National screening for colorectal cancer is associated with stage shift to earlier diagnosis.

BACKGROUND: Australia's National Bowel Cancer Screening Program consists of an immunohistochemical faecal occult blood test, targeting adults aged 50-74. Existing literature supports the principle of early detection of colorectal cancer (CRC) via national screening, but little is known about the association between colonoscopy or polypectomy rates and CRC stage over time. The aim of this study is to identify the longitudinal change to colonoscopy and polypectomy rates, and any stage shift associated with this screening program. METHODS: A retrospective data-linkage study was performed using the Australian national health database (Medicare) to obtain colonoscopy and polypectomy rates between 1998 and 2017. A second prospective database of CRC resection specimens was analysed for this period. The cohort was divided based on time intervals related to the National Bowel Cancer Screening Program: pre-commencement 1998-2006 (Period A), immediately post-commencement 2007-2011 (Period B), and subsequent years 2012-2017 (Period C). Linear regression was used to test relation between annualized predictor and response variables. RESULTS: Annual colonoscopy rates doubled, and polypectomy rates tripled during the study (P < 0.001). Annual colonoscopy rate correlated to a lower T-stage (P = 0.038) and lower N-stage (P = 0.026), and there was a 7% increase in early CRC (stage I-II) in Period C (P < 0.001). Across the study period there was also a significant increase in right-sided tumours, and concurrent MMR deficiency and BRAF mutation. CONCLUSION: Polypectomy and colonoscopy rates increased after the introduction of the National Bowel Cancer screening program. There was a clinically significant shift to earlier CRC stage which manifested 5 years after its implementation.

Irritable bowel syndrome worsens faecal incontinence after primary repair of major obstetric anal sphincter injuries.

AIM: Obstetric anal sphincter injuries (OASIS) occur in approximately 3%-6% of vaginal deliveries and are the leading risk factor for late-onset faecal incontinence, which is an underdiagnosed pathology. The aim of this work was to use a validated scoring system to quantify the effect of irritable bowel syndrome (IBS) on the severity of faecal incontinence symptoms after primary repair of major OASIS (Grade IIIb-IV). METHOD: A prospective cohort study was performed on all women who underwent primary repair of major OASIS over a 6-year period. They were assessed with ultrasonography within 12 weeks. Two control groups (who did not have OASIS) were women who underwent elective caesarean section and primigravid women. Questionnaires were sent at least 12 months after delivery, or at first consultation for primigravids, which generated the main outcome measures: Cleveland Clinic faecal incontinence severity scores and the presence of IBS based on Rome III criteria. RESULTS: There was a total of 211 patients included in the three groups and the mean follow-up time was 26 months after sphincter repair. Ultrasonographic sphincter defects were detected in 37% but did not affect the faecal incontinence score (p = 0.47), except in patients with IBS. Within each group, patients with IBS had significantly worse faecal incontinence than those without. Women with both OASIS and IBS had the most severe faecal incontinence scores. CONCLUSION: OASIS has a limited negative effect on faecal incontinence, independent of whether residual ultrasonographic sphincter defects are present. However, the presence of IBS has a significant compounding effect on faecal incontinence in OASIS patients. The effect of IBS on faecal incontinence is also notable in caesarean section patients and primigravids, suggesting that IBS is an independent risk-factor that should have its place in predelivery assessment and counselling.

Mucosal Microbiome in Patients with Early Bowel Polyps: Inferences from Short-Read and Long-Read 16S rRNA Sequencing.

Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with Ruminococcus gnavus and Escherichia coli were elevated in mucosa from polyp patients, while ASVs associated with Parabacteroides merdae, Veillonella nakazawae, and Sutterella wadsworthensis were relatively decreased. Only R. gnavus was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche.

CD11c+ and IRF8+ cell densities in rectal cancer biopsies predict outcomes of neoadjuvant chemoradiotherapy.

Approximately 20% of locally advanced rectal cancer (LARC) patients treated preoperatively with chemoradiotherapy (CRT) achieve pathologically confirmed complete regression. However, there are no clinically implemented biomarkers measurable in biopsies that are predictive of tumor regression. Here, we conducted multiplexed immunophenotyping of rectal cancer diagnostic biopsies from 16 LARC patients treated preoperatively with CRT. We identified that patients with greater tumor regression had higher tumor infiltration of pan-T cells and IRF8+HLA-DR+ cells prior to CRT. High IRF8+HLA-DR+ cell density was further associated with prolonged disease-specific survival with 83% survival at 5 y compared to 28% in patients with low infiltration. Contrastingly, low CD11c+ myeloid cell infiltration prior to CRT was a putative biomarker associated with longer 3- and 5-y disease-free survival. The results demonstrate the potential use of rectal cancer diagnostic biopsies to measure IRF8+ HLA-DR+ cells as predictors of CRT-induced tumor regression and CD11c+ myeloid cells as predictors of LARC patient survival.

The Effects of a Field-Based Priming Session on Perceptual, Physiological, and Performance Markers in Female Rugby Sevens Players.

PURPOSE: This study aimed to determine the effects of a field-based priming session on perceptual, physiological, and performance responses in female rugby sevens athletes. METHODS: Thirteen highly trained female rugby sevens players (age: 20.7 [2.0] y; height: 169.3 [4.8] cm; weight: 68.8 [7.9] kg) completed either a 20-minute field-based priming session or a control condition. Perceptual, physiological, and performance variables were collected at baseline (PRE) and 5 (POST5), 30 (POST30), and 120 minutes (POST120) postintervention. Data were analyzed using Bayesian mixed effects models. RESULTS: The priming protocol had a larger increase in mental readiness (maximum a posteriori [MAP] = 20, 95% high-density intervals [HDI] = -4 to 42, probability of direction [PD]% = 95, % in region of practical equivalence [ROPE] = 9.7), physical readiness (MAP = 20.1, 95% HDI = -4.6 to 42.1, PD% = 93, % in ROPE = 10.6), and testosterone (MAP = 14.9, 95% HDI = 0.5 to 27.7, PD% = 98, % in ROPE = 5.6) than the control POST30. Cognitive performance decreased POST120 in the priming condition for congruent (MAP = 0.02, 95% HDI = -0.06 to 0.00, PD% = 95, % in ROPE = 6.4) and incongruent tasks (MAP = 0.00, 95% HDI = -0.07 to 0.00, PD% = 98, % in ROPE = 3.2) when compared with the control. CONCLUSIONS: Perceptual and physiological markers improved POST30 in the priming condition. Findings indicate that perceptual and physiological responses to priming were not coupled with performance improvements. Priming was not accompanied by perceptual, physiological, or performance improvements at POST120.

Quantification of short-chain fatty acids in human stool samples by LC-MS/MS following derivatization with aniline analogues.

The gut microbiome produces a range of short chain fatty acids (SCFA) crucially linked with diet and nutrition, metabolism, gastrointestinal health and homeostasis. SCFA are primarily measured using gas or liquid chromatography-mass spectrometry (LC/MS) after undergoing chemical derivatization. Here we assess the merits of a derivatization protocol using aniline and two aniline analogues (3-phenoxyaniline and 4-(benzyloxy)aniline) for the targeted LC-MS/MS quantification of nine SCFA (acetic, propionic, butyric, valeric, caproic acid, isobutyric, isovaleric, 2-methylbutyric, and 2-ethylbutyric acid). Evaluation of product ion spectra and optimization of MS detection conditions, provided superior detection sensitivity for 3-phenoxyaniline and 4-(benzyloxy)aniline compared to aniline. We developed a facile SCFA derivatization method using 3-phenoxyaniline under mild reaction conditions which allows for the simultaneous quantification of these SCFA in human stool samples in under eleven minutes using multiple reaction monitoring LC-MS/MS. The method was successfully validated and demonstrates intra- and inter-day accuracy (88.5-103% and 86.0-109%) and precision (CV of 0.55-7.00% and 0.33-9.55%) with recoveries (80.1-87.2% for LLOQ, 88.5-93.0% for ULOQ) and carry-over of (2.68-17.9%). Selectivity, stability and matrix effects were also assessed and satisfied validation criteria. Method applicability was demonstrated by analysing SCFA profiles in DNA-stabilized human stool samples from newly diagnosed colorectal cancer patients prior to surgery. The development of this improved method and its compatibility to measure SCFAs from DNA-stabilized stool will facilitate studies investigating the gut microbiome in health and disease.

Lipid-polymer nanocarrier platform enables X-ray induced photodynamic therapy against human colorectal cancer cells.

In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU) and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells' growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Deep Sequencing of Early T Stage Colorectal Cancers Reveals Disruption of Homologous Recombination Repair in Microsatellite Stable Tumours with High Mutational Burdens.

Early T stage colorectal cancers (CRC) that invade lymph nodes (Stage IIIA) are rare and greatly under-represented in large-scale genomic mapping projects. We retrieved 10 Stage IIIA CRC cases, matched these to 16 Stage 1 CRC cases (T1 depth without lymph node metastasis) and carried out deep sequencing of 409 genes using the IonTorrent system. Tumour mutational burdens (TMB) ranged from 2.4 to 77.2/Mb sequenced. No stage-related mutational differences were observed, consistent with reanalysis of The Cancer Genome Atlas (TCGA) Stage I and IIIA datasets. We next examined mutational burdens and observed that the top five cancers were microsatellite stable (MSS) genotypes (mean TMB 49.3/Mb), while the other 16 MSS cancers had a mean TMB of 5.9/Mb. To facilitate comparison with TCGA hypermutator CRC, we included four microsatellite instability-high (MSI-H) samples with the high mutation burden MSS cases to form a TMB-High group. Comparison of TMB-High with TMB-Low groups revealed differences in mutational frequency of ATM, ALK, NSD1, UBR5, BCL9, CARD11, KDM5C, MN1, PTPRT and PIK3CA, with ATM and UBR5 validated in reanalysis of TCGA hypermutator Stages I and IIIA samples. Variants in ATM were restricted to the TMB-High group, and in four of five MSS specimens, we observed the co-occurrence of mutations in homologous recombination repair (HRR) genes in either two of ATM, CDK12, PTEN or ATR, with at least one of these being a likely pathogenic truncating mutation. No MSI-H specimens carried nonsense mutations in HRR genes. These findings add to our knowledge of early T stage CRC and highlight a potential therapeutic vulnerability in the HRR pathway of TMB-H MSS CRC.

Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals.

BACKGROUND: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3-5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states. METHODS: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals. RESULTS: Tumour testing approaches differed between hospitals, with 0-19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients). CONCLUSIONS: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.

Population-level utilisation of neoadjuvant radiotherapy for the treatment of rectal cancer.

PURPOSE: International clinical guidelines recommend long- or short-course neoadjuvant radiotherapy for locally advanced rectal cancer. This study aims to examine variation in the use of neoadjuvant radiotherapy for rectal cancer and identify patient and hospital factors that underpin this variation. METHODS AND MATERIALS: We conducted a retrospective, consecutive cohort study using statewide hospitalisation and radiotherapy data from New South Wales, Australia, 2013-2018. Included participants had a primary rectal adenocarcinoma and underwent surgical resection. Factors associated with the use or not of any neoadjuvant radiotherapy, and short versus long-course were explored using multilevel logistic regression models. RESULTS: Of the 2912 people included in the study, 43% received neoadjuvant radiotherapy. There was significant variation in the use of neoadjuvant radiotherapy depending on geographic location. Abdominoperineal excision (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.53-2.28) and having surgery in a public hospital (OR = 2.34, 95% CI = 1.92-2.87) were both predictors of use. Among those receiving neoadjuvant radiotherapy, 17% received short-course therapy, with short-course declining over the study period. CONCLUSIONS: The use of neoadjuvant radiotherapy for rectal cancer is highly variable, with differences only partially explained by assessable patient-or hospital-level factors. Understanding neoadjuvant radiotherapy utilisation patterns may assist in identifying barriers and opportunities to improve adherence to clinical guidelines.

Attitudes towards Enhanced Recovery after Surgery (ERAS) interventions in colorectal surgery: nationwide survey of Australia and New Zealand colorectal surgeons.

BACKGROUND: Whilst Enhanced Recovery after Surgery (ERAS) has been widely accepted in the international colorectal surgery community, there remains significant variations in ERAS programme implementations, compliance rates and best practice recommendations in international guidelines. METHODS: A questionnaire was distributed to colorectal surgeons from Australia and New Zealand after ethics approval. It evaluated specialist attitudes towards the effectiveness of specific ERAS interventions in improving short term outcomes after colorectal surgery. The data were analysed using a rating scale and graded response model in item response theory (IRT) on Stata MP, version 15 (StataCorp LP, College Station, TX). RESULTS: Of 300 colorectal surgeons, 95 (31.7%) participated in the survey. Of eighteen ERAS interventions, this study identified eight strategies as most effective in improving ERAS programmes alongside early oral feeding and mobilisation. These included pre-operative iron infusion for anaemic patients (IRT score = 7.82 [95% CI: 6.01-9.16]), minimally invasive surgery (IRT score = 7.77 [95% CI: 5.96-9.07]), early in-dwelling catheter removal (IRT score = 7.69 [95% CI: 5.83-9.01]), pre-operative smoking cessation (IRT score = 7.68 [95% CI: 5.49-9.18]), pre-operative counselling (IRT score = 7.44 [95% CI: 5.58-8.88]), avoiding drains in colon surgery (IRT score = 7.37 [95% CI: 5.17-8.95]), avoiding nasogastric tubes (IRT score = 7.29 [95% CI: 5.32-8.8]) and early drain removal in rectal surgery (IRT score = 5.64 [95% CI: 3.49-7.66]). CONCLUSIONS: This survey has demonstrated the current attitudes of colorectal surgeons from Australia and New Zealand regarding ERAS interventions. Eight of the interventions assessed in this study including pre-operative iron infusion for anaemic patients, minimally invasive surgery, early in-dwelling catheter removal, pre-operative smoking cessation, pre-operative counselling, avoidance of drains in colon surgery, avoiding nasogastric tubes and early drain removal in rectal surgery should be considered an important part of colorectal ERAS programmes.

Effects of Knowledge of Results and Change-Oriented Feedback on Swimming Performance.

PURPOSE: This study examined the effect of providing knowledge of results (KR) with, and without, promotion- and change-oriented feedback on repeated-sprint ability in swimmers. METHODS: Twenty-nine male and female swimmers (age = 16 [1] y, height = 1.74 [0.07] m, body mass = 61.0 [8.4] kg) were randomly allocated into 2 different feedback conditions, or a condition without feedback (NoFb), as a crossover, repeated-measures design. In one feedback condition, the swimmers were provided with lap completion times as KR. The other feedback condition was athlete-driven, where the swimmers were asked to estimate their lap completion times, and the investigators responded on whether their actual sprint times were faster (promotion-oriented), slower (change-oriented), or the same. RESULTS: The results showed significantly faster average completion times during the repeated-sprint swim protocol in the athlete-driven KR (P = .014) and KR condition (P = .023), when compared with the NoFb condition. However, significantly faster best completion time was only found in the KR condition (P = .012), when compared with the NoFb condition. Furthermore, the stroke rate was significantly greater during the athlete-driven KR (P = .009) and KR (P = .021) conditions, when compared with the NoFb condition. CONCLUSIONS: The KR condition exhibited the greatest benefit for improving several swimming performance measures during a repeated-sprint protocol, and the increase in stroke rate may have contributed to this performance enhancement. Thus, it is recommended that swimmers receive lap completion times during repeated-sprint training sessions to optimize training quality.

Computed tomography (CT)-defined sarcopenia and myosteatosis are prevalent in patients with neuroendocrine neoplasms (NENs) treated with peptide receptor radionuclide therapy (PRRT).

BACKGROUND/OBJECTIVES: Neuroendocrine neoplasms (NEN) may predispose patients to malnutrition. CT-defined sarcopenia and myosteatosis are common in other tumour types and recognized adverse prognostic factors. However, the prevalence and prognostic impact of sarcopenia and myosteatosis remain undetermined in NEN patients to date. METHODS: A retrospective study of NEN patients treated with peptide receptor radionuclide therapy (PRRT) at a tertiary institution from 2012 to 2017. Patients with PET/CT imaging at baseline and follow-up were included. The L3 slice of the co-localizing CT was analysed using the Alberta Protocol. Skeletal muscle cross-sectional area and muscle attenuation were measured and compared with pre-defined cut-offs. The primary endpoint was the prevalence of sarcopenia and myosteatosis according to previously published cut-offs. RESULTS: Fourty-nine patients (median age 64 (range 26-80) years) were included. The most common primary sites of tumour were the small bowel (51%) and pancreas (26%). Baseline sarcopenia was prevalent in 67% of patients and myosteatosis in 71%. Forty-five percent of patients gained weight over the course of PRRT. The presence of baseline sarcopenia was not associated with progression-free survival (20.8 mo vs. 20.7 mo, HR 0.86, p = 0.70) nor overall survival. Similarly, baseline myosteatosis (PFS 19.5 mo vs. 20.8 mo, HR 0.77, p = 0.47) was not significantly associated with survival outcomes. The mean (SD) age of those with myosteatosis was 60.8 ± 11.6 years compared to 49.7 ± 12.7 years for those without (p = 0.003). CONCLUSIONS: Body composition analysis is feasible using routinely acquired PET/CT data for patients with NEN. CT-defined sarcopenia and myosteatosis are prevalent in NEN patients, although myosteatosis is more common with increasing age. These findings were not associated with worsened overall or progression-free survival in the current study.

Effect of a Fundamental Motor Skills Intervention on Fundamental Motor Skill and Physical Activity in a Preschool Setting: A Cluster Randomized Controlled Trial.

PURPOSE: To determine the effect of a 12-week fundamental motor skill (FMS) program on FMS and physical activity (PA) on preschool-aged children. METHOD: A cluster randomized controlled trial. The intervention (PhysicaL ActivitY and Fundamental Motor Skills in Pre-schoolers [PLAYFun] Program) was a 12-week games-based program, delivered directly to the children in childcare centers by exercise physiologists. Children in the control arm received the usual preschool curriculum. Outcomes included FMS competence (Test of Gross Motor Development-2) and PA (accelerometer) assessed at baseline, 12 weeks, and 24 weeks (12-wk postintervention). RESULTS: Fifty children (mean age = 4.0 [0.6] y; 54% male) were recruited from 4 childcare centers. Two centers were randomized to PLAYFun and 2 centers were randomized to the waitlist control group. Children attended on average 2.0 (1.0) 40-minute sessions per week. The PLAYFun participants demonstrated significant increases in object control (P < .001) and total FMS (P = .010) competence at week 12, compared with controls in a group × time interaction. Girls, but not boys, in PLAYFun significantly increased moderate to vigorous PA after the intervention (P = .004). These increases were not maintained 12-week postcompletion of PLAYFun. CONCLUSIONS: The PLAYFun Program is effective at improving FMS competence in boys and girls and increasing PA in girls. However, improvements are not maintained when opportunities to practice are not sustained.

Highly specific detection of KRAS single nucleotide polymorphism by asymmetric PCR/SERS assay.

The molecular diagnosis of KRAS mutations has become crucial for clinical decision-making in colorectal cancer (CRC) treatments. Currently, the common methods for detecting mutations are based on quantitative PCR, DNA sequencing and droplet digital PCR (ddPCR), which require expensive specialized equipment and testing reagents. Herein, we propose a simple and specific strategy by integrating asymmetric PCR with surface-enhanced Raman spectroscopy (Asy-PCR/SERS) for the detection of KRAS G12V mutation, one of the most common driver mutations in CRC. To discriminate mutant targets from non-targets, Asy-PCR was applied to obtain single-stranded DNA (ssDNA) with unequal amounts of forward and reverse primers, subsequently, detection of the target mutant ssDNA amplicons was attempted by hybridization with Raman reporter-coded and allele-specific oligonucleotide-functionalized gold nanoparticles (SERS nanotags). The oligo encoding of the KRAS G12V mutant sequence could be identified by using a portable Raman spectrometer where the characteristic spectra of SERS nanotags indicate the presence of mutant targets. The Asy-PCR/SERS method showed high specificity and sensitivity for identifying as few as 0.1% mutant alleles of KRAS G12V mutation from non-target sequences. Using colorectal polyp biopsies, we demonstrated that Asy-PCR/SERS assay could distinguish KRAS G12V (c.35G > T) and KRAS G12D (c.35G > A) which occur at the same nucleotide location. As KRAS G12V is a driver oncogene in other cancers including lung, pancreatic, ovarian and endometrial cancers, the proposed assay shows great potential for application in additional tumor streams.

Correction: Serum bicarbonate is a marker of peri-operative mortality but is not associated with long term survival in colorectal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0228466.].

Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps.

Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium, known as polyps. Polyps themselves arise through the accumulation of mutations that disrupt the function of key tumour suppressor genes, activate proto-oncogenes and allow proliferation in an environment where immune control has been compromised. Consequently, colonoscopic surveillance and polypectomy are central pillars of cancer control strategies. Recent advances in genomic sequencing technologies have enhanced our knowledge of key driver mutations in polyp lesions that likely contribute to CRC. In accordance with the prognostic significance of Immunoscores for CRC survival, there is also a likely role for early immunological changes in polyps, including an increase in regulatory T cells and a decrease in mature dendritic cell numbers. Gut microbiotas are under increasing research interest for their potential contribution to CRC evolution, and changes in the gut microbiome have been reported from analyses of adenomas. Given that early changes to molecular components of bowel polyps may have a direct impact on cancer development and/or act as indicators of early disease, we review the molecular landscape of colorectal polyps, with an emphasis on immunological and microbial alterations occurring in the gut and propose the potential clinical utility of these data.

Liposome technologies towards colorectal cancer therapeutics.

Colorectal cancer (CRC) is the third most common cancer and the fourth most common deadly cancer worldwide. After treatment with curative intent recurrence rates vary with staging 0-13% in Stage 1, 11-61% in S2 and 28-73% in Stage 3. The toxicity to healthy tissues from chemotherapy and radiotherapy and drug resistance severely affect the quality of life and cancer specific outcomes of CRC patients. To overcome some of these limitations, many efforts have been made to develop nanomaterial-based drug delivery systems. Among these nanocarriers, liposomes represented one of the most successful candidates in delivering targeted oncological treatment, improving safety profile and therapeutic efficacy of encapsulated drugs. In this review we will discuss liposome design with a particular focus on the targeting feature and triggering functions. We will also summarise the recent advances in liposomal delivery system for CRC treatment in both the preclinical and clinical studies. We will finally provide our perspectives on the liposome technology development for the future clinical translation. STATEMENT OF SIGNIFICANCE: Conventional treatments for colorectal cancer (CRC) severely affect the therapeutic effects for advanced patients. With the development of nanomedicines, liposomal delivery system appears to be one of the most promising nanocarriers for CRC treatment. In last three years several reviews in this area have been published focusing on the preclinical research and drug delivery function, which is a fairly narrow focus in the field of liposome technology for CRC therapy. Our review presented the most recent advances of the liposome technology (both clinical and preclinical applications) for CRC with strong potential for further clinical translation. We believe it will attract lots of attention from various audiences, including researchers, clinicians and the industry.

Bowel Preparation and Oral Antibiotic Agents for Selective Decontamination in Colorectal Surgery: Current Practice, Perspectives, and Trends in Australia and New Zealand, 2019-2020.

Background: There has been much debate as to the importance of mechanical bowel preparation (MBP) and oral antibiotic agents (OAB) prior to elective colorectal surgery over the past two decades. There is no consensus between international guidelines. Methods: The Australia and New Zealand Mechanical Bowel Preparation and Oral Antibiotics (ANZ-MBP-OAB) questionnaire was distributed to colorectal surgeons after institutional board approval assessing specialist attitudes toward 18 enhanced recovery after surgery (ERAS) interventions. Data were analyzed using a rating scale and graded response model in item response theory (IRT) on Stata MP, version 15 (StataCorp LP, College Station, TX). Specialist attitudes toward the effectiveness of MBP and OAB strategies in providing better short-term outcomes was ranked alongside other ERAS interventions. This was followed by specific questions examining current practice, perspectives, and trends. Results: Ninety-five of 300 (31.7%) colorectal surgeons in Australia and New Zealand participated in the survey. Statistical modeling was achieved in 13 ERAS interventions. Compared with other ERAS interventions, the use of MBP with OAB and MBP alone ranked nine of 13 and 10 of 13, respectively, in order of effectiveness in providing better short-term outcomes after colorectal surgery. Oral antibiotic agents alone was not considered effective. Mechanical bowel preparation with OAB was considered to be the best strategy in both colon (37%) and rectal surgery (48%) but current practice varied substantially from perspective. Mechanical bowel preparation alone was strongly favored in rectal surgery (81%) with only 14% using MBP with OAB. In colon surgery, only 10% used MBP with OAB, with MBP alone (45%) and no preparation (45%) being equally the most commonly used strategies. Conclusions: Among Australian and New Zealand colorectal surgeons, MBP with OAB was considered the best bowel preparation strategy. However, despite an awareness of its benefits, MBP with OAB has yet to be widely adopted into clinical practice or guidelines in Australia and New Zealand.