The Importance of CT Pneumocolon in Detecting Colonic Lesions

Background: Colonic masses are clinically important because some of them are malignant and others have a tendency to become malignant such as polyps. CT pneumocolon may have a role in the evaluation and diagnosis of these masses. Objective: To determine the accuracy of computed tomography (CT) pmeumocolon in the detection of colonic masses compared with colonoscopy. Patients and Methods: A total of 60 patients with colorectal symptoms underwent evaluation for the presence of colorectal neoplasms by using both colonoscopy and CT pneumocolon and a comparison was made between them. Results: On colonoscopy, 10 out of 60 patients were having a negative colonoscopy. The results of colonoscopy of the other 50 patients were as follow; three out of fifty colonoscopies revealed invasive colorectal carcinomas in threse patients. The remaining 47 colonoscopies for 47 patients revealed benign polyps. The sizes of these polyps were as follows; (6 polyps were ˃1 cm in diameter), (17 polyps were 6-9 mm), and (24 polyps were ≤5 mm). CT pneumocolon detected all 3 malignant masses seen and biopsied by colonoscopy, but only (28 single polyps) which according to their size (4 polyps were ≥ 1cm), (11 polyps were 6-9 mm) and (13 polyps ≤5 mm), this gives CT pneumocolon a sensitivity of (63%), specificity of (70%) and accuracy (63%). Conclusion: CT pneumocolon has high sensitivity and specificity for a detection of large-sized masses, but not for small ones. CT pneumocolon may be suitable for investigating patients with symptomatic colorectal masses noninvasively. Keywords: Pneumocolon, colonoscopy, polyp, colonic carcinoma

Molecular pathways, targeted therapies and proteomic investigations of colorectal cancer

According to the GLOBOCAN 2020 data, colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death. The risk factors for colorectal cancer include a diet abundant with fat, refined carbohydrates, animal protein, low fiber content, alcoholism, obesity, long-term cigarette smoking, low physical inactivity, and aging. Colorectal carcinomas are classified as adenocarcinoma, neuroendocrine, squamous cell, adenosquamous, spindle cell, and undifferentiated carcinomas. In addition, many variants of colorectal carcinomas are recently distinguished based on histological, immunological, and molecular characteristics. Recently developed targeted molecules in conjunction with standard chemotherapeutics or immune checkpoint inhibitors provide promising treatment protocols for colorectal cancer. However, the benefit of targeted therapies is strictly dependent on the mutational status of signaling molecules (e.g., KRAS) or mismatch repair systems. Here it is aimed to provide a comprehensive view of colorectal cancer types, molecular pathways-associated, recently developed targeted therapies as well as proteomic investigations applied to colorectal cancer for the discovery of novel biomarkers as well as new targets for treatment protocols.

Pyruvate Kinase M1 Regulates Butyrate Metabolism in Cancerous Colonocytes

Colorectal cancer (CRC) cells shift metabolism toward aerobic glycolysis and away from using oxidative substrates such as butyrate. Pyruvate kinase M1/2 (PKM) is an enzyme that catalyzes the last step in glycolysis, which converts phosphoenolpyruvate to pyruvate. M1 and M2 are alternatively spliced isoforms of the Pkm gene. The PKM1 isoform promotes oxidative metabolism, whereas PKM2 enhances aerobic glycolysis. We hypothesize that the PKM isoforms are involved in the shift away from butyrate oxidation towards glycolysis in CRC cells. Here, we find that PKM2 is increased and PKM1 is decreased in human colorectal carcinomas as compared to non-cancerous tissue. To test whether PKM1/2 alter colonocyte metabolism, we created a knockdown of PKM2 and PKM1 in CRC cells to analyze how butyrate oxidation and glycolysis would be impacted. We report that butyrate oxidation in CRC cells is regulated by PKM1 levels, not PKM2. Decreased butyrate oxidation observed through knockdown of PKM1 and PKM2 is rescued through re-addition of PKM1. Diminished PKM1 lowered mitochondrial basal respiration and decreased mitochondrial spare capacity. We demonstrate that PKM1 suppresses glycolysis and inhibits hypoxia-inducible factor-1 alpha. These data suggest that reduced PKM1 is, in part, responsible for increased glycolysis and diminished butyrate oxidation in CRC cells.

Profiling diverse sequence tandem repeats in colorectal cancer reveals co-occurrence of microsatellite and chromosomal instability involving Chromosome 8

We developed a sensitive sequencing approach that simultaneously profiles microsatellite instability, chromosomal instability, and subclonal structure in cancer. We assessed diverse repeat motifs across 225 microsatellites on colorectal carcinomas. Our study identified elevated alterations at both selected tetranucleotide and conventional mononucleotide repeats. Many colorectal carcinomas had a mix of genomic instability states that are normally considered exclusive. An MSH3 mutation may have contributed to the mixed states. Increased copy number of chromosome arm 8q was most prevalent among tumors with microsatellite instability, including a case of translocation involving 8q. Subclonal analysis identified co-occurring driver mutations previously known to be exclusive.

Poorly differentiated clusters and tumor budding are important prognostic factors in colorectal carcinomas

The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - TB (GBd) and poorly differentiated clusters - PDCs (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timișoara. CRC cases were classified based on haematoxylin-eosin slides, using the conventional grading system, GBd and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently, we evaluated associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t) most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p<0.0001), tumor stage (p=0.0003), lymphovascular invasion (p<0.0001), perineural invasion (p=0.005) and the tumor border configuration (p<0.0001). High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC.Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.