Including the bowel within the iceball during cryoablation: a retrospective single-center review of adverse events.

PURPOSE: To evaluate the safety of including bowel in the ice-ball during cryoablation. MATERIALS AND METHODS: 43 patients who underwent 50 cryoablations between 1/1/2012 and 2/1/2023 were retrospectively reviewed and compared to a control cohort of those undergoing cryoablation without bowel involvement (n=86). Adverse events (AEs) were stratified by the Society of Interventional Radiology Adverse Events classification system, 2017 (1). Adverse events occurring within 12 months and factors that may affect the AE rate, such as degree of bowel involvement and portion of bowel involved, were reviewed. RESULTS: Fourteen AEs occurred in 13 patients (13/43, 30.2%). This included 7 grade 1 AEs (7/43,16.3%), 3 grade 2 (3/43,7.0%) and 4 grade 3 (4/43,9.3%). Of them 1 grade 3 AE was judged to be related to bowel involvement (1/43,2.3%). When comparing AEs by degree of bowel wall involvement, there were more injuries with the full thickness bowel wall cases (6/9,66.7%), compared with partial thickness, but the findings were not statistically significant (p=0.140). When looking at AEs by portion of the intestine involved, it was found that 7 (7/14,50%), 10 (10/17,58.8%), and 4 (4/19, 21.1%,p=0.055) were found when stomach, small bowel or large bowel was involved respectively. No significant difference in AEs (13/43,30.2% vs 31/86,36%,p=0.511) or severe AEs (4/43, 9.3% vs 9/86, 10.5%, p=0.836) was found between the study and control cohorts. CONCLUSION: Findings from this single center retrospective experience suggest that bowel wall involvement by the ice ball during cryoablation resulted in a lower-than-expected rate of adverse events for bowel-related injuries.

A New G-Quadruplex with Hairpin Loop Immediately Upstream of the Human BCL2 P1 Promoter Modulates Transcription.

The abnormal overexpression of the BCL2 gene is associated with many human tumors. We found a new 28-mer G-quadruplex-forming sequence, P1G4, immediately upstream of the human BCL2 gene P1 promoter. The P1G4 is shown to be a transcription repressor using a promoter-driven luciferase assay; its inhibitory effect can be markedly enhanced by the G-quadruplex-interactive compound TMPyP4. G-quadruplex can readily form in the P1G4 sequence under physiological salt condition as shown by DMS footprinting. P1G4 and previously identified Pu39 G-quadruplexes appear to form independently in adjacent regions in the BCL2 P1 promoter. In the extended BCL2 P1 promoter region containing both Pu39 and P1G4, P1G4 appears to play a more dominant role in repressing the transcriptional activity. Using NMR spectroscopy, the P1G4 G-quadruplex appears to be a novel dynamic equilibrium of two parallel structures, one regular with two 1-nt loops and a 12-nt middle loop and another broken-strand with three 1-nt loops and a 11-nt middle loop; both structures adopt a novel hairpin (stem-loop duplex) conformation in the long loop. The dynamic equilibrium of two closely related structures and the unique hairpin loop conformation are specific to the P1G4 sequence and distinguish the P1G4 quadruplex from other parallel structures. The presence of P1G4 and Pu39 in adjacent regions of the BCL2 P1 promoter suggests a mechanism for precise regulation of BCL2 gene transcription. The unique P1G4 G-quadruplex may provide a specific target for small molecules to modulate BCL2 gene transcription.

Cryoablation in the liver: how accurately does the iceball predict the ablation zone?

PURPOSE: To evaluate the accuracy with which the iceball predicts the realized ablation zone in patients undergoing cryoablation of the liver. MATERIALS AND METHODS: Continuous patients who underwent cryoablation of primary or secondary malignancies of the liver were retrospectively reviewed. Iceball and ablation zone dimensions on 1 month follow up imaging were collected in three orientations, the long axis (LA), perpendicular transverse (PTR), and perpendicular craniocaudal (PCC). Factors which may predict differences in the measurements were evaluated with regression analysis. Oncologic outcomes were also collected. RESULTS: The mean size of the iceball was 5.5 ± 1.1 cm, 3.9 ± 1.1 cm, and 4.4 ± 1.4 cm in the LA, PTR, and PCC orientations, respectively. The mean size of the one-month ablation cavity was 4.3 ± 1.3 cm, 3 ± 1.1 cm, and 3 ± 1.3 cm in the LA, PTR, and PCC orientations, respectively. The iceball was significantly larger than the ablation zone in all orientations (p < 0.001). When comparing HCC and non-HCC patients the Kaplan-Meier analysis of TTLP, the Kaplan Meier curves deviated significantly (p = 0.015, HR 2.26 (95%CI 1.17-4.37)). When a similar analysis was performed looking at TTP again the curves diverged significantly (p = 0.002, HR 2.4 (95%CI 1.37-4.19)). CONCLUSION: The iceball seems to overestimate the realized ablation zone by about 1 cm in all orientations during hepatic cryoablation.