLUSIONS: Many of the identified genes and microbes among all models have previously established associations with CRC. However, the ability of RF models to account for inter-feature relationships within the underlying decision trees may yield a more sensitive and biologically interconnected set of genomic and microbial biomarkers.

Rectal swabs are a reliable method of assessing the colonic microbiome.

BACKGROUND: Advances in genome sequencing have enabled detailed microbiome analysis; however, the ideal specimen type for sequencing is yet to be determined. Rectal swabs may offer a rapid and convenient modality for colonic microbiome analysis. The aim of this study is to evaluate the use of rectal swabs compared to faecal specimens. METHODS AND RESULTS: Twenty health professionals participated in this study and provided a faecal specimen, a self-collected rectal swab and a rectal swab taken by a clinician. DNA was extracted and 16S rRNA gene sequencing was carried out for microbiome analysis. Alpha diversity was higher in swabs compared to faecal specimens; however, the difference was only significant when comparing clinician-obtained swabs to faeces. Analysis of beta diversity consistently showed that few taxa were affected by sample type. We found sample type accounted for only 6.8% of community variation (R2 = 0.067, p < 0.001, permanova). Notably, there were only six genera identified in clinician-obtained swabs that were not also found in the self-taken swabs. CONCLUSIONS: Both self-collected and clinician obtained rectal swabs are a reliable method of analysing the colonic microbiome. Obtaining specimens for microbiome analysis is often time-critical due to therapy, such as antibiotics, influencing the microbiome. Rectal swabs are shown to be a valid and convenient modality for microbiome analysis.

Distinct changes in the colonic microbiome associated with acute diverticulitis.

AIM: The pathogenesis of acute diverticulitis (AD) remains incompletely understood, despite it being one of the most common gastrointestinal conditions worldwide. The aim of this study was to investigate the role of the colonic microbiome in the pathogenesis of AD. METHOD: A prospective case-control study was performed, comparing the microbiome of AD patients with that of controls, using 16S rRNA sequencing of rectal swab samples. RESULTS: The microbiome of individuals with AD showed lower diversity than that of controls. There were significant compositional differences observed, with a lower abundance of commensal bacterial families and genera such as Lachnospiraceae, Ruminococcus and Faecalibacterium in AD patients compared with controls, and there was an increase in several genera with known pathogenic roles including Fusobacteria, Prevotella and Paraprevotella. CONCLUSION: This is the largest study to date to examine the microbiota of AD patients, and adds evidence to the proposed hypothesis that alterations in the colonic microbiome play a role in the pathogenesis of AD.

Acute Diverticulitis in Young Patients: A Review of the Changing Epidemiology and Etiology.

Acute diverticulitis is one of the leading gastrointestinal causes for hospitalization. The incidence of acute diverticulitis has been increasing in recent years, especially in patients under 50 years old. Historically, acute diverticulitis in younger patients was felt to represent a separate entity, being more virulent and associated with a higher rate of recurrence. Accordingly, young patients were often managed differently to older counterparts. Our understanding of the natural history of this condition has evolved, and current clinical practice guidelines suggest age should not alter management. The purpose of this review is to evaluate the changing epidemiology of acute diverticulitis, consider potential explanations for the observed increased incidence in younger patients, as well as review the natural history of acute diverticulitis in the younger population.

Surgical outcomes following colorectal cancer resections in patients aged 80 years and over: results from the Australia and New Zealand Binational Colorectal Cancer Audit.

AIM: The primary aim was to compare the 30-day morbidity and mortality in patients aged ≥80 years undergoing surgery for colorectal cancer with those aged <80 years. The secondary aim was to identify independent outcome predictors. METHOD: This was a retrospective study of patients undergoing surgery for colorectal cancer between January 2007 and February 2018. Patients were divided into those <80 years and those ≥80 years at the time of surgery. Data had been collected prospectively by the Australasian Binational Colorectal Cancer Audit and included patient demographics, site and stage of tumour, comorbidity, operative details, American Society of Anesthesiologists score (ASA), pathological staging, 30-day mortality and morbidity (medical and surgical). Univariate and multivariate analyses were used to identify predictors of 30-day morbidity and mortality. RESULTS: During the study period, 4600 out of 20 463 (22.5%) patients were ≥80 years. They had a greater 30-day mortality after both colonic (97/2975 [3.3%] vs. 66/7010 [0.9%], P < 0.001) and rectal resections (50/1625 [3.1%] vs. 36/9006 [0.4%], P < 0.001) compared with younger patients. They also had an increased length of stay (colon cancer, 9 vs. 7 days; rectal cancer, 10 vs. 8 days; P < 0.001) and medical complications (colon cancer, 23.5% vs. 12.7%; rectal cancer, 25.2% vs. 11.2%; P < 0.001). Surgical complications were equivalent. Age ≥80 years was not an independent predictor of 30-day morbidity or mortality. Patients ≥80 years who were ASA 2/3 and had rectal cancer seemed to fare worse in terms of 30-day mortality (ASA 2, 22%, 95% CI 9%-36%, P < 0.001; ASA 3, 11%, 95% CI 4%-19%, P< 0.001). CONCLUSIONS: Postoperative morbidity and mortality are significantly greater in patients ≥80 years undergoing colorectal cancer surgery. Any recommendation for surgery in this age group should take into account patient comorbidity and not be based on age alone.

Complications After Extended Radical Resections for Locally Advanced and Recurrent Pelvic Malignancies: A 25-Year Experience.

BACKGROUND: The oncological role of pelvic exenteration for locally advanced and recurrent pelvic malignancies arising from the anorectum, gynaecological, or urological systems is now well-established. Despite this, the surgical community has been slow to accept pelvic exenteration, undoubtedly due to concerns about high morbidity and mortality rates. This study assessed the general major complications and predictors of morbidity following extended radical resections for locally advanced and recurrent pelvic malignancies. METHODS: Data were collected from prospective databases at two high-volume institutions specialising in beyond TME surgery for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary outcome measures were major complications (Clavien-Dindo 3 or above) and predictors for morbidity. RESULTS: A total of 646 consecutive patients required extended surgery for local advanced pelvic malignancies. The median age was 63 (range 19-89) years, and the majority were female (371; 57.4%). One or more major complications were observed in 106 patients (16.4%). The most common major complications were intra-abdominal collection (43.7%; n = 59/135) and wound infection (14.1%; n = 19/135). The overall inpatient mortality rate was 0.46% (n = 3/646). Independent predictors for major morbidity following surgery for locally advanced or recurrent pelvic malignancies were squamous cell carcinoma of anus, sacrectomy, and blood transfusion requirement. CONCLUSIONS: This series adds increasing evidence that good outcomes can be achieved for extended radical resections in locally advanced and recurrent pelvic malignancies. A coordinated approach in specialist centres for beyond TME surgery demonstrates that this is a safe and feasible procedure, offering low major complication rates.

Sarcopenia, as Assessed by Psoas Cross-Sectional Area, Is Predictive of Adverse Postoperative Outcomes in Patients Undergoing Colorectal Cancer Surgery.

BACKGROUND: Frailty and sarcopenia are important concepts in surgical practice because of their association with adverse postoperative outcomes. Radiologically assessed psoas muscle mass has been proposed as a surrogate for sarcopenia and may be predictive of poor postoperative outcomes. OBJECTIVE: This study aimed to determine the association between sarcopenia, as assessed by psoas cross-sectional area, and postoperative outcomes in patients undergoing colorectal cancer surgery. DESIGN: This was a retrospective review of patient records from 2014 to 2016. SETTINGS: This study was conducted at a single tertiary center. PATIENTS: Patients undergoing elective resection of colorectal cancer were included. MAIN OUTCOME MEASURES: Sarcopenia was assessed using the total psoas index, calculated by measuring the cross-sectional area of the psoas muscle at the third lumbar vertebra and normalized for patient height. Preoperative and intraoperative variables, including the presence of preoperative sarcopenia, were evaluated as potential risk factors for adverse postoperative outcomes. RESULTS: Of 350 patients, 115 (32.9%) were identified as sarcopenic. Sarcopenia was associated with a significantly increased length of stay (13 days vs 7 days; OR, 1.31; 95% CI, 1.23-1.42; p < 0.01) and 1-year mortality (13.9% vs 0.9%; OR, 16.2; 95% CI, 4.34-83.4; p < 0.01). Sarcopenia was also associated with a significant increased risk of any complication (85.2% vs 34.5%; OR, 15.4; 95% CI, 8.39-29.7; p < 0.01) and of major complications (30.4% vs 8.9%; OR, 15.1; 95% CI, 7.16-33.2; p < 0.01). LIMITATIONS: This study was limited by its retrospective design and by being conducted in a single institution. Although reduced muscle mass is suggestive of sarcopenia, it does not assess a patient's physical function or other components of the frailty phenotype. CONCLUSION: Radiological sarcopenia is an important predictive risk factor for adverse postoperative outcomes in surgical patients. Computed tomography scans, which are routinely performed as part of staging, provide an opportunity to assess for sarcopenia preoperatively. See Video Abstract at http://links.lww.com/DCR/B201. LA SARCOPENIA, EVALUADA POR EL ÁREA TRANSVERSAL DE PSOAS, PREDICE RESULTADOS POSTOPERATORIOS ADVERSOS EN PACIENTES SOMETIDOS A CIRUGÍA DE CÁNCER COLORECTAL: La fragilidad y la sarcopenia son conceptos importantes en la práctica quirúrgica debido a su asociación con los resultados postoperatorios adversos. La masa muscular del psoas evaluada radiológicamente se ha propuesto como un sustituto de la sarcopenia y puede predecir resultados postoperatorios deficientes.Determinar la asociación entre la sarcopenia, según lo evaluado por el área transversal del psoas, y los resultados postoperatorios en pacientes sometidos a cirugía de cáncer colorrectal.Esta fue una revisión retrospectiva de los registros de pacientes de 2014 a 2016.Este estudio se llevo a cabo en un solo centro terciario.Se incluyeron pacientes sometidos a resección electiva de cáncer colorrectal.La sarcopenia se evaluó utilizando el índice de psoas total (TPI), calculado midiendo el área de la sección transversal del músculo psoas en la tercera vértebra lumbar y normalizado para la altura del paciente.Se evaluaron las variables preoperatorias e intraoperatorias, incluida la presencia de sarcopenia preoperatoria, como posibles factores de riesgo de resultados postoperatorios adversos.De 350 pacientes, 115 (32,9%) fueron identificados como sarcopénicos. La sarcopenia se asoció con un aumento significativo de la duración de la estancia (13 días frente a 7 días, OR 1.31, IC 95% 1.23-1.42, p < 0.01) y de la mortalidad al año (13.9% vs 0.9%, OR 16.2, IC 95% 4.34-83.4, p < 0.01). La sarcopenia también se asoció con un aumento significativo del riesgo de cualquier complicación (85.2% vs 34.5%, OR 15.4, IC 95% 8.39-29.7, p < 0.01) y de complicaciones mayores (30.4% vs 8.9%, OR 15.1 IC 95% 7.16-33,2, p < 0,01).Este estudio estuvo limitado por su diseño retrospectivo y por el hecho de que se realizó en una sola institución. Aunque la reducción de la masa muscular es un indicio de sarcopenia, no evalúa la función física del paciente ni otros componentes del fenotipo de fragilidad.La sarcopenia radiológica es un importante factor de riesgo predictivo para resultados postoperatorios adversos en pacientes quirúrgicos. Las tomografías computarizadas, que se realizan rutinariamente como parte de la estadificación, brindan la oportunidad de evaluar la sarcopenia antes de la operación. Consulte Video Resumen en http://links.lww.com/DCR/B201. (Traducción-Dr. Gonzalo Hagerman).

Increasing Incidence of Young-Onset Colorectal Carcinoma A 3-Country Population Analysis.

BACKGROUND: The overall incidence of colorectal carcinoma is declining in Western populations; however, single country series demonstrate an increase in young-onset (<50 years) colorectal carcinoma. OBJECTIVE: The purpose of this study was to determine whether the pattern of increasing incidence of young-onset colorectal carcinoma is consistent across 3 Western populations. DESIGN: This is a population incidence study. SETTINGS: National cancer registries of New Zealand, Sweden, and Scotland were used. PATIENTS: The incidence of colorectal carcinoma was calculated from population data for 3 countries over 2 to 4 decades. MAIN OUTCOME MEASURES: The incidence of colorectal carcinoma was measured. Incidence rate ratios were determined and data were stratified by subsite (colon versus rectum), sex, and age (<50, 50-79, and ≥80 y). RESULTS: Overall colorectal carcinoma rates declined in New Zealand, remained stable in Scotland, and increased in Sweden. In all 3 populations, there was an increasing incidence of rectal carcinoma in those aged <50 years. Young-onset rectal carcinoma increased in New Zealand (1995-2012: incidence rate ratio = 1.18 (men) and 1.13 (women)), with declining incidence in all other age groups. Colon carcinoma did not increase in the population aged <50 years, with the exception of distal colonic carcinoma in men. Overall, rectal carcinoma incidence increased (1970-2014) in Sweden; however, increases in those <50 years of age exceeded increases in other age groups (incidence rate ratio = 1.14 (males) and 1.12 (females)). Distal colon carcinoma increases were most marked in the population aged <50 years. In Scotland (1990-2014), young-onset rectal carcinoma incidence increased (incidence rate ratio = 1.23 (males) and 1.27 (females)), with a smaller increase in colon carcinoma. LIMITATIONS: Limitations include its registry-based, population incidence research. CONCLUSIONS: This study shows an increase in young-onset rectal carcinoma in 3 national populations; this observation may provide a focus for looking at the role of environmental influences on the etiology of this increase and therefore to explore strategies for prevention. See Video Abstract at http://links.lww.com/DCR/B194. AUMENTO DE LA INCIDENCIA DE CARCINOMA COLORRECTAL DE INICIO JOVEN: UN ANÁLISIS DE POBLACIÓN DE TRES PAÍSES: La incidencia global de carcinoma colorrectal está disminuyendo en las poblaciones occidentales. Sin embargo, las series de un solo país demuestran un aumento en el carcinoma colorrectal de inicio joven (pacientes menores de 50 años).Determinar si el patrón de incidencia en aumento de carcinoma colorrectal de inicio joven es consistente en tres poblaciones occidentales.Estudio de incidencias de población en tres países.Registros nacionales de cáncer de Nueva Zelanda, Suecia y Escocia.la incidencia de carcinoma colorrectal se calculó a partir de datos de población de tres países durante dos o a cuatro décadas.Incidencia de carcinoma colorrectal. Se determinaron las tasas de incidencia y los datos se estratificaron por subsitio (colon versus recto), además de sexo y edad (<50, 50-79 y ≥ 80).las tasas generales de carcinoma colorrectal disminuyeron en Nueva Zelanda, se mantuvieron estables en Escocia y aumentaron en Suecia. En las tres poblaciones, hubo una incidencia creciente de carcinoma rectal en pacientes menores de 50 años. El carcinoma rectal de inicio juvenil aumentó en Nueva Zelanda (1995-2012): tasa de incidencia de 1,18 [varones] y 1,13 [mujeres], con una disminución de la incidencia en todos los demás grupos de edad. El carcinoma de colon no aumentó en la población de < 50 años, con la excepción del carcinoma de colon distal en hombres. En general, la incidencia de carcinoma rectal aumentó (1970-2014) en Suecia; sin embargo, los aumentos en aquellos de <50 años excedieron los aumentos en otros grupos de edad: tasa de incidencia 1.14 [hombres] y 1.12 [mujeres]. Los aumentos del carcinoma de colon distal fueron más marcados en la población de < 50 años. En Escocia (1990-2014), la incidencia de carcinoma rectal de inicio juvenil aumentó: relación de tasa de incidencia 1.23 [hombres] y 1.27 [mujeres], con un aumento menor en el carcinoma de colon.Investigación de incidencia poblacional basada en registros nacionales.Este estudio muestra un aumento en el carcinoma rectal de inicio joven en tres poblaciones nacionales. Esta observación puede indicar un enfoque para la examinación de influencias ambientales en la etiología de este aumento y, por lo tanto, explorar estrategias para la prevención. Consulte Video Resumen en http://links.lww.com/DCR/B194. (Traducción-Dr Adrián Ortega).

O2 No Longer the Go2: A Systematic Review and Meta-Analysis Comparing the Effects of Giving Perioperative Oxygen Therapy of 30% FiO2 to 80% FiO2 on Surgical Site Infection and Mortality.

OBJECTIVE: To determine the effects of perioperative high (80%) versus low (30%) fraction of inspired oxygen (FiO2) on surgical site infection (SSI) and mortality in adult surgical patients. BACKGROUND: The routine use of high fraction perioperative oxygen in patients is "standard of care" and recommended by the World Health Organisation; however, whether there is truly any benefit to this therapy has been challenged by some authors. Questions have also been raised about the possibility of harm from oxygen therapy. METHOD: Randomised control trials comparing high-to-low FiO2 were located by searching MEDLINE, Embase, CENTRAL and Web of Science. The primary outcomes were SSI up to 15 days and up to any time point postoperatively and mortality up to 30 days. The data were analysed using random effects meta-analysis. RESULTS: Twelve studies involving 10,212 participants were included. At 15 days postoperatively, and at the longest point of post-operative follow-up, there was no statistically significant reduction in the risk of SSI when comparing patients who received a perioperative FiO2 of 30% to those with an FiO2 of 80% (RR 1.41, 95% CI 1.00-2.01, p 0.05 and RR 1.23, 95% CI 1.00-1.51, p 0.05). There was no statistically significant difference in mortality between the 30% FiO2 and the 80% FiO2 groups (RR 1.12, 95% CI 0.56-2.22, p 0.76). CONCLUSION: This meta-analysis showed no statistically significant difference in post-operative SSI or mortality when comparing patients receiving an FiO2 of 80% to those receiving an FiO2 of 30%.

Predictors of overall survival following extended radical resections for locally advanced and recurrent pelvic malignancies.

PURPOSE: In an era of personalised medicine, there is an overwhelming effort for predicting patients who will benefit from extended radical resections for locally advanced pelvic malignancy. However, there is paucity of data on the effect of comorbidities and postoperative complications on long-term overall survival (OS). The aim of this study was to define predictors of 1-year and 5-year OS. METHODS: Data were collected from prospective databases at two high-volume institutions specialising in beyond TME surgery for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary outcome measures were 1-year and 5-year OS. RESULTS: A total of 646 consecutive extended radical resections were performed between 1990 and 2015. The majority were female patients (371, 57.4%) and the median age was 63 years (range 19-89 years). One-year OS, primary rectal adenocarcinoma had the best survival while recurrent colon cancer had the worse survival (p = 0.047). The 5-year OS between primary and recurrent cancers were 64.7% and 53%, respectively (p = 0.004). Poor independent prognostic markers for 5-year OS were increasing ASA score, cardiovascular disease, recurrent cancers, ovarian cancers, pulmonary embolus and acute respiratory distress syndrome. A positive survival benefit was demonstrated with preoperative radiotherapy (HR 0.55; 95% CI 0.4-0.75, p < 0.001). CONCLUSION: Patient comorbidities and specific complications can influence long-term survival following extended radical resections. This study highlights important predictors, enabling clinicians to better inform patients of the potential short- and long-term outcomes in the management of locally advanced and recurrent pelvic malignancy.

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.

Complications and 5-year survival after radical resections which include urological organs for locally advanced and recurrent pelvic malignancies: analysis of 646 consecutive cases.

BACKGROUND: Extensive multi-visceral resection, including components of the urinary tract, is often required to achieve clear resection margins, which is now well established as a key predictor of long-term survival for locally advanced pelvic tumours. The aims of this study were to analyse major morbidity and factors predicting complications and long-term outcomes following a urological procedure within extended radical resections. METHODS: Data were collected from prospective databases at two high-volume institutions specialising in extended radical resections for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary endpoints were general major complications (Clavien-Dindo ≥ 3) and factors influencing complications and overall survival after urological resection. RESULTS: A total of 646 consecutive patients requiring an extended radical resection for locally advanced or recurrent pelvic malignancies were identified. The median age was 63 years (range 19-89 years) and the majority were female (371; 57.4%). A urological resection was performed as part of the resection in 226 patients (35.0%). The overall 30-day major complication rate was significantly higher in the urological intervention group (23%; n = 52) compared to the non-urological group (12.9%; n = 54 patients; p = 0.001). Intestinal anastomotic leak (p = 0.001) and intra-abdominal collections (p = 0.001) were more common in the urological cohort. Ileal conduit formation was an independent predictor of major morbidity (OR 1.95; 95% CI 1.24-3.07; p = 0.004). Independent prognostic markers for poor 5-year survival following urological procedures were recurrent tumour, cardiovascular disease, previous thromboembolic event and postoperative pulmonary embolism. CONCLUSIONS: Extended radical resections which include a urological resection are associated with significantly more major morbidity than those without urological resection. Ileal conduit formation is independently associated with the development of major morbidity. Five-year overall survival is no different for patients who had or did not have urological resection as part of extended radical surgery for locally advanced or recurrent pelvic malignancy.

SPAR - a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial.

BACKGROUND: Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG). METHODS: A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1-2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4-5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018. DISCUSSION: When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations. TRIAL REGISTRATION: ANZ Clinical Trials Register ACTRN12617001087347. (www.anzctr.org.au, registered 26/7/2017) Protocol Version: 1.1 (June 2017).

The ALCCaS Trial: A Randomized Controlled Trial Comparing Quality of Life Following Laparoscopic Versus Open Colectomy for Colon Cancer.

BACKGROUND: This study reports the quality-of-life assessment of the ALCCaS trial. The ALCCaS trial compared laparoscopic and open resection for colon cancer. It reported equivalence of survival at 5 years. Quality of life was measured as a secondary outcome. OBJECTIVE: This study aimed to report on the quality of life data of the ALCCaS Trial. DESIGN: This study reports a randomized controlled trial comparing laparoscopic with open colonic resection. SETTINGS: The study was conducted in Australasia. PATIENTS: Patients with a single adenocarcinoma of the right, left, or sigmoid colon, presenting for elective treatment, were eligible for randomization. INTERVENTIONS: Open and laparoscopic colonic resections were performed. MAIN OUTCOME MEASURES: Patient symptoms and quality of life were measured using the Symptoms Distress Scale, the Quality of Life Index, and the Global Quality of Life Score preoperatively, and at 2 days, 2 weeks, and 2 months postoperatively. RESULTS: Of the 592 patients enrolled in ALCCaS, 425 completed at least 1 quality-of-life measure at 4 time points (71.8% of cohort). Those who received the laparoscopic intervention had better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01), Quality of Life Index (p < 0.01), and Global Quality of Life (p < 0.01). In intention-to-treat analyses, those assigned to laparoscopic surgery had a better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01) and Quality of Life Index (p < 0.01), whereas Global Quality of Life was not significant (p = 0.056). The subscales better for laparoscopic resection at all 3 postoperative time points were appetite, insomnia, pain, fatigue, bowel, daily living, and health (p < 0.05). LIMITATIONS: The primary limitation was the different response rates for the 3 quality-of-life measures. CONCLUSIONS: There was a short-term gain in quality of life maintained at 2 months postsurgery for those who received laparoscopic relative to open colonic resection. See Video Abstract at http://links.lww.com/DCR/A691.

Frailty in surgical patients.

OBJECTIVE: To describe the current definitions, aetiology, assessment tools and clinical implications of frailty in modern surgical practice. BACKGROUND: Frailty is a critical issue in modern surgical practice due to its association with adverse health events and poor post-operative outcomes. The global population is rapidly ageing resulting in more older patients presenting for surgery. With this, the number of frail patients presenting for surgery is also increasing. Despite the identification of frailty as a significant predictor of poor health outcomes, there is currently no consensus on how to define, measure and diagnose this important syndrome. METHODS: Relevant references were identified through keyword searches of the Cochran, MEDLINE and EMbase databases. RESULTS: Despite the lack of a gold standard operational definition, frailty can be conceptualised as a state of increased vulnerability resulting from a decline in physiological reserve and function across multiple organ systems, such that the ability to withstand stressors is impaired. Multiple studies have shown a strong association between frailty and adverse peri-operative outcomes. Frailty may be assessed using multiple tools; however, the ideal tool for use in a clinical setting has yet to be identified. Despite the association between frailty and adverse outcomes, few interventions have been shown to improve outcomes in these patients. CONCLUSION: Frailty encompasses a group of individuals at high risk of adverse post-operative outcomes. Further work exploring ways to optimally assess and target interventions towards these patients should be the focus of ongoing research.

Data Sharing Statements for Clinical Trials: A Requirement of the International Committee of Medical Journal Editors.

The International Committee of Medical Journal Editors announces requirements that a data sharing plan be prospectively registered, and a data sharing statement be included in submitted manuscripts, for clinical trials to be published in ICMJE journals.