Operative and Pathological Factors in Right-Sided Colon Cancers: How Can We Improve the Outcomes?

INTRODUCTION: Though the tumour-node-metastasis staging classification is the standard approach to risk stratification in patients with colorectal cancer, several other important variables including the presence of extramural venous invasion (EMVI), the tumour mismatch repair status, as well as surgical technique and its influence on lymph node yield all have an impact on long-term survival. This study aims to review both the impact of the type of operation on lymph node yield: complete mesocolic excision (CME) versus right hemicolectomy, and the impact of EMVI and microsatellite instability in predicting overall survival in patients undergoing a right hemicolectomy for colon cancer. METHODS: Data of all patients who underwent an elective or emergency right hemicolectomy with curative intent for colon cancer between January 2013 and June 2022 (inclusive) was collected for this single-centre retrospective study. Kaplan-Meier survival curves were calculated using the Statistical Package for the Social Sciences (SPSS version 28, IBM Corp., Armonk, NY) software, and the log-rank (Mantel-Cox) test was used to compare survival distribution between different groups. RESULTS: A total of 421 patients underwent a right hemicolectomy for colon cancer with curative intent during the study period. EMVI was present in 173 (41%) tumours. Survival analysis showed significantly reduced cancer-related survival in patients with EMVI-positive tumours (p < 0.001), with five-year survival rates of 70% in EMVI-positive groups versus 96% in EMVI-negative groups. Subgroup analysis showed a significant difference in survival between node-positive and node-negative tumours in cancers found to have EMVI (p < 0.001). Mean lymph node yield was significantly higher in the CME group versus the standard right hemicolectomy group (p < 0.001). We found no significant difference in survival between patients with microsatellite instability-high (MSI-H) tumours and microsatellite stable (MSS) tumours (p = 0.432). CONCLUSION: Consideration of tumour biology and adopting the optimum surgical technique are factors that may influence long-term survival in patients with colorectal cancer. Extramural venous invasion is an important prognostic indicator of adverse outcomes in patients with right-sided colon cancer. Our study demonstrates a reduction in survival in patients with EMVI-positive tumours when undertaking subgroup analysis by the presence or absence of nodal disease. Further research needs to be undertaken to compare the relative efficacy of neoadjuvant versus adjuvant chemotherapy in right-sided cancers known to be EMVI-positive as some patients will fail to have adjuvant chemotherapy due to postoperative complications, thereby delaying recovery and missing the optimum window for treatment.

A Feasibility Study of Multisite Networked Digital Pathology Reporting in England.

BACKGROUND: The objective of the project was to evaluate the feasibility of introducing a single-networked digital histopathology reporting platform in the Southwest Peninsula region of England by allowing pathologists to experience the technology and recording their perceptions. This information was then used in planning future service development. The project was funded by the National Health Service (NHS) Peninsula Cancer Alliance and took place in 2020 during the COVID-19 pandemic. MATERIALS AND METHODS: Digital slides of 500 cases from Taunton were reported remotely in Truro, Plymouth, Exeter, Bristol, or Bath by using a single remote reporting platform located on the secure Health and Social Care Network (HSCN) that links NHS sites. These were mainly small gastrointestinal, skin, and gynecological specimens. The digital diagnoses were compared with the diagnoses issued on reporting the glass slides. At the end of the project, the pathologists completed a Google Forms questionnaire of their perceptions of digital pathology. The results were presented at a meeting with the funder and discussed. RESULTS: From the 500 cases there were nine cases of significant diagnostic discrepancy, seven of which involved the misrecognition of Helicobacter pylori in gastric biopsies. The questionnaire at the end of the project showed that there was a general agreement that the platform was easy to use, and the image quality was acceptable. It was agreed that extra work, such as deeper levels, was easy to request on the software platform. Most pathologists did not agree that digital reporting was quicker than glass slide reporting. Some were less confident in their digital diagnoses than glass diagnoses. They agreed that some types of specimens cannot easily be reported digitally. All users indicated that they would like to report at least half of their work digitally in the future if they could, and all strongly agreed that digital pathology would improve access to expert opinions, teaching, and multidisciplinary meetings. It was difficult to find pathologists with time to undertake remote digital reporting, in addition to their existing commitments. CONCLUSIONS: Overall, the pathologists developed a positive perception of digital pathology and wished to continue using it.

Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium.

Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype in adult mouse oesophageal epithelium and is present in the human condition. These data suggest that induction of HNF4α is a key early step in the formation of Barrett's metaplasia and are consistent with an origin of Barrett's metaplasia from the oesophageal epithelium.

A pathologist's survey on the reporting of sessile serrated adenomas/polyps.

AIM: The purpose of this survey was to ascertain reporting habits of pathologists towards sessile serrated adenomas/polyps (SSA/P). METHODS: A questionnaire designed to highlight diagnostic criteria, approach and clinical implications of SSA/P was circulated electronically to 45 pathologists in the UK and North America. RESULTS: Forty-three of 45 pathologists agreed to participate. The vast majority (88%) had a special interest in gastrointestinal (GI) pathology, had great exposure to GI polyps in general with 40% diagnosing SSA/P at least once a week if not more, abnormal architecture was thought by all participants to be histologically diagnostic, and 11% would make the diagnosis if a single diagnostic histological feature was present in one crypt only, while a further 19% would diagnose SSA/P in one crypt if more than one diagnostic feature was present. The vast majority agreed that deeper sections were useful and 88% did not feel proliferation markers were useful. More than one-third did not know whether, or did not feel that, their clinicians were aware of the implications of SSA/P. CONCLUSIONS: 98% of pathologists surveyed are aware that SSA/P is a precursor lesion to colorectal cancer, the majority agree on diagnostic criteria, and a significant number feel that there needs to be greater communication and awareness among pathologists and gastroenterologists about SSA/P.