Pan-Cancer DNA Methylation Analysis and Tumor Origin Identification of Carcinoma of Unknown Primary Site Based on Multi-Omics

The metastatic cancer of unknown primary (CUP) sites remains a leading cause of cancer death with few therapeutic options. The aberrant DNA methylation (DNAm) is the most important risk factor for cancer, which has certain tissue specificity. However, how DNAm alterations in tumors differ among the regulatory network of multi-omics remains largely unexplored. Therefore, there is room for improvement in our accuracy in the prediction of tumor origin sites and a need for better understanding of the underlying mechanisms. In our study, an integrative analysis based on multi-omics data and molecular regulatory network uncovered genome-wide methylation mechanism and identified 23 epi-driver genes. Apart from the promoter region, we also found that the aberrant methylation within the gene body or intergenic region was significantly associated with gene expression. Significant enrichment analysis of the epi-driver genes indicated that these genes were highly related to cellular mechanisms of tumorigenesis, including T-cell differentiation, cell proliferation, and signal transduction. Based on the ensemble algorithm, six CpG sites located in five epi-driver genes were selected to construct a tissue-specific classifier with a better accuracy (>95%) using TCGA datasets. In the independent datasets and the metastatic cancer datasets from GEO, the accuracy of distinguishing tumor subtypes or original sites was more than 90%, showing better robustness and stability. In summary, the integration analysis of large-scale omics data revealed complex regulation of DNAm across various cancer types and identified the epi-driver genes participating in tumorigenesis. Based on the aberrant methylation status located in epi-driver genes, a classifier that provided the highest accuracy in tracing back to the primary sites of metastatic cancer was established. Our study provides a comprehensive and multi-omics view of DNAm-associated changes across cancer types and has potential for clinical application.

Modified autotransplantation technique for surgical resection of complex pericardial synovial sarcoma

Technical details for complex cardiac tumor resection are sparse. We describe the operative technique of modified autotransplantation for resection of a complex pericardial synovial sarcoma in a 63-year-old, Caucasian female. Surgical exposure demonstrated tumor origin at the superior cavoatrial junction and invasion of the aorta, main pulmonary artery, superior pulmonary veins, and left atrial roof. Full macroscopic surgical resection was achieved. The patient received adjuvant radiation for microscopic positive margins and remains alive and with no tumor progression at one year postoperatively. We conclude that modified autotransplantation is a challenging but effective surgical technique when performed with careful patient selection and availability of skilled, cardiothoracic surgeons at a cardiac center of excellence.

Choice of treatment method of obstructive jaundice in patients with tumors of the hepatopancreatobiliary region

The leading criteria for choosing minimally invasive surgical treatment of mechanical jaundice of tumor origin in the hepatopancreatobiliary zone are substantiated, which increase the effectiveness of surgical intervention and reduce the number of complications and mortality. The examination and surgical treatment results of 325 patients with mechanical jaundice of tumor origin, who underwent minimally invasive decompression of the biliary tract after clinical and laboratory diagnostics following national clinical recommendations, were analyzed. Based on the treatment results, the leading criteria that affect the selection of the method of minimally invasive drainage surgery are identified. The main criteria influencing the choice of minimally invasive intervention to decompress the bile ducts were as follows: level of bile duct block, severity of mechanical jaundice (according to the classification of E.I. Galperin), and the operability of the patient. Endoscopic stenting was the method of choice in inoperable cases at the level of block I with mechanical jaundice of classes A and B. Moreover, endoscopic stenting was the most successful intervention with a minimum number of complications in people with block II level. The indication for percutaneous transhepatic biliary drainage was a level III biliary tract block, as well as the ineffectiveness of endoscopic stenting. Cholecystostomy is the safest and most effective in patients with block level I with class C mechanical jaundice and in operable cases with the same block level. In general, results of surgical interventions aimed at eliminating mechanical jaundice of tumor origin, conducted using modern examination methods of patients and taking into account the assessment of criteria such as the block level of the bile ducts, severity of mechanical jaundice, and general condition allow us to justify the choice of the most successful and safe option for its elimination.

Tumor-Agnostic Biomarkers: Heed Caution, and Why Cell of Origin Still Matters

Since the very beginnings of cancer therapy with chemotherapy, tumors have been treated according to the organ or tissue of origin. The advent of precision medicine however, has recently led to growing promise for tumor-agnostic biomarkers for targeted therapies and immunotherapies, such as NTRK fusions. Despite this, prominent examples such as BRAF V600E mutations in melanoma compared to colorectal cancer, in which the site of tumor origin dramatically influences the efficacy of targeted therapies, heeds caution against disregarding the importance of cell of origin. Indeed, another illustrative example, is the almost complete absence outside of cancers originating from the lung of the classical activating EGFR mutations—exon 19 deletions and exon 21 L858R mutations. Consequently, an understanding of lineage dependency and lineage-survival oncogenes may still offer significant mechanistic insights into the malignant transformation of tumors to ultimately identify further therapeutic vulnerabilities.

Schwannoma of the Intermediate Nerve: A Rare Type of Cerebellopontine Angle Tumor

Background: Schwannoma of the Intermediate Nerve is rare. The most majority of Cerebellopontine angle (CPA) lesions are Vestibular Schwannomas. Case description: A 50-year-old woman presented with ear pain, facial palsy and hypoacusis. MRI revealed a CPA tumor. A left retrosigmoid approach and microsurgery was performed and the tumor origin was from the intermediate nerve. intraoperative neurophysiologic monitoring (MNIO) was used during the surgery. Conclusion: Schwannomas of the intermediate nerve is indistinguishable from vestibular schwannomas on preoperatory image, however it’s possible to identify tumor origin during microsurgery dissection with aid of MNIO and origin from intermediate nerve is a reality.

Pathological syndromes of decompression of the biliary tract.

Summary. The circle of pathological conditions that develop in the post-decompression phase of BT with OX is indicated, and an effective pathognomonic conditioned treatment algorithm for patients has been developed. The results of examination and treatment of 216 patients with OX who underwent various options for BT decompression were analyzed. OX of tumor origin was observed in 112 (51.8%) patients, benign - in 104 (48.2%). The main group was -112, the control group - 104. Two-stage tactics were undertaken in 133 (61.6%) cases, 83 (38.4%) were operated on in one stage. The accelerated decompression syndrome developed in 31 (14.3%) cases (in the control -26, main-5). Violations of the water-electrolyte balance occurred in 32 (46.4%) patients with complete external abduction of bile. Digestive remodeling syndrome was present in 44 (33.1%) patients.

Machine Learning Protocols in Early Cancer Detection Based on Liquid Biopsy: A Survey

With the advances of liquid biopsy technology, there is increasing evidence that body fluid such as blood, urine, and saliva could harbor the potential biomarkers associated with tumor origin. Traditional correlation analysis methods are no longer sufficient to capture the high-resolution complex relationships between biomarkers and cancer subtype heterogeneity. To address the challenge, researchers proposed machine learning techniques with liquid biopsy data to explore the essence of tumor origin together. In this survey, we review the machine learning protocols and provide corresponding code demos for the approaches mentioned. We discuss algorithmic principles and frameworks extensively developed to reveal cancer mechanisms and consider the future prospects in biomarker exploration and cancer diagnostics.

EXPERIENCE OF STAGED SURGICAL TREATMENT OF ACUTE OBSTRUCTIVE INTESTINAL OBSTRUCTION OF TUMOR ORIGIN

Summary. Objective: to improve the results of surgical treatment of patients with acute intestinal obstruction of tumor origin. Materials and methods of research. During the period from 2014 to 2020 in the surgical clinics of the Military Medical Clinical Center of the Southern Region (Odessa) 186 patients were treated with acute obstructive colonic obstruction of tumor origin. Research results and their discussion. In 34 (18.3 %) patients with GOKN during the applied conservative measures positive dynamics was observed, which allowed to examine patients in detail and prepare for surgery. In 6 (3.2 %) elderly patients with severe comorbidities, tumor recanalization and stent placement were performed. In 146 (78.5 %) patients, conservative measures were unsuccessful and were operated on according to vital signs, the first stage of which was intestinal fatigue. Conclusions. Step-by-step tactics of surgical treatment of acute intestinal obstruction of tumor origin with the use of laparoscopic colostomy in the first stage were used in 60.3 % of patients, which allowed final verification of the diagnosis, safe compensation of electrolyte and nutritional disorders in the patient and further treatment and correction.