Cryobiopsy as a Salvage Technique Following Negative Flexible Forceps Biopsy of the Pleura Under Rapid On‐Site Evaluation Guidance: A Prospective Study

A diffusely thickened or hard pleura is a special type of macroscopic appearance associated with benign or malignant conditions. Medical thoracoscopy (MT) is the gold standard for pleural pathology, but its diagnostic yield is imperfect. Although cryobiopsy may provide greater and deeper tissue, its impact on the diagnostic yield remains uncertain, and safety concerns persist. We evaluated the efficacy and safety of cryoprobe biopsy as a salvage technique following negative or inconclusive flexible forceps biopsy during MT under the guidance of rapid on-site evaluation (ROSE). This prospective study enrolled 280 patients with undiagnosed exudative pleural effusion who underwent MT. After the initial flexible forceps biopsy and ROSE, 37 patients with negative ROSE results underwent cryoprobe biopsy. A total of 37 (21 males and 16 females) patients, aged 56.43 ± 16.09 (range: 22-78) years with negative ROSE results, underwent cryoprobe biopsy. CB established a definitive histopathological diagnosis in 33/37 (89.2%) patients, which was significantly higher than that achieved with FFB, i.e., 21/37 (56.8%; <i>p</i>=0.002). CB resulted in significantly larger pleural specimens (9.86 ± 2.69 mm) in comparison to FFB (2.89 ± 1.15 mm, 95% confidence interval [CI]: 6.01-7.93; <i>p</i> < 0.001). Furthermore, CB was faster than FFB (median durations of 15 and 31 min, respectively; <i>p</i> < 0.001). CB had improved tissue quality for CGP testing in 20 NSCLC patients compared to FFB (18/20 versus 8/15, <i>p</i>=0.036). No significant complications were noted. Cryoprobe biopsy is a safe and effective salvage technique for patients with undiagnosed pleural effusion who show negative results on flexible forceps biopsy during MT. It provides larger, higher-quality specimens with a higher positivity rate, potentially avoiding the need for repeat procedures and facilitating timely diagnosis and treatment.