A Predictive Noninvasive Single-Nucleotide Variation-Based Biomarker Signature for Resectable Pancreatic Cancer: Protocol for a Prospective Validation Study.

BACKGROUND: Single-nucleotide variations (SNVs; formerly SNPs) are inherited genetic variants that can be easily determined in routine clinical practice using a simple blood or saliva test. SNVs have potential to serve as noninvasive biomarkers for predicting cancer-specific patient outcomes after resection of pancreatic ductal adenocarcinoma (PDAC). Two recent analyses led to the identification and validation of three SNVs in the CD44 and CHI3L2 genes (rs187115, rs353630, and rs684559), which can be used as predictive biomarkers to help select patients most likely to benefit from pancreatic resection. These variants were associated with an over 2-fold increased risk for tumor-related death in three independent PDAC study cohorts from Europe and the United States, including The Cancer Genome Atlas cohorts (reaching a P value of 1×10-8). However, these analyses were limited by the inherent biases of a retrospective study design, such as selection and publication biases, thereby limiting the clinical use of these promising biomarkers in guiding PDAC therapy. OBJECTIVE: To overcome the limitations of previous retrospectively designed studies and translate the findings into clinical practice, we aim to validate the association of the identified SNVs with survival in a controlled setting using a prospective cohort of patients with PDAC following pancreatic resection. METHODS: All patients with PDAC who will undergo pancreatic resection at three participating hospitals in Switzerland and fulfill the inclusion criteria will be included in the study consecutively. The SNV genotypes will be determined using standard genotyping techniques from patient blood samples. For each genotyped locus, log-rank and Cox multivariate regression tests will be performed, accounting for the relevant covariates American Joint Committee on Cancer stage and resection status. Clinical follow-up data will be collected for at least 3 years. Sample size calculation resulted in a required sample of 150 patients to sufficiently power the analysis. RESULTS: The follow-up data collection started in August 2019 and the estimated end of data collection will be in May 2027. The study is still recruiting participants and 142 patients have been recruited as of November 2023. The DNA extraction and genotyping of the SNVs will be performed after inclusion of the last patient. Since no SNV genotypes have been determined, no data analysis has been performed to date. The results are expected to be published in 2027. CONCLUSIONS: This is the first prospective study of the CD44 and CHI3L2 SNV-based biomarker signature in PDAC. A prospective validation of this signature would enable its clinical use as a noninvasive predictive biomarker of survival after pancreatic resection that is readily available at the time of diagnosis and can assist in guiding PDAC therapy. The results of this study may help to individualize treatment decisions and potentially improve patient outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54042.

Interdisciplinary approach in emergency revascularization and treatment for acute mesenteric ischemia.

BACKGROUND: Mesenteric ischemia is associated with poor outcome and high overall mortality. The aim was to analyze an interdisciplinary treatment approach of vascular and visceral specialists focusing on the in-hospital outcome and follow-up in patients with acute and acute-on-chronic mesenteric ischemia. METHODS: From 2010 until 2017, 26 consecutive patients with acute or acute on chronic mesenteric ischemia were treated by an interdisciplinary team. Data were prospectively collected and retrospectively evaluated. Throughout the initial examination, the extent of bowel resection was determined by the visceral surgeon and the appropriate mode of revascularization by the vascular surgeon. The routine follow-up included clinical examination and ultrasound- or CT-imaging for patency assessment and overall survival as primary endpoint of the study. RESULTS: Out of 26 patients, 18 (69.2%) were rendered for open repair. Ten patients (38.5%) received reconstruction of the superior mesenteric artery with an iliac-mesenteric bypass. Seven patients (26.9%) underwent thrombembolectomy of the mesenteric artery. One patient received an infra-diaphragmatic aorto-celiac-mesenteric bypass. Out of the 8 patients, who were not suitable for open revascularization, 2 patients (7.7%) were treated endovascularly and 6 (23.1%) underwent explorative laparotomy. The in-hospital mortality was 23% (n = 6). The mean survival of the revascularized group (n = 20) was 51.8 months (95% CI 39.1-64.5) compared to 15.7 months in the non-revascularized group (n = 6) (95% CI - 4.8-36.1; p = 0.08). The median follow-up was 64.6 months. Primary patency in the 16 patients after open and 2 after interventional revascularization was 100% and 89.9% in the follow-up. CONCLUSION: The interdisciplinary treatment of mesenteric ischemia improves survival if carried out in time. Hereby open revascularization measures are advantageous as they allow bowel assessment, resection, and revascularization in a one-stop fashion especially in advanced cases.

Perception of semiquantitative terms in surgery.

OBJECTIVE: To assess whether semiquantitative terms (eg, "often" or "rare"), which are often used for achieving informed consent, have the same meaning for laypersons and physicians. BACKGROUND: To obtain informed consent, physicians have to make their patients aware of the risks of an operation. Thereby, semiquantitative terms are often used. METHODS: Questionnaire interview among surgeons and randomly approached laypersons. A set of semiquantitative terms was presented to participants for quantification. Pertinent to 8 exemplary complications of common operations, these values were compared among the 2 interviewed groups and corresponding rates in scientific literature. RESULTS: The questionnaire was completed by 48 surgeons and 582 laypersons in Switzerland. Confronted with corresponding complication rates in literature, laypersons underestimated the risk significantly in 6 of 8 cases. After a simulated informed consent conversation with a surgeon by using semiquantitative terms, laypersons overestimated the complication rate significantly in 7 of 8 cases. An interaction analysis did not show any significant difference between correct estimations of complication rates of respondents who graduated, who had a professional medical background or who had had prior contact with the health care system (eg, medical consultation, hospitalization, operation) compared with the others. CONCLUSIONS: Laypersons overestimate probabilities of semiquantitative terms named by surgeons. We recommend using "percentages" or "odds ratios" to achieve a more reliable preoperative informed consent.

Relation of depression to various markers of coagulation and fibrinolysis in patients with and without coronary artery disease.

BACKGROUND: It has been suggested that changes in blood coagulation and fibrinolysis might explain the observed association between depression and coronary artery disease (CAD). So far, only a few coagulation factors have been investigated in this regard, and the results were not consistent. DESIGN: The aim of our study was to analyse a broad range of coagulation and fibrinolytic factors, with emphasis on factors directly involved in clot formation and degradation or reflecting coagulation activation, in patients with CAD and controls without CAD, as assessed by coronary angiography, who also underwent a diagnostic procedure for depression. METHODS: We screened 306 patients with CAD and controls without CAD for depression using the Hospital Anxiety and Depression Scale and Allgemeine Depressions Skala-L questionnaires. In participants with positive screening result, diagnosis of major depression was confirmed or excluded by a structured interview. We analysed the following coagulation and fibrinolytic factors: fibrinogen, prothrombin fragment F1+2, factor XIII A-subunit, factor XIII B-subunit, tissue plasminogen activator, plasminogen activator inhibitor-1, thrombin-activable fibrinolysis inhibitor, and D-dimer. RESULTS: We did not observe significant associations between depression and CAD, nor between depression and cardiovascular risk factors. Coagulation and fibrinolytic factors showed no differences between patients with CAD and controls, but they were associated with several cardiovascular risk factors. Depression was not associated with coagulation and fibrinolytic factors. No associations were found either when both CAD and depression were taken into account. CONCLUSION: Our study gives no evidence that there is a significant relation among depression, CAD, and blood coagulation and fibrinolysis.