Envoi Specialist Pathologists

In the face of increasing climate hazards and the growing complexity of urban environments, soils emerge as a key interface between water, vegetation, infrastructure and human uses. Their role goes far beyond that of a simple support: soils condition hydrological functioning, environmental quality, the adaptive capacity of developed spaces, and the long-term sustainability of projects. Yet, in many urban and peri-urban contexts, soils remain insufficiently integrated into design and management processes.This presentation will present feedback from scientists and engineers involved in urban development, regeneration and environmental management projects. Drawing on several concrete case studies, it illustrates how an integrated diagnostic approach to soils, water and land use can guide the design of more resilient projects, from the planning stage through to operational implementation.The examples cover a wide range of situations: the rehabilitation of degraded or contaminated soils, the creation of engineered soils from secondary materials, integrated stormwater management using vegetated systems, and the design of growing media capable of functioning sustainably under high urban constraints. These projects demonstrate how operational choices based on the physical, chemical and biological properties of soils can simultaneously address issues of water management, environmental quality and ecological functionality.Particular attention is given to the way these parameters are translated into operational design criteria: infiltration and storage targets, the ability of soils to filter or immobilize contaminants, their capacity to support diverse vegetation, and their compatibility with structural and use-related constraints. The monitoring and evaluation methods implemented to verify the long-term performance of these systems are also discussed.By offering a cross-cutting perspective on the role of soils in urban projects, this contribution aims to show how soil engineering and nature-based solutions can be integrated in a coherent and pragmatic way into real-world operations, and how these approaches help to build more adaptive, functional and resilient urban landscapes.

Previous stage I-III colon cancer trials demonstrated improved peri-operative and similar long-term oncological outcomes with minimally invasive approaches compared with open surgery. Subsequent technical developments, including intracorporeal anastomosis, complete mesocolic excision (CME), refined pathologic grading systems and robotic approaches are increasingly used despite minimal supporting evidence. This international phase II trial aims to assess patient, surgical and pathological outcomes following robotic (RRHC) with laparoscopic right hemicolectomy (LRHC) for right sided colon cancer. Prospective, international multicentre pilot randomised phase II trial for patients with right colon adenocarcinoma, randomised 2:1 to robotic (RRHC) or laparoscopic (LRHC) surgery performed by accredited surgeons. Primary outcome was 90-day surgical morbidity measured using the Comprehensive Complication Index (CCI). Standardised pathology reviews, patient reported quality of life and surgeon task load index data was captured. RRHC vs. LRHC surgery allocation was 19 vs. 10, mean operative time 3.8 vs. 3.1 h with no operative mortality, all had R0 resection, CME rate 53 vs. 50% and intact mesocolon 94 v 100%. CCI was significantly lower at 30 and 90 days after RRHC (median (Q1, Q3): 0 (0, 9) vs. 21 (21, 26); median difference: 21; 95% CI 9-26; p = 0.005 at 30 days; p = 0.008 at 90 days). No significant differences in pathological nor quality of life data was observed. Surgeons task load data tended to favour robotic procedures. Median follow-up was 6 months. Limited funding led to early study closure. RRHC improved short-term surgical morbidity and surgeon physical demand and performance whilst obtaining similar quality of life and pathological specimen quality compared to LRHC for right sided colon cancer, supporting the case for larger randomised trials. ACTRN12620001378910.

To document the prevalence and incidence rate of infection in dogs undergoing partial tarsal arthrodesis (PTA). For context, findings were compared with the prevalence of infection following tibial plateau leveling osteotomy (TPLO) at the same institution. Independent variables associated with infection were also identified. Case-control study. Eighty-nine dogs underwent PTA; 292 dogs underwent TPLO. Medical records for dogs that underwent PTA from 2017 to 2023 and dogs that underwent TPLO between January 2022 and December 2022 were reviewed. The prevalence, incidence rate, odds and incidence rate ratio of infection were calculated. The prevalence of infection following PTA was 43%; following TPLO it was 13%. The incidence rate of infection was 0.00276 (95% CI: 0.00198-0.00375) and 0.00010 (95% CI: 0.00007-0.00013) infections per dog-week, respectively. The odds ratio and incidence rate ratio for infection following PTA were 5.0 (95% CI: 3.1-9.0) and 28.2 (95% CI: 17.7-45.0), respectively. The prevalence and incidence rate of infection were higher following PTA than TPLO. Dogs that underwent PTA were five times more likely to develop infection than dogs that underwent TPLO, and developed infection at 28 times the rate of dogs that underwent TPLO. Dogs with open wounds, no postoperative bandage, and treated with a combined medial and lateral approach, had a higher point prevalence of infection.

Adequate nutrition depends on the ingestion of a suitable diet and its proper digestion, absorption and metabolism. Malnutrition can result from inadequacy of one or more of these functions. Protein-calorie malnutrition results from severe dietary protein deficiency and is largely a problem in developing countries, with the highest prevalence in south-central Asia and Sub-Saharan Africa. The proximal small intestine is the principal site of nutrient absorption, so, not surprisingly, most malabsorption disorders result from disease of this site. Upper gastrointestinal tract endoscopy is a routine investigation for malabsorption, potentially providing tissue for histopathology, biochemical samples for disaccharidase levels and jejunal fluid for microbial culture. Gluten sensitivity affecting non-enteric sites is primarily manifest as an intra-epithelial lymphocytosis. The endoscopic features of gluten-induced enteropathy include a reduction in the number of circular folds, scalloping of folds, mucosal fissures and a mosaic or nodular mucosa.

When broadly defined as projections from the colonic mucosal surface, polyps of the large intestine are readily detected and encompass a wide range of lesions. Most of these are adenomas and serrated polyps, but other lesions of the mucosa and submucosa may be observed at the time of colonoscopy or radiological imaging as mucosal elevations. Conventional adenomas, well-characterised and commonly seen in gastrointestinal pathology practice, are the precursor lesions for almost three-quarters of colorectal adenocarcinomas. Endoscopic polypectomy techniques for small polyps are changing with the increased recognition that cold-snare resection has a lower risk of post-polypectomy complications such as bleeding. Serrated polyps are so named because they show a serrated or ‘saw-tooth’ appearance on histology as a result of crypt epithelial cell accumulation and luminal inbudding secondary to inhibition of apoptosis. Colorectal adenomatous polyposis syndromes comprise multiple genetic conditions inherited in a dominant or recessive manner.

Abstract A 10‐year‐old, female, spayed golden retriever crossbreed dog was referred for persistent vomiting and hypersalivation after eating. Thoracic radiographs showed a small, circular soft tissue opacityin the region of the mid‐caudal thoracic oesophagus An intraluminal, pedunculated mid‐caudal thoracic oesophageal mass was identified on subsequent computed tomography of the thorax. Oesophagoscopy guided endoscopic biopsies were consistent with a plasmacytoma, a neoplasm rarely diagnosed in the canine oesophagus. Thoracotomy via a rib pivot method, longitudinal oesophagotomy and partial longitudinal oesophagectomy were performed with successful mass excision. Histopathology confirmed the diagnosis of plasmacytoma excised with complete surgical margins, and the dog's clinical signs resolved. Repeat computed tomography and oesophagoscopy 7 months following surgical excision showed no recurrence, and the dog remained clinically well.

The microbiome has long been suspected of a role in colorectal cancer (CRC) tumorigenesis. The mutational signature SBS88 mechanistically links CRC development with the strain of Escherichia coli harboring the pks island that produces the genotoxin colibactin, but the genomic, pathological and survival characteristics associated with SBS88-positive tumors are unknown. SBS88-positive CRCs were identified from targeted sequencing data from 5,292 CRCs from 17 studies and tested for their association with clinico-pathological features, oncogenic pathways, genomic characteristics and survival. In total, 7.5% (398/5,292) of the CRCs were SBS88-positive, of which 98.7% (392/398) were microsatellite stable/microsatellite instability low (MSS/MSI-L), compared with 80% (3916/4894) of SBS88 negative tumors (p=1.5x10-28). Analysis of MSS/MSI-L CRCs demonstrated that SBS88 positive CRCs were associated with the distal colon (OR=1.84, 95% CI=1.40-2.42, p=1x10-5) and rectum (OR=1.90, 95% CI=1.44-2.51, p=6x10-6) tumor sites compared with the proximal colon. The top seven recurrent somatic mutations associated with SBS88-positive CRCs demonstrated mutational contexts associated with colibactin-induced DNA damage, the strongest of which was the APC:c.835-8A>G mutation (OR=65.5, 95%CI=39.0-110.0, p=3x10-80). Large copy number alterations (CNAs) including CNA loss on 14q and gains on 13q, 16q and 20p were significantly enriched in SBS88-positive CRCs. SBS88-positive CRCs were associated with better CRC-specific survival (p=0.007; hazard ratio of 0.69, 95% CI=0.52-0.90) when stratified by age, sex, study, and by stage. SBS88-positivity, a biomarker of colibactin-induced DNA damage, can identify a novel subtype of CRC characterized by recurrent somatic mutations, copy number alterations and better survival. These findings provide new insights for treatment and prevention strategies for this subtype of CRC.

Introduction: The serrated pathway accounts for 25% of colorectal cancers; however, sessile serrated lesions with dysplasia (SSL-Ds) are only encountered at colonoscopy in 0.5% of average-risk patients. There is significant heterogeneity in published SSL detection rates, and although pathologist and colonoscopist variability is well described, geographic variation in prevalence is also possible. Data on SSL-D prevalence in Australia is limited. We aim to present SSL-D prevalence in a large colonoscopy cohort with high detector colonoscopists. Methods: A retrospective study was conducted using a prospective colonoscopy quality database of patients undergoing colonoscopy at a single center from January 2018 to December 2022. Univariate analysis (Wilcoxon Rank-Sum test and Pearson Chi-Square test) and multivariate analysis (multiple logistic regression) were performed. Results: In 5 years, 21,903 colonoscopies were completed with 5,261 SSLs detected (24% detection rate). 70 SSL-Ds were identified at 62 colonoscopies (1.2% of procedures with SSL identified). SSL-D patients were older (median age 75 vs 58 years, P < 0.001) with a trend towards female association (67% vs 57%, P = 0.09). SSL-Ds were more often found at surveillance colonoscopy than index (77% vs 23%). On multivariate analysis, only older age was an independent predictor of SSL-D (odds ratio 1.07, 95% confidence interval 1.05-1.1). SSL-Ds were mainly found in the proximal colon (89%), with a mean size of 12mm (range 1 to 40mm) and were treated with cold snare (50%) or cold EMR (41%). 80% of SSL-Ds had surveillance at a median interval of 6 months. SSL-D residuals were encountered in only 4 (5.7% of total SSL-D). These returned bland on histology and cured with repeat cold snare resection, though one required cecumectomy due to location. Serrated polyposis syndrome was diagnosed in 21.4% of SSL-D patients. Conclusion: We present one of Australia’s largest colonoscopy-based SSL-D cohorts. SSL-Ds were more common on surveillance, which is a reminder to colonoscopists to remain vigilant, although multivariant analysis suggests that this may be a surrogate marker for increasing age. Majority of SSL-Ds were successfully managed endoscopically with residual dysplasia detected in a minority of cases which were cured with repeat cold snare resection. A sole SSL-D residual was confirmed at the appendiceal orifice polyp which ultimately proceeded to cecumectomy. Overall, SSL-Ds are relatively uncommon even within a high SSL prevalence cohort in Australia.

Abstract Germline pathogenic variants in the DNA mismatch (MMR) repair genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. However, mosaic variants in the MMR genes have been rarely described. We identified a likely de novo mosaic MSH6:c.1135_1139del p.Arg379* pathogenic variant in a patient diagnosed with suspected Lynch syndrome/Lynch-like syndrome. The patient developed MSH6-deficient EC and CRC at 54 and 58 years of age, respectively, without a detectable germline MMR pathogenic variant. Multigene panel sequencing of tumor and blood-derived DNA identified an MSH6 somatic mutation (MSH6:c.1135_1139del p.Arg379*) common to both the EC and CRC, raising suspicion of mosaicism. A droplet digital polymerase chain reaction (ddPCR) assay detected the MSH6 variant at 5.34% frequency in normal colonic tissue, 3.49% in saliva and 1.64% in blood DNA, demonstrating the presence of the MSH6 variant in all three germ layers. This study highlights the utility of tumor sequencing to guide sensitive ddPCR testing to detect low-level mosaicism in the MMR genes. Further investigation of the prevalence of MMR mosaicism is needed to inform routine diagnostic approaches and genetic counselling.

&lt;div&gt;AbstractPurpose:&lt;p&gt;While evidence indicates that &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; (&lt;i&gt;F. nucleatum&lt;/i&gt;) may promote colorectal carcinogenesis through its suppressive effect on T-cell–mediated antitumor immunity, the specific T-cell subsets involved remain uncertain.&lt;/p&gt;Experimental Design:&lt;p&gt;We measured &lt;i&gt;F. nucleatum&lt;/i&gt; DNA within tumor tissue by quantitative PCR on 933 cases (including 128 &lt;i&gt;F. nucleatum&lt;/i&gt;–positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on &lt;i&gt;Bifidobacterium&lt;/i&gt;, microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages [TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay]. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between &lt;i&gt;F. nucleatum&lt;/i&gt; and T-cell subsets.&lt;/p&gt;Results:&lt;p&gt;The amount of &lt;i&gt;F. nucleatum&lt;/i&gt; was inversely associated with tumor stromal CD3&lt;sup&gt;+&lt;/sup&gt; lymphocytes [multivariable OR, 0.47; 95% confidence interval (CI), 0.28–0.79, for &lt;i&gt;F. nucleatum&lt;/i&gt;–high vs. -negative category; &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;trend&lt;/sub&gt; = 0.0004] and specifically stromal CD3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD45RO&lt;sup&gt;+&lt;/sup&gt; cells (corresponding multivariable OR, 0.52; 95% CI, 0.32–0.85; &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;trend&lt;/sub&gt; = 0.003). These relationships did not substantially differ by MSI status, neoantigen load, or exome-wide tumor mutational burden. &lt;i&gt;F. nucleatum&lt;/i&gt; was not significantly associated with tumor intraepithelial T cells or with M1 or M2 TAMs.&lt;/p&gt;Conclusions:&lt;p&gt;The amount of tissue &lt;i&gt;F. nucleatum&lt;/i&gt; is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells.&lt;/p&gt;&lt;/div&gt;