Search

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy. [Display omitted] • The potential of in vivo spatiotemporal metabolomics was explored for evaluating the chemotherapy outcome. • SPME microprobes were employed with global metabolite profiling. • Metabolic phenotypes were identified during the local delivery of oxaliplatin to the porcine lung. • Massive alterations in the metabolic patterns were recognized being indicative of acute lung injury (ALI). • Spatiotemporal metabolomics may improve ALI diagnosis and facilitate adjustments to the chemotherapy regimen. [ABSTRACT FROM AUTHOR]

To evaluate the prognostic value of tumor budding and tumor-stroma ratio (TSR) in resected pulmonary metastases of colorectal carcinoma (CRC). In total, 106 pulmonary metastasectomies were performed to 74 patients in two study hospitals during 2000–2020. All relevant clinical data were retrospectively collected. Tumor budding based on the International Tumor Budding Consensus Conference recommendations and TSR in the first resected pulmonary metastases and primary tumors were evaluated from diagnostic hematoxylin-eosin-stained histopathological slides. 60 patients (85.7%) had low tumor budding (≤5 buds/field) and 10 patients (14.3%) had high tumor budding (>5 buds/field) in their first pulmonary metastases of CRC. 5-year overall survival rates of pulmonary metastasectomy in low and high total tumor budding were 28.3% and 37.3% (p = 0.387), respectively. 19 patients (27.1%) had low TSR and 51 patients (72.9%) had high TSR. The 5-year overall survival rates were 32.9% in low and 28.6% in high TSR of first pulmonary metastases (p = 0.746). Tumor budding and TSR did not provide prognostic value in Cox multivariate analysis. Tumor budding and TSR in resected pulmonary metastases were not associated with those of the primary tumor. Tumor budding and TSR in the resected pulmonary metastases of CRC showed no statistically significant prognostic value, however, additional well-powered confirmatory studies are needed. [ABSTRACT FROM AUTHOR]

The utility of repeated surgical interventions in hepatoblastoma to achieve no evidence of disease (NED) is not well-defined. We examined the effect of aggressive pursuit of NED status on event-free (EFS) and overall survival (OS) in hepatoblastoma with subgroup analysis of high-risk patients. Hospital records were queried for patients with hepatoblastoma from 2005 to 2021. Primary outcomes were OS and EFS stratified by risk and NED status. Group comparisons were performed using univariate analysis and simple logistic regression. Survival differences were compared with log-rank tests. Fifty consecutive patients with hepatoblastoma were treated. Forty-one (82%) were rendered NED. NED was inversely correlated with 5-year mortality (OR 0.006; CI 0.001–0.056; P <.01). Ten-year OS (P <.01) and EFS (P <.01) were improved by achieving NED. Ten-year OS was similar between 24 high-risk and 26 not high-risk patients when NED was attained (P =.83). Fourteen high-risk patients underwent a median of 2.5 pulmonary metastasectomies, 7 for unilateral disease, and 7 for bilateral, with a median of 4.5 nodules resected. Five high-risk patients relapsed, and three were salvaged. NED status is necessary for survival in hepatoblastoma. Repeated pulmonary metastasectomy and/or complex local control strategies to obtain NED can achieve long-term survival in high-risk patients. Level III – Treatment Study - Retrospective Comparative Study. • NED status was defined as normal AFP and absence of detectable radiographic disease on interval surveillance imaging after chemotherapy, resection of the patient's primary tumor, and metastasectomy, if indicated. • NED status is necessary for survival in hepatoblastoma. • Repeated pulmonary metastasectomy and/or complex local control strategies to obtain NED benefit high-risk patients. [ABSTRACT FROM AUTHOR]

The lung is the most common site of metastasis for gestational trophoblastic neoplasia (GTN). However, the level of influence of lung metastases on the prognosis of GTN and the degree to which lung metastases are considered in assessments of disease treatment options are unclear. Moreover, it is unclear which characteristics of lung metastases impact the disease. In this study, we evaluated the influence of lung metastases on the clinical course of GTN and identified lung imaging characteristics that impact treatment outcomes. A retrospective cohort study was conducted on GTN patients treated at Peking Union Medical College Hospital between 2002 and 2018. The baseline characteristics, first-line treatment outcomes and final outcomes of patients with lung metastases (Group 1) and those without lung metastases (Group 2) were compared. The emergence of resistance occurred significantly more frequently in Group 1 (n = 994) than in Group 2 (n = 570) (19.52% versus 14.56%, p = 0.019), and the death rate was higher in Group 1 (0.91% versus 0%, p = 0.031). Among the patients treated with multi-agent chemotherapy, the rate of resistance and the number of treatment courses were significantly higher in Group 1 than in Group 2 (p = 0.002 and < 0.001, respectively). The lung imaging characteristics that impacted prognosis included the number of nodules, whether there were multiple nodules or a single nodule, and the number of nodules sized >1 cm. Multivariate analysis showed that a nodule measuring ≥1.8 cm was an independent risk factor for first-line treatment resistance and recurrence. Although pulmonary metastases do not affect overall survival in GTN patients, the presence of lung metastases before treatment is associated with increased risk of disease recurrence and resistance to first-line multidrug chemotherapy, especially when pulmonary nodules are larger than 1.8 cm. N.A. • Lung metastases are a risk factor for chemotherapy resistance and recurrence in GTN. • A single lung nodule <1 cm has a small impact on chemoresistance and recurrence. • Lung metastases ≥1.8 cm significantly impact first-line multidrug chemotherapy and recurrence. [ABSTRACT FROM AUTHOR]

Routine lymphadenectomy during metastasectomy for pulmonary metastases of colorectal cancer has been recommended by several recent expert consensus meetings. However, evidence supporting lymphadenectomy is limited. The aim of this study was to perform a systematic review of the literature on the impact of simultaneous lymph node metastases on patient survival during metastasectomy for colorectal pulmonary metastases (CRPM). A systematic review was conducted according to the PRISMA guidelines of studies on lymphadenectomy during pulmonary metastasectomy for CRPM. Articles published between 2000 and 2020 were identified from Medline, Embase and the Cochrane Library without language restriction. Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the risk of bias and applicability of included studies. Survival rates were assessed and compared for the presence and level of nodal involvement. Following review of 8054 studies by paper and abstract, 27 studies comprising 3619 patients were included in the analysis. All patients included in these studies underwent lymphadenectomy during pulmonary metastasectomy for CRPM. A total of 690 patients (19.1%) had simultaneous lymph node metastases. Five-year overall survival for patients with and without lymph node metastases was 18.2% and 51.3%, respectively (p <.001). Median survival for patients with lymph node metastases was 27.9 months compared to 58.9 months in patients without lymph node metastases (p <.001). Five-year overall survival for patients with N1 and N2 lymph node metastases was 40.7% and 10.9%, respectively (p =.064). Simultaneous lymph node metastases of CRPM have a detrimental impact on survival and this is most apparent for mediastinal lymph node metastases. Therefore, lymphadenectomy during pulmonary metastasectomy for CRPM can be advised to obtain important prognostic value. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a meta-analysis assessing clinical outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) for treating lung cancer.Methods: Databases were searched up to 2017 to identify high-quality studies. The results were presented as pooled estimates with 95% confidence intervals (CIs).Results: Fifty-three studies were included, and up to 3,432 patients were pooled. The estimated 1-, 2-, 3-, 4-, and 5-year overall survival (OS) rates were higher for RFA-treated patients compared with those treated by MWA. The median OS, median progression-free survival (PFS), median local tumor PFS, complete ablation rate, and adverse events did not differ significantly. Subgroup analyses by tumor type showed that the median OS for RFA-treated patients with pulmonary metastases was higher than that of the MWA-treated patients.Conclusion: Thermal ablation, both RFA and MWA, is an effective approach for treating lung cancer with low risk of adverse events. RFA is associated with longer survival than MWA, and patients with pulmonary metastases showed better survival after RFA compared with MWA-treated patients. [ABSTRACT FROM AUTHOR]

• We observed excellent long-term disease control with SBRT and potential for prolonged survival particularly among patients with oligometastatic disease at the time of SBRT. • The 24-month cumulative incidence of local failure was 7.4% after SBRT for pulmonary sarcoma metastases. • We observed low rates of toxicity, including no grade 3 or greater toxicity. This cohort included patients with ultra-central lesions and multiple pulmonary metastases treated with SBRT simultaneously. • SBRT is an important treatment modality for patients with sarcoma pulmonary metastases, particularly patients who are unfit for surgery or have unresectable metastases. Stereotactic body radiation therapy (SBRT) is standard for patients with inoperable early-stage NSCLC. We hypothesized that SBRT for sarcoma pulmonary metastases would achieve high rates of local control with acceptable toxicity and that patients with oligometastatic disease may achieve prolonged survival following SBRT. This retrospective review included consecutive patients at our institution treated with SBRT for sarcoma pulmonary metastases. Cumulative incidence of local failure (LF) was estimated using a competing risks framework. We identified 66 patients treated to 95 pulmonary metastases with SBRT. The median follow-up from the time of SBRT was 36 months (95% CI 34 – 53 months). The cumulative incidence of LF at 12 and 24 months was 3.1% (95% CI 0.9 – 10.6%) and 7.4% (95% CI 4.0% - 13.9%), respectively. The 12- and 24-month overall survival was 74% (95% CI 64 – 86%) and 49% (38 – 63%), respectively. Oligometastatic disease, intrathoracic only disease, and performance status were associated with improved survival on univariable analysis. Three patients had grade 2 pneumonitis, and one patient had grade 2 esophagitis. No patients had ≥ grade 3+ toxicities. To the best of our knowledge, this is the largest series of patients treated with SBRT for pulmonary sarcoma metastases. We observed that SBRT offers an effective alternative to surgical resection with excellent local control and low proportions of toxicity. [ABSTRACT FROM AUTHOR]

Objective: To compare three different reconstruction techniques of CT data for the detection of pulmonary nodules in children under 13 years. Secondly to assess the prevalence of perifissural nodular opacities.Materials and Methods: The study consisted of chest CTs of 31 children (median age 6.9 years, range 2.1-12.7), of whom 17 had known extra-thoracic malignancies. Four observers assessed three techniques for the presence of nodules: axial 5 mm maximum intensity projections (MIPs) used in conjunction with 1 mm slices (mode A), 1 mm slices alone (mode B) and 3 mm slices (mode C). All modes were available in 3D. Per mode sensitivities were determined above a certain threshold of reader agreement. Confidence level and reader agreement for identification of an opacity as nodule served as surrogate for quality of nodule characterization.Results: 103 nodules (median size 2.0 mm) were detected. Mode A yielded the highest interreader agreement (κ 0.336) and a superior sensitivity (71%, p = 0.003) compared to mode B and C (κ 0.218, sensitivity 57% and κ 0.247, sensitivity 56%, respectively). Mode B provided the highest confidence level and interreader agreement with respect to nodule identification (mean 4.3/5, κw 0.508). Double reading improved and evened interreader agreement for all modes (κ 0.450), mode A maintained the highest sensitivity (89.1%, p = 0.05-0.08). A median of 1 intrapulmonary lymph node/patient was seen in children with and without malignancy.Conclusion: MIP improves the detection of pulmonary nodules in chest CTs of children, but overall interreader agreement is only fair. Double reading represents a powerful tool to increase diagnostic reliability in chest CTs of children with a malignancy. Nodule characterization is best with 1 mm slices. Intrapulmonary lymph nodes occur in children with and without malignancy. [ABSTRACT FROM AUTHOR]

Exosomes have recently emerged as a promising drug delivery system with low immunogenicity, high biocompatibility, and high efficacy of delivery. We demonstrated earlier that macrophage-derived exosomes (exo) loaded with a potent anticancer agent paclitaxel (PTX) represent a novel nanoformulation (exoPTX) that shows high anticancer efficacy in a mouse model of pulmonary metastases. We now report the manufacture of targeted exosome-based formulations with superior structure and therapeutic indices for systemic administration. Herein, we developed and optimized a formulation of PTX-loaded exosomes with incorporated aminoethylanisamide-polyethylene glycol (AA-PEG) vector moiety to target the sigma receptor, which is overexpressed by lung cancer cells. The AA-PEG-vectorized exosomes loaded with PTX (AA-PEG-exoPTX) possessed a high loading capacity, profound ability to accumulate in cancer cells upon systemic administration, and improved therapeutic outcomes. The combination of targeting ability with the biocompatibility of exosome-based drug formulations offers a powerful and novel delivery platform for anticancer therapy. [ABSTRACT FROM AUTHOR]

Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve thoracic cancer resections. There are no large-scale studies to guide surgeons in patient selection or imaging agent choice. Here, we report our institutional experience with IMI for lung and pleural tumor resection in 500 patients over a decade. Between December 2011 and November 2021, patients with lung or pleural nodules undergoing resection were preoperatively infused with 1 of 4 optical contrast tracers: EC17, TumorGlow, pafolacianine, or SGM-101. Then, during resection, IMI was used to identify pulmonary nodules, confirm margins, and identify synchronous lesions. We retrospectively reviewed patient demographic data, lesion diagnoses, and IMI tumor-to-background ratios (TBRs). Five hundred patients underwent resection of 677 lesions. We found that there were 4 types of clinical utility of IMI: detection of positive margins (n = 32, 6.4% of patients), identification of residual disease after resection (n = 37, 7.4%), detection of synchronous cancers not predicted on preoperative imaging (n = 26, 5.2%), and minimally invasive localization of nonpalpable lesions (n = 101 lesions, 14.9%). Pafolacianine was most effective for adenocarcinoma-spectrum malignancies (mean TBR, 2.84), and TumorGlow was most effective for metastatic disease and mesothelioma (TBR, 3.1). False-negative fluorescence was primarily seen in mucinous adenocarcinomas (mean TBR, 1.8), heavy smokers (>30 pack years; TBR, 1.9), and tumors greater than 2.0 cm from the pleural surface (TBR, 1.3). IMI may be effective in improving resection of lung and pleural tumors. The choice of IMI tracer should vary by the surgical indication and the primary clinical challenge. [ABSTRACT FROM AUTHOR]

Background The role of chemotherapy in the setting of resected colorectal cancer pulmonary metastases (CRCPM) is not well defined. Here we describe utilization of peri-operative chemotherapy and outcomes among patients with resected CRCPM in the general population. Methods All cases of CRCPM who underwent resection from 2002 to 2009 were identified using the Ontario Cancer Registry (OCR). Electronic treatment records identified peri-operative chemotherapy delivered within 16 weeks before or after pulmonary metastasectomy (PM). Modified Poisson regression was used to evaluate factors associated with chemotherapy delivery. Cox proportional models were used to explore the association between post-operative chemotherapy and cancer-specific (CSS) and overall survival (OS). Results The study population included 420 patients. Thirty-six percent of patients (151/420) received peri-operative chemotherapy. Among these patients, 75% (113/151) received post-operative chemotherapy. Factors that were independently associated with use of post-operative chemotherapy included higher socioeconomic status (SES) and no prior adjuvant chemotherapy (p < 0.01). In adjusted analyses post-operative chemotherapy was not associated with improved CSS (HR 0.99, 95% CI 0.67–1.47) or OS (HR 0.93 95% CI 0.66–1.31). In exploratory analyses, among those patients who did not receive previous adjuvant therapy for the primary colorectal cancer, post-operative chemotherapy following lung metastasectomy was associated with HR 0.50 (95% CI 0.27–0.95) for OS and HR 0.59 (95% CI 0.27–1.27) for CSS. Conclusion One third of patients with resected CRCPM in routine practice receive peri-operative chemotherapy. A randomized controlled trial is warranted to evaluate whether chemotherapy following resection of CRCPM is associated with improved survival. [ABSTRACT FROM AUTHOR]

Background and purpose This study was aimed to identify the clinical and dosimetric parameters that predict symptomatic radiation pneumonitis (SRP, radiation pneumonitis ≥ 2 grade) in patients with pulmonary metastasis from hepatocellular carcinoma (HCC) after helical tomotherapy (HT) hypofractionated simultaneous multitarget radiotherapy. Materials and Methods 62 patients with 407 pulmonary metastases from HCC were consecutively treated with HT. The median radiation dose was a 49.7 Gy in 4.0 Gy/fraction to 95% of the planning target volume (PTV). The associations between the clinical and dosimetric data and incidences of SRP were analyzed. The dose–pneumonitis relationship was analyzed based on Biologically Effective Dose (BED). Results Univariate analysis showed that the gross tumor volume (GTV), PTV, median lung dose (MLD), the number of pulmonary metastatic lesions (NPML), and the percentage of non-target normal lung (NTNL) volume receiving more than a BED of 3–50 Gy (V BED3-50 ) were associated with SRP. Multivariate logistic regression analysis showed that V BED20 and NPML were significant parameters (both P < 0.001) Conclusions Our findings indicated that SRP can be predicted with NPML > 5 and V BED20 ≥ 30.4% with the α/β ratio of 3 Gy. [ABSTRACT FROM AUTHOR]

Purpose Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. Methods Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. Results A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1–31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). Conclusions Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate how often distant metastases occur in localized oral squamous cell carcinomas (OSCC). The investigators hypothesize that abdominal sonography and chest X-ray may not be necessary for initial staging of early oral squamous cell carcinoma in UICC stage I/II. Material and methods The investigators implemented a retrospective study. The study collective was composed of 124 patients with OSCC, who were treated in the department of oral and maxillofacial surgery during the years 2011–2015 at the University Medical Center Hamburg Eppendorf, Germany. We focused on age, gender, date of diagnosis, tumour stage (clinical and pathological), HPV status, occurrence of metastases, recurrences, date and frequency of staging and restaging (abdominal sonography, chest X-ray, CT Abdomen/Thorax, PET CT), follow up time and date of death. Descriptive and bivariate statistics were computed (chi-square test) and the P value was set at .05. Results 19 distant metastases were found in 13 out of 124 patients (10.48%). Of those 20 metastases 5 were found in the liver (26.32%), 11 in the lung (57.89%) and 4 in the bone (15.79%). Hepatic metastases co-occurred in every case with pulmonary metastases. In one case bone metastases occurred without the presence of pulmonary metastases. There was no significant correlation of metastasis rate to T stage. But distant metastases were solely found in node positive patients. This was significant for pulmonary metastases, not for liver metastases. Only one out of 11 pulmonary metastases was diagnosed by chest X-ray. Conclusion Abdominal sonography and chest X-ray can be omitted as a standard procedure in staging of localized node negative oral squamous cell carcinoma. A thoracic CT including the liver should be performed in patients with suspected lymph nodes metastases in the neck on CT. A skeletal scintigraphy or alternatively a PET/PET-CT should be added if there are signs and symptoms suspicious for bone metastases. [ABSTRACT FROM AUTHOR]

Objective: CT is the recommended technique for the detection of pulmonary metastases in patients affected by osteosarcoma, though claimed to show several limits compared to manual palpation. We retrospectively analyzed CT features of suspected lesions submitted to surgery to address its current accuracy and to investigate criteria for predicting histology.Materials and Methods: CT scans of 70 patients submitted to thoracotomy between 2007-2013 were reviewed. Overall, 123 thoracotomies were performed and 283 lesions seen on CT were resected. Shape, size, presence and type of calcification, evolution of each lesion were analyzed. Number and histology of nodules detected at thoracotomy were recorded and compared to CT data.Results: 234/283--82.7% Lesions were metastases; 143--61.1% were calcified; most metastases were nodular (201/234--85.9%), but in 33/234--14.1% other findings were detected (striae, consolidations, pleural plaques/masses, cavitations, ground glass opacities, irregular shapes, halo sign). Malignant lesions were more frequently calcified, larger, with progression over time--p<0.0001. Manual palpation identified 314 lesions, 248 metastatic--79.0%: CT missed 31/314--9.9% lesions, whereof 14/31--45.2% were metastases.Conclusions: Though most lesions are nodular and calcified, up to 40% are not calcified and atypical findings are not uncommon (14.1%). The identification of the atypical radiological presentation of metastases could be the key for improving CT accuracy. [ABSTRACT FROM AUTHOR]

Background Radiofrequency ablation (RFA) is a well-established treatment modality for colorectal hepatic metastases, the success of which has prompted its use to treat other lesions such as colorectal pulmonary metastases (CRPM). Our aim was to perform a systematic review of the evidence and to assess the safety and effectiveness of ablative techniques in the management of CRPM. Method A literature search was performed using PubMed, Embase, Cochrane Library, CINAHL and Google scholar databases to identify studies, which analysed ablative techniques and their effectiveness in the management of CRPM. The primary outcome measures were overall survival, local recurrence rates and disease free survival. Secondary outcome measures were complication (major/minor), chest drain insertion rates and follow up duration. Results Eight studies were included in the review with a total of 903 patients and all of which used RFA for ablation. Mortality from ablation was <1% with overall survival ranging from 31 to 67 months. 1, 3 and 5 year survival ranges of 84–95%, 35–72% and 20–54% respectively. Local progression following ablation ranged from 9 to 21%. Major complication rates were noted in 0.5%–8% of patients with minor complications ranging between 7% and 33%. 23% of patients required chest drain insertion post procedure. Conclusion s: RFA is a safe and effective technique for the management of CRPM. However, in the absence of large randomised controlled trials it is unclear where RFA should sit in the treatment algorithm for patients with CRPM. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the impact of treated extra-pulmonary metastatic disease on overall (OS) and event-free survival (EFS) for pediatric osteosarcoma patients undergoing pulmonary metastatectomy. Methods We retrospectively reviewed pediatric patients who were treated for osteosarcoma at our institution from 2001 to 2011 and received pulmonary metastatectomy (n = 76). We compared OS and EFS between patients with metastases limited to the lungs (Group A, n = 58) to those with treated extra-pulmonary metastases (Group B, n = 18) at the time of first pulmonary metastatectomy. Results The estimated median OS and EFS from first pulmonary metastatectomy were 2.0 years (95% CI 1.5–2.8 years) and 5.5 months (95% CI 3.0–8.1 months), respectively. Median OS was significantly greater for Group A (2.6 years, 95% CI 1.9–3.8) compared to Group B (0.9 years, 95% CI 0.6–1.5) (log rank p = 0.0001). Median EFS was significantly greater for Group A (7.9 months, 95% CI 5.0–10.7) compared to Group B (1.6 months, 95% CI 0.8–2.7) (log rank p < 0.0001). Independent predictors of OS included extra-pulmonary metastatic disease at the time of first thoracotomy, bilateral pulmonary metastases, and > 4 nodules resected at first thoracotomy (all p < 0.001). Conclusions Osteosarcoma patients with treated extra-pulmonary metastatic disease at the time of pulmonary metastatectomy have significantly worse survival compared to those with disease limited to the lungs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the potential role of nidogen 1 (NID1), a basement membrane component, in the growth and metastasis of salivary gland adenoid cystic carcinoma (SACC) and the underlying molecular mechanism.Methods: High-throughput next-generation sequencing was used to compare the gene expression profiles of SACC with and without lung metastasis. Luciferase gene reporter assays were used to measure the NID1 promoter activity. BALB/c nude mice were used to establish a lung metastasis model of SACC to evaluate the prometastatic activity of NID1. ChIP and dual-luciferase reporter assays were performed to confirm the HIF-1α-binding site in the NID1 promoter.Results: NID1 expression in SACC was significantly increased and associated with lung metastasis (P = 0.011). The elevated NID1 expression was a predictor of poor outcomes in patients with SACC (P < 0.05). Overexpression of NID1 promoted cancer cell migration and invasion through PI3K/AKT pathway activation and subsequent epithelial-mesenchymal transition (EMT), as indicated by the upregulation of N-cadherin and vimentin. Furthermore, in vivo live monitoring of a mouse model of lung cancer demonstrated the pro-metastatic role of NID1 in SACC cell lung metastasis. Hypoxia-inducible factor 1α (HIF-1α) upregulation via transfection of an HIF-1α-overexpressing plasmid enhanced HIF-1α binding to the NID1 promoter and the subsequent transcriptional activity and expression of NID1.Conclusion: HIF-1α-activated NID1 overexpression promotes SACC cell metastasis via PI3K/AKT pathway activation and EMT. Thus, NID1 could be a novel biomarker and therapeutic target for preventing metastasis and treating patients with SACC in future. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this study was to determine what factors predict recurrent lung metastatic disease in pediatric oncology patients. Methods: A retrospective review of 50 patients who underwent resection of lung nodules that were positive for metastatic disease from 1998 to 2011 was performed. Risk factors for recurrence were determined by multi-variable logistic regression models. Results: Fifty pediatric oncology patients underwent resection of discrete lung nodules seen on CT scans during work-up for metastasis or for routine surveillance. Out of this patient cohort, 23 (46%) patients had recurrent disease. The only significant factors that influenced risk of recurrence were original PET positive study (p<0.05) and patients with osteosarcoma (p<0.002). The type of surgical procedure, margins of original resection, race, age, gender, size, or the number of original nodules was not found to be significant. Conclusion: Patients with osteosarcoma and PET positive disease at original presentation appear to be at the highest risk of recurrent pulmonary metastatic disease. New pulmonary lesions in these patients should undergo biopsy to confirm metastatic disease. [Copyright &y& Elsevier]

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder presenting with multiple pulmonary nodules in association with a typical mosaic perfusion pattern on computed tomography. In this case, the absence of mosaic perfusion led to an erroneous initial diagnosis of pulmonary metastases from an unknown primary malignancy. This illustrates the importance of considering differential diagnoses when presented with imaging findings compatible with pulmonary metastases from an unknown primary, and highlights the importance of histopathologic confirmation in such cases. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the study was to evaluate the computed tomographic (CT) features and growth rates of pulmonary metastases from colorectal cancer (CRC) on serial CT scans. The study included 17 patients (28 pulmonary metastases) who underwent metastasectomy from CRC. The characteristic CT features include well-defined round or oval nodules in the peripheral or subpleural/fissural lung with frequent feeding vessel sign. The mean tumor volume doubling time was calculated as 160 days. With these growth rates, short-term follow-up (i.e., 5–6 months) would be helpful. [Copyright &y& Elsevier]

Rationale and Objectives: We evaluated the accuracy and reproducibility of three-dimensional (3D) measurements of lung phantoms and patient tumors from x-ray computed tomography (CT) and compared these to one-dimensional (1D) and two-dimensional (2D) measurements. Materials and Methods: CT images of three spherical and three irregularly shaped tumor phantoms were evaluated by three observers who performed five repeated measurements. Additionally, three observers manually segmented 29 patient lung tumors five times each. Follow-up imaging was performed for 23 tumors and response criteria were compared. For a single subject, imaging was performed on nine occasions over 2 years to evaluate multidimensional tumor response. To evaluate measurement accuracy, we compared imaging measurements to ground truth using analysis of variance. For estimates of precision, intraobserver and interobserver coefficients of variation and intraclass correlations (ICC) were used. Linear regression and Pearson correlations were used to evaluate agreement and tumor response was descriptively compared. Results: For spherical shaped phantoms, all measurements were highly accurate, but for irregularly shaped phantoms, only 3D measurements were in high agreement with ground truth measurements. All phantom and patient measurements showed high intra- and interobserver reproducibility (ICC >0.900). Over a 2-year period for a single patient, there was disagreement between tumor response classifications based on 3D measurements and those generated using 1D and 2D measurements. Conclusion: Tumor volume measurements were highly reproducible and accurate for irregular, spherical phantoms and patient tumors with nonuniform dimensions. Response classifications obtained from multidimensional measurements suggest that 3D measurements provide higher sensitivity to tumor response. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of this single-center study was to analyze factors predicting long-term outcomes following surgical resection of pulmonary metastases in patients with renal cell carcinoma. Methods: Two hundred two consecutive patients entered the study. Overall survival was analyzed by the Kaplan-Meier method. Multivariate analysis was performed using Cox regression models. Results: In 175 cases (87%), curative resection of the pulmonary metastases was achievable, with median survival of 43 months. Multivariate analysis revealed complete metastasectomy (R0), metastasis size >3 cm, positive nodal status of the primary tumor, synchronous metastases, pleural infiltration, and tumor-infiltrated hilar or mediastinal lymph nodes as independent prognostic factors for survival. On the basis of these findings, a new scoring system (the Munich score) was established to predict survival, which discriminates 3 groups with low, intermediate, and high risk for poor outcomes (median survival, 90, 31, and 14 months, respectively, P < .001). Conclusions: The aim of the Munich score is to define patients with low, intermediate, and high risk for poor survival and will help identify patients who may benefit from further adjuvant therapy. [Copyright &y& Elsevier]

Abstract: Background: The 3-year survival after pulmonary metastasectomy for osteosarcoma (OS) is approximately 30%. Resection of metastatic disease can prolong life in pediatric patients with OS. Our objective is to assess the outcome of pediatric patients with pulmonary metastases located centrally as compared with peripheral lesions. Methods: A retrospective review of patients 0 to 21 years old with a diagnosis of OS with pulmonary metastases on computed tomographic scan between 1985 and 2000 was completed. Demographics, metastasis location, survival, morbidity, and mortality were evaluated. Results: Of 115 patients who had pulmonary metastasis secondary to OS, there were 96 wedge resections and 13 lobectomy/pneumonectomies in 84 patients. The morbidity of wedge resection was 9% and lobectomy/pneumonectomy was 8%. There were no deaths from surgery. The median survival for patients undergoing lobectomy compared with wedge resection was 0.61 and 1.14 years, respectively, but did not reach statistical significance. The median overall survival for the entire cohort was 0.75 years. The median overall survival after initial detection of metastatic disease was 1.06 years among the patients with peripheral disease, compared with 0.38 years in patients with central disease (P = .008). Conclusion: Patients with central pulmonary metastases in OS have a very poor prognosis, even after operative treatment, compared with those with peripheral disease. Patients with central lesions may benefit from other nonsurgical treatment options. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of the study was to develop a prediction rule regarding the factors that most accurately predict the diagnosis of a malignancy in a lung nodule in the pediatric oncology patient. Methods: A retrospective review of pediatric oncology patients that underwent lung nodule resection between 1998 and 2007 was performed. Multivariable logistic regression was used to create a prediction rule. Results: Fifty pediatric oncology patients underwent 21 thoracotomies and 48 thoracoscopies to resect discrete lung nodules seen on computed tomographic scans during workup for metastasis or routine surveillance. The mean nodule size was 10.43 ± 7.08 mm. The most significant predictors of malignancy in a nodule were peripheral location (odds ratio [OR], 9.1); size between 5 and 10 mm (OR, 2.78); location within the right lower lobe (OR, 2.43); and patients with osteosarcoma (OR, 10.8), Ewing sarcoma (OR, 3.05), or hepatocellular carcinoma (OR, 2.38). Conclusions: Lesions that are between 5 and 10 mm in size and peripherally located in patients with osteosarcoma, Ewing sarcoma, or hepatocellular carcinoma are most likely to be malignant. Use of a prediction rule can help guide clinical practice by determining which patients should undergo surgical resection of lung nodules and which patients may be closely observed with continued radiologic studies. [Copyright &y& Elsevier]

Surgeons play a pivotal role in the decision-making and multidisciplinary management of childhood solid tumours.1 Evidence-based medicine-"aims to optimise decision making by emphasising on the use of best evidence from well-designed conducted research." This article offers a brief overview in an effort to demonstrate how a selection of well-conducted, recently published studies can help address some topical and controversial themes in paediatric surgical oncology practice. [ABSTRACT FROM AUTHOR]

Abstract: Detection of focal pulmonary lesions is limited by quantum and anatomic noise and highly influenced by variable perception capacity of the reader. Multiple studies have proven that lesions – missed at time of primary interpretation – were visible on the chest radiographs in retrospect. Computer-aided diagnosis (CAD) schemes do not alter the anatomic noise but aim at decreasing the intrinsic limitations and variations of human perception by alerting the reader to suspicious areas in a chest radiograph when used as a ‘second reader’. Multiple studies have shown that the detection performance can be improved using CAD especially for less experienced readers at a variable amount of decreased specificity. There seem to be a substantial learning process for both, experienced and inexperienced readers, to be able to optimally differentiate between false positive and true positive lesions and to build up sufficient trust in the capabilities of these systems to be able to use them at their full advantage. Studies so far focussed on stand-alone performance of the CAD schemes to reveal the magnitude of potential impact or on retrospective evaluation of CAD as a second reader for selected study groups. Further research is needed to assess the performance of these systems in clinical routine and to determine the trade-off between performance increase in terms of increased sensitivity and decreased inter-reader variability and loss of specificity and secondary indicated follow-up examinations for further diagnostic workup. [Copyright &y& Elsevier]

Introduction: Multimodal therapies (especially surgery of metastases and "aggressive" chemotherapy) in patients with metastases of colorectal cancers (CRC) are increasingly performed and may provide long-term survival in selected patients with more than one location of metastases. In the current literature, there are only few studies with relatively low patient numbers reporting on the outcome after resection of both hepatic and pulmonary metastases of CRC. We therefore evaluated survival of patients who underwent sequential resection of hepatic and pulmonary metastases under potentially curative intention.Material and Methods: From 1987 until 2006, 44 patients (32% female; median age, 58 years) with hepatic and pulmonary CRC metastases underwent resections at both metastatic sites. The primary CRCs were in 50% rectal and in 50% colonic carcinomas (61% node positive, all with free resection margins). Metastases occurred synchronously (regarding primary CRC) in 32% of the patients. In 86%, liver resection was performed prior to pulmonary resection. The first resection of metastases was performed a median of 16 months after resection of the primary CRC; the median interval between the first and the second resection of metastases was 7 months. Forty-seven percent of the patients also underwent at least a third metastasectomy. During resection of the first and second site of metastases, free margins were achieved in 98% and 95%, respectively. Survival analysis was performed using Kaplan-Meier and Cox regression methods.Results: The 5-year survival rates (SV) were 64% after initial surgery of CRC, 42% after the first resection of metastases, and 27% after the last metastasectomy. Patients with synchronous metastases had a 5-year SV after first metastasectomy of 43% and in patients with metachronous metastases of 41% (n.s.). The location of the primary tumor (20% 5-year SV in rectal vs. 57% in colonic cancer; p < 0.02) and the lung as primary site of metastatic disease (5-year SV 0% vs. 60% in patients with primarily hepatic metastases only; p < 0.001) significantly influenced survival in univariate analysis. Patients with rectal cancer had a significantly higher frequency of the lung as first metastatic site (46%) compared to patients with colonic cancer (14%; p < 0.03). Multivariate survival analysis revealed the lung as first metastatic site and as the sole significant independent factor for the outcome (p < 0.001; relative risk vs. liver first metastases 4.7).Conclusion: In selected patients with metastasized CRC resection of both hepatic and pulmonary metastases may improve survival rates or even provide long-term survival. Patients with lung as the first site of metastatic disease (either lung only or in combination with hepatic metastases) have a significantly worse outcome than patients with metastases primarily confined to the liver. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a member of the carcinoembryonic antigen family of immunoglobulin-like adhesion molecules. The aim of this study was to test the hypothesis that loss of CEACAM1 expression in hepatoblastoma cells may promote hematogeneous metastasis and function as an adverse prognostic factor. Methods: Immunohistochemical expression of CEACAM1 in surgically resected specimens from 19 patients with hepatoblastoma was examined retrospectively. The CEACAM1 expression in the epithelial area of the tumor was classified into 2 categories as follows: diffuse expression, characterized by positive staining throughout the tumor specimen, or loss of expression, in which there were distinct areas of negative staining within the tumor specimen. Results: Of the 19 patients, 12 were classified as having tumors with diffuse expression, and 7 had loss-of-expression tumors. Survival after treatment was significantly worse in patients with tumors with loss of CEACAM1 expression (cumulative 5-year survival rate, 29%) than in patients with diffuse CEACAM1 expression (cumulative 5-year survival rate, 92%; P = .0062). Loss of CEACAM1 expression was a significant risk factor for metachronous pulmonary metastases (P = .0105). Conclusions: Loss of CEACAM1 expression may reflect a high metastatic potential and thus indicate a poor prognosis for patients with hepatoblastoma. [Copyright &y& Elsevier]

Abstract: Purpose: Children presenting with osteosarcoma and pulmonary metastases have poor survival rates. The standard approach to treating unilateral metastases is ipsilateral thoracotomy with complete resection of the metastases whenever possible. We analyzed whether contralateral exploratory thoracotomy is beneficial in these patients. Methods: We reviewed the records of all osteosarcoma patients presenting with or developing early pulmonary metastases (within 24 months of diagnosis) at the St Jude Children''s Research Hospital (Memphis, Tenn) between June 1980 and September 2005. Demographics, imaging results, treatment protocols, surgical procedures, and recurrence, survival, and timeline data were assessed. Results: Of the 109 patients, initial pulmonary involvement was radiographically identified as unilateral in 81 (74%) and bilateral in 28 (26%) patients. Of the patients presenting with unilateral pulmonary metastases, 2 years later, 13 (16%) had recurrence in the ipsilateral and 19 (23%) in the contralateral lung. In 2 (2.4%) patients, metastases recurred bilaterally. There was no evidence of statistically significant difference between the incidence of recurrence in the ipsilateral and contralateral lung (P = .18). Conclusions: Children with osteosarcoma and unilateral pulmonary metastases had similar incidence of recurrence in the ipsilateral and contralateral lung. Their survival rates were also not significantly different. Therefore, contralateral exploratory thoracotomy in patients presenting with unilateral pulmonary metastases will probably not improve survival. [Copyright &y& Elsevier]

The purpose of this study was to evaluate the postrelapse survival of relapsed osteosarcoma with pulmonary metastases in patients who received pulmonary metastasectomy using intent to treat and propensity score analysis. Patients with osteosarcoma who relapsed with pulmonary metastases between 2004 and 2018 who were treated in a hospital affiliated with a medical school were included. All the enrolled patients were evaluated as operable with assessment algorithm at the time of diagnosis of pulmonary relapse and intent to treat analysis was done. Multiple propensity score methods (eg, matching, stratification, covariate adjustment, and inverse probability of treatment weighting) were performed to balance confounding bias. Cox proportional hazards regression and the Kaplan-Meier method were used to evaluate patient survival. A total of 125 patients met the study criteria. Of these, 59 (47.2%) patients received pulmonary metastasectomy combined with chemotherapy and 66 (52.8%) received chemotherapy alone. The 2-year and 5-year postrelapse survival rate of metastasectomy group and nonmetastasectomy group were 68.4% versus 25.0% and 41.0% versus 0%, respectively. The median postrelapse survival was 24.9 versus 13.5 months, respectively. Pulmonary metastasectomy was independently associated with improved survival (hazard ratio, 0.185; 95% confidence interval, 0.103-0.330; P <.001). These results were confirmed by multiple propensity score analyses. Further stratified analysis revealed that the survival advantage associated with metastasectomy was not significant in patients with metastases involving ≥3 lung lobes and patients with very high pretreatment serum alkaline phosphatase (more than twice the upper limit). Pulmonary metastasectomy is associated with improved survival in patients with recurrent osteosarcoma. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: Since 1998, we have treated primary and oligometastatic lung tumors with stereotactic body radiotherapy (SBRT). The term “oligometastasis” is used to indicate a small number of metastases limited to an organ. We evaluated our clinical experience of SBRT for oligometastatic lung tumors. Methods and Materials: A total of 34 patients with oligometastatic lung tumors were included in this study. The primary involved organs were the lung (n = 15), colorectum (n = 9), head and neck (n = 5), kidney (n = 3), breast (n = 1), and bone (n = 1). Five to seven, noncoplanar, static 6-MV photon beams were used to deliver 48 Gy (n = 18) or 60 Gy (n = 16) at the isocenter, with 12 Gy/fraction within 4–18 days (median, 12 days). Results: The overall survival rate, local relapse-free rate, and progression-free rate at 2 years was 84.3%, 90.0%, and 34.8%, respectively. No local progression was observed in tumors irradiated with 60 Gy. SBRT-related pulmonary toxicities were observed in 4 (12%) Grade 2 cases and 1 (3%) Grade 3 case. Patients with a longer disease-free interval had a greater overall survival rate. Conclusion: The clinical result of SBRT for oligometastatic lung tumors in our institute was comparable to that after surgical metastasectomy; thus, SBRT could be an effective treatment of pulmonary oligometastases. [Copyright &y& Elsevier]

Purpose: To evaluate the effect of whole lung radiotherapy on event-free and overall survival of children with Stage IV Wilms'' tumor with pulmonary metastases at diagnosis and to ascertain factors that may have led to the decision to withhold radiotherapy. Methods and Materials: We compared recurrence and mortality risks of patients with pulmonary metastases at diagnosis enrolled in the UKW2 and UKW3 clinical trials (1986–2001) according to treatment with pulmonary radiotherapy. Results: Of 102 eligible patients (43 patients in UKW2 and 59 patients in UKW3), 72 (71%) received pulmonary radiotherapy; 30 (29%) did not. After a median follow-up of 9.3 years (range, 0.6–14.1 years), event-free survival was 79.2% (95% confidence interval [CI], 67.8–86.9%) in patients who received pulmonary radiotherapy compared with 53.3% (95% CI, 34.3–69.1%) in patients who did not receive it (p = 0.006), with a hazard ratio of 2.66 (95% CI, 1.28–5.52; p = 0.009). There was no difference in overall survival (84.7% [95% CI, 74.1–91.2%] vs. 73.2% [95% CI, 53.4–85.6%], respectively; p = 0.157). Pulmonary radiotherapy reduced the chance of lung relapse (8.3% vs. 23.3%; p = 0.039). The omission of radiotherapy did not seem to be consistently associated with any specific clinical or radiologic features. Conclusions: Outcome may be compromised if pulmonary radiotherapy is omitted in children with Wilms'' tumor with pulmonary metastases. There was a significant effect on event-free survival; the risk of an event, particularly lung recurrence, was increased nearly threefold. Strategies for selection of children for avoidance of pulmonary irradiation need to be developed in a controlled fashion. [Copyright &y& Elsevier]

Summary: Background: Surgical resection is the treatment of choice of pulmonary metastases from colorectal cancer. We retrospectively reviewed our experience of pulmonary resections of single metastases from colorectal cancer, in order to document postoperative clinical outcome and survival. Materials and methods: In the years 1997–2007, in 23 patients we performed 26 curative resections of pulmonary metastases from colorectal cancer (19 rectal and 7 colon; 12 males and 11 females; mean age 64.5 years). All patients had single lung metastasis. Three of the 23 patients underwent re-resection of the lung for treatment of a subsequent lung metastasis. Interval between resection of primary tumor and diagnosis of lung metastasis (disease-free interval (DFI)) was >36 months in 19 patients (73%) and was <36 months in 7 patients (27%). In 21 patients the metastases were metachronous; in 2 patients metastases were synchronous with primary colorectal cancer. The type of lung resection was wedge resection in 18 cases (70%); lobectomy in 6 cases (23%); pneumonectomy in 2 cases (7%). Of the 18 wedge resections, 12 (66%) were done thoracoscopically. After lung metastasectomy patients were followed up for 5–121 months (median: 61 months). Results: We had 1 early postoperative mortality (after re-resection) from cardiac complication (3.8%). Postoperative morbidity (within 30 days) was observed in 7 cases (27%): 1 pneumonia, 1 empyema, 1 arrhythmia and 4 prolonged air leaks requiring chest drainage >7 days. Median survival was 74months (Kaplan–Meier). Conclusions: Resection of single metachronous lung metastases from colorectal cancer has low mortality and morbidity and in our experience it correlated with prolonged postoperative survival. Re-resection of the lung for treatment of subsequent metachronous metastases carries higher risk. [Copyright &y& Elsevier]

Summary: Hepatic resection for colorectal metastases, limited to the liver, has become the standard of care, and currently remains the only potentially curative therapy. Numerous single institutional reports have demonstrated long-term survival and there are no other treatment options that have shown a survival plateau. However, curative resection is possible in less than 25% of those patients with disease limited to the liver, which translates into only 5–10% of the original group developing colorectal cancer. To increase the number of patients who could benefit from hepatic resection, the last decade has seen considerable effort being directed towards novel approaches to permit curative hepatic resection such as: neoadjuvant systemic and regional chemotherapy, pre-operative portal vein embolization for hypertrophy of future liver remnant, staged hepatic resection and radio frequency ablation combined with resection for addressing multiple bilobar metastases. This article reviews development of these innovative multidisciplinary modalities and the aggressive surgical approach that has been adopted to extend the frontiers of surgical therapy for colorectal hepatic metastases. [Copyright &y& Elsevier]

This article describes the technique of transpulmonary chemoembolization for the palliative treatment of unresectable lung tumors. Early utilization of this method has resulted in reduction in tumor volume and alleviation of patient symptoms. After superselective catheterization, cytotoxic agents are administered, and the pulmonary arterial supply of the tumor is occluded by injection of microspheres and ethiodized oil. Emerging data suggest that this approach is well tolerated. [Copyright &y& Elsevier]

Summary: Bone and soft tissue sarcomas metastasize to the lung in about one-third of patients. Surgery of lung metastases is possible in at least 35% of patients who have undergone primary surgery. Thoracotomy may be bilateral if necessary. Wedge resection is preferred; lobectomy or pneumonectomy is reserved for metastases in the hilum. The average overall survival following resection at 5-years is 37%. Results are influenced by the specific histotype of the primary tumour, by the interval between pulmonary metastases and treatment of the primary sarcoma, and by the number of metastases. [Copyright &y& Elsevier]

Non-viral polymer/pDNA complexes were formed using linear polyethylenimine (LPEI) Mw 25 k conjugated to cholesterol in a T-shaped geometry (LPC-T) and pDNA encoding murine interleukin-12 (pmIL-12e). These complexes were subsequently injected weekly into BALB/c mice intravenously and locally for the treatment of murine renal cell adenocarcinoma (Renca) induced pulmonary metastases and subcutaneous (SC) Renca tumors, respectively. At the cessation of the pulmonary metastases study, the number of pulmonary metastases was significantly less (p < 0.001) with systemic injections of LPC-T/pmIL-12e formulations than with pmIL-12e alone or pmIL-12e complexed with LPEI, branched polyethylenimine (BPEI) Mw 25 k, or an LPEI/pEGFP control. In addition, biodistribution studies showed increased pulmonary levels of both the LPC-T carrier and pmIL-12e vector up to 3 hr after systemic injection of the LPC-T/pmIL-12e complexes into mice carrying pulmonary metastases. Furthermore, mice systemically treated with LPC-T/pmIL-12e showed a near linear profile in weight gain in the course of the pulmonary metastases study that suggests increased biocompatibility. Finally, due to favorable characteristics in vitro, LPC-T was also used for local (peritumoral) injection of SC Renca tumors. Tumor stasis and slight tumor regression were seen only with the LPC-T/pmIL-12e treated mice compared to BPEI/pmIL-12e, LPEI/pmIL-12e, and naked pmIL-12e controls. Thus, it was concluded that LPC-T is an effective carrier for passive targeting of the pulmonary tissue, treatment of Renca-induced pulmonary metastases, and local administration of Renca cell SC tumors. [Copyright &y& Elsevier]

The use of video-assisted thoracic surgery (VATS) has allowed surgeons to perform complex procedures that previously required a thoracotomy. While VATS is well accepted in the management of benign thoracic disease, its role in the management of lung cancer continues to evolve. VATS is utilized in many aspects of the management of lung cancer including the evaluation of indeterminate pulmonary nodules and pleural effusions, staging of mediastinal lymph nodes, and the resection of primary and metastatic tumors. However, concerns regarding cost, training issues, and adherence to oncological principles have caused some surgeons to proceed more slowly. This review discusses the current role of thoracoscopy in the management of lung cancer. [Copyright &y& Elsevier]

Pulmonary metastases are common in patients with soft tissue sarcoma. The majority of patients who develop pulmonary metastases are asymptomatic and are diagnosed during routine follow-up visits. There is evidence to suggest that pulmonary metastasectomy is associated with improved overall survival but only in patients with complete surgical resection. There are several criterion to identify patients for resection. The majority of resectable patients have peripheral lesions that are amenable to wedge resection. There is little evidence to suggest that chemotherapy improves survival. Future research is needed to better identify patients for metastasectomy, to determine the role of minimally invasive procedures, and to develop better adjuvant therapy. Copyright 2002, Elsevier Science (USA). All rights reserved. [ABSTRACT FROM AUTHOR]

• Subcutaneous administration of a vaccine inhibited pulmonary metastases from cervical cancer. • The vaccination induced increased pulmonary infiltration of CD4 + and CD8 + T cells. • The vaccination induced decreased immunosuppressive cells including MDSCs and TAMs. • The vaccination induced the inhibited proliferation of tumor cells and decreased p53 expression. • The vaccination induced the alteration of cytokines, chemokines and MMPs in the lungs. Metastasis, particularly hematogenous metastasis, is associated with poor prognosis in patients with cervical cancer. The lungs are the most common site for hematogenous metastasis of cervical cancer. The currently available therapeutic modalities, including surgery, radiotherapy, or chemotherapy do not provide satisfactory clinical outcome for patients with pulmonary metastases. Therefore, it is necessary to investigate an alternative efficacious treatment modality. Therapeutic vaccines may evoke tumor-specific immune responses in patients to attack tumor cells, representing an attractive treatment option for controlling metastatic tumors. Our previous study demonstrated that a single administration of a human papillomavirus 16 E7 peptide vaccine, adjuvanted with unmethylated CpG-oligodeoxynucleotides, induced the clearance of subcutaneous xenograft cervical cancer. In this study, we investigated the anti-metastases responses induced by this vaccine using a murine model of pulmonary metastases from cervical cancer. The results showed that subcutaneous administration of the vaccine inhibited the growth of pulmonary metastases, which may be attributed to the increased infiltration of CD4 + and CD8 + T cells, and decreased number of immunosuppressive cells (including myeloid-derived suppressive cells and tumor-associated macrophages) in the lungs. Meanwhile, the alteration in a panel of cytokines, chemokines, and matrix metalloproteinases induced by the vaccination may contribute to the re-modulation of the local suppressive environment and inhibition of pulmonary metastases. To the best of our knowledge, this is the first report on the efficacy of the vaccine formula against murine pulmonary metastases from cervical cancer. [ABSTRACT FROM AUTHOR]

An elderly gentleman presented with bilateral pulmonary nodules found incidentally during the workup of acute pancreatitis. He did not have any respiratory or urogenital symptoms. A biopsy of the lung nodule revealed myxoid mesenchymal neoplasm of extraosseous origin. As the patient was asymptomatic, only the increased uptake in the penile shaft base on the whole-body PET-CT study yielded a diagnosis of primary penile chondrosarcoma after biopsy. A rare presentation of chondrosarcoma in an elderly gentleman highlighting the importance of obtaining a histopathological specimen, as the prognosis of metastatic diseases is widely variable. [ABSTRACT FROM AUTHOR]

• Pre-treatment inflammatory markers had significant prognostic value in POSM patients. • Nomogram may be practical in assessment of therapeutic strategy and prognosis. • Features of pulmonary metastatic foci affected survival outcome in POSM patients. The inflammatory markers were important factors affecting proliferation, invasiveness and metastasis of tumors. However, the prognostic value of inflammatory markers and related nomogram in patients with pulmonary-only synchronous metastases (POSM) from colorectal cancer has not been reported. A total of 98 POSM patients undergoing resection of colorectal cancer were included. The Kaplan-Meier survival analysis and Cox regression analysis were used to estimate the overall survival (OS) and progression-free survival (PFS). The nomogram was built based on multivariate Cox analysis model and evaluated by calibration curve, concordance index (C-index) and receiver operating characteristics (ROC). The multivariate analysis showed that neutrophil-to-lymphocyte ratio (NLR) was prognostic factor of OS (HR = 2.73, 95%CI: 1.54–4.84) and PFS (HR = 1.78, 95%CI: 1.13–2.82). Elevated alkaline phosphatase (ALP) also was predictor of poor OS (HR = 1.99, 95%CI: 1.12–3.51) and PFS (HR = 2.23, 95%CI: 1.40–3.55). The early N stage and solitary pulmonary metastases had significant survival benefit for OS, while advanced T stage was independently related with worse PFS. Nomograms were consist of above significant risk factors, with C-index of 0.742 for OS and 0.656 for PFS. The calibration curves showed non-significant deviations between predicted and actual probability of OS and PFS. Pre-treatment NLR and ALP were independently associated with OS and PFS in POSM patients. The nomograms involving inflammatory markers and clinicopathological factors were practical in predicting survival, which may help to guide use of therapeutic strategy and cancer surveillance. [ABSTRACT FROM AUTHOR]

We present an autopsy case of repetitive stroke due to tumor emboli, indistinguishable from thromboembolism with a hypercoagulable state in its clinical course. A 72-year-old man diagnosed with stage IVA oropharyngeal squamous cell carcinoma received chemoradiotherapy. Follow-up imaging revealed mediastinal lymph nodes and pulmonary metastasis. One year later, the patient experienced right arm weakness, and brain magnetic resonance imaging showed acute ischemic lesions in multiple vascular territories. He was diagnosed with paradoxical cerebral embolism due to cancer-associated venous thrombosis and treated with rivaroxaban. However, newly developed cerebral infarcts were confirmed 1 month later. Then, rivaroxaban treatment was switched to subcutaneous unfractionated heparin injection. He was admitted again for stroke recurrence and died of respiratory failure 8 days after admission. Autopsy demonstrated pulmonary metastasis invading the veins and tumor emboli in the culprit cerebral arteries. D-dimer was kept constant at a slightly higher level, ranging from 1 to 3 µg/mL during the course of recurrence. We should consider tumor embolism in the differential diagnosis of recurrent stroke along with pulmonary tumor and resistance to heparin preparations with unchanged D-dimer levels. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aim of this retrospective study was to evaluate technical efficacy and the impact of CT-guided pulmonary radiofrequency ablation (RFA) on survival in patients with pulmonary metastases from nasopharyngeal carcinoma (NPC). Materials and methods: Between 2000 and 2009, 480 patients were pathologically or clinically confirmed pulmonary metastases from NPC. And ten included patients of them had a total of 23 pulmonary metastases treated with percutaneous RFA under the real-time CT fluoroscopy. Safety, local tumor progression, and survival were evaluated in our institutions. Matched-pair survival was compared using Kaplan–Meier analysis. Results: A total of 25 ablations were performed to 23 pulmonary metastases in 13 RFA sessions. Pneumothorax requiring chest tube placement developed in 3 of 13 (23.1%) RFA sessions. The median metastatic overall survival was 36.1 months for all the 480 NPC patients with pulmonary metastases. Furthermore, matched-pair analysis demonstrated patients with RFA treatment had a greater metastatic overall survival than patients without RFA treatment (77.1 months vs 32.4 months, log-rank test, p =0.009). There were no statistically significant differences in the survival probability of patients with RFA treatment (n =10) and surgical resection of pulmonary metastases (n =27) (log-rank test, p =0.75). Conclusion: CT-guided pulmonary RFA is safe and offers a treatment alternative for local tumor control, providing promising survival in selected patients with pulmonary metastases from NPC. [Copyright &y& Elsevier]

Abstract: Although pulmonary metastases from colorectal carcinoma (CRC) often represent systemic and uncontrolled tumour growth, in a number of patients lung disease is limited and the patient remains well. When the metastases can be removed, long term survival is a possibility, with 5- and 10-year survivals in the order of 44% and 25%. Chemotherapy, the only alternative treatment only very rarely leads to survival beyond 24 months. Pulmonary metastases which are suitable for resection are usually detected on chest radiography, especially when carried out during monitoring of patients. They are rarely a cause of symptoms and the majority of patients have otherwise healthy lungs. CT scans supplemented by PET scans usually confirm the diagnosis, but percutaneous biopsy is sometimes necessary to exclude a primary lung cancer. The criteria for resecting CRC pulmonary metastases are (1) the primary tumour is controlled or is controllable; (2) complete resection is possible; and (3) the patient has adequate pulmonary reserve to tolerate the planned resection. Surgical approaches include posterolateral thoracotomy, staged bilateral thoracotomies, median sternotomy, clamshell incision, and video-assisted thoracic surgery. Each has its advantages and disadvantages. The majority of patients having resection of pulmonary metastases from CRC recover well with very few post-operative complications. Following resection favourable prognostic factors include a long disease-free interval, small number and small size of metastases, a normal carcinoembryonic antigen level, and an absence of concomitant liver metastases and mediastinal lymph node spread. Surgery for pulmonary metastases of CRC remains the best means of local control and the best way to render the patient disease-free. Patients with complete resection of pulmonary metastases have an improved long-term survival when compared to patients with unresected metastases. [Copyright &y& Elsevier]