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UNASSIGNED: Immunotherapy is revolutionizing the management of multiple cancer types. However, only a subset of patients responds to immunotherapy. One mechanism of resistance is the absence of immune infiltrates within the tumor. In situ vaccine with local means of tumor destruction that can induce immunogenic cell death have been shown to enhance tumor T cell infiltration and increase efficacy of immune checkpoint blockade.
UNASSIGNED: Here, we compare three different forms of localize tumor destruction therapies: radiation therapy (RT), vascular targeted photodynamic therapy (VTP) and cryoablation (Cryo), which are known to induce immunogenic cell death, with their ability to induce local and systemic immune responses in a mouse 4T1 breast cancer model. The effects of combining RT, VTP, Cryo with anti-PD1 was also assessed.
UNASSIGNED: We observed that RT, VTP and Cryo significantly delayed tumor growth and extended overall survival. In addition, they also induced regression of non-treated distant tumors in a bilateral model suggesting a systemic immune response. Flow cytometry showed that VTP and Cryo are associated with a reduction in CD11b+ myeloid cells (granulocytes, monocytes, and macrophages) in tumor and periphery. An increase in CD8+ T cell infiltration into tumors was observed only in the RT group. VTP and Cryo were associated with an increase in CD4+ and CD8+ cells in the periphery.
UNASSIGNED: These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT.

BACKGROUND: Ultrasound-guided percutaneous cryoablation (PCA) for early-stage breast cancer (ESBC) can be performed under local anesthesia in an outpatient clinic. This study continues a pilot stage to examine local control, safety, patient quality of life (QoL), satisfaction and cosmetic outcomes of cryoablation for ESBC.
METHODS: PCA was performed under local anesthesia for patients with primary ESBC, followed by radiation and endocrine therapies. Oncologic outcomes were examined by imaging (mammography, ultrasound, MRI) at baseline and 1, 6, 12, 24, 36, and 60 months post-cryoablation. EQ-VAS, EQ-5D-5L, subjective satisfaction and Moiré topography were used to measure health-related QoL outcomes.
RESULTS: Eighteen patients, mean aged 59.0 ± 9.0 years, mean tumor size 9.8 ± 2.3 mm, ER + , PR + (17/18), HER2-, Ki67 < 20% (15/18), underwent PCA and were followed for a mean of 44.3 months. No serious adverse events were reported, and no patients had local recurrence or distant metastasis in the 5-year follow-up. Cosmetic outcomes, satisfaction level, and QoL all improved post-cryoablation. Five-year average reduction rates of the cryolesion long, short, and depth diameters, on US, were 61.3%, 42.3%, and 22.8%, respectively, compared to the 86.2% volume reduction rate on MRI. The correlation coefficient between MRI and US measurement criteria was highest for the long diameter. During follow-up, calcification of the treated area was observed in 13/18 cases.
CONCLUSIONS: Cryoablation for ESBC is an effective and safe procedure with excellent cosmetic outcomes and improved QoL. This study contributes to the growing evidence supporting cryoablation as a potential standard treatment for ESBC, given compliance to pre-defined patient selection criteria.

OBJECTIVE: Maintaining hemodynamic stability during cardiac ablation under general anesthesia is challenging. Remimazolam, a novel ultrashort-acting benzodiazepine, is characterized by maintaining comparatively stable blood pressure and does not influence the cardiac conduction system, which renders it a reasonable choice for general anesthesia for cardiac ablation. We aimed to evaluate whether remimazolam is associated with a decreased incidence of intraoperative hypotension compared with desflurane.
METHODS: In this single-centre, parallel-group, prospective, single-blind, randomized clinical trial, we randomized patients (1:1) into a remimazolam group (remimazolam-based total intravenous anesthesia) or desflurane group (propofol-induced and desflurane-maintained inhalational anesthesia) during cardiac ablation procedures for arrhythmia. The primary outcome was the incidence of intraoperative hypotensive events, defined as mean arterial pressure of < 60 mm Hg at any period.
RESULTS: Overall, we enrolled 96 patients between 2 August 2022 and 19 May 2023 (47 and 49 patients in the remimazolam and desflurane groups, respectively). The remimazolam group showed a significantly lower incidence of hypotensive events (14/47, 30%) than the desflurane group (29/49, 59%; relative risk [RR], 0.5; 95% confidence interval [CI], 0.31 to 0.83; P = 0.004). Remimazolam was associated with a lower requirement for bolus or continuous vasopressor infusion than desflurane was (23/47, 49% vs 43/49, 88%; RR, 0.56; 95% CI, 0.41 to 0.76; P < 0.001). No between-group differences existed in the incidence of perioperative complications such as nausea, vomiting, oxygen desaturation, delayed emergence, or pain.
CONCLUSIONS: Remimazolam was a viable option for general anesthesia for cardiac ablation. Remimazolam-based total intravenous anesthesia was associated with significantly fewer hypotensive events and vasopressor requirements than desflurane-based inhalational anesthesia was, without significantly more complications.
BACKGROUND: ClinicalTrials.gov (NCT05486377); first submitted 1 August 2022.
RéSUMé: OBJECTIF: Le maintien de la stabilité hémodynamique lors d’une ablation cardiaque sous anesthésie générale est un défi. Le remimazolam, une nouvelle benzodiazépine à action ultra-courte, se caractérise par le maintien d’une tension artérielle relativement stable et son absence d’influence sur le système de conduction cardiaque, ce qui en fait un choix raisonnable pour l’anesthésie générale pour l’ablation cardiaque. Nous avons cherché à déterminer si le remimazolam est associé à une diminution de l’incidence d’hypotension peropératoire comparativement au desflurane. MéTHODE: Dans cette étude clinique randomisée, prospective, en simple aveugle, en groupes parallèles et monocentrique, nous avons randomisé des patient·es (1:1) dans un groupe remimazolam (anesthésie intraveineuse totale à base de remimazolam) et un groupe desflurane (anesthésie volatile induite par propofol et maintenue par desflurane) pendant des interventions d’ablation cardiaque pour arythmie. Le critère d’évaluation principal était l’incidence d’événements hypotensifs peropératoires, définis comme une tension artérielle moyenne de < 60 mm Hg à n’importe quelle période. RéSULTATS: Au total, nous avons recruté 96 patient·es entre le 2 août 2022 et le 19 mai 2023 (47 et 49 personnes dans les groupes remimazolam et desflurane, respectivement). Le groupe remimazolam a montré une incidence significativement plus faible d’événements hypotensifs (14/47, 30 %) que le groupe desflurane (29/49, 59 %; risque relatif [RR], 0,5; intervalle de confiance [IC] à 95 %, 0,31 à 0,83; P = 0,004). Le remimazolam a été associé à des besoins plus faibles de bolus ou de perfusion continue de vasopresseurs que le desflurane (23/47, 49 % vs 43/49, 88 %; RR, 0,56; IC 95 %, 0,41 à 0,76; P < 0,001). Il n’y avait pas de différences entre les groupes dans l’incidence des complications périopératoires telles que les nausées, les vomissements, la désaturation en oxygène, l’émergence retardée ou la douleur. CONCLUSION: Le remimazolam a constitué une option viable pour l’anesthésie générale en vue d’une ablation cardiaque. L’anesthésie intraveineuse totale à base de remimazolam a été associée à un nombre significativement plus faible d’événements d’hypotension et de besoins en vasopresseurs que l’anesthésie par inhalation à base de desflurane, sans complications significativement plus nombreuses. ENREGISTREMENT DE L’éTUDE: ClinicalTrials.gov (NCT05486377); soumis pour la première fois le 1er août 2022.

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

OBJECTIVE: To evaluate the safety and efficacy of cryoablation (CYA) and microwave ablation (MWA) in the treatment of patients with perivascular hepatocellular carcinoma (HCC).
METHODS: Patients with perivascular HCC who underwent computed tomography (CT)-guided percutaneous CYA or MVA treatment in our hospital from August 2009 to March 2019 were included. Propensity score matching (PSM) was performed to adjust for potential baseline differences in the two groups. The technical success rate (TS), complications, and visual analog scale (VAS) were analyzed. The overall survival (OS) was evaluated using Kaplan-Meier curves and Cox proportional hazards models.
RESULTS: After PSM, 32 patients from each group were selected. The technical success rate was 94 % for CYA and 91 % for MWA, and 13 patients developed recurrence (CYA, n = 5, 2 local, 3 distant; MWA, n = 8, 6 local, 2 distant). There were no significant differences in OS (36-months OS: CYA 53.1 % vs, MWA 40.6 %; P = 0.191). No intraoperative deaths or complication-related deaths were observed, and 19 patients (CYA, n = 8; MWA, n = 11) experienced complications (P = 0.435). The VAS in the MWA group (5.38 ± 1.21) was significantly higher than that in the CYA group (2.22 ± 0.87; P < 0.001).
CONCLUSIONS: While CYA has equal safety and high primary efficacy as MWA in the treatment of perivascular HCC, it is associated with less periprocedural pain.

Purpose: To assess the ability to deliver full-thickness bladder wall cryoablation through a cystoscopic approach using a new closed-loop 6F cryocatheter and thermal dose-controlled protocol. Materials and Methods: Evaluations were conducted using a chronic porcine model wherein 10 lesions/animal were created throughout the bladder (bladder wall, trigone region, ureteral orifice, and distal ureter). A 6F cryocatheter was passed through the working channel of a flexible cystoscope. Single 1- and 1.5-minute freeze protocols in a saline environment were evaluated and resultant lesion size was determined. A laparoscopic approach was utilized to observe the transmural extension of the ice propagation. Results: Studies demonstrated the generation of transmural lesions characterized by full-thickness histologic necrosis after freezing for 1.5 minutes regardless of tissue thickness (range 2-12 mm). All animals were found to have good overall health (maintained weight, appetite, mobility, and energy levels) throughout the recovery period. No significant deviations were noted in complete blood count and serum chemistry bloodwork except for elevated creatine kinase levels. Importantly, no fistulas or perforations were noted. Conclusions: The cryocatheter was able to rapidly and effectively freeze the bladder wall through a cystoscopic approach. The results showed the ability to consistently ablate an ∼1 cm diameter and up to 1.2 cm deep using a single 1.5-minute freeze protocol. Analysis of the ablation efficacy revealed ∼80% destruction within the frozen mass. Although further testing and refinement are needed, these studies demonstrate the potential of this new approach to provide a next-generation strategy for the treatment of bladder cancer.

BACKGROUND: Cryoablation during minimally invasive repair for pectus excavatum (MIRPE) reduces opioid use and hospital length of stay. Skin hypoesthesia of the chest wall also occurs. This study sought to determine the frequency, onset, duration, and location of sensory changes and neuropathic pain after cryoablation.
METHODS: A prospective study was conducted on patients aged ≤21 years undergoing MIRPE with cryoablation of T3 to T7 dermatomes bilaterally for 120 s at a single institution between March 2021 to December 2022. Patients underwent sensory testing of the chest wall and neuropathic pain surveys (S-LANSS) preoperatively and then postoperatively for 6 months. Incidence and duration of hypoesthesia and neuropathic pain were evaluated.
RESULTS: Of 61 patients enrolled in the study, 45 completed evaluations at six months postoperatively. All patients had skin hypoesthesia on postoperative day (POD)1. The mean percentage of the treated anterior chest wall surface area (TACWSA) with hypoesthesia to cold stimulus was 52% (±29.3) on POD 0 and 55% (±19.7) on POD 1. Sensation returned over time, with hypoesthesia affecting 11.1% (±15.5) TACWSA at 6 months. At study completion 58% of patients (26/45) had complete return of sensation; hypoesthesia was found at: 1 dermatome 13% (2/45), 2 dermatomes 22% (11/45), and 3 dermatomes 4% (2/45). Neuropathic pain (S-LANSS ≥12) was documented in 16% (9/55) of patients at hospital discharge but decreased to 6.7% of patients at 6 months.
CONCLUSIONS: Onset of skin hypoesthesia after cryoablation occurred on POD0 and affected 52% of the TACWSA. All patients experienced return of sensation to varying degrees, with 58% experiencing normal sensation in all dermatomes by 6 months. The etiology of persistent hypoesthesia to select dermatomes is unknown but may be related to operative technique or cryoablation. Chronic neuropathic pain is uncommon.
METHODS: II.
METHODS: Prognosis Study.

OBJECTIVE: This study aimed to compare the immune responses induced by microwave ablation (MWA), radiofrequency ablation (RFA), and cryoablation (CRYO) in hepatocellular carcinoma (HCC) and identify differences in immune responses and the timing of immune changes.
METHODS: A bilateral subcutaneous model was established in C57 mice, and the successfully modeled mice were divided into the microwave (n = 15), radiofrequency (n = 15), CRYO (n = 15), control (n = 9), and blank groups (n = 3). Mice in the control group were dissected before ablation, whereas mice in the three ablation groups underwent ultrasound-guided ablation of one axillary tumor. Three mice were sacrificed and dissected at 1-4 weeks after ablation. After tissue processing, flow cytometry was used to detect the levels of CD8 + T and regulatory T (Treg) cells in the tissue, and western blotting was used to assess the level of programmed cell death ligand 1 (PD-L1) protein in the tumor tissue.
RESULTS: The pattern of immune changes after the three types of ablation was consistent, with immune changes occurring at 3-4 weeks. CRYO induced the most significant increase in the percentage of CD8 + T cells. There were no significant differences in the levels of Treg cells and the level of PD-L1 protein among the three types of ablation (p > 0.05), but the decline in Treg cells and PD-L1 protein level caused by CRYO was the most pronounced.
CONCLUSIONS: In the HCC mouse model, the immune changes following the three types of ablation were consistent, with immune changes occurring at 3-4 weeks. Among them, CRYO elicited the strongest adaptive immune response, and RFA outperformed MWA.

There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT. In the CRA intervention arm, 84% consented (95% confidence interval [CI] 64-95%) and 76% (95% CI 55-91%) received CRA; 100% (95% CI 86-100%) of the control arm underwent RPN. The retention rate was 90% (95% CI 79-96%) at 6 mo. In the RPN group 2/25 (8%) were converted intra-operative to radical nephrectomy. Postoperative complications (Clavien-Dindo grade 1-2) occurred in 12% of the CRA group and 29% of the RPN group. The median length of hospital stay was shorter for CRA (1 vs 2 d; p = 0.019). At 6 mo, the mean change in renal function was -5.0 ml/min/1.73 m2 after CRA and -5.8 ml/min/1.73 m2 after RPN. This study demonstrates the feasibility of a cohort-embedded RCT comparing CRA and RPN. These data can be used to inform multicentre trials on SRM management. PATIENT SUMMARY: We assessed whether patients with a small kidney tumour would consent to a trial comparing two different treatments: cryoablation (passing small needles through the skin to freeze the kidney tumour) and surgery to remove part of the kidney. We found that most patients agreed and a full trial would therefore be feasible.