Comparison of quality of life, symptom and functional outcomes following surgical treatment for colorectal neoplasia.

BACKGROUND: Colorectal surgical procedures can have a significant impact on quality-of-life (QoL), functional and symptom outcomes. This retrospective study conducted in a tertiary care center evaluated the influence of four colorectal surgical procedures on patient-reported outcome measures (PROMs). METHODS: 512 patients undergoing colorectal neoplasia surgery between June 2015 and December 2017 were identified via the Cabrini Monash Colorectal Neoplasia database. Primary outcomes measured were the mean changes in PROMs following surgery utilizing the International Consortium of Health Outcome Measures colorectal cancer (CRC) PROMs. RESULTS: 242 patients from 483 eligible patients responded (50% participation rate). Responders and non-responders were comparable in median age (72 vs. 70 years), gender (48% vs. 52% male), time from surgery (<1 and >1 year), overall stage at diagnosis and type of surgery. Respondents underwent either a right hemicolectomy, ultra-low anterior resection, abdominoperineal resection or a transanal endoscopic microsurgery/transanal minimally invasive surgery. Right hemicolectomy patients reported the best post-operative function and reduced symptoms, significantly better (P < 0.01) than ultra-low anterior resection patients who reported the worst outcomes in multiple areas (body image, embarrassment, flatulence, diarrhoea, stool frequency). Furthermore, patients undergoing an abdominoperineal resection reported the worst scores for body image, urinary frequency, urinary incontinence, buttock pain, faecal incontinence and male impotence. CONCLUSIONS: The differences in PROMs in CRC surgical procedures is demonstrable. The worst post-operative functional and symptom scores were reported after either an ultra-low anterior resection or an abdominoperineal resection. Implementation of PROMs will identify and aid early patient referral to allied health and support services.

Factors affecting the post-operative outcomes in patients aged over 80 following colorectal cancer surgery.

PURPOSE: In 2019, in Australia, there were 500,000 people aged 85 and over. Traditionally, clinicians have adopted the view that surgery is not desirable in this cohort due to increasing perioperative risk, perceived minimal clinical benefit, and shortened life expectancy. This cohort study is aimed at investigating postoperative outcomes from elective and non-elective colorectal cancer surgery in patients aged 80 and over. METHODS: A retrospective analysis was conducted on patients from 2010 to 2020 on a prospectively maintained colorectal database. Patients aged over 80 who underwent surgical resection for colorectal cancer were reviewed. Oncological characteristics, short-term outcomes, overall survival, and relapse-free survival rates were analysed. RESULTS: A total of 832 patients were identified from the database. Females comprised 55% of patients aged 80 and above. The median age was 84 for octogenarians and 92 for nonagenarians. Most patients were ASA 2 (212) or ASA 3 (501). ASA 3 and 4 and stage III pathology were associated with higher postoperative complications. Fifty percent of over 80 s and 37% of over 90 s were surgically discharged to their own home. Overall survival at 30, 180, and 360 days and 5 years was 98.1%, 93.1%, 87.2%, and 57.2% for the over 80 s and 98.1%, 88.9%, 74.9%, and 24.4% for the over 90 s. CONCLUSION: Our results demonstrate that surgical treatment of older patients is safe with acceptable short-, medium-, and long-term survival. Nonetheless, efforts are needed to reduce the rates of complications in older patients, including utilisation of multi-disciplinary teams to assess the optimal treatment strategy and postoperative care.

The effect of anti-spasmodic administration on the accuracy of magnetic resonance imaging staging of rectal cancer.

BACKGROUNDS: Magnetic resonance imaging is the primary method for local staging in rectal cancer patients. Administration of intravenous (IV) hyoscine butylbromide is thought to improve accuracy, but there are contraindications and potential adverse effects. The aim was to assess the efficacy of IV hyoscine butylbromide on the accuracy of MRI rectal cancer staging of T2 and T3 rectal cancers. METHODS: A retrospective cohort study was carried out on patients prospectively recorded on the Cabrini Monash colorectal neoplasia database. A total of 74 patients (53 males, 21 females) MRI pelvis and rectums with antispasmodics were performed at multiple centres in the pre-operative setting between 2010 and 2016. Each patient underwent total mesorectal excision of rectal cancer. The excision specimens were assessed and given a pathological TNM stage, which was considered the reference standard. RESULTS: There was no statistically significant impact on the overall accuracy of MRI rectal cancer staging between patient groups who received IV hyoscine butylbromide and groups who did not receive IV hyoscine butylbromide. The accuracy of T2 and T3 staged rectal cancers was more likely to be correct (compared with T1 cancers) with the administration of IV hyoscine butylbromide. Still, there was no improvement in the accuracy of N-staging. CONCLUSION: Given the potential side effects and adverse outcomes of IV anti-spasmodic agents, department protocols may need to be re-assessed regarding the prescription of these medications for MRI rectal cancer staging.

Impact of Anastomotic Leak on Long-term Oncological Outcomes After Restorative Surgery for Rectal Cancer: A Retrospective Cohort Study.

BACKGROUND: Anastomotic leak after restorative surgery for rectal cancer is a major complication and may lead to worse long-term oncological and survival outcomes. OBJECTIVE: The purpose of this study was to identify risk factors associated with anastomotic leak and to assess the perioperative and long-term oncological impact of anastomotic leak in our cohort of patients with rectal cancer. DESIGN: A retrospective analysis was performed on data from the prospectively maintained Cabrini Monash colorectal neoplasia database. Patients who had undergone rectal cancer resection and subsequently received anastomosis between November 2009 and May 2020 were included in this study. Patient and tumor characteristics, technical risk factors, and short-term and perioperative as well as long-term oncological and survival outcomes were assessed. SETTINGS: The study was conducted in 3 tertiary hospitals. PATIENTS: A total of 693 patients met the inclusion criteria for this study. MAIN OUTCOME MEASURES: Univariate analyses were performed to assess the relationship between anastomotic leak and patient and technical risk factors, as well as perioperative and long-term outcomes. Univariate and multivariate proportional HR models of overall and disease-free survival were calculated. Kaplan-Meier survival analyses assessed disease-free and overall survival. RESULTS: Anastomotic leak rate was 3.75%. Males had an increased risk of anastomotic leak, as did patients with hypertension and ischemic heart disease. Patients who experience an anastomotic leak were more likely to require reoperation and hospital readmission and were more likely to experience an inpatient death. Disease-free and overall survival were also negatively impacted by anastomotic leaks. LIMITATIONS: This is a retrospective analysis of data from only 3 centers with the usual limitations. However, these effects have been minimized because of the high quality and completeness of the prospective data collection. CONCLUSIONS: Anastomotic leaks after restorative surgery negatively affect long-term oncological and survival outcomes for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/C81 . IMPACTO DE LA FUGA ANASTOMTICA EN LOS RESULTADOS ONCOLGICOS A LARGO PLAZO TRAS CIRUGA RESTAURADORA PARA EL CNCER DE RECTO UN ESTUDIO DE COHORTE RETROSPECTIVO: ANTECEDENTES:La fuga anastomótica tras una cirugía restauradora para el cáncer de recto es una complicación mayor y puede conducir a peores resultados oncológicos y de supervivencia a largo plazo.OBJETIVO:El propósito de este estudio fue identificar los factores de riesgo asociados con la fuga anastomótica y evaluar el impacto oncológico perioperatorio y a largo plazo de la fuga anastomótica en nuestra cohorte de pacientes con cáncer de recto.DISEÑO:Se realizó un análisis retrospectivo de datos obtenidos de la base de datos Cabrini Monash sobre neoplasia colorrectal la cual es mantenida prospectivamente. Se incluyeron en este estudio pacientes que fueron sometidos a una resección del cáncer de recto y que posteriormente recibieron una anastomosis entre noviembre de 2009 y mayo de 2020. Se evaluaron las características del paciente y del tumor, los factores de riesgo relacionados a la técnica, los resultados oncológicos y de supervivencia perioperatorio, así como los resultados a corto y largo plazo.AJUSTES:El estudio se realizó en tres hospitales terciarios.PACIENTES:Un total de 693 pacientes cumplieron con los criterios de inclusión para este estudio.PRINCIPALES MEDIDAS DE RESULTADO:Se realizaron análisis univariados para evaluar la relación entre la fuga anastomótica y aquellos factores relacionados al paciente, a la técnica, así como los resultados perioperatorios y a largo plazo. Se calcularon modelos de razón de riesgo proporcional univariante y multivariante de supervivencia global y libre de enfermedad. Los análisis de supervivencia de Kaplan-Meier evaluaron la supervivencia libre de enfermedad y la supervivencia global.RESULTADOS:La tasa de fuga anastomótica fue del 3,75%. Los hombres tenían un mayor riesgo de fuga anastomótica al igual que aquellos pacientes con hipertensión y cardiopatía isquémica. Los pacientes que sufrieron una fuga anastomótica tuvieron mayores probabilidades de requerir una reintervención y reingreso hospitalario, así como también tuvieron mayores probabilidades de sufrir una muerte hospitalaria. La supervivencia libre de enfermedad y general también se vio afectada negativamente por las fugas anastomóticas.LIMITACIONES:Este es un análisis retrospectivo de datos de solo tres centros con las limitaciones habituales. Sin embargo, estos efectos han sido minimizados debido a la alta calidad y la exhaustividad de la recopilación prospectiva de datos.CONCLUSIONES:Las fugas anastomóticas después de una cirugía restauradora afectan negativamente los resultados oncológicos y de supervivencia a largo plazo para los pacientes con cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/C81 . (Traducción-Dr. Osvaldo Gauto ).

Preferential Antibody and Drug Conjugate Targeting of the ADAM10 Metalloprotease in Tumours.

ADAM10 is a transmembrane metalloprotease that sheds a variety of cell surface proteins, including receptors and ligands that regulate a range of developmental processes which re-emerge during tumour development. While ADAM10 is ubiquitously expressed, its activity is normally tightly regulated, but becomes deregulated in tumours. We previously reported the generation of a monoclonal antibody, 8C7, which preferentially recognises an active form of ADAM10 in human and mouse tumours. We now report our investigation of the mechanism of this specificity, and the preferential targeting of 8C7 to human tumour cell xenografts in mice. We also report the development of novel 8C7 antibody-drug conjugates that preferentially kill cells displaying the 8C7 epitope, and that can inhibit tumour growth in mice. This study provides the first demonstration that antibody-drug conjugates targeting an active conformer of ADAM10, a widely expressed transmembrane metalloprotease, enable tumour-selective targeting and inhibition.

A comparison of extracorporeal side to side or end to side anastomosis following a laparoscopic right hemicolectomy for colon cancer.

BACKGROUND: This study aimed to investigate whether an extracorporeal side-to-side (SS) or end-to-side (ES) stapled anastomosis impacts short-term and long-term outcomes after an oncological laparoscopic right hemicolectomy. METHODS: A retrospective cohort study of prospectively collected data from two Victorian tertiary referral hospitals was performed. Patients who underwent oncological resection for colorectal cancer between February 2010 and September 2020 were selected from the colorectal neoplasia database. Patients were divided into two groups depending on the type of stapled anastomosis: Group 1 (functional end-to-end/side-to-side (SS)); and Group 2 (end-to-side (ES)). Primary outcomes were anastomotic leak, postoperative ileus, mortality and morbidity, length of stay post-surgery, readmission to hospital, and 30-day mortality. RESULTS: This large case series of 1040 patients (SS = 625, ES = 415) demonstrated that the type of stapling technique impacted operative duration and postoperative ileus rates. Patients in the SS group had a faster operation of 108 min rather than 130 min in the ES group (p < 0.001). The SS group were more likely to experience a post-operative ileus (p < 0.001) with no impact on length of stay (SS, 7 days versus ES, 7 days; p = 0.14). There were no differences between the two groups with respect to lymph node yield, lymph node ratio, anastomotic leaks, return to theatre, 30-day mortality and 5-year overall survival. DISCUSSION: The type of extracorporeal stapled anastomosis following an oncological laparoscopic right hemicolectomy has minimal impact on morbidity and survival outcomes; however, a side-to-side stapled anastomosis is more likely to be a faster operation with a higher postoperative ileus rate.

Modeling colorectal cancer: A bio-resource of 50 patient-derived organoid lines.

BACKGROUND AND AIM: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. To improve outcomes for these patients, we need to develop new treatment strategies. Personalized cancer medicine, where patients are treated based on the characteristics of their own tumor, has gained significant interest for its promise to improve outcomes and reduce unnecessary side effects. The purpose of this study was to examine the potential utility of patient-derived colorectal cancer organoids (PDCOs) in a personalized cancer medicine setting. METHODS: Patient-derived colorectal cancer organoids were derived from tissue obtained from treatment-naïve patients undergoing surgical resection for the treatment of CRC. We examined the recapitulation of key histopathological, molecular, and phenotypic characteristics of the primary tumor. RESULTS: We created a bio-resource of PDCOs from primary and metastatic CRCs. Key histopathological features were retained in PDCOs when compared with the primary tumor. Additionally, a cohort of 12 PDCOs, and their corresponding primary tumors and normal sample, were characterized through whole exome sequencing and somatic variant calling. These PDCOs exhibited a high level of concordance in key driver mutations when compared with the primary tumor. CONCLUSIONS: Patient-derived colorectal cancer organoids recapitulate characteristics of the tissue from which they are derived and are a powerful tool for cancer research. Further research will determine their utility for predicting patient outcomes in a personalized cancer medicine setting.

Subjective Well-Being and Parenthood in Chile.

Being a parent plays an important role in people's life trajectory and identity. Though the general cultural perception is that having children is a source of subjective well-being, there is evidence that, at least in some societies, the subjective well-being of those who are parents is worse, in some aspects, than that of those who are not. This gap has been the object of interest and controversy. The aim of this study was to compare Chilean adults with and without children in a broad set of well-being indicators, controlling for other sociodemographic variables. A public national probabilistic database was used. The results show that, in terms of positive and negative affect, those who are not parents achieve greater well-being than those who have children. Other results also pointed in that direction. The implications of the social context and gender, which are aspects that pose a burden for the exercise of parenthood in Chile, are discussed.

Rectum versus colon: should malignant polyps be treated differently?

BACKGROUND: The management of malignant colorectal polyps removed at endoscopy remains controversial with patients either undergoing surgical resection or regular endoscopic surveillance. Lymph node (LN) metastases occur in 6-16% of patients with malignant polyps. This study assessed the rate of LN metastases in patients undergoing surgical resection for malignant polyps removed endoscopically to determine if there is a difference in the rate of LN metastases between colonic and rectal polyps. METHODS: A retrospective review of a prospectively maintained database was performed from 2010 to 2018. All patients who underwent surgical resection following endoscopic removal of a malignant colorectal polyp were reviewed. Clinical data including patient demographics and tumour characteristics were examined. RESULTS: A total of 177 patients underwent surgical resection in the study period. The median age at diagnosis was 65 years (range 22-88 years) with females comprising 52% of the patient cohort (n = 92/177). Polyps were located in the colon in 60.5% of cases with the remainder located in the rectum. The median number of LN harvested was 14 (range 0-44) with malignant LN (including a mesenteric tumour deposit) identified in 8.5% of resection specimens (n = 15/177). Malignant LNs were retrieved in 5.5% of right-sided tumours, 5.6% of left-sided tumours and 12.9% of rectal tumours (P = 0.090). CONCLUSION: A small proportion of patients with malignant polyps removed endoscopically will have LN metastases. The results of this study suggest that the tumour location might be a useful predictive marker; however, a further study with increased patient numbers is required to properly establish this finding.

Log odds of positive lymph nodes is prognostically equivalent to lymph node ratio in non-metastatic colon cancer.

BACKGROUND: Globally, colorectal cancer (CRC) is the third and second leading cancer in men and women respectively with 600,000 deaths per year. Traditionally, clinicians have relied solely on nodal disease involvement, and measurements such as lymph node ratio (LNR; the ratio of metastatic/positive lymph nodes to total number of lymph nodes examined), when determining patient prognosis in CRC. The log odds of positive lymph nodes (LODDS) is a logistic transformation formula that uses pathologic lymph node data to stratify survival differences among patients within a single stage of disease. This formula allows clinicians to identify whether patients with clinically aggressive tumours fall into higher-risk groups regardless of nodal positivity and can potentially guide adjuvant treatment modalities. The aim of this study was to investigate whether LODDS in colon cancer provides better prognostication compared to LNR. METHODS: A retrospective study of patients on the prospectively maintained Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from hospitals in Melbourne Australia, identified patients entered between January 2010 and March 2016. Association of LODDS and LNR with clinical variables were analysed. Disease-free (DFS) and overall (OS) survival were investigated with Cox regression and Kaplan-Meier survival analyses. RESULTS: There were 862 treatment episodes identified in the database (402 male, 47%). The median patient age was 73 (range 22-100 years). There were 799 colonic cancers and 63 rectosigmoid cancers. The lymph node yield (LNY) was suboptimal (< 12) in 168 patients (19.5%) (p = 0.05). The 5-year OS for the different LNR groups were 86, 91 and 61% (p < 0.001) for LNR0 (655 episodes), LNR1 (128 episodes) and LNR2 (78 episodes), respectively. For LODDS, they were 85, 91 and 61% (p < 0.001) in LODDS0 (569 episodes), LODDS1 (217 episodes) and LODDS2 (75 episodes) groups (p < 0.001). Overall survival rates were comparable between the LNR and LODDS group and for LNY < 12 and stage III patients when each were sub-grouped by LODDS and LNR. CONCLUSION: This study has shown for that the prognostic impact of LODDS is comparable to LNR for colon cancer patients. Accordingly, LNR is recommended for prognostication given its ease of calculation.

Predictive factors of complete pathological response in patients with locally advanced rectal cancer.

PURPOSE: Patients with locally advanced rectal cancer who achieve pathologic complete response (pCR) following neoadjuvant therapy have better long-term outcomes and could be spared from the perioperative and long-term morbidity of rectal resection. The aim of this study was to identify factors that predict the ability to achieve pCR at completion of conventional neoadjuvant therapy, therefore determining their suitability for non-surgical management. METHODS: A retrospective analysis was performed on data obtained from a prospectively maintained colorectal neoplasia database. Patients treated for biopsy-proven primary rectal adenocarcinoma between January 1, 2010, and February 28, 2018, who received neoadjuvant radiotherapy or chemoradiotherapy and had undergone surgical resection, were included in this study. Five-year oncologic outcome data was also obtained for 144 patients. Clinicopathological tumour characteristics and treatment regimens were analysed for correlation to clinical outcome. RESULTS: Three hundred fifty-four patients met inclusion criteria for this study. We identified significant differences between patients achieving a pCR and those that did not for tumour type (adenocarcinoma vs. mucinous/signet ring; p = 0.008), pre-treatment serum CEA level (

Patient-Derived Colorectal Cancer Organoids Upregulate Revival Stem Cell Marker Genes following Chemotherapeutic Treatment.

Colorectal cancer stem cells have been proposed to drive disease progression, tumour recurrence and chemoresistance. However, studies ablating leucine rich repeat containing G protein-coupled receptor 5 (LGR5)-positive stem cells have shown that they are rapidly replenished in primary tumours. Following injury in normal tissue, LGR5+ stem cells are replaced by a newly defined, transient population of revival stem cells. We investigated whether markers of the revival stem cell population are present in colorectal tumours and how this signature relates to chemoresistance. We examined the expression of different stem cell markers in a cohort of patient-derived colorectal cancer organoids and correlated expression with sensitivity to 5-fluorouracil (5-FU) treatment. Our findings revealed that there was inter-tumour variability in the expression of stem cell markers. Clusterin (CLU), a marker of the revival stem cell population, was significantly enriched following 5-FU treatment and expression correlated with the level of drug resistance. Patient outcome data revealed that CLU expression is associated with both lower patient survival and an increase in disease recurrence. This suggests that CLU is a marker of drug resistance and may identify cells that drive colorectal cancer progression.

Molecular signature of interleukin-22 in colon carcinoma cells and organoid models.

Interleukin (IL)-22 activates STAT (signal transducer and activator of transcription) 3 and antiapoptotic and proproliferative pathways; but beyond this, the molecular mechanisms by which IL-22 promotes carcinogenesis are poorly understood. Characterizing the molecular signature of IL-22 in human DLD-1 colon carcinoma cells, we observed increased expression of 26 genes, including NNMT (nicotinamide N-methyltransferase, ≤10-fold) and CEA (carcinoembryonic antigen, ≤7-fold), both known to promote intestinal carcinogenesis. ERP27 (endoplasmic reticulum protein-27, function unknown, ≤5-fold) and the proinflammatory ICAM1 (intercellular adhesion molecule-1, ≤4-fold) were also increased. The effect on CEA was partly STAT3-mediated, as STAT3-silencing reduced IL-22-induced CEA by ≤56%. Silencing of CEA or NNMT inhibited IL-22-induced proliferation/migration of DLD-1, Caco-2, and SW480 colon carcinoma cells. To validate these results in primary tissues, we assessed IL-22-induced gene expression in organoids from human healthy colon and colon cancer patients, and from normal mouse small intestine and colon. Gene regulation by IL-22 was similar in DLD-1 cells and human and mouse healthy organoids. CEA was an exception with no induction by IL-22 in organoids, indicating the 3-dimensional organization of the tissue may produce signals absent in 2D cell culture. Importantly, augmentation of NNMT was 5-14-fold greater in human cancerous compared to normal organoids, supporting a role for NNMT in IL-22-mediated colon carcinogenesis. Thus, NNMT and CEA emerge as mediators of the tumor-promoting effects of IL-22 in the intestine. These data advance our understanding of the multifaceted role of IL-22 in the gut and suggest the IL-22 pathway may represent a therapeutic target in colon cancer.

The role of preoperative CEA in the management of colorectal cancer: A cohort study from two cancer centres.

BACKGROUND: The primary aim of this study was to investigate whether a preoperative elevation in serum CEA is an independent prognostic factor for both 5-year overall and disease-free survival within an Australian patient cohort. MATERIALS AND METHODS: A retrospective study of a prospectively maintained colorectal neoplasia database for patients between January 2010 and June 2016 was performed. Patients were categorized into two groups according to the preoperative serum CEA level: low (<2.5), high CEA (≥2.5), and elevated (≥5 ng/ml); and further stratified by disease stage. Inclusion criteria were patients having had a resection for either a colonic or upper third rectal adenocarcinoma and with a preoperative CEA value. Data on patient demographics, mortality, and morbidity and survival were compiled. Five-year estimates of overall (OS) and disease-free survival (DFS) were assessed. RESULTS: 623 patients met the inclusion criteria. The median patient age was 73 (range 22-97) and 55% female (n = 340). There were 572 colonic cancers and 51 rectal cancers. The median follow-up time was 25 months (range 1-71). Eight patients (1%) had a local recurrence and 62 patients (10%) had evidence of metastatic disease after the initial curative resection. The 5-year OS and DFS rates for patients with CEA level <2.5 ng/ml were 85% and 86% respectively, which were higher than those with CEA level ≥2.5 ng/ml (73% and 79% respectively). Independent predictors of recurrence were a CEA ≥5 ng/ml (HR 1.8; 95% CI 1.09-3.00; p = 0.002) and stage II (HR 5.33; 95% CI 1.59-17.90; p = 0.007) and stage III (HR 10.91; 95% CI 3.34-35.60; p=<0.001). A CEA ≥5 ng/ml was associated with a higher risk of death (HR 1.79; 95% CI 1.00-3.19; p = 0.046). CONCLUSION: Preoperative CEA levels were associated with age, BMI, ASA and tumour stage. Overall, CEA remains a reliable predictor of recurrence and survival after curative surgery in patients with colorectal cancer.

Immunohistochemistry testing for mismatch repair deficiency in Stage 2 colon cancer: A cohort study of two cancer centres.

BACKGROUND/OBJECTIVES: Adjuvant chemotherapy for Stage II colon cancer offers a small (2-3%) overall survival benefit and is not universally recommended. Mismatch repair deficiency (dMMR) confers an improved prognosis identifying patients unlikely to benefit from adjuvant chemotherapy. The aim of this study was to investigate the use of dMMR immunohistochemistry in two major cancer treatment centres. METHODS: Prospective data were collected on all patients with resected Stage II colon cancer between 2010 and 2015 across two large Australian hospitals. Data collected included patient demographics, tumour histology, dMMR immunohistochemistry, chemotherapy use, and outcomes. RESULTS: All 355 patients (56.1% female, median age 81) with resected Stage 2 Colon cancer entered on to the surgical database were included in this analysis. MMR testing was performed on 167 patient samples (47%), most occurred post-2013 (73.1% vs. 26.9% patients). dMMR rates were 34.1%. 25 (7.3%) received adjuvant chemotherapy, with no patient >80 years receiving treatment. Presence of ≥2 high-risk feature increased the likelihood of adjuvant chemotherapy. Only 3.6% dMMR patients received chemotherapy; both were young with high-risk features. 27/288 (7.6%) patients (with follow up) relapsed, with 7 disease-free post-resection of metastatic disease, 9 are alive with metastatic disease, and 11 deceased. CONCLUSIONS: Unlike clinical trial populations, Stage 2 colon cancer patients are often elderly, have high rates of dMMR tumours, are rarely offered chemotherapy, yet still have excellent outcomes. dMMR immunohistochemistry is being increasingly used to identify Stage 2 patients who do not require chemotherapy.

New Monoclonal Antibodies to Defined Cell Surface Proteins on Human Pluripotent Stem Cells.

The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types. Stem Cells 2017;35:626-640.

The Effect of Diabetes on the Perioperative Outcomes of Colorectal Cancer Surgery Patients.

There are approximately 1.3 million patients in Australia with diabetes. Conflicting reports exist in the literature as to the effect of diabetes on the outcomes of colorectal cancer patients. We hypothesized that patients with diabetes would have poorer perioperative outcomes, and that diabetes was an independent risk factor for both 30-day mortality and perioperative morbidity. The aim of this study was to assess the impact of diabetes on perioperative colorectal cancer surgery outcomes, as compared to a diabetes-free reference population, and to examine factors affecting perioperative risk. We conducted an analysis of a prospectively collected, clinician-led colorectal cancer database of patients from 2010-2015. Patients with diabetes were compared to patients without diabetes on a range of perioperative outcomes. Pearson χ-squared tests, Wilcoxon rank sum tests and t-tests were employed for univariate analyses. Confounding factors were controlled for by separate logistic and linear regression analyses. The Huber-White Sandwich Estimator was used to calculate robust standard errors. A total of 1725 patients were analysed over 1745 treatment episodes in the study period with 267 patients (268 episodes) with diabetes studied. Diabetes contributed to medical, surgical complications, and increased length of inpatient stay in univariate analyses. Multivariable analysis adjusted for variables independently associated with each outcome revealed that diabetes was an independent contributor to an increased risk of surgical complications, with no significant effect on medical complications, return to the operating room, 30-day mortality, or readmission within 30 days. In this study, where overall baseline morbidity and mortality levels are low, the effect of diabetes alone on perioperative surgical outcomes appears to be overstated with control of associated perioperative risk factors such as cardiac, renal and respiratory factors being more important.

Bifactor Modeling of the Behavior Rating Inventory of Executive Function (BRIEF) in a Chilean Sample.

The Behavior Rating Inventory of Executive Functions evaluates executive functioning through the observation of students' performance in real contexts. Most psychometric studies of the scale have only tested the first-order structure, despite the hierarchical configuration of its theoretical model. A bifactor model was conducted on a normative sample of 5- to 18-year-old Chileans (M age = 11.3 years, SD = 3.7) to test a hierarchical structure of three first-order factors and an independent second-order factor. Bifactor analyses showed best fit for the proposed hierarchical structure. Findings supported a method to evaluate executive functioning models that provides a general global factor score that may complement existing indices and thus help clinicians to make better inferences.

Colorectal Cancer Surgery in the Very Elderly: Nonagenarians.

BACKGROUND: Surgery in the very elderly is a topic that has not been well studied, despite the steady rise in this population. With the rise in this population, there is now discussion on the safety of surgery in this cohort for colorectal cancer. OBJECTIVE: The purpose of this study was to investigate elective and nonelective colorectal cancer surgery outcomes in patients aged ≥90 years at both private and public hospitals in Melbourne, Victoria, Australia. DESIGN: This was a retrospective analysis of patients aged ≥90 years who were included in the prospectively maintained Cabrini Monash University Department of Surgery colorectal neoplasia database for patients entered between January 2010 and February 2015. Comorbidity, ASA score, acuity of surgery, treatment, mortality, morbidity, and survival were analyzed. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: A total of 48 patients were identified from the database. The majority of these patients were women (58.0%), ASA score III to IV (91.7%), and treated in an elective setting (79.2%). The median age was 91.8 years. MAIN OUTCOME MEASURES: We measured 30-day mortality, 180-day mortality, and perioperative morbidity. RESULTS: Thirty-day mortality rate was 2.1%. The 180-day mortality rate was 10.4%. A total of 29.2% of patients had a perioperative complication. Median follow-up was 21 months (range, 13-54 months). In 180-day mortality, minimally invasive surgery was associated with a lower mortality rate vs open surgery (p = 0.043). Perioperative complications were associated with nonelective surgery (p = 0.045), open surgery procedures (p = 0.014), and higher stages of disease (p = 0.014). A total of 81.3% of patients were able to return home after surgery. LIMITATIONS: This was a retrospective study with the usual limitations; however, these have been minimized with the use of a high-quality, prospective data collection database. The median follow-up was 21 months. CONCLUSIONS: Colorectal surgery was generally safe for nonagenarians in this study. This study demonstrates that excellent outcomes can be achieved in a selected group. Additional prospective studies with larger numbers and 5-year follow-up are recommended.

Complete Pathological Response After Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer and Its Relationship to the Degree of T3 Mesorectal Invasion.

BACKGROUND: Many studies have shown significantly improved outcomes (reduced local recurrence and improved overall survival) for patients achieving a complete pathological response from neoadjuvant chemoradiotherapy. OBJECTIVE: This study aimed to document the complete pathological response rate and outcomes in patients receiving preoperative long-course chemoradiotherapy stratified for the extent of T3 mesorectal invasion measured on preoperative imaging. DESIGN: This is a retrospective study of prospectively collected data, of patients with rectal cancer in the Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from Cabrini Hospital and The Alfred Hospital, identifying patients entered between January 2010 and June 2014. PATIENTS AND SETTINGS: One hundred eighteen patients with T3 rectal cancer met the selection criteria for the study; 26 achieved complete pathological response (22%). MAIN OUTCOME MEASURES: Outcomes in terms of complete pathological response and oncological outcomes such as disease-free and overall survival were analyzed. RESULTS: Patients with complete pathological response had significantly less preoperative invasion than those with no complete pathological response (p < 0.001). Depth of invasion was the only variable associated with complete pathological response (p < 0.002), and the likelihood of complete pathological response decreased by 35% for every millimeter of invasion. Complete pathological response was associated with increased disease-free survival (p = 0.018) and a lower risk of cancer progression (p = 0.046). Depth of invasion was associated with an increased risk of death after surgery; HR increased by 1.07 (95% CI, 1.00-1.15) for each 1-mm increase in invasion. LIMITATIONS: This was a retrospective study with the usual limitations, although these were minimized through the use of a clinician-driven prospective database. CONCLUSIONS: The smaller the degree of T3 invasion, the higher the chance of achieving complete pathological response (up to 35%), which is associated with improved disease-free and overall survival. A higher complete pathological response rate is observed in early T3 disease in comparison with more extensive T3 invasion.