Correlative study of preoperative transthoracic core cutting needle biopsy of focal thoracic lesions and thoracotomy findings.

We conducted a retrospective study to determine the clinical utility of percutaneous core needle biopsy (PCNBx) in 36 patients with peripheral focal chest lesions who later underwent thoracic surgery for diagnostic or therapeutic purposes. PCNBx provided adequate material in 31/36 cases, giving an overall sample yield of 86.1%. PCNBx diagnosis was confirmed by surgery in 27/31 patients, giving a sensitivity of 91.6% and a specificity of 87.5%. In 4 patients, the lesions were misdiagnosed by PCNBx. In 5 patients with benign processes, surgical intervention could have been avoided, according to PCNBx results. The rate of PCNBx-induced pneumothorax was 11%. Radiologically guided PCNBx is an easy and safe procedure that can provide important preoperative diagnostic information and can circumvent the need for exploratory diagnostic surgery in cases of benign lesions. PCNBx also allows better preoperative planning in cases of malignancy.

Percutaneous core needle biopsy vs. fine needle aspiration in diagnosing benign lung lesions.

OBJECTIVE: To determine the diagnostic value of percutaneous core needle biopsy (PCNB) in comparison with fine needle aspiration (FNA) in patients with benign pulmonary lesions. STUDY DESIGN: A retrospective review was undertaken of computed tomography-guided PCNBs and FNAs performed between 1988 and 1997. Both FNA and PCNB biopsies were carried out sequentially at the same visit in every patient. RESULTS: A specific benign diagnosis was made in 10/60 cases (16.7%) by FNA and in 49/60 (81.7%) by PCNB. PCNB findings resulted in significant modification of the diagnosis established by FNA. The only significant complication encountered was pneumothorax, at a rate of 11.7%, which is compatible with that reported in the literature for complications induced by FNA alone. CONCLUSION: Radiologically guided PCNB is a safe procedure, can provide sufficient histologic material for a specific diagnosis of peripheral lung disease and can avoid more-invasive surgical procedures in many cases. Our experience demonstrated that the histologic analysis provided by PCNB can greatly increase the diagnostic accuracy in benign pulmonary diseases as compared with the yield of FNA.

Percutaneous core needle biopsy in the diagnosis of mediastinal tumors.

OBJECTIVE: to determine the contribution of percutaneous core cutting needle biopsy (PCNB) in the diagnosis of mediastinal tumors. DESIGN: retrospective review of 70 patients with mediastinal lesions who underwent CT-guided PCNB between 1988 and 1996. RESULTS: PCNB provided adequate material in 62/70 cases, giving a total sample rate of 88.6%. Of these 62 patients, 57 were diagnosed correctly by PCNB whereas 5/62 were misdiagnosed as nonspecific inflammation, providing an overall sensitivity of 91.9%. PCNB established a specific histologic diagnosis in 90.3% of the patients, mainly in cases of lymphoma, bronchogenic carcinoma, and thymoma. Pneumothorax was the most commonly encountered complication (11%). Hemoptysis (30-50 ml) occurred in only one (1.6%) of the patients. CONCLUSION: CT guided PCNB is an easy and safe procedure which can provide a precise diagnosis in the majority of mediastinal tumors and can obviate the need for exploratory thoracic surgery in cases which are medically treatable or non-resectable.

Percutaneous core cutting needle biopsy compared with fine-needle aspiration in the diagnosis of peripheral lung malignant lesions: results in 156 patients.

BACKGROUND: The authors attempted to determine the utility of percutaneous core needle biopsy (PCNB) compared with fine-needle aspiration (FNA) in the diagnosis of peripheral lung carcinoma. METHODS: A retrospective review was undertaken of 156 computed tomography (CT)-guided PCNBs and FNAs of malignant lung lesions between 1988-1996. Both CT-guided FNA and PCNB biopsies were performed sequentially at the same visit for each subject. RESULTS: The authors reviewed 156 malignant lesions whose specific diagnosis was obtained by FNA in 133 cases (85.3%) and by PCNB in 121 cases (77.6%) (P < 0.05). PCNB confirmed the FNA diagnosis in 90 patients (57.7%), provided additional information in 17 patients (10.9%), and was less informative than FNA in 35 patients (22.4%), mostly those with nonsmall cell carcinoma. The PCNB was marginally superior to FNA only in cases of metastatic carcinoma. The only significant complication encountered was a 24% rate of pneumothorax, which is comparable to the reported rate for FNA alone-induced complications. CONCLUSIONS: PCNB offers no substantial advantage over FNA in the evaluation of peripheral malignant lung lesions. Therefore, the authors recommend the use of FNA biopsy as the initial diagnostic procedure in all cases of suspected malignancy. The use of the PCNB technique is recommended when the diagnosis of malignancy by FNA is uncertain, or when a more detailed characterization of the lesion is required.

Additional information from percutaneous cutting needle biopsy following fine-needle aspiration in the diagnosis of chest lesions.

OBJECTIVE: To determine the contribution of percutaneous cutting needle biopsy (PNB) subsequent to fine-needle aspiration (FNA) in the diagnosis of chest lesions. DESIGN: A retrospective review of 220 patients who underwent CT-guided FNA followed immediately by PNB performed at our center between 1988 and 1995 was undertaken. Thirty-eight patients were excluded because FNA and/or PNB specimens were nondiagnostic, yielding a study group of 182 patients. RESULTS: A diagnosis of malignancy was made in 141 (77.5%) and nonmalignancy in 41 (22.5%) cases. The yield of histospecific diagnosis due to FNA was marginally higher than PNB in malignant lesions (86.5% vs 78%, respectively). In contrast, PNB was superior to FNA for the histospecific diagnosis of benign lesions (87.8% for PNB vs 31.7% for FNA, p<0.00001) and lymphomas (88% for PNB vs 56% for FNA, p<0.05). In 58.8% of the patients with benign lesions and in 37.5% of the patients with lymphoma, PNB performances altered clinical management, either by avoiding further surgery or allowing specific medical treatment. Pneumothorax occurred in 24.7% of the cases but only five patients (2.7%) required hospitalization. CONCLUSION: PNB is extremely effective for making a specific diagnosis in benign lesions compared with FNA. PNB does not increase the yield of histospecific diagnosis for malignant lesions except for the subset of lymphoma, where it seems to provide important additional information in many instances. We recommend that FNA be performed as the initial procedure, followed by PNB in cases of equivocal diagnosis of carcinoma, for lymphoma and for suspected benign lesions.

Metastatic potential and multidrug resistance correlation in the B16 melanoma system.

The question of whether metastatic potential and drug resistance are related phenotypes was addressed by comparing the biological behavior of the parental B16 melanoma and a multidrug resistant variant derived from it, the B16/Col/R. A more pronounced metastatic spread to lungs was observed in mice inoculated i.v. with the B16/Col/R variant than in those bearing the parental line. In addition, in the mice injected with the drug resistant melanoma, unusual tumor masses were observed. Large abdominal and spinal cord growths were seen with the MDR variant but not encountered in mice inoculated with the original B16 melanoma. We further attempted to test the capacity of the two cell types to perform several cellular functions relevant to the metastatic process. The B16/Col/R cells displayed a higher aggregability and cell motility than did the B16 cells. Adherence to endothelial cells was higher in the parental line than in the B16/Col/R, possibly supporting a more efficient extravasation of the variant cells. The drug resistant variant displayed a higher capacity to grow locally in kidney, spleen, cecum and peritoneum, as compared to the parental melanoma, indicating a higher ability of homing and growth in these potential target organs for metastasis. A correlation between metastatic potential and multidrug resistance appears therefore to exist in the system examined.

Metastasis-associated cell functions in AKR lymphoma malignancy variants.

Multiple structural and functional cell properties are responsible for the complex phenotype of the metastatic cell. Cells derived from AKR lymphoma malignancy variants were compared with regard to several cellular functions relevant to the metastatic behavior. Metastatic behavior correlated with relevant in vitro cell activities, such as cell motility, homotypic and heterotypic adhesion as well as proteolytic activity. The Variant displaying the highest degree of malignancy, TAU-42, exhibited the most elevated ability to perform almost each of the cell functions examined: motility, aggregability, capacity to adhere to endothelium and extracellular matrix, heparanase and protease activity and ability to grow in the spleen. The TAU-33 variant was second in rank in the performance of the above activities. The TAU-44 variant cells, the third in rank of malignancy, displayed some peculiar functional behavior: while manifesting the lowest homotypic adherence and heparanase activity, they had a high predilection for growth in kidney.

Expression level of the nm23 gene in clonal populations of metastatic murine and human neoplasms.

The purpose of this study was to determine whether nm23 steady-state mRNA expression levels correlate with metastatic potential of mouse K-1735 melanoma cells, human KM12 colon cancer cells, and human SN12 renal cancer cells. Since neoplasms are heterogeneous and contain subpopulations of cells with different metastatic potentials, we analyzed multiple sets of nonmetastatic and metastatic clones isolated from each neoplasm. In addition, we also examined nine somatic cell hybrids produced by the fusion of nonmetastatic and metastatic K-1735 clones. In the mouse melanoma, we found heterogeneity in nm23-1 steady-state expression levels among the clones and hybrids that did not correlate with their metastatic phenotype. Clones isolated from human colon or renal carcinomas expressed similar levels of nm23-HI regardless of metastatic potential in nude mice. All of the human tumor cells were heterozygous for the nm23-HI-specific allelic DNA fragments, with no allelic deletions or gross alterations detected. Since the failure of tumor cells to produce metastasis can be due to multiple deficiencies, these data stress the importance of using independent clones with different metastatic potentials for the analysis of gene regulation of this process.

The use of molecular genetic markers to demonstrate the effect of organ environment on clonal dominance in a human renal-cell carcinoma grown in nude mice.

Transduction of the SN12C human renal-cell carcinoma line with the neoR gene produces a genetically "tagged" cell population within which individual clones can be identified if they dominate the tumor during its growth in vivo. We used this technique to determine whether the clones that dominate the primary local tumor and its metastases are the same or different when the tumor is growing in different organ sites in nude mice. The results show that clonal dominance is influenced by the organ environment in which the primary tumor grows, i.e., distinct clones dominated in the kidney, colon and subcutaneous sites. In addition, tumors grown in the orthotopic site (kidney) were all populated by the same dominant clones, and each distant visceral metastasis retained the same clonality. SN12C neoR-cells grown in an epithelial, ectopic site (colon) produced tumors with uniquely different dominant clones, and their visceral metastases retained the dominant pattern expressed by the parent tumor from which they were derived. In contrast, SN12C tumors growing subcutaneously showed a random pattern of clonal dominance in both their primary and metastatic sites. Parallel cytogenetic analyses could not demonstrate these patterns. We conclude that the organ environment significantly influences clonal dominance of human renal carcinoma and that tumor injection into orthotopic sites may produce a more reproducible selection of dominant clones.

Specific chromosomal defects associated with metastatic potential in K-1735 melanoma clones. Involvement of chromosomes 4 and 14.

In this study we sought to identify specific cytogenetic defects associated with the metastatic phenotypes in clones isolated from the parental K-1735 murine melanoma. All nonmetastatic clones (C-3, C-10, and C-19) exhibited trisomy of chromosomes 1, 3, 12, and 15. The only structural defect present in these clones was an interstitial deletion in a chromosome 4. In contrast, the highly metastatic clones (C-4, M-2, BB1, and X-21) exhibited trisomy of chromosomes 1, 3, 12, and 15, plus structural abnormalities of chromosomes 4 and 14, with the net result of a deletion in both. Parental K-1735 cells and clone C-16 cells, which are intermediate in their metastatic potential, had some cells with 4 and 14 alterations and others with only a deletion of chromosome 4. Clone C-16 revealed other non-clonal structural abnormalities. Our results indicate that structural anomaly of chromosome 4 and numerical alterations of certain autosomes may be associated with tumorigenic properties. In addition, structural defect in chromosome 14 is associated with high metastatic potential of K-1735 melanoma cells.

Site-dependent differences in response of the UV-2237 murine fibrosarcoma to systemic therapy with adriamycin.

Murine fibrosarcoma UV-2237MM cells were implanted into different organs of syngeneic C3H/HeN mice. The resultant tumors were treated by i.v. administration of Adriamycin (ADR). Despite the high sensitivity of the fibrosarcoma cells to ADR in vitro, the established tumors growing in vivo exhibited marked differences in their responses to ADR. Tumors growing in the subcutis and the spleen were ADR-sensitive, whereas lung metastases were not. The resistance of lung metastases to ADR was not due to selection of a drug-resistant population since tumor cells isolated from lung metastases were highly sensitive to ADR under in vitro conditions. The responsiveness of skin and spleen tumors to ADR was due neither to increased blood supply nor to preferential accumulation of ADR, since both parameters were higher in lung metastases. Protein kinase C activity levels correlated with ADR resistance in the closely related murine fibrosarcoma cell line UV-2237 and its ADR-selected multidrug-resistant variants. However, nearly identical levels of protein kinase C activity were found in UV-2237MM tumors growing in the lung, spleen, and subcutis, indicating that protein kinase C activity levels did not account for the different responses to ADR. The present studies suggest that the organ environment influences the response of UV-2237MM to ADR administered systemically. This finding may have implications for the design of animal models for therapy of disseminated cancer.