Hepatocellular ballooning in NASH.

BACKGROUND & AIMS: Hepatocellular ballooning is a key finding in nonalcoholic steatohepatitis (NASH). It is conventionally defined by hemotoxylin and eosin (H&E) staining showing enlarged cells with rarefied cytoplasm and recently by changes in the cytoskeleton. Fat droplets are emerging as important organelles in cell metabolism. To address a possible relation between fat droplets and ballooning, we studied fat staining, H&E, and keratin 18 staining in human NASH. METHODS: Sequential staining and high resolution imaging were used to study freshly prepared cryo-sections from 10 patients with histologically confirmed steatohepatitis using oil red O for fat droplet identification, H&E to identify ballooning, and anti-K18 to confirm cytoskeletal changes. High resolution images were captured at each stage using the Aperio Scanscope. To provide ultrastructural correlation, glutaraldehyde-fixed specimens were studied using transmission electron microscopy (TEM) with serial sectioning for localization of ballooned cells by light microscopy and TEM in identical specimens. RESULTS: Serial staining consistently demonstrated that hepatocellular ballooning is associated with fat droplet accumulation evident by oil red O positivity and depletion of cytoplasmic keratin 18 with K-18 positive Mallory-Denk bodies (MDB). TEM confirmed the association between osmium stained fat droplets, MDB formation, and cellular enlargement and suggested droplet-associated dilation of the endoplasmic reticulum. CONCLUSIONS: These results indicate a relationship between cellular ballooning, fat droplet accumulation, and cytoskeletal injury in NASH. We speculate that injury to multiple, organelles including fat droplets and endoplasmic reticulum, contribute to this characteristic finding.

Radiotracer-guided thoracoscopic resection is a cost-effective technique for the evaluation of subcentimeter pulmonary nodules.

BACKGROUND: Excisional biopsy of small subcentimeter pulmonary nodules can be difficult using standard thoracoscopic techniques and may require thoracotomy. Radiotracer-guided thoracoscopic resection (RGTR) was developed to facilitate resection of intraparenchymal subcentimeter pulmonary nodules. Decision analysis, used to model cost and effectiveness, is useful to compare treatment options. We hypothesize that RGTR strategy is more cost-effective compared with thoracotomy for subcentimeter pulmonary nodules. METHODS: The cost-effectiveness of RGTR versus thoracotomy for evaluating highly suspicious subcentimeter pulmonary nodules was examined with a decision analysis model (Fig 1). A 40-patient institutional cohort who underwent RGTR was used to estimate probabilities and costs of the two treatment options within the model. Effectiveness was estimated using 5-year, stage-specific cancer survival and population survival curves. The Society of Thoracic Surgeons General Thoracic Database was queried obtaining mortality estimates for thoracotomy and thoracoscopic wedge resections. These were used to adjust the 5-year survival estimates of patients with benign disease. Sensitivity analyses determined model robustness and the thresholds at which the most cost-effective strategy changed. RESULTS: Radiotracer-guided thoracoscopic resection was 95% successful with no mortality. The average cost-to-effectiveness ratio of RGTR strategy was $27,887 versus $32,271 for thoracotomy. Sensitivity analyses demonstrated that the thoracotomy strategy was more cost-effective if the estimated cost of RGTR increased by 33% or the estimated cost-effectiveness of thoracotomy decreased by 14% or more. Radiotracer-guided thoracoscopic resection was more cost-effective as long as the probability of success was greater than 44%. CONCLUSIONS: Decision analysis is a useful tool to evaluate treatment options for thoracic surgeons, and RGTR is a more cost-effective strategy than thoracotomy for subcentimeter pulmonary nodules.

Identification of small lung nodules: technique of radiotracer-guided thoracoscopic biopsy.

BACKGROUND: This study describes a thoracoscopic technique to reliably locate and excise lung nodules that were not thought to be thoracoscopically visible or instrumentally palpable. METHODS: Initial laboratory studies succeeded in selecting a technetium 99m gamma-emitting solution, technetium 99m macro-aggregated albumin, that remained localized in lung parenchyma after percutaneous placement. Subsequently, 84 patients with solitary small nodules underwent computed tomography (CT)-guided percutaneous placement of this technetium solution in or near the nodule. Thoracoscopic localization with a radioprobe and excisional biopsy followed. RESULTS: In 3 patients, the previous lesion was not present on the CT scan done on the day of surgery. The 81 remaining patients underwent radiotracer placement and operation. No tracer activity was present in the lung in 4 patients, and open thoracotomy was necessary to locate the lesion. The lesion was successfully localized and excised in 77 patients (95.1%), and 71 underwent thoracoscopic excisional biopsy. Four underwent intentional thoracotomy for deep small nodules in which the tracer was used to guide the open biopsy. Two required conversion from thoracoscopy to thoracotomy because the anatomic location of the lesion prevented a thoracoscopic staple excision. Fifty percent of the lesions were benign, 39% were primary lung cancers, and additional 11% were either solitary metastatic lesions or lymphoma. No patients died, and morbidity rate was 16% (arrhythmias or pneumothoraces). CONCLUSIONS: Radiotracer-guided thoracoscopic biopsy was 95% reliable for subsequent surgical successful localization and excision of small nodules. This technique can be expanded to localize deep lesions for open thoracotomy and be used to prevent thoracotomy in 50% of patients with benign disease.