Cytotoxic Effect of Trabectedin In Human Adrenocortical Carcinoma Cell Lines and Primary Cells.

Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy including etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Evidence indicates that ACC seems to be sensitive to alkylating agents. Trabectedin is an anti-tumor drug that acts as an alkylating agent with a complex mechanism of action. Here, we investigated whether trabectedin could exert a cytotoxic activity in in vitro cell models of ACC. Cell viability was evaluated by MTT assay on ACC cell lines and primary cell cultures. The gene expression was evaluated by q-RT-PCR, while protein expression and localization were studied by Western blot and immunocytochemistry. Combination experiments were performed to evaluate their interaction on ACC cell line viability. Trabectedin demonstrated high cytotoxicity at sub-nanomolar concentrations in ACC cell lines and patient-derived primary cell cultures. The drug was able to reduce /ß catenin nuclear localization, although it is unclear whether this effect is involved in the observed cytotoxicity. Trabectedin/mitotane combination exerted a synergic cytotoxic effect in NCI-H295R cells. Trabectedin has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of trabectedin with mitotane provides the rationale for testing this combination in a clinical study.

Two synchronous lung metastases from malignant melanoma: the same patient but different morphological patterns.

Malignant melanoma is an aggressive cancer with a high metastatic potential. Among the multiple sites of metastatic disease, the lung is one of the most frequently involved sites. Typically, pulmonary metastases from malignant melanoma occur as solid nodules. Rarely, pulmonary involvement in metastatic melanoma occurs as subsolid nodules. The present article describes an unusual case of a patient with malignant melanoma that developed two synchronous pulmonary metastases with two different densities on CT images (one solid and the other subsolid) and different morphological patterns on histologic images. The radiologic-pathologic correlation of these two patterns of presentation was also reported.

Radioguided lung lesion localization: introducing a fluoroscopy system in a SPECT/CT scan.

PURPOSE: The purpose was to report our experience in the use of radiotracer localization and resection of small, indistinct, or nonpalpable pulmonary lesions. We developed an innovative technique implementing a fluoroscopy system on a single-photon emission computed tomography/computed tomography (SPECT/CT) scan that allowed to perform CT-guided injection of radiotracer directly on SPECT/CT. PATIENTS AND METHODS: Patients were selected for the radiotracer procedure in presence of difficulties in locating nodules with video-assisted thoracoscopic surgery (VATS). Overall, 0.2 ml of technetium-99m macroaggregated albumin and 0.3 ml of nonionic iodinated contrast were injected under CT guidance. During the VATS procedure, an endoscopic gamma detecting probe was introduced to scan the lung surface. The area of major radioactivity, which matched with the area of the nodule, was resected. RESULTS: Between January 2016 and October 2018, 37 patients underwent CT-guided radiotracer injection. The mean nodule size was 11 mm. CT nodule morphology characteristics were as follows: 15 nodules were ground glass, 12 were solid, and 10 were partly solid. No significant adverse events occurred. In one patient, the surgeons decided for an open thoracotomy after unsuccessfully VATS. Overall, lobectomy was performed in two patients, segmentectomy in one, and wedge resection in 33 patients. No mortality occurred. The pathological diagnosis was 15 (42%) primary lung cancer, eight (22%) metastases, and 13 (36%) benign lesions. CONCLUSION: Radioguided pulmonary nodule localization is a reliable procedure with a high rate of success, minimal complications, and lower risk of failures, with no associated mortality or significant morbidity. Our SPECT/CT system is the first to benefit from the technological improvement with successfully implementation and application of fluoroscopy to SPECT/CT.

Pulmonary adenocarcinomas presenting as ground-glass opacities on multidetector CT: three-dimensional computer-assisted analysis of growth pattern and doubling time.

PURPOSE: We aimed to evaluate the growth pattern and doubling time (DT) of pulmonary adenocarcinomas exhibiting ground-glass opacities (GGOs) on multidetector computed tomography (CT). METHODS: The growth pattern and DT of 22 pulmonary adenocarcinomas exhibiting GGOs were retrospectively analyzed using three-dimensional semiautomatic software. Analysis of each lesion was based on calculations of volume and mass changes and their respective DTs throughout CT follow-up. Three-dimensional segmentation was performed by a single radiologist on each CT scan. The same observer and another radiologist independently repeated the segmentation at the baseline and the last CT scan to determine the variability of the measurements. The relationships among DTs, histopathology, and initial CT features of the lesions were also analyzed. RESULTS: Pulmonary adenocarcinomas presenting as GGOs exhibited different growth patterns: some lesions grew rapidly and some grew slowly, whereas others alternated between periods of growth, stability, or shrinkage. A significant increase in volume and mass that exceeded the coefficient of repeatability of interobserver variability was observed in 72.7% and 84.2% of GGOs, respectively. The volume-DTs and mass-DTs were heterogeneous throughout the follow-up CT scan (range, -4293 to 21928 and -3113 to 17020 days, respectively), and their intra- and interobserver variabilities were moderately high. The volume-DTs and mass-DTs were not correlated with the initial CT features of GGOs; however, they were significantly shorter in invasive adenocarcinomas (P = 0.002 and P = 0.001, respectively). CONCLUSION: Pulmonary adenocarcinomas exhibiting GGOs show heterogeneous growth patterns with a trend toward a progressive increase in size. DTs may be useful for predicting tumor aggressiveness.