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Background Considerable epidemiological studies have examined the correlation between polymorphic single‐nucleotide variants (SNPs) in miRNA genes and colorectal carcinoma (CRC) risk, yielding inconsistent results. Herein, we sought to systematically investigate the association between miRNA‐SNPs and CRC susceptibility by combined evaluation using pairwise and network meta‐analysis, the FPRP analysis (false positive report probability), and the Thakkinstian's algorithm. Methods The MEDLINE, EMBASE, WOS, and Cochrane Library databases were searched through May 2024 to find relevant association literatures. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed by the pairwise meta‐analysis. Network meta‐analysis and the Thakkinstian's method were applied for determining the potentially optimal genetic models; additionally, the FPRP was used to identify noteworthy associations. Results Totally, 39 case–control trials involving 18,028 CRC cases, and 21,816 normal participants were included in the study. Eleven SNPs within nine genes were examined for their predisposition to CRC. miR‐27a (rs895819) was found to significantly increase CRC risk among overall population (OR 1.58, 95% CI: 1.32–1.89) and Asians (OR 1.62, 95% CI: 1.31–2.01), with the recessive models identified as the optimal models. Furthermore, miR‐196a2 (rs11614913), miR‐143/145 (rs41291957), and miR‐34b/c (rs4938723) were significantly related to reduced CRC risk among Asian descendants under the optimal dominant (OR 0.75, 95% CI: 0.65–0.86), recessive (OR 0.72, 95% CI: 0.60–0.85), and recessive models (OR 0.69, 95% CI: 0.56–0.85), respectively. The results were also proposed by the network meta‐analysis or the Thakkinstian's method and confirmed by the FPRP criterion. Conclusion The miR‐27a (rs895819) is correlated with elevated CRC risk among overall population and Asians, and the recessive model is found to be optimal for predicting CRC risk. Additionally, the miR‐196a2 (rs11614913), miR‐143/145 (rs41291957), and miR‐34b/c (rs4938723), with the dominant, recessive, and recessive models identified as the optimal, might confer protective effects against CRC among Asians.

Introduction. Microwave imaging can obtain 360° anatomical and functional images of the colon representing the existing contrast in dielectric properties between different tissues. Microwaves are safe (nonionizing) and have the potential of reducing the visualization problems of conventional colonoscopy. This study assessed the efficacy of a microwave-based colonoscopy device to detect neoplastic lesions in an ex vivo human colon model. Methods. Fresh surgically excised colorectal specimens containing cancer or polyps were fixed to a 3D positioning system, and the accessory device was introduced horizontally inside the ex vivo colon lumen and moved along it simulating a real colonoscopy exploration. Measurements of the colon were taken every 4 mm with the microwave-based colonoscopy device and processed with a microwave imaging algorithm. Results. 14 ex vivo human colorectal specimens with carcinomas (n=11) or adenomas with high grade dysplasia (n=3) were examined with a microwave-based device. Using a detection threshold of 2.79 for the dielectric property contrast, all lesions were detected without false positives or false negatives. Conclusions. This study demonstrates the use of a microwave-based device to be used as an accessory of a standard colonoscope to detect neoplastic lesions in surgically excised colorectal specimens.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to identify the germline causative alteration to provide intensified surveillance to those at risk and allow early diagnosis and cancer prevention. Current approaches for LS molecular diagnosis typically involve screening of the MMR genes by targeted gene-panel sequencing and rearrangement screening. We report the identification and characterization of a novel germline structural variant encompassing 48.757 kb, involving the 3’-ends of the MLH1 and LRRFIP2 genes, as the cause of LS in a family of Ecuador. Whole-genome sequencing and transcriptomics allowed the identification of the genomic rearrangement and highlights the importance of the use of these additional approaches to achieve a comprehensive molecular diagnosis in some LS patients.

We developed a measurement setup and protocol reliably relating complex permittivity measurements with tissue characterization and specific histological features. We measured 148 fresh human tissue samples across 14 tissue types at 51 frequencies ranging from 200 MHz to 20 GHz, using an open-ended coaxial slim probe. Tissue samples were collected using a punch biopsy, ensuring that the sampled area encompassed the region where complex permittivity measurements were performed. This approach minimized experimental uncertainty related to potential position-dependent variations in permittivity. Once measured, the samples were then formalin-fixed and paraffin-embedded (FFPE) to obtain histological slides for microscopic analysis of tissue features. We observed that complex permittivity values are strongly associated with key histological features, including fat content, necrosis, and fibrosis. Most tissue samples exhibiting these features could be differentiated from nominal values for that tissue type, even accounting for statistical variability and instrumental uncertainties. These findings demonstrate the potential of incorporating fast in situ complex permittivity for fresh tissue characterization in pathology workflows. Furthermore, our work lays the groundwork for enhancing databases where complex permittivity values are measured under histological control, enabling precise correlations between permittivity values, tissue characterization, and histological features.

Ex vivo Fusion Confocal Microscopy (eFuCM) is a promising new technique for real-time histological diagnosis, requiring minimal tissue preparation and avoiding tissue waste. This study aimed to evaluate the feasibility of eFuCM in identifying key liver biopsy lesions and patterns, and to assess the impact of eFuCM reading experience on diagnostic accuracy. Twenty-three fresh liver biopsies were analyzed using eFuCM to produce H&E-like digital images, which were reviewed by two pathologists and compared with a conventional H&E diagnosis. The liver architecture was clearly visible on the eFuCM images. Pathologist 1, with no prior eFuCM experience, achieved a substantial agreement with the H&E diagnosis (κ = 0.65), while Pathologist 2, with eFuCM experience, reached almost perfect agreement (κ = 0.88). However, lower agreement levels were found in the evaluation of inflammation. Importantly, tissue preparation for eFuCM did not compromise subsequent conventional histological processing. These findings suggest that eFuCM has great potential as a time- and material-saving tool in liver pathology, though its diagnostic accuracy improves with pathologist experience, indicating that there is a learning curve related to its use.

Lymph node (LN) metastasis is an important prognostic factor in colorectal cancer (CRC). We aimed to demonstrate the presence of lymphatic vessels (LV) in the mucosa of in-situ (pTis) CRC, and of detectable tumour burden in regional LNs. This is an observational retrospective study of 39 surgically resected in situ CRCs. The number of LVs was evaluated in both pTis and normal mucosa using D2-40 immunostains. All LNs were assessed with both H&E and the One Step Nucleic Acid Amplification (OSNA) assay, and the results were correlated with clinicopathological features. D2-40 immunohistochemisty revealed LVs in the lamina propria of all pTis CRC (100%), being absent in normal mucosa. A median of 16 LNs were freshly dissected per patient, and all cases were pN0 with H&E. Molecular LN analysis with OSNA revealed the presence of low amounts of tumour burden in 11/39 (28%) cases (range 400 to 4270 CK19 mRNA copies/µL), which had no clinical consequences. This study demonstrates the presence of LVs in the lamina propria in 100% of pTis CRC, as well as the presence of low amounts of tumour burden in regional LNs, only detected by molecular methods. Given the prognostic value of LN tumour burden, its molecular quantification may help a patient’s clinical management.

Lymph node (LN)-negative colorectal cancer (CRC) patients may be understaged by conventional hematoxylin and eosin for its low sensitivity for detecting LN micrometastasis (LNM). The one-step nucleic acid amplification assay (OSNA) has shown superior performance in detecting LNM. To date, OSNA studies in CRC have analyzed part of the LN tissue with OSNA and part with H&E, introducing a tissue allocation bias for LNM detection. We aimed to evaluate the prognostic significance of the whole LN molecular analysis using OSNA in CRC patients. This prospective multicenter study analyzed LNs from stage I-III CRC by both cytology smears (CS) and OSNA, the latter analyzing the whole LN tissue and reported as the Total Tumor Load (TTL). X-tile software was used to determine the optimal TTL threshold. Cox proportional hazard and Kaplan–Meier estimation were used to assess the prognostic significance of TTL for both cancer-specific survival (CSS) and recurrence-free survival (RFS). 158 CRC patients were included, with 156 eligible for survival analysis. A TTL of 15,000 copies/µL was identified as the optimal cut-off, stratifying CRC patients into low and high risk for both CSS and RFS ( P  < 0.05). Conversely, CS pN-positive patients with TTL ≤ 15,000 copies/μL had comparable long-term outcomes to CS pN-negative patients ( P  > 0.05). A TTL threshold of > 15,000 copies/μL has prognostic value as it identifies CRC patients with significantly reduced CSS and RFS. The clinical implementation of the whole LN analysis by OSNA allows accurate patient risk stratification and optimizes postsurgical management.

Background/objective: The palmaris longus muscle is a variable and often inconsistent muscle in the anterior compartment of the forearm. This fusiform-shaped muscle originates at the medial epicondyle of the humerus bone following a long and narrow tendon that inserts at the palmar aponeurosis. That tendon is used in reconstructive surgery, and for this reason, detailed information from an ultrasound is used to detect the tendon and the possible variations in the muscle. The present study aimed to investigate the palmaris longus muscle and its variations through ultrasound, anatomical, and histological analysis with clinical and surgical applications. Methods: A total of 72 upper limbs from 33 females and 39 males, 32 right and 40 left, were evaluated in ultrasound, anatomical, and histological studies. The main objective was to prove the existence of the palmaris longus muscle and its variations, as well as to measure the tendon for surgical applications. Results: Ultrasound analysis showed that it is possible to determine the existence of the muscle (76.4%) and its variations (23.6%), as well as its absence (15.3%). The anatomical results proved the ultrasound results. The width of the tendon was between 0.4 and 0.38 mm. by ultrasound and anatomical analysis. Also, normal palmaris longus tendons were not a direct cause of compression of the median nerve. Conclusions: It is important to confirm the existence and possible variations in the palmaris longus muscle and tendon through ultrasound before surgical reconstruction and for clinical diagnostics.

Background CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). Methods After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed β-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. Results Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. Conclusions Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.