The prognostication of colorectal cancer (CRC) has traditionally relied on staging as defined by the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) TNM staging classifications. However, clinically, there appears to be differences in survival patterns independent of stage, suggesting a complex interaction of stage, pathological features, and biomarkers playing a role in guiding prognosis, risk stratification, and guiding neoadjuvant and adjuvant therapies. Histological features such as tumour budding, perineural invasion, apical lymph node involvement, lymph node yield, lymph node ratio, and molecular features such as MSI, KRAS, BRAF, and CDX2 may assist in prognostication and optimising adjuvant treatment. This study provides a comprehensive review of the pathological features and biomarkers that are important in the prognostication and treatment of CRC. We review the importance of pathological features and biomarkers that may be important in colorectal cancer based on the current evidence in the literature.

The human intestine contains numerous mononuclear phagocytes (MNP), including subsets of conventional dendritic cells (cDC), macrophages (Mf) and monocytes, each playing their own unique role within the intestinal immune system and homeostasis. The ability to isolate and interrogate MNPs from fresh human tissue is crucial if we are to understand the role of these cells in homeostasis, disease settings and immunotherapies. However, liberating these cells from tissue is problematic as many of the key surface identification markers they express are susceptible to enzymatic cleavage and they are highly susceptible to cell death. In addition, the extraction process triggers immunological activation/maturation which alters their functional phenotype. Identifying the evolving, complex and highly heterogenous repertoire of MNPs by flow cytometry therefore requires careful selection of digestive enzyme blends that liberate viable cells and preserve recognition epitopes involving careful selection of antibody clones to enable analysis and sorting for functional assays. Here we describe a method for the anatomical separation of mucosa and submucosa as well as isolating lymphoid follicles from human jejunum, ileum and colon. We also describe in detail the optimised enzyme digestion methods needed to acquire functionally immature and biologically functional intestinal MNPs. A comprehensive list of screened antibody clones is also presented which allows for the development of high parameter flow cytometry panels to discriminate all currently identified human tissue MNP subsets including pDCs, cDC1, cDC2 (langerin+ and langerin-), newly described DC3, monocytes, Mf1, Mf2, Mf3 and Mf4. We also present a novel method to account for autofluorescent signal from tissue macrophages. Finally, we demonstrate that these methods can successfully be used to sort functional, immature intestinal DCs that can be used for functional assays such as cytokine production assays.

Background Intestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans. Methods Human intestinal biopsies were collected from Crohn’s disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score. Results A significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P < .0001) and unaffected CD (P < .0001), with transitional CD specimens also showing greater staining than controls (P < .05) and unaffected CD (P < .05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P < .0001) and unaffected CD (P < .0001) and was significantly higher in transitional CD than in controls (P < .0001) and unaffected CD (P < .0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P < .05), unaffected CD (P < .0001) and transitional CD (P < .05), with transitional CD specimens showing greater staining than unaffected CD (P < .01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment. Conclusion These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.

Introduction: Sigmoid volvulus is a potentially devastating and life-threatening condition associated with sigmoid colon redundancy. Many of the classical radiological signs are considered to represent the two adjacent loops of bowel in a mesentero-axial volvulus. However, limited case reports and series have reported on an organo-axial subtype of sigmoid volvulus. This clinical entity is not widely understood. In this study, we assess the radiological and clinical features of mesentero-axial and organo-axial sigmoid volvulus. Methods: After institutional board approval (CH62/6/2016-228), all computed tomography (CT) studies from 2011 to 2017 reported as sigmoid volvulus at a single institution were reviewed. The cases were reviewed by three radiologists retrospectively and the course of the bowel followed with a focus on assessing its rotational axis. In each case, the sigmoid volvulus was independently subclassified as mesentero-axial or organo-axial volvulus based on the axis of rotation of the volvulus. In addition, X-ray signs including disproportionate sigmoid dilatation, distended inverted 'U' in sigmoid, coffee bean sign, opposed wall sign, direction of apex of sigmoid loop, liver overlap sign, northern exposure sign and proximal colonic dilatation and CT features including whirl sign, 'X' marks the spot sign, split wall sign and number of transition points were reported for each case. The clinical management and outcomes including morbidity, mortality, endoscopic decompression and need for surgery were also evaluated. The subtype of volvulus was correlated with the above X-ray signs, CT features and clinical management and outcomes. Statistical analysis was conducted using Stata/MP, version 15 (StataCorp LP, College Station, TX, USA). Results: A total of 38 scans were reviewed. There were 19 patients identified. Of these, six (32%) were reported as mesentero-axial and 13 (68%) as organo-axial volvulus. No X-ray signs were able to distinguish the two types of volvulus. The number of transition points on CT was predictive of volvulus subtype (OR 25, 95% CI: 1.30-1295.30, P = 0.01). Within the limitations of a small cohort, there was no statistically significant difference in unsuccessful endoscopic decompression, need for colectomy, repeated admissions or mortality between the groups. Conclusion: This study has demonstrated that organo-axial sigmoid volvulus may be as common as mesentero-axial volvulus. Distinguishing organo-axial from mesentero-axial volvulus can be achieved on CT, but not on abdominal X-ray. The number of transition points (two for mesentero-axial and one for organo-axial) may be used as a diagnostic feature for differentiating the two forms of volvulus.

Background: Intra-abdominal abscess (IAA) post-appendicectomy occurs in 1.4-4.4% of cases. Non-operative management of small (<4 cm) post-appendicectomy IAA in children is well established, but minimal evidence exists in adults. Percutaneous catheter drainage is considered standard treatment for IAA, yet outcome data for post-appendicectomy IAA are sparse. The aims of this study were to assess the effectiveness of non-operative management of small (<4 cm diameter) IAA and the outcomes of percutaneous drainage for larger (>4 cm) IAA post-appendicectomy. Methods: A retrospective case note review of a series of patients with a postappendicectomy IAA between 2006 and 2017 was conducted. IAAs were treated selectively; small (<4 cm) IAAs were managed non-operatively and larger IAAs were managed with percutaneous drainage. Results: A total of 4901 patients had an appendicectomy. Forty-two (0.9%) developed a post-operative IAA. Sixteen (38%) had a percutaneous drainage and 26 (62%) had non-operative management. The percutaneous drainage group had a higher proportion of complicated appendicitis (75%) compared to the non-operative group (42%, P = 0.04). The percutaneous drainage group had a significantly higher leucocytosis (P = 0.01) and C-reactive protein (P = 0.02). All patients managed non-operatively resolved without the need for invasive procedures. In the percutaneous drainage group, six had aspiration alone, nine had a percutaneous drain and one was abandoned. Three required repeat percutaneous drainage and four (25%) required operative drainage. Seven patients (34%) of the percutaneous drainage group had grade II or III complications. Conclusion: This case series study provides support that small (<4 cm) IAA postappendicectomy can be safely and effectively managed non-operatively.

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.

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