Commonalities and differences in the mutational signature and somatic driver mutation landscape across solid and hollow viscus organs.

Advances in sequencing have revealed a highly variegated landscape of mutational signatures and somatic driver mutations in a range of normal tissues. Normal tissues accumulate mutations at varying rates ranging from 11 per cell per year in the liver, to 1879 per cell per year in the bladder. In addition, some normal tissues are also comprised of a large proportion of cells which possess driver mutations while appearing phenotypically normal, as in the oesophagus where a majority of cells harbour driver mutations.

Biallelic FBXW7 knockout induces AKAP8-mediated DNA damage in neighbouring wildtype cells.

Colorectal cancer possesses marked intratumoral heterogeneity. While subclonal interactions between Vogelstein driver mutations have been extensively studied, less is known about competitive or cooperative effects between subclonal populations with other cancer driver mutations. FBXW7 is a cancer driver mutation which is present in close to 17% of colorectal cancer cells.

Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles.

Generation and immunofluorescent validation of gene knockouts in adult human colonic organoids using multi-guide RNA CRISPR-Cas9.

While readily achieved in cell lines, the application of CRISPR-Cas9 gene editing in human-derived organoids suffers from limited efficacy and complex protocols. Here, we describe a multi-guide RNA CRISPR-Cas9 gene-editing protocol which efficiently achieves complete gene knockout in adult human colonic organoids. This protocol also describes crucial steps including how to harvest patient tissue to maximize gene-editing efficacy and a technique to validate gene knockout following editing with immunofluorescent staining of the organoids against the target protein.

Primary tumour immune response and lymph node yields in colon cancer.

Background: The mechanism underlying improved survival in non-metastatic colon cancer with higher lymph node (LN) yield is unknown. This study aimed to identify whether molecular features in the primary tumour were predictive of LN yield.

Methods: Clinical, genomic, transcriptomic, proteomic and methylation data of non-metastatic, colon cancers studied in The Cancer Genome Atlas were interrogated for associations with LN yield.

Perioperative and oncologic outcomes in young and octogenarian patients with colorectal cancer: a comparison at the extremes.

Introduction: In colorectal cancer (CRC), surgical outcomes in the young (< 50) and octogenarian populations are believed to be poor due to an aggressive phenotype in the former, and increased frailty in the latter. Given that age-related effects are inversely related between groups, we compared short- and long-term outcomes of young and octogenarian patients with CRC to determine the dominance of one age-related factor over another.

Methods: A prospectively collected database from 2015 to 2020 of all CRC was analyzed.

Tumour heterogeneity and evolutionary dynamics in colorectal cancer.

Colorectal cancer (CRC) has a global burden of disease. Our current understanding of CRC has progressed from initial discoveries which focused on the stepwise accumulation of key driver mutations, as encapsulated in the Vogelstein model, to one in which marked heterogeneity leads to a complex interplay between clonal populations. Current evidence suggests that an initial explosion, or "Big Bang", of genetic diversity is followed by a period of neutral dynamics.

Chemotherapy and adverse cardiovascular events in colorectal cancer patients undergoing surgical resection.

Background: Colorectal cancer patients undergoing surgical resection are at increased short-term risk of post-operative adverse events. However, specific predictors for long-term major adverse cardiac and cerebrovascular events (MACCE) are unclear. We hypothesised that patients who receive chemotherapy are at higher risk of MACCE than those who did not.

Continuous wound infusion with ropivacaine alone provides adequate analgesia following laparotomy.

Background: Although continuous wound infusion (CWI) with local anaesthetic has been used as an adjunct for pain relief following laparotomy, its use as the main modality has not been studied. This approach negates side effects related to intravenous opioid administration, therefore promoting enhanced recovery from surgery. We conducted this study to investigate the feasibility and efficacy of CWI following laparotomy.

Lymphocyte-White Cell Ratio Is a Novel Marker of Morbidity Following Colorectal Cancer Surgery.

Background: A preoperative marker for morbidity in patients with colorectal cancer would help to risk stratify patients and allow for timely intervention to avert poor outcomes. We conducted this study to evaluate preoperative lymphocyte-white blood cell ratio (LWR) as a marker of postoperative morbidity.

Methods: A prospective cohort of patients who underwent elective surgery for colorectal cancer was reviewed.

A simple prediction score for prolonged length of stay following elective colorectal cancer surgery.

Background: Current enhanced recovery after surgery (ERAS) protocols are designed for all patients without tailored programmes for at-risk groups. A risk score to determine elective colorectal cancer patients at risk for prolonged length of stay (LOS) would help to identify this group for preoperative intervention.

Methods: Multivariate analysis of demographic and preoperative variables was performed to identify independent risk factors for prolonged LOS, defined as 7 days or more.

Indocyanine green fluorescence angiography decreases the risk of colorectal anastomotic leakage: Systematic review and meta-analysis.

Background: Anastomotic leakage after a colorectal resection results in devastating consequences for patients. Indocyanine green fluorescence angiography is a modality to visualize vascular perfusion at the anastomotic site and can help surgeons decide the viability of the anastomosis. We performed this systematic review and meta-analysis to evaluate the efficacy of indocyanine green fluorescence angiography in decreasing anastomotic leakage.

Stenting versus surgery in obstructed malignant colorectal cancer-a review of short and long-term results.

Obstructed colorectal cancers (CRCs) continue to be challenging to manage. Apart from surgical resection, the use of self-expanding metallic stents (SEMS) has become increasingly popular. SEMS could potentially allow for the conversion of an emergency operation into a semi-elective procedure, allow for the optimization of the patient's physiology, avoid the requirement for a stoma, as well as allow for a minimally-invasive approach to be adopted.

Age is an independent risk factor for increased morbidity in elective colorectal cancer surgery despite an ERAS protocol.

Introduction: Elderly patients with colorectal cancer are high-risk surgical candidates. ERAS protocols have been developed to mitigate against these risks. We performed this study to quantify the risks which elderly patients face and then to determine independent risk factors for short-term ERAS-specific outcomes.

Enhanced recovery program versus conventional care after colorectal surgery in the geriatric population: a systematic review and meta-analysis.

Introduction: Enhanced recovery after surgery (ERAS) programs for patients undergoing colorectal surgery has yielded promising results. However, there remains controversy regarding the application of ERAS protocols in an elderly population. The aim of this review is to compare the clinical outcomes between ERAS versus conventional peri-operative care (Non-ERAS) for colorectal surgery in patients aged ≥ 65 years old.

Nasal Cavity Metastasis From Colorectal Cancer Represents End-Stage Disease and Should Be Palliated.

Nasal metastases from colorectal cancer is rare. The presentation of nasal metastases is often very similar to primary nasal sinus adenocarcinoma. A high index of suspicion is required, especially in patients who have had a previous history of colorectal carcinoma.

Diagnostic and management strategies for lateral pelvic lymph nodes in low rectal cancer-a review of the evidence.

Patients with low rectal cancer who have enlarged lateral pelvic lymph nodes are known to have a worse prognosis. There is however uncertainty over what constitutes a lateral pelvic lymph node of clinical significance. As the main modality for the detection of such lymph nodes is magnetic resonance imaging (MRI), characteristics of these lateral lymph nodes identified may have prognostic value and assist with guiding treatment.

Journey for patients following ileostomy creation is not straightforward.

Background: An ileostomy is usually created to avert systemic sepsis in a patient with a tenuous anastomosis. However, what is often not reported are the numerous issues facing these patients subsequently, ranging from readmissions, non-reversal of the stoma, and complications from the closure. This study was performed to identify these issues among patients following creation of an ileostomy.

Increased Morbidity and Mortality of Emergency Laparotomy in Elderly Patients.

Background: There is an increasing incidence of elderly patients requiring emergency laparotomy. Our study compares the outcomes of elderly patients undergoing emergency laparotomy against the outcomes of non-elderly patients.

Methodology: Patients who underwent emergency laparotomy between 2015 and 2017 from the National University Hospital, Singapore, were included.

Adherence to surveillance guidelines following colonic polypectomy is abysmal.

Background: Surveillance guidelines following excision of colonic tubular adenomas are well established. However, adherence to the guidelines are rarely audited. The aim of our study was to evaluate the rate of compliance to the recommended guidelines following polyp removal.