Occurrence Of Pulmonary Metastasis Research Articles

Benign extracranial meningioma with pulmonary metastasis: a case report and review of literature

BackgroundMeningiomas are common central nervous system tumors, predominantly intracranial, they rarely develop extracranially. Moreover, benign meningiomas seldom metastasize.Case presentationThis article presents a case report of a 55-year-old Chinese male patient with a primary World Health Organization grade 1 meningioma originating from the petrous apex of the temporal bone, accompanied by pulmonary metastasis. Following two incomplete resections of the primary tumor, the patient underwent radiotherapy and has since maintained a stable condition.ConclusionThe case report highlights the rare occurrence of pulmonary metastasis in a benign World Health Organization grade 1 meningioma originating from an extracranial site. It also illustrates the important role of radiotherapy in treating patients with meningioma. Additionally, a review of related literature is provided to gain insights for the diagnosis and treatment of the disease.

The pathological significance of LOXL2 in pre-metastatic niche formation of HCC and its related molecular mechanism

ObjectiveThe mechanisms underlying the contribution of primary tumour to pre-metastatic niche formation remains largely unknown in hepatocellular carcinoma (HCC). We previously reported that the released LOXL2 from HCC cells under higher stiffness stimulation facilitated the formation of lung pre-metastatic niche. Here, we further clarified the pathological role of LOXL2 in promoting lung pre-metastatic niche formation and lung metastasis occurrence in HCC and its relevant molecular mechanism. MethodsUsing two different animal models and an in vitro system of mechanically tuneable gel mirroring lung tissue stiffness, we explored the underlying mechanism of LOXL2 in pre-metastatic niche formation. ResultsWe applied tail vein injection of CM-LV-LOXL2-OEsimulating tumour-released soluble factors to induce lung pre-metastatic niche formation and found that the injected LOXL2 remarkably enhanced CD11b+/CD45+ bone marrow-derived cells (BMDCs) recruitment and fibronectin expression in lung. Subsequently, LOXL2-overexpressed xenograft HCC models validated that tumour-secreted LOXL2 significantly promoted the occurrence of pulmonary metastasis. In vitro, LOXL2 and LOXL2-caused matrix stiffening not only obviously upregulated the expressions of MMP9 and fibronectin in lung fibroblasts, but also evidently increased the number of adherent HCC cells and the expression of chemokine CXCL12. The activation of PI3K-AKT pathway mediated LOXL2-upregulated fibronectin. HCC patients in High-LOXL2 group had higher ratio of tumour recurrence than HCC patients in Low-LOXL2 group, supporting a significance of LOXL2 in HCC progression and unfavourable outcome. ConclusionPrimary tumour-released LOXL2 promotes lung pre-metastatic niche formation and lung metastasis occurrence. LOXL2-caused matrix stiffening synergistically regulates lung pre-metastatic niche formation. Targeting LOXL2-induced lung pre-metastatic niche may be a novel intervention approach against HCC metastasis.

Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis

Osteosarcoma (OS) is the most common pediatric malignant bone tumor, and occurrence of pulmonary metastasis generally causes a rapid and fatal outcome. Here we aimed to provide clues for exploring the mechanism of tumorigenesis and pulmonary metastasis for OS by comprehensive analysis of microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in primary OS and OS pulmonary metastasis. In this study, deep sequencing with samples from primary OS (n = 3), pulmonary metastatic OS (n = 3), and normal controls (n = 3) was conducted and differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and mRNAs (DEmRNAs) between primary OS and normal controls as well as pulmonary metastatic and primary OS were identified. A total of 65 DEmiRNAs, 233 DElncRNAs, and 1405 DEmRNAs were obtained between primary OS and normal controls; 48 DEmiRNAs, 50 DElncRNAs, and 307 DEmRNAs were obtained between pulmonary metastatic and primary OS. Then, the target DEmRNAs and DElncRNAs regulated by the same DEmiRNAs were searched and the OS tumorigenesis-related and OS pulmonary metastasis-related competing endogenous RNA (ceRNA) networks were constructed, respectively. Based on these ceRNA networks and Venn diagram analysis, we obtained 3 DEmiRNAs, 15 DElncRNAs, and 100 DEmRNAs, and eight target pairs including miR-223-5p/(CLSTN2, AC009951.1, LINC01705, AC090673.1), miR-378b/(ALX4, IGSF3, SULF1), and miR-323b-3p/TGFBR3 were involved in both tumorigenesis and pulmonary metastasis of OS. The TGF-β superfamily co-receptor TGFBR3, which is regulated by miR-323b-3p, acts as a tumor suppressor in OS tumorigenesis and acts as a tumor promoter in pulmonary metastatic OS via activation of the epithelial–mesenchymal transition (EMT) program.In conclusion, the OS transcriptome (miRNA, lncRNA, and mRNA) is dynamically regulated. These analyses might provide new clues to uncover the molecular mechanisms and signaling networks that contribute to OS progression, toward patient-tailored and novel-targeted treatments.

Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma.

BackgroundThe study aimed to explore the correlation between the expression of TREX1 and the metastasis and the survival time of patients with osteosarcoma as well as biological characteristics of osteosarcoma cells for the prognosis judgment of osteosarcoma.MethodThe correlation between the expression of TREX1 protein and the occurrence of pulmonary metastasis in 45 cases of osteosarcoma was analyzed. The CD133+ and CD133− cell subsets of osteosarcoma stem cells were sorted by the flow cytometry. The tumorsphere culture, clone formation, growth curve, osteogenic and adipogenic differentiation, tumor-formation ability in nude mice, sensitivity of chemotherapeutic drugs, and other cytobiology behaviors were compared between the cell subsets in two groups; the expressions of stem cell-related genes Nanog and Oct4 were compared; The expressions of TREX1 protein and mRNA were compared between the cell subsets in two groups. The data was statistically analyzed. The measurement data between the two groups were compared using t test. The count data between the two groups were compared using χ 2 test and Kaplan–Meier survival analysis. A P value <0.05 indicated that the difference was statistically significant.ResultsThe expression of TREX1 protein in patients with osteosarcoma in the metastasis group was significantly lower than that in the non-metastasis group. The difference was statistically significant (P < 0.05). Up to the last follow-up visit, the former average survival time was significantly lower than that of the latter, and the difference was statistically significant (P < 0.05). The expression of TREX1 in human osteosarcoma CD133+ cell subsets was significantly lower than that in CD133- cell subsets. Stemness-related genes Nanog and Oct4 were highly expressed in human osteosarcoma CD133+ cell subsets with lower expression of TREX1; the biological characteristics identification experiment showed that human CD133+ cell subsets with low TREX1 expression could form tumorspheres, the number of colony forming was more, the cell proliferation ability was strong, the osteogenic and adipogenic differentiation potential was big, the tumor-forming ability in nude mice was strong, and the sensibility of chemotherapeutics drugs on cisplatin was low.ConclusionsThe expression of TREX1 may be related to metastasis in patients with osteosarcoma. The expression of TREX1 was closely related to the cytobiology characteristics of osteosarcoma stem cell. TREX1 can play an important role in the occurrence and development processes. And, TREX1 is expected to become an effective new index for the evaluation of the prognosis.

Solitary Pulmonary Nodule: Primary, Metastatic, or Both?

The lung is the most common site for metastasis from colorectal cancer, which is among the most common neoplasms in developed countries. Simultaneous occurrence of pulmonary metastasis of colorectal origin and primary carcinoma has been reported. We describe the case of a 65-year-old man who underwent low anterior resection for colorectal adenocarcinoma in 2007. Follow-up computed tomography revealed a pulmonary nodule that was classified as metastatic. The patient was referred to our thoracic surgery department, where the nodule was resected. The pathology confirmed that the nodule was neoplastic, and histologic and immunohistochemical examination showed the presence of colorectal metastasis and lung adenocarcinoma. Evidence of metastasis was also found in 2 of the lymph nodes analyzed, 1 with features identical to the primary pulmonary adenocarcinoma, and 1 with features identical to the colorectal metastasis.

Nódulo pulmonar solitario: ¿primario, metastásico o ambos?

The lung is the most common site for metastasis from colorectal cancer, which is among the most common neoplasms in developed countries. Simultaneous occurrence of pulmonary metastasis of colorectal origin and primary carcinoma has been reported. We describe the case of a 65-year-old man who underwent low anterior resection for colorectal adenocarcinoma in 2007. Follow-up computed tomography revealed a pulmonary nodule that was classified as metastatic. The patient was referred to our thoracic surgery department, where the nodule was resected. The pathology confirmed that the nodule was neoplastic, and histologic and immunohistochemical examination showed the presence of colorectal metastasis and lung adenocarcinoma. Evidence of metastasis was also found in 2 of the lymph nodes analyzed, 1 with features identical to the primary pulmonary adenocarcinoma, and 1 with features identical to the colorectal metastasis.

Improved survival with pulmonary metastasectomy: An analysis of 1720 patients with pulmonary metastatic melanoma

The outcomes of patients with metastatic melanoma are poor. Although prognostic models have been developed to predict the occurrence of pulmonary metastasis from cutaneous melanoma, few data exist to define the outcomes of these patients once metastasis has occurred. The objective of this study was to discriminate predictors of survival for patients with pulmonary metastatic melanoma. We found 1720 patients with pulmonary metastasis listed in a prospective comprehensive cancer center database of 14,057 consecutive patients with melanoma (Jan 1, 1970-June 1, 2004). Demographic and histopathologic data, time and location of recurrences, number of pulmonary nodules, and subsequent therapies were collected. Univariate and multivariate Cox proportional hazards models were used to identify predictors of survival for patients with pulmonary metastatic melanoma. The median survival was 7.3 months after development of pulmonary metastasis. Significant predictors of survival from the multivariate model included nodular histologic type (P = .033), disease-free interval (P < .001), number of pulmonary metastases (P = .012), presence of extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy (P < .001). Interactions were identified between metastasectomy and disease-free interval and presence of extrathoracic metastasis. Surgery was associated with a survival advantage of 12 months for patients with a disease-free interval longer than 5 years (19 vs 7 months, P < .01) and of 10 months for patients without extrathoracic metastasis (18 vs 8 months, P < .01). When all other identified risk factors were controlled for mathematically, metastasectomy maintained a significant survival advantage for patients with pulmonary metastatic melanoma. These data support the role of surgery for a select subset of patients with pulmonary metastasis.

Presence of telomerase activity in different musculoskeletal tumor histotypes and correlation with aggressiveness

Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. Telomerase activity was observed and correlated with aggressiveness in different neoplasms such as breast, prostate, blood and brain cancers, among others. To investigate whether telomerase activity is an index of aggressiveness in bone and soft tissue lesions of the extremities, 66 biopsy samples from our tissue bank were studied. These samples included 43 high-grade sarcomas, 9 aggressive benign tumors and 14 totally benign lesions. The samples were collected from patients homogeneously treated at the Rizzoli Orthopaedic Institute with a follow-up ranging from 4 to 11 years (median, 7 years). A non-radioactive polymerase chain reaction-based enzyme-linked immunosorbent assay was used for the study. All tumors investigated were positive for telomerase activity. Among benign lesions, only 2 aneurysmal bone cysts showed higher telomerase activity than the cut-off point, whereas all the other benign lesions had lower activity. Our results indicate that high levels of telomerase activity in bone and soft tissue lesions correlate with more aggressive clinical behavior in patients treated with surgery alone. An interesting inverse correlation between telomerase activity and occurrence of pulmonary metastasis was detected in osteosarcoma patients treated with chemotherapy. A parallel increase of telomerase activity and malignancy was observed in the adipose and cartilagineous tissue lesions. Our data suggest that telomerase activity could be considered a marker of tumor aggressiveness for bone and soft tissue lesions. The results obtained in osteosarcoma samples suggest that low levels of telomerase activity may be predictive of the prognosis and should influence the therapeutic protocol.

Subcentimeter Pulmonary Nodules Detected in Patients with Sarcoma

Background. Subcentimeter pulmonary nodules are being detected with increasing frequency in patients with sarcoma due to the greater use of chest CT, the advent of helical (spiral) CT scanning and multidetector scanners, and the attendant decrease in image section thickness.Assessing the clinical significance of these pulmonary nodules is of particular importance in sarcoma patients, due to the frequent occurrence of pulmonary metastasis from sarcomas. Purpose. This article reviews the technical advances that have contributed to the increased detection of subcentimeter pulmonary nodules, statistics about subcentimeter pulmonary nodules and options for evaluating such nodules.

A clinicopathological study of postoperative pulmonary metastasis of uterine cervical carcinomas.

To investigate the clinicopathological backgrounds and prognostic factors of uterine cervical carcinomas metastatic to the lung. A total of 519 patients with invasive cervical carcinoma (Stage pTIb-IIb) treated by abdominal radical hysterectomy at the Saitama Cancer Center from January 1, 1976 to December 31, 1989 were analyzed clinicopathologically. The frequencies of pulmonary metastasis were 6.4% (24/377) and 11.3% (16/142) in patients with negative and positive pelvic lymph nodes, respectively. Among 24 negative lymph node patients, 15 had pulmonary metastasis only. The overall 5-year survival rate of these 15 patients was 36% after relapse. Of the 15, the prognosis of 12 patients with 1-3 pulmonary metastases only was better, that is, 46% after surgical resection (mean size of resectable tumor = 2.8 cm) and/or chemotherapy. But the other patients died within 3.3 years after relapse. The occurrence of pulmonary metastasis only, its number (1-3) and size (mean size = 2.8 cm), and no lymph node metastasis are important prognostic factors. For these patients, active surgical resection of the pulmonary lesion(s) and further chemotherapy are recommended in order to improve their prognosis.

Analysis of morphological factors of hepatocellular carcinoma in 98 autopsy cases with respect to pulmonary metastasis.

The morphological features of ninety-eight autopsy cases of hepatocellular carcinoma (HCC) were analyzed in relation to pulmonary metastasis. Extrahepatic hematogenous metastasis was observed in 64% and lung was most frequently involved (62%). A close relationship was observed between intrahepatic vascular invasion and extrahepatic hematogenous metastasis to lungs. Portal vein-invasion was found in 80% of cases and significant correlations were recognized between the rates of portal vein-invasion and hepatic vein-invasion, and between the rates of portal vein-invasion and pulmonary metastasis. There was a close correlation among the macroscopic growth-pattern, incidence of vascular invasion, and pulmonary metastasis, and their degrees. Namely, the expansive type HCC showed significantly lower rates of vascular invasion and pulmonary metastasis than the infiltrative or mixed type HCC. These rates were particularly low in the expansive type, single nodular subtype HCC with size of a primary tumor less than 10 cm. Significantly low rates of pulmonary metastasis and portal vein-invasion were also noted in well-differentiated carcinoma (Grade I or II). The existence of cirrhosis or fibrosis of liver in cases with HCC was not definitely related to the occurrence of pulmonary metastasis. It was originally clarified that invasion to the portal vein and the size of HCC played a main role in pulmonary metastasis.

Different metastatic modes of malignant melanoma implanted in the ear of young and old mice.

An attempt has been made to determine (a) whether aging plays an important role in resistance against metastasis and (b) whether dithiothreitol, an effective in vitro mitogenic potentiator of splenic cells of young and old mice, can modulate the occurrence of pulmonary metastasis. B16-F10 melanoma cells were injected into the outer ear of young and old female C57BL/6 mice; and the growth of the primary tumor, the palpable size of the cervical lymph node, and the number of lung metastases were then determined at various intervals. The ear was amputated when the primary tumor reached 4 mm in mean diameter. The following results were obtained. (a) The growth rate of the primary tumor in young mice is comparable to that in old mice. (b) Enlargement of the cervical lymph node occurs earlier in old than in young mice. (c) Old mice are more vulnerable to pulmonary metastases, but small metastasized pulmonary colonies are more prominent in old than in young mice. (d) Dithiothreitol (100 micrograms) injected every 2 days after the inoculation of tumor cells is effective in reducing the incidence of pulmonary metastases in old mice.

Are growth rates of tumors of any clinical importance?

The tumor doubling times were determined in 142 rounded pulmonary lesions of 78 patients (13 bronchial carcinomas, 7 benign pulmonary tumors, and 122 pulmonary metastases). They varied between +12 and +8863 days of tumor growth and of -1810 days of decrease in tumor mass. Forty-four percent of all pulmonary metastases doubled their volume within 60 to 250 days. The growth rates during the period of observation varied greatly in several pulmonary metastases of the same patient, even for the same solitary circular lung focus of the same person. There is no relationship between tumor doubling time and histological type of the tumor, nor between the interval between operative removal of the primary tumor and the occurrence of pulmonary metastases. In patients between the ages of 10 and 30 years only rapidly growing pulmonary metastases with a tumor doubling time of less than 60 days could be found; even though there is no proved relationship between growth rate and age. The tumor doubling time gives no useful information on the nature of a circular lung focus, and there are no clinical consequences for diagnosis.

Hat die Berechnung der Geschwindigkeit des Geschwulstwachstums klinische Bedeutung?

In 142 circular lung foci of 78 patients we determined the tumor doubling times (13 bronchial carcinomas, 7 benign pulmonary tumors, and 122 pulmonary metastases). They fluctuated between + 12 and + 8,863 days of tumor growth and a diminuation of -1,810 days of half-life. 44% of all pulmonary metastases doubled their volumes within 60 to 250 days. During the observation period the times of tumor growth varied not only in different pulmonary metastases of the same patient, but also in solitary circular lung foci of the same person considerably. There is no connexion between tumor doubling time and histological tumor type as well as the interval between surgery of the primary tumor and occurrence of pulmonary metastases. Though we found in patients of 10 to 30 years of age only quickly growing pulmonary metastases with a tumor doubling time of less than 60 days a corrlation between time of tumor growth and age could not be proved. By the determination of the tumor doubling time neither binding statements on the nature of a circular lung focus can be made nor clinical consequences for diagnostics or therapy be drawn.

Metastatic osteosarcoma to lung.A clinicopathologic study of surgical biopsies and resections

Metastatic tumor to the lungs is one of the most important factors in the poor prognosis of primary osteosarcoma of bone. Until recently, pulmonary resection alone was the only therapeutic method available to salvage these patients. Previous investigators have reviewed a number of clinical and pathologic parameters which may possibly relate to the prognosis of osteosarcoma and the occurrence of pulmonary metastases. The pathologic features of these latter lesions have received little attention other than to state that they generally are less differentiated than the primary tumor. A review of multiple pulmonary nodules resected from 15 patients has demonstrated that 66% of all lesions were essentially identical to the primary tumor. The 5-year survival from the original amputation was 33% in this series; however, it was not possible to prognosticate a favorable outcome from the metastasis, a similar type of observation which has been made by others in relation to the primary osteosarcoma.

Time of occurrence of pulmonary metastasis from carcinoma of colon and rectum.

Time of occurrence of pulmonary metastasis from carcinoma of colon and rectum.

Cancer of the colon and rectum: A study of the routes of metastases

In twenty-eight patients with surgically “curable” carcinomas of the colon, tumor cells were identified in the peripheral blood in 12.5 per cent of the patients and in the regional blood of 36 per cent of the patients. There may be a slight increase in the occurrence of tumor cells in the peritoneal cavity and serosal invasion by the tumor in the patients with tumor cells in the blood. No relationship was apparent to blood vessel invasion, invasion of adjacent tissues, metastases to lymph nodes or ascites and tumor implants. Tumor cells were identified in the peripheral blood of 6.6 per cent of sixty-five patients with surgically “curable” rectal cancer, and in the regional blood of 14 per cent of these patients. The finding of tumor cells in the peritoneal cavity was associated with serosal invasion by the tumor, but no relationship was apparent between the occurrence of tumor cells in the blood and the finding of tumor cells in the peritoneal cavity, serosal invasion, blood vessel invasion, invasion of adjacent tissues, lymph node metastases or the presence of ascites or tumor implants. The lymph from the thoracic duct does not appear to be an important route for the spread of tumor cells from colon or rectal cancer, and the occurrence of pulmonary metastasis may indicate vascular rather than lymphatic spread. It appears that each route of dissemination of cancer cells in patients with colon or rectal carcinoma is relatively independent of other factors, and must be considered separately in any surgical efforts to control the disease.

Metastasizing Hepatoma in a Hog (Sus Scrofa)

The literature on the occurrence of hepatoma in animals was reviewed in another communication (1) in which were described two cases of primary carcinoma of the liver of cattle. From information obtained from published reports it is evident that primary carcinoma of the liver is not one of the common tumors of the lower animals. It has been observed in the following species: dogs, horses, cattle, cats, hogs, woodchucks, and chickens. The most comprehensive description of the disease appears to have been contributed by Trotter, who observed 119 cases among 39,704 cattle that were examined at necropsy during one year at a Glasgow, Scotland, abattoir (2). That the disease is of infrequent occurrence in swine is evident from the figures accompanying Sticker's report (3). Among 1,206 primary carcinomas of domesticated animals only 35 had their origin in the liver and but one of these occurred in a hog. My collection of neoplasms of swine consists at the present of 110 specimens and only 2 of these are tumors which arose from the parenchymal cells of the liver. One of the tumors, which was obtained several years ago, was situated rather deeply in the left central lobe. The tumor nodule was approximately 4 cm. in diameter and was icteric. Metastasis had not occurred and microscopically there was no convincing evidence of an aggressive malignant type of growth. This tumor was therefore considered a benign hepatoma. The other liver-cell tumor which was obtained from a hog was of particular interest because of the multiplicity of the hepatic lesions and the occurrence of pulmonary metastasis.