Usefulness of Transbronchial Lung Cryobiopsy When Starting Antifibrotic Treatment and Predicting Progressive Fibrosing Interstitial Lung Disease: Descriptive Research.

BACKGROUND: Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents. METHODS: We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing. RESULTS: In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC-based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow-up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure. CONCLUSIONS: TBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.

The particularities of connective fibers from the wall of varicose veins extirpated by cryostripping.

INTRODUCTION: The varicose vein affects more than 30% of the general population. Significantly increased rates were noticed in women and older population. From the histopathological point of view, venous arterialization, smooth muscle cell hypertrophy, and hyperplasia are the main changes noticed in varicose vein disease. Some of the main therapeutic methods used in the management of varicose disease are injection sclerotherapy, conservative, surgical, saphenous vein inversion and removal, high saphenous ligation, ambulatory phlebectomy, transilluminated powered phlebectomy, endovascular management, cryostripping. AIM: The aim of this study was to evaluate the morphology of connective fibers from the wall of the varicose veins extirpated by cryostripping. PATIENTS, MATERIALS AND METHODS: The study included 109 samples taken by cryostripping method. Hematoxylin-Eosin, Masson's trichrome, Silver and Orcein staining were applied. The assessment of fibers was made according to score values between 0 and 3. RESULTS: It was found no major structural differences in terms of alterations of collagen fibers induced by the applied surgical procedure. It was noticed duplications and multiplications of the internal elastic lamina, as diffuse and nodular forms. Depletion of elastic fibers at the media was a lesion identified in most of the specimens. The depletion of reticulin fibers correlates with the accumulation of collagen fibers, which partially or completely replace the network in the media and intima. No correlation was found between changes in the reticulin network and the time between prelevation and buffered formalin fixation, the maximum time investigated being five days. CONCLUSIONS: The Orcein staining in the venous vessel evaluation panel may be a useful investigation.

Cryoablation combined with dual immune checkpoint blockade enhances antitumor efficacy in hepatocellular carcinoma model mice.

BACKGROUND: Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood. PD-1 and CTLA-4 monoclonal antibodies are immune checkpoint inhibitors used in immunotherapy for tumors. The combined use of these antibodies with Cryo may enhance the immune effect. METHODS: A Balb/c mouse model of HCC was established and treated with Cryo, immune checkpoint blockade (ICB), or Cryo + ICB (combination therapy). The growth trend of right untreated tumors and survival time of mice were determined. The expression of apoptosis-related proteins was detected by Western blot (WB) assay. The percentages of immune cells and immunosuppressive cells were analyzed by flow cytometry. The numbers of infiltrating T lymphocytes were checked by immunohistochemistry, and the levels of T-cell-associated cytokines were detected by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) assays and Enzyme-Linked Immunosorbent Assays (ELISA) assays. RESULTS: Cryo + ICB inhibited the growth of right untreated tumors, promoted tumor cell apoptosis, and prolonged the survival time of mice. Local T-cell infiltration in right tumor tissues increased after the combination therapy, while the number of immunosuppressive cells was significantly reduced. In addition, the combination therapy may induce the production of multiple Th1-type cytokines but reduce the production of Th2-type cytokines. CONCLUSIONS: Cryo can activate CD8+ and CD4+ T-cell immune responses. Cryo + ICB can relieve the immunosuppressive tumor microenvironment and shift the Th1/Th2 balance toward Th1 dominance, further enhancing the Cryo-induced T-cell immune response and resulting in a stronger antitumor immune response.

Influence of cryoablation versus operation on circulating lymphocyte subsets in patients with early-stage renal cell carcinoma.

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described.The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group.We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months.Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.

The efficacy and safety of modified transbronchial cryobiopsy in the diagnosis of interstitial lung disease.

The objective of this study is to investigate the efficacy and safety of flexible transbronchial cryobiopsy (TBCB) in the diagnosis of diffuse parenchymal lung disease (DPLD) in a routine bronchoscopy examination room under analgesia and sedation, using neither endotracheal intubation or rigid bronchoscope nor fluoroscopy or general anesthesia. The data from 50 DPLD patients with unknown etiology who were treated in the Affiliated Hospital of Guilin Medical College from May 2018 to September 2020 were collected, and 43 were eventually included. The specimens obtained from these 43 patients were subjected to pathological examination, pathogenic microorganism culture, etc, and were analyzed in the clinical-radiological-pathological diagnosis mode to confirm the efficacy of TBCB in diagnosing the cause of DPLD. Subsequently, the intraoperative and postoperative complications of TBCB and their severity were closely observed and recorded to comprehensively evaluate the safety of TBCB. For the 43 patients included, a total of 85 TBCB biopsies were performed (1.98 [1, 4] times/case), and 82 valid tissue specimens were obtained (1.91 [1, 4] pieces/case), accounting for 96.5% (82/85) of the total sample. The average specimen size was 12.41 (1, 30) mm2. Eventually, 38 cases were diagnosed, including 11 cases of idiopathic pulmonary fibrosis, 5 cases of connective tissue-related interstitial lung disease, 5 cases of nonspecific interstitial pneumonia, 4 cases of tuberculosis, 4 cases of occupational lung injury, 3 cases of interstitial pneumonia with autoimmune characteristics, 1 case of lung cancer, 2 cases of interstitial lung disease (unclassified interstitial lung disease), 1 case of hypersensitivity pneumonitis, 1 case of pulmonary alveolar proteinosis, and 1 case of fungal infection. The remaining 5 cases were unclarified. For infectious diseases, the overall etiological diagnosis rate was 88.4% (38/43). With respect to complications, pneumothorax occurred in 4 cases (9.3%, 4/43, including 1 mild case and 3 moderate cases), of which 3 cases (75%) were closed by thoracic drainage and 1 case (25%) was absorbed without treatment. In addition, 22 cases experienced no bleeding (51.2%) and 21 cases suffered bleeding to varying degrees based on different severity assessment methods. TBCB is a minimally invasive, rapid, economical, effective, and safe diagnostic technique.

Ultrasound-Guided Percutaneous Cryoneurolysis of the Antebrachial Cutaneous Nerves for the Management of Prolonged Acute Post-Surgical Forearm Pain: A Report of Two Cases.

Prolonged acute postsurgical pain (PAPSP) contributes to the development of chronic postsurgical pain, impaired rehabilitation, longer hospital stays, and decreased quality of life. For upper extremity analgesia, the duration of postoperative pain management with continuous brachial plexus peripheral nerve blocks is limited due to the risk of infection. Ultrasound-guided percutaneous cryoneurolysis provides extended analgesia and avoids the risks and inconveniences of indwelling catheters. We present 2 cases of PAPSP of the forearm effectively managed by the use of ultrasound-guided percutaneous cryoneurolysis to treat the medial, lateral, and posterior antebrachial cutaneous nerves.

A novel technique for conducting flexible bronchoscopy cryobiopsy under conscious sedation: An observational study.

Transbronchial lung cryobiopsy (TBCB) is a reliable method for obtaining histopathological findings in interstitial lung diseases. TBCB is traditionally performed during rigid bronchoscopy, positioning an endobronchial balloon blocker to facilitate bleeding management. Therefore, it can be challenging to implement in Centers without access to anesthesiologic support or dedicated beds for endoscopic procedures. We present a series of 11 patients who underwent 12 TBCBs using a flexible bronchoscope and a 5 Fr endobronchial blocker passing through an uncuffed endotracheal tube, under moderate sedation and spontaneous breathing. All procedures were carried out in an endoscopy suite, using fluoroscopy guidance but without requiring anesthesiologic assistance. TBCB was feasible in all cases, and it demonstrated similar or improved diagnostic yield (90.1%) and safety compared to rigid bronchoscopy. In 1 case, it was successfully repeated due to an inconclusive histological definition at the first attempt. The size of the samples was consistent with the literature, as it was the incidence of pneumothorax (16.6%). Four cases of moderate bleeding and 4 cases of severe bleeding were managed without further complications. To our knowledge, this is the first description of a technique allowing to perform TBCB through an artificial airway without need for either rigid bronchoscopy or general anesthesia. We believe this technique could make TBCB faster, cost-effective, and feasible even in resource-limited settings without compromising on safety. However, further studies are needed to validate these findings.

A danish healthcare-focused economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation.

INTRODUCTION: Three randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective. METHODS: Individual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis. RESULTS: First-line cryoablation is dominant, meaning it results in lower costs (-€2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of €23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive ∼ 1.2 ablation procedures over a lifetime horizon. CONCLUSION: First-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system.

[EBUS-guided cryobiopsy in the diagnosis of mediastinal lesions - step by step]. / EBUS-gestützte Kryobiopsie mediastinaler Läsionen ­ Schritt für Schritt.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the gold standard in the diagnosis of mediastinal and hilar lesions. For certain purposes, such as the diagnosis and subtyping of lymphoproliferative disorders or molecular pathology, a larger amount of intact sample material is required. EBUS cryobiopsy is a new and efficient tool for this purpose. As it is a new approach, there is still no standardised workflow. In this review, we present the procedure step by step as it is performed at the Ruhrlandklinik in Essen.

Optical Sensing of Tissue Freezing Depth by Sapphire Cryo-Applicator and Steady-State Diffuse Reflectance Analysis.

This work describes a sapphire cryo-applicator with the ability to sense tissue freezing depth during cryosurgery by illumination of tissue and analyzing diffuse optical signals in a steady-state regime. The applicator was manufactured by the crystal growth technique and has several spatially resolved internal channels for accommodating optical fibers. The method of reconstructing freezing depth proposed in this work requires one illumination and two detection channels. The analysis of the detected intensities yields the estimation of the time evolution of the effective attenuation coefficient, which is compared with the theoretically calculated values obtained for a number of combinations of tissue parameters. The experimental test of the proposed applicator and approach for freezing depth reconstruction was performed using gelatin-based tissue phantom and rat liver tissue in vivo. It revealed the ability to estimate depth up to 8 mm. The in vivo study confirmed the feasibility of the applicator to sense the freezing depth of living tissues despite the possible diversity of their optical parameters. The results justify the potential of the described design of a sapphire instrument for cryosurgery.

Ultrasound-guided cryoablation: Our experience in percutaneous treatment as an alternative to surgery for fibroadenomas of the breast lesions.

OBJECTIVES: To review the tolerance to and medium-term efficacy of ultrasound-guided cryoablation as an alternative to surgical treatment of fibroadenomas of the breast in our hospital. METHODS: We analyzed data from the 12 patients with fibroadenomas treated with ultrasound-guided cryoablation in our hospital between November 2020 and July 2022. Cryoablation was performed with a system using argon gas (Galil Boston Scientific®) or liquid nitrogen (Prosense Ice Cure®) following a triple-phase (freeze-thaw-freeze) protocol of variable duration depending on the size of the lesion. Patients were followed up with ultrasonography at 3, 6, 12, and 18 months. RESULTS: All patients tolerated the procedure well. Two patients reported moderate pain in the hours immediately after the procedure; no other complications occurred. The findings during follow-up included decreased volume of the fibroadenoma (47.07% at 3 months, 77.79% at 6 months, 81.77% at 12 months, and 88.81% at 18 months), blurring of the nodule's margins, a significantly reduced or absent signal within the lesion in the Doppler study, an echogenic band (representing edema, hemorrhage, and fat necrosis), and hypoechoic areas suggestive of fibrosis surrounding the fibroadenoma. CONCLUSIONS: Cryoablation is done on an outpatient basis, avoiding general anesthesia, thus making it less expensive. Cryoablation yields better cosmetic results than surgery.

Novel method of attaching a suction tube externally to a tracheal tube as an insertion route for a Fogarty catheter in cryobiopsy: Retrospective comparative study.

BACKGROUND: Cryobiopsy use is anticipated to become more common in diagnosing lung diseases. In Japan, inserting a Fogarty catheter through a suction channel above the endotracheal tube's cuff for hemostasis is common practice. However, the rigid nature of the endotracheal tube poses challenges to tracheal intubation using a bronchoscope. The endotracheal tube cuff must be removed to prevent interference during Fogarty catheter insertion. To simplify the procedure and enhance safety, we devised and implemented a method of inserting a hemostatic Fogarty catheter with a suction tube externally attached to a softer endotracheal tube. This study aimed to evaluate the sustainability of this Fogarty catheter insertion method using suction tubes. METHODS: The hemostatic Fogarty catheter insertion method was retrospectively validated. We compared outcomes between 60 patients who underwent the conventional method with a suction channel above the cuff and 50 patients who underwent the novel approach with an externally attached suction tube. RESULTS: The physicians performing bronchoscopy and inserting the Fogarty catheter in the group in which the suction tube was externally attached for Fogarty catheter insertion had little experience. However, the overall bronchoscopy time was shorter; the two groups showed no significant differences in complications. CONCLUSION: Regarding cryobiopsy procedures, using an externally attached suction tube for Fogarty catheter insertion was practical and comparable to the conventional method of using a suction channel above the cuff. This method made the procedure more simple and safe.

Treatment of chronic mini-thoracotomy wound pain and lung herniation with intercostal cryoablation and surgical mesh repair: a case report.

BACKGROUND: The incidence of minimally invasive heart surgery via mini-thoracotomy (MT; right anterior thoracotomy) is on the rise, accompanied by an increase in post-MT intercostal nerve neuralgia and the risk of lung herniation through the incision site. While various methods have been proposed to address these issues, none have been commonly effective. In this case report, we attempted to simultaneously address these problems by performing intercostal cryoablation (IC) and mesh repair. CASE PRESENTATION: A 43-year-old male was referred to our hospital for chronic post-thoracotomy neuralgia following heart surgery via MT, involving patch closure of an atrial septal defect and tricuspid annuloplasty. He presented with intercostal nerve neuralgia and lung herniation accompanied by severe pain. Despite medication and lidocaine injections, there was no relief. Consequently, he underwent surgical treatment with IC for chronic MT wound pain and simultaneously underwent mesh repair for a lung hernia. He was discharged from hospital free of complications. Subsequently, he no longer required further pain medication and experienced a favorable recovery. CONCLUSION: Our findings suggest that concurrent IC and mesh repair can effectively relieve chronic post-MT intercostal nerve neuralgia and severe lung herniation pain in patients who underwent MT surgery, leading to a decrease in opioid medication usage.

Lesion durability found during mandated percutaneous catheter ablation after surgical cryo-ablation for treatment of non-paroxysmal atrial fibrillation.

OBJECTIVES: Current recommendations support surgical treatment of atrial fibrillation (AF) in patients indicated for cardiac surgery. These procedures are referred to as concomitant and may be carried out using radiofrequency energy or cryo-ablation. This study aimed to assess the electrophysiological findings in patients undergoing concomitant cryo-ablation. METHODS: Patients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement were included in the trial if concomitant cryo-ablation was part of the treatment plan according to current guidelines. The patients reported in this study were assigned to undergo staged percutaneous radiofrequency catheter ablation (PRFCA), i.e., hybrid treatment, as a part of the SURHYB trial protocol. RESULTS: We analyzed 103 patients who underwent PRFCA 105 ± 35 days after surgery. Left and right pulmonary veins (PVs) were found isolated in 65 (63.1%) and 63 (61.2%) patients, respectively. The LA posterior wall isolation and mitral isthmus conduction block were found in 38 (36.9%) and 18 (20.0%) patients, respectively. Electrical reconnections (gaps) in the left PVs were more often localized superiorly than inferiorly (57.9% vs. 26.3%, P = 0.005) and anteriorly than posteriorly (65.8% vs. 31.6%, P = 0.003). Gaps in the right PVs were more equally distributed anteroposteriorly but dominated in superior segments (72.5% vs. 40.0%, P = 0.003). There was a higher number of gaps on the roof line compared to the inferior line (131 (67.2%) vs. 67 (42.2%), P < 0.001). Compared to epicardial cryo-ablation, endocardial was more effective in creating PVs and LA posterior wall isolation (P < 0.05). Cryo-ablation using nitrous oxide (N20) or argon (Ar) gas as cooling agents was similarly effective (P = NS). CONCLUSIONS: The effectiveness of surgical cryo-ablation in achieving transmural and durable lesions in the left atrium is surprisingly low. Gaps are located predominantly in the superior and anterior portions of the PVs and on the roof line. Endocardial cryo-ablation is more effective than epicardial ablation, irrespective of the cooling agent used.

A cost-consequence analysis comparing three cardiac ablation strategies for the treatment of paroxysmal atrial fibrillation.

BACKGROUND AND AIMS: Cardiac ablation is a well-established method for treating atrial fibrillation (AF). Pulsed field ablation (PFA) is a non-thermal therapeutic alternative to radiofrequency ablation (RFA) and cryoballoon ablation (CRYO). PFA uses high-voltage electric pulses to target cells. The present analysis aims to quantify the costs, outcomes, and resources associated with these three ablation strategies for paroxysmal AF. METHODS: Real-world clinical data were prospectively collected during index hospitalization by three European medical centers (Belgium, Germany, the Netherlands) specialized in cardiac ablation. These data included procedure times (pre-procedural, skin-to-skin and post-procedural), resource use, and staff burden. Data regarding complications associated with each of the three treatment options and redo procedures were extracted from the literature. Costs were collected from hospital economic formularies and published cost databases. A cost-consequence model from the hospital perspective was built to estimate the impact of the three treatment options in terms of effectiveness and costs. RESULTS: Across the three centers, N = 91 patients were included over a period of 12 months. A significant difference was seen in pre-procedural time (mean ± SD, PFA: 13.6 ± 3.7 min, CRYO: 18.8 ± 6.6 min, RFA: 20.4 ± 6.4 min; p < .001). Procedural time (skin-to-skin) was also different across alternatives (PFA: 50.9 ± 22.4 min, CRYO: 74.5 ± 24.5 min, RFA: 140.2 ± 82.4 min; p < .0001). The model reported an overall cost of €216,535 per 100 patients treated with PFA, €301,510 per 100 patients treated with CRYO and €346,594 per 100 patients treated with RFA. Overall, the cumulative savings associated with PFA (excluding kit costs) were €850 and €1,301 per patient compared to CRYO and RFA, respectively. CONCLUSION: PFA demonstrated shorter procedure time compared to CRYO and RFA. Model estimates indicate that these time savings result in cost savings for hospitals and reduce outlay on redo procedures. Clinical practice in individual hospitals varies and may impact the ability to transfer the results of this analysis to other settings.

Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study.

OBJECTIVES: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model. METHOD: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model. RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826. CONCLUSION: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.