Background Colon cancer (CC) is a heterogeneous disease. Novel prognostic factors beyond pathological staging are required to accurately identify patients at higher risk of relapse. Integrating these new biological factors, such as plasma circulating tumour DNA (ctDNA), CDX2 staining, inflammation-associated cytokines and transcriptomic consensus molecular subtypes (CMS) classification, into a multimodal approach may improve our accuracy in determining risk of recurrence. Methods One hundred and fifty patients consecutively diagnosed with localised CC were prospectively enrolled in our study. ctDNA was tracked to detect minimal residual disease by droplet digital PCR. CDX2 expression was analysed by immunostaining. Plasma levels of cytokines potentially involved in disease progression were measured using ELISAs. A 96 custom gene panel for nCounter assay was used to classify CC into colorectal cancer assigner and CMS. Results Most patients were classified into CMS4 (37%) and CMS2 (28%), followed by CMS1 (20%) and CMS3 (15%) groups. CDX2-negative tumours were enriched in CMS1 and CMS4 subtypes. In univariable analysis, prognosis was influenced by primary tumour location, stage, vascular and perineural invasion together with high interleukin-6 plasma levels at baseline, tumours belonging to CMS 1 vs CMS2 +CMS3, ctDNA presence in plasma and CDX2 loss. However, only positive ctDNA in plasma samples (HR 13.64; p=0.002) and lack of CDX2 expression (HR 23.12; p=0.001) were found to be independent prognostic factors for disease-free survival in the multivariable model. Conclusions ctDNA detection after surgery and lack of CDX2 expression identified patients at very high risk of recurrence in localised CC.

Purpose: To analyze the treatment outcomes for sigmoid volvulus (SV) and identify risk factors of complications and mortality. Methods: Observational study of all consecutive adult patients diagnosed with SV who were admitted from January 2000 to December 2020 in a tertiary university institution for conservative management, urgent or elective surgery. Primary outcomes were 30-day postoperative morbidity, mortality and 2-year overall survival (OS), including analysis of risk factors for postoperative morbidity or mortality and prognostic factors for 2-year OS. Results: A total of 92 patients were included. Conservative management was performed in 43 cases (46.7%), 27 patients (29.4%) underwent emergent surgery and 22 (23.9%) were scheduled for elective surgery. Successful decompression was achieved in 87.8% of cases, but the recurrence rate was 47.2%. Mortality rates following episodes were higher for conservative treatment than for urgent or elective surgery (37.2%, 22.2%, 9.1%, respectively; p = 0.044). ASA score > III was an independent risk factor for complications (OR = 5.570, 95% CI = 1.740–17.829, p < 0.001) and mortality (OR = 6.139, 95% CI = 2.629–14.335, p < 0.001) in the 30 days after admission. Patients who underwent elective surgery showed higher 2-year OS than those with conservative treatment (p = 0.011). Elective surgery (HR = 2.604, 95% CI = 1.185–5.714, p = 0.017) and ASA score > III (HR = 0.351, 95% CI = 0.192–0.641, p = 0.001) were independent prognostic factors for 2-year OS. Conclusion: Successful endoscopic decompression can be achieved in most SV patients, but with the drawbacks of high recurrence, morbidity and mortality rates. Concurrent severe comorbidities and conservative treatment were independent prognostic factors for morbidity and survival in SV.

In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting a higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study, we assess the potential value of adding white blood cells (WBCs) to tumor tissue sequencing to enhance the accuracy of sequencing results. A total of 148 patients diagnosed with localized CC were prospectively recruited at the Hospital Clínico Universitario in Valencia (Spain). Employing a custom 29-gene panel, sequencing was conducted on tumor tissue, plasma and corresponding WBCs. Droplet digital PCR and amplicon-based NGS were performed on plasma samples post-surgery to track MRD. Oncogenic somatic variants were identified by annotating with COSMIC, OncoKB and an internal repository of pathogenic mutations database. A variant prioritization analysis, mainly characterized by the match of oncogenic mutations with the evidence levels defined in OncoKB, was carried out to select specific targeted therapies. Utilizing paired tumor and WBCs sequencing, we identified somatic mutations in all patients (100%) within our cohort, compared to 89% using only tumor tissue. Consequently, the top 10 most frequently mutated genes for plasma monitoring were altered. The sequencing of WBCs identified 9% of patients with pathogenic mutations in the germline, with APC and TP53 being the most frequently mutated genes. Additionally, mutations in genes related to clonal hematopoiesis of indeterminate potential were detected in 27% of the cohort, with TP53, KRAS, and KMT2C being the most frequently altered genes. There were no observed differences in the sensitivity of monitoring MRD using ddPCR or amplicon-based NGS (p = 1). Ultimately, 41% of the patients harbored potentially targetable alterations at diagnosis. The germline testing method not only enhanced sequencing results and raised the proportion of patients eligible for plasma monitoring, but also uncovered the existence of pathogenic germline variations, thereby aiding in the identification of patients at a higher risk of hereditary cancer syndromes.