The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma

The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous β-catenin, γ-catenin, p120-catenin, and E-cadherin, as well as nuclear β-catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of β-catenin was inversely related to distant metastases

Spatial modelling with R-INLA: A review

Coming up with Bayesian models for spatial data is easy, but performing inference with them can be challenging. Writing fast inference code for a complex spatial model with realistically-sized datasets from scratch is time-consuming, and if changes are made to the model, there is little guarantee that the code performs well. The key advantages of R-INLA are the ease with which complex models can be created and modified, without the need to write complex code, and the speed at which inference can be done even for spatial problems with hundreds of thousands of observations. R-INLA handles latent Gaussian models, where fixed effects, structured and unstructured Gaussian random effects are combined linearly in a linear predictor, and the elements of the linear predictor are observed through one or more likelihoods. The structured random effects can be both standard areal model such as the Besag and the BYM models, and geostatistical models from a subset of the Mat\'ern Gaussian random fields. In this review, we discuss the large success of spatial modelling with R-INLA and the types of spatial models that can be fitted, we give an overview of recent developments for areal models, and we give an overview of the stochastic partial differential equation (SPDE) approach and some of the ways it can be extended beyond the assumptions of isotropy and separability. In particular, we describe how slight changes to the SPDE approach leads to straight-forward approaches for non-stationary spatial models and non-separable space-time models.Comment: Extensive update, restructuring of section

DNA Sequence Profiles of the Colorectal Cancer Critical Gene Set KRAS-BRAF-PIK3CA-PTEN-TP53 Related to Age at Disease Onset

The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients

Value of the surgeon’s sightline on hologram registration and targeting in mixed reality

Purpose Mixed reality (MR) is being evaluated as a visual tool for surgical navigation. Current literature presents unclear results on intraoperative accuracy using the Microsoft HoloLens 1®. This study aims to assess the impact of the surgeon’s sightline in an inside-out marker-based MR navigation system for open surgery. Methods Surgeons at Akershus University Hospital tested this system. A custom-made phantom was used, containing 18 wire target crosses within its inner walls. A CT scan was obtained in order to segment all wire targets into a single 3D-model (hologram). An in-house software application (CTrue), developed for the Microsoft HoloLens 1, uploaded 3D-models and automatically registered the 3D-model with the phantom. Based on the surgeon’s sightline while registering and targeting (free sightline /F/or a strictly perpendicular sightline /P/), 4 scenarios were developed (FF-PF-FP-PP). Target error distance (TED) was obtained in three different working axes-(XYZ). Results Six surgeons (5 males, age 29–62) were enrolled. A total of 864 measurements were collected in 4 scenarios, twice. Scenario PP showed the smallest TED in XYZ-axes mean = 2.98 mm±SD 1.33; 2.28 mm±SD 1.45; 2.78 mm±SD 1.91, respectively. Scenario FF showed the largest TED in XYZ-axes with mean = 10.03 mm±SD 3.19; 6.36 mm±SD 3.36; 16.11 mm±SD 8.91, respectively. Multiple comparison tests, grouped in scenarios and axes, showed that the majority of scenario comparisons had significantly different TED values (p <0.05). Y-axis always presented the smallest TED regardless of scenario tested. Conclusion A strictly perpendicular working sightline in relation to the 3D-model achieves the best accuracy results. Shortcomings in this technology, as an intraoperative visual cue, can be overcome by sightline correction. Incidentally, this is the preferred working angle for open surgery

Defining minimal clearances for adequate lymphatic resection relevant to right colectomy for cancer: a post-mortem study

Background There has been a lengthy discussion on the extent of lymphatic resection for right-sided colon cancer and the central borders of the mesentery that are not yet defined. The objectives of this study are to define minimal clearances for adequate lymphatic resection in regard to colic artery origins and the superior mesenteric artery (SMA) and vein (SMV) relevant to right colectomy. Methods Central mesenteric lymph vessels, nodes, and blood vessels were dissected in 16 cadavers. Cranial–caudal clearances were defined as distances between an individual colic artery origin (ileocolic, right colic, and median colic artery) and the outermost lymphatic vessel within its lymphovascular bundle, cranial and caudal along the SMA. Long lymphatic vessels crossing the SMV between arterial bundles were counted and they constituted the medial clearances. An arbitrary watershed between small bowel and colonic lymph was localized. Immunohistochemistry was performed to histologically verify lymphatic vessels. Results Cranial–caudal clearances were ileocolic 3.6 ± 1.9 and 5.7 ± 1.9; right colic 2.8 ± 1.6 and 3.3 ± 1.0; middle colic artery bundle 6.3 ± 2.7 and 5.9 ± 2.4 mm, respectively. Long lymphatic vessels crossing the SMV between arterial buntles and approaching the SMA were found in all cadavers (antero/posteriorly in 12, only anteriorly in 4), median 3.5 (1–7) long lymphatic vessels anteriorly, and 1.5 (0–5) posteriorly per cadaver. Conclusions Right colonic lymphovascular bundles are volumes of mesenteric tissue that surround the superior mesenteric vessels anteriorly and posteriorly. Long lymphatic vessels traverse the superior mesenteric vein anteriorly/posteriorly approaching the superior mesenteric artery between arterial bundles and placing the medial clearance on the left side of the artery. These do not correlate to arterial crossing patterns. Cranial–caudal clearances determine the tissue to be removed superior/ inferior to arterial origins together with long lymphatic vessels transversing independently between the lymphovascular bundles placing the weight of lymphatic resection on the mesenteric tissue and not on the level of vessel division (High tie)

Right Colectomy with Extended D3 Mesenterectomy: Anterior and Posterior to the Mesenteric Vessels

BACKGROUND: In right colectomy for cancer, complete mesocolic excision and D3 lymphadenectomy each leave behind lymphatic tissue anterior and posterior to the superior mesenteric vein (SMV) and artery (SMA). In this article, we present D3 extended mesenterectomy: a surgical technique that excises the lymphatic tissue en bloc with the right colectomy specimen. MATERIAL AND METHODS: A 3D map of the mesentery of the right colon was reconstructed from staging CT-angiogram scans. The surgical technique of right colectomy with D3 extended mesenterectomy consisted of eight steps: 1) reveal the SMV and SMA; 2) isolate the ileocolic artery; 3) isolate the middle colic artery; 4) resolve the anterior mesenteric flap; 5) specimen de-vascularization; 6) colectomy; 7) resolve the posterior mesenteric flap; and 8) anastomosis. RESULTS: One-hundred-seventy-six patients (77 men) 66 years of age were operated upon from February 2011 to January 2017. There were 169 adenocarcinomas: 16.0% Stage I, 49.1% Stage II, 33.7% Stage III, 1.2% Stage IV. Tumor locations were 50.6% cecum, 41.5% ascending colon, 4.5% hepatic flexure, and 2.3% transverse colon. Mean operating time was 200 minutes, blood loss 273 ml, and length of stay 7.9 days. There were 9 anastomotic leakages and 15 reoperations. One patient underwent small bowel resection due to SMA tear. There was no postoperative mortality. The mean number of lymph nodes per specimen (40.9) was comprised of 27.1 in the D2 volume and 13.8 in the D3 volume. The mean number of metastatic lymph nodes was 1.2 in the D2 volume and 0.13 in D3. There were 7 patients with lymph node metastasis in D3, 2 of whom had node metastasis solely within D3. CONCLUSION: This study shows that 1.2% of patients would have been incorrectly diagnosed as Stage II if extended D3 mesenterectomy had not been performed. Similarly, lymph node metastases would have been left behind in 4.1% of patients if extended D3 mesenterectomy had not been performed

Right colectomy with extended D3 mesenterectomy: anterior and posterior to the mesenteric vessels

BACKGROUND: In right colectomy for cancer, complete mesocolic excision and D3 lymphadenectomy each leave behind lymphatic tissue anterior and posterior to the superior mesenteric vein (SMV) and artery (SMA). In this article, we present D3 extended mesenterectomy: a surgical technique that excises the lymphatic tissue en bloc with the right colectomy specimen. MATERIAL AND METHODS: A 3D map of the mesentery of the right colon was reconstructed from staging CT-angiogram scans. The surgical technique of right colectomy with D3 extended mesenterectomy consisted of eight steps: 1) reveal the SMV and SMA; 2) isolate the ileocolic artery; 3) isolate the middle colic artery; 4) resolve the anterior mesenteric flap; 5) specimen de-vascularization; 6) colectomy; 7) resolve the posterior mesenteric flap; and 8) anastomosis. RESULTS: One-hundred-seventy-six patients (77 men) 66 years of age were operated upon from February 2011 to January 2017. There were 169 adenocarcinomas: 16.0% Stage I, 49.1% Stage II, 33.7% Stage III, 1.2% Stage IV. Tumor locations were 50.6% cecum, 41.5% ascending colon, 4.5% hepatic flexure, and 2.3% transverse colon. Mean operating time was 200 minutes, blood loss 273 ml, and length of stay 7.9 days. There were 9 anastomotic leakages and 15 reoperations. One patient underwent small bowel resection due to SMA tear. There was no postoperative mortality. The mean number of lymph nodes per specimen (40.9) was comprised of 27.1 in the D2 volume and 13.8 in the D3 volume. The mean number of metastatic lymph nodes was 1.2 in the D2 volume and 0.13 in D3. There were 7 patients with lymph node metastasis in D3, 2 of whom had node metastasis solely within D3. CONCLUSION: This study shows that 1.2% of patients would have been incorrectly diagnosed as Stage II if extended D3 mesenterectomy had not been performed. Similarly, lymph node metastases would have been left behind in 4.1% of patients if extended D3 mesenterectomy had not been performed