Interventional radiological therapies in colorectal hepatic metastases

Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases

Revascularization of Chronic Iliac Vein Occlusion Using Balloon-Assisted Transseptal Needle Puncture Technique

Objectives To evaluate the utility of a transseptal needle for balloon-assisted sharp recanalization of chronically occluded central venous structures. Background Chronically occluded central veins are not an uncommon problem, which may arise due to a plethora of reasons. Traditionally, wire and catheter techniques are often used first in an attempt to reestablish flow. When these methods fail, more aggressive techniques are employed, such as sharp recanalization using the back end of wires, Teflon-coated wires, or Rosch–Uchida or Colapinto needles. However, utilization of transseptal needles, traditionally reserved for cardiac procedures, has rarely been described. Methods Transseptal needle was utilized for balloon-assisted sharp recanalization after traditional wire and catheter techniques failed in revascularization of chronically occluded iliac veins. Results Transseptal needle was utilized successfully in two cases in revascularization of chronically occluded central veins. Conclusion Transseptal needle is a viable tool to add to the interventional radiologists’ armamentarium in reestablishing flow in chronically occluded central veins

Provocative mesenteric angiography for occult gastrointestinal bleeding: a systematic review

Abstract Occult gastrointestinal bleeding (GIB) is a challenge for physicians to diagnose and treat. A systematic literature search of the PubMed and Embase databases was conducted up to January 1, 2023. Eligible studies included primary research studies with patients undergoing provocative mesenteric angiography (PMA) for diagnosis or localization of occult GIB. Twenty-seven articles (230 patients) were included in the review. Most patients (64.8%) presented with lower GIB. The average positivity rate for provocative angiography was 48.7% (58% with heparin and 46.7% in thrombolytics). Embolization was performed in 46.4% of patients, and surgical management was performed in 37.5%. Complications were rare. PMA can be an important diagnostic and treatment tool but studies with high-level evidence and standardized protocols are needed to establish its safety and optimal use

Associating Genes with Gene Ontology Codes Using a Maximum Entropy Analysis of Biomedical Literature

Functional characterizations of thousands of gene products from many species are described in the published literature. These discussions are extremely valuable for characterizing the functions not only of these gene products, but also of their homologs in other organisms. The Gene Ontology (GO) is an effort to create a controlled terminology for labeling gene functions in a more precise, reliable, computer-readable manner. Currently, the best annotations of gene function with the GO are performed by highly trained biologists who read the literature and select appropriate codes. In this study, we explored the possibility that statistical natural language processing techniques can be used to assign GO codes. We compared three document classification methods (maximum entropy modeling, naïve Bayes classification, and nearest-neighbor classification) to the problem of associating a set of GO codes (for biological process) to literature abstracts and thus to the genes associated with the abstracts. We showed that maximum entropy modeling outperforms the other methods and achieves an accuracy of 72% when ascertaining the function discussed within an abstract. The maximum entropy method provides confidence measures that correlate well with performance. We conclude that statistical methods may be used to assign GO codes and may be useful for the difficult task of reassignment as terminology standards evolve over time

Coordinate Regulation of the Oxygen-Dependent Degradation Domains of Hypoxia-Inducible Factor 1α

Oxygen-dependent proteolysis is the primary means of regulating the hypoxia-inducible factor (HIF) family of transcription factors. The alpha-subunit of HIF factor 1 (HIF-1) contains two highly conserved oxygen-dependent degradation domains (402 ODD and 564 ODD), each of which includes a proline that is hydroxylated in the presence of oxygen, allowing the von Hippel-Lindau (VHL) E3 ubiquitin ligase to interact and target HIF-1α to the proteasome for degradation. Mutation of either proline is sufficient to partially stabilize HIF-1α under conditions of normoxia, but the specific contributions of each hydroxylation event to the regulation of HIF-1α are unknown. Here we show that the two ODDs of HIF-1α have independent yet interactive roles in the regulation of HIF-1α protein turnover, with the relative involvement of each ODD depending on the levels of oxygen. Using hydroxylation-specific antibodies, we found that under conditions of normoxia proline 564 is hydroxylated prior to proline 402, and mutation of proline 564 results in a significant reduction in the hydroxylation of proline 402. Mutation of proline 402, however, has little effect on the hydroxylation of proline 564. To determine whether the more rapid hydroxylation of the proline 564 under conditions of normoxia is due to a preference for the particular sequence surrounding proline 564 or for that site within the protein, we exchanged the degradation domains within the full-length HIF-1α protein. In these domain-swapping experiments, prolyl hydroxylase domain 1 (PHD1) and PHD2 preferentially hydroxylated the proline located in the site of the original 564 ODD, while PHD3 preferred the proline 564 sequence, regardless of its location. At limiting oxygen tensions, we found that proline 402 exhibits an oxygen-dependent decrease in hydroxylation at higher oxygen tensions relative to proline 564 hydroxylation. These results indicate that hydroxylation of proline 402 is highly responsive to physiologic changes in oxygen and, therefore, plays a more important role in HIF-1α regulation under conditions of hypoxia than under conditions of normoxia. Together, these findings demonstrate that each hydroxylated proline of HIF-1α has a distinct activity in controlling HIF-1α stability in response to different levels of oxygenation

Additional file 1 of Provocative mesenteric angiography for occult gastrointestinal bleeding: a systematic review

Additional file 1: Table S1. Quality assessment. Table S2. Treatment details and outcomes- heparin provocation. Table S3. Treatment details for studies that used thrombolytics/other agents. Table S4. Drug dose details

Oxygen Sensitivity of Reporter Genes: Implications for Preclinical Imaging of Tumor Hypoxia

Reporter gene techniques have been applied toward studying the physiologic phenomena associated with tumor hypoxia, a negative prognostic indicator. The purpose of this study was to assess the potential adverse effects of hypoxic conditions on the effectiveness of four commonly used reporter genes: Renilla luciferase, monomeric red fluorescent protein, thymidine kinase, and lacZ . Tumor-forming A375 cells expressing a trifusion reporter consisting of Renilla luciferase, monomeric red fluorescent protein, and thymidine kinase were subjected to decreasing oxygen tensions and assayed for reporter expression and activity. A375 cells expressing β-galactosidase were similarly exposed to hypoxia, with activity of the reporter monitored by cleavage of the fluorescent substrate 7-hydroxy-9 H -(1, 3-dichloro-9, 9-dimethylacridin-2-one)-β-galactoside (DDAOG). Generation of signal in in vivo tumor models expressing bioluminescent or β-galactosidase reporters were also examined over the course of hypoxic stresses, either by tumor clamping or the antivascular agent 5, 6-dimethylxanthenone-4-acetic acid (DMXAA). Our findings indicate that bioluminescent and fluorescent reporter activity are decreased under hypoxia despite minimal variations in protein production, whereas β-galactosidase reporter activity per unit protein was unchanged. These results demonstrate that combining β-galactosidase with the DDAOG optical probe may be a robust reporter system for the in vivo study of tumor hypoxia