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).

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.

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).

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.

Laparoscopic Lavage in the Management of Hinchey Grade III Diverticulitis: A Systematic Review.

OBJECTIVE: To compare the outcomes of laparoscopic lavage and sigmoid resection in perforated diverticulitis with purulent peritonitis. BACKGROUND: Peritonitis secondary to perforated diverticulitis has conventionally been managed by resection and stoma formation. Case series have suggested that patients can be safely managed with laparoscopic lavage, resulting in reduced mortality and stoma formation. Recently, 3 randomized controlled trials have published contradictory conclusions. METHODS: MEDLINE from 1946 to present, Cochrane Database of Systematic Reviews, and Cochrane database of Registered clinical trials and EMBASE (all via OVID) were searched using the terms "laparoscopy" AND ("primary resection" OR "Hartmann procedure", OR "sigmoidectomy"), AND "Diverticulitis", AND "Peritonitis" AND "therapeutic irrigation" or "lavage" AND randomized controlled trial and any derivatives of those terms. We included all randomized controlled trials. Data were extracted from each study using a purpose-designed template. Statistical analysis was undertaken using Revman 5. RESULTS: Three randomized controlled trials were identified from 48 potential studies. The analysis included 307 patients of whom 159 underwent laparoscopic lavage. Overall, the rate of reintervention within 30 days postoperatively was 45/159 (28.3%) in the lavage group and 13/148 (8.8%) in the resection group (relative risk 3.01, 95% confidence interval 1.15-7.90). There was no significant difference in Intensive Care Unit admissions, 30 and 90-day mortality, or stoma rates at 12 months. CONCLUSION: Laparoscopic lavage used in the management of Hinchey grade III diverticulitis leads to more reinterventions within 30 days postoperatively, but does not increase the 30 or 90-day mortality rates compared with sigmoid resection.

The Outcomes and Patterns of Treatment Failure After Surgery for Locally Recurrent Rectal Cancer.

OBJECTIVE: To assess the outcomes and patterns of treatment failure of patients who underwent pelvic exenteration surgery for recurrent rectal cancer. BACKGROUND: Despite advances in the management of rectal cancer, local recurrence still occurs. For appropriately selected patients, pelvic exenteration surgery can achieve long-term disease control. METHODS: Prospectively maintained databases of 5 high volume institutions for pelvic exenteration surgery were reviewed and data combined. We assessed the combined endpoints of overall 5-year survival, cancer-specific 5-year mortality, local recurrence, and the development of metastatic disease. RESULTS: Five hundred thirty-three patients who had undergone surgery for locally recurrent rectal cancer were identified. Five-year cancer-specific survival for patients with a complete (R0) resection is 44%, which was achieved in 59% of patients. For those with R1 and R2 resections, the 5-year survival was 26% and 10%, respectively. Radical resection required sacrectomy in 170 patients (32%), and total cystectomy in 105 patients (20%). Treatment failure included local recurrence alone in 75 patients (14%) and systemic metastases with or without local recurrence in 226 patients (42%). Chemoradiotherapy before exenteration was associated with a significant (P < 0.05) improvement in overall 5-year cancer-specific survival for those patients with an R0 resection. Postoperative chemotherapy did not alter outcomes. CONCLUSIONS: R0 resection of the pelvic recurrence is the most significant factor affecting overall and disease-free survival. The surgery is complex and often highly morbid, and where possible patients should be given perioperative chemoradiotherapy. Further investigations are required to determine the role of adjuvant chemotherapy.

Screening for enterotoxigenic Bacteroides fragilis in stool samples.

Bacteroides fragilis is a commensal bacterium found in the gut of most humans, however enterotoxigenic B. fragilis strains (ETBF) have been associated with diarrhoea and colorectal cancer (CRC). The purpose of this study was to establish a method of screening for the Bacteroides fragilis toxin (bft) gene in stool samples, as a means of determining if carriage of ETBF is detected more often in CRC patients than in age-matched healthy controls. Stool samples from 71 patients recently diagnosed with CRC, and 71 age-matched controls, were screened by standard and quantitative PCR using primers specific for the detection of the bft gene. Bacterial template DNA from stool samples was prepared by two methods: a sweep, where all colonies growing on Bacteroides Bile Esculin agar following stool culture for 48 h at 37 °C in an anaerobic environment were swept into sterile water and heat treated; and a direct DNA extraction from each stool sample. The bft gene was detected more frequently from DNA isolated from bacterial sweeps than from matched direct DNA extractions. qPCR was found to be more sensitive than standard PCR in detecting bft. The cumulative total of positive qPCR assays from both sample types revealed that 19 of the CRC patients had evidence of the toxin gene in their stool sample (27%), compared to seven of the age-matched controls (10%). This difference was significant (P = 0.016). Overall, ETBF carriage was detected more often in CRC patient stool samples compared to controls, but disparate findings from the different DNA preparations and testing methods suggests that poor sensitivity may limit molecular detection of ETBF in stool samples.