Pulmonary Spread Research Articles

COVID-19 infection: from stress-related cortisol levels to adrenal glands infarction.

Cortisol is a key element in acute stress including a severe infection. However, in coronavirus-associated disease, 20% of subjects experience hypocortisolemia due to direct or immune damage of pituitary and adrenal glands. One extreme form of adrenal insufficiency is found in 2∕3 of cases with viral and post-viral adrenal infarction (AI) (with∕without adrenal hemorrhage) that is mostly associated with a severe coronavirus disease 2019 (COVID-19) infection; it requires prompt glucocorticoid intervention. Some reports are incidental findings at computed tomography (CT)∕magnetic resonance imaging (MRI) scans for non-adrenal complications like pulmonary spreading and others are seen on post-mortem analysis. This is a review of PubMed-accessible, English papers focusing on AI in addition to the infection, between March 1, 2020 and November 1, 2021. Exclusion criteria were acute adrenal insufficiency without the histopathological (HP) and∕or imaging report of adrenal enlargement, necrosis, etc., respective adrenal failure due to pituitary causes, or non-COVID-19-related adrenal events. We identified a total of 84 patients (different levels of statistical evidence), as follows: a retrospective study on 51 individuals, two post-mortem studies comprising nine, respectively 12 patients, a case series of five subjects, seven single-case reports. HP aspects include necrosis associated with ischemia, cortical lipid degeneration (+/- focal adrenalitis), and infarcts at the level of adrenal cortex, blood clot into vessels, acute fibrinoid necrosis in arterioles and capsules, as well as subendothelial vacuolization. Collateral potential contributors to adrenal damage are thrombotic events, coagulation anomalies, antiphospholipid syndrome, endothelial dysfunction, severe COVID-19 infection with multiorgan failure, etc. Clinical picture is variable from acute primary adrenal insufficiency to asymptomatic or mild evolution, even a retrospective diagnostic; it may be a part of long COVID-19 syndrome; glucocorticoid therapy for non-adrenal considerations might mask cortisol deficient status due to AI∕hemorrhage. Despite its rarity, the COVID-19-associated AI/hemorrhage represents a challenging new chapter, a condition that is essential to be recognized due to its gravity since prompt intervention with glucocorticoid replacement is lifesaving.

Liposarcoma subtype recurrence and survival: A UK regional cohort study

<h2>Summary</h2><h3>Background</h3> Clinical outcome data in the United Kingdom, Europe, and the United States have yet to facilitate appropriately specific surveillance for liposarcoma histological subtypes, despite being one of the most common soft tissue sarcomas. Therefore, this study aims to demonstrate histologic-specific differences in liposarcoma recurrence, disease progression, and survival and discuss the implications. <h3>Methods and findings</h3> This cohort study involves patients from a regional sarcoma service in the UK who have had a primary surgical excision of liposarcoma between October 2002 and September 2019. The median follow-up is five years. Confirmed histopathological diagnoses of liposarcoma (<i>n</i> = 193) are organised according to the World Health Organisation recognised subtypes: atypical lipomatous tumours (ALT), myxoid, pleomorphic, and dedifferentiated liposarcomas. In addition, retroperitoneal variants (<i>n</i> = 34) are included to illustrate the broader spectrum of phenotypes. The primary outcomes were local recurrence, distant disease progression, and disease-specific death, and compared using Kaplan–Meier analyses and tumour variables using Cox proportional hazard analyses. All three primary outcomes significantly differed (<i>P</i> < 0.0001, <i>n</i> = 193). There were no metastases or disease-specific death in patients with ALT (<i>n</i> = 92) and no metastases of their retroperitoneal counterparts (<i>n</i> = 17). Amongst the metastasising cases of rarer subtypes, there were pulmonary spread of pleomorphic (8/9, <i>n</i> = 20), dedifferentiated (4/5, <i>n</i> = 18), and myxoid (2/3, <i>n</i> = 29) liposarcomas. <h3>Conclusion</h3> An absence of metastases of ALT should be considered alongside global evidence. Surveillance protocols could better differentiate between these subtypes and, in doing so, save patients a considerable amount of irradiation, time, fear, and anxiety.

Pulmonary spread of embolization material following portal vein embolization and hepatic resection: a cautionary tale.

ANZ Journal of SurgeryVolume 91, Issue 11 p. 2527-2529 IMAGES FOR SURGEONS Pulmonary spread of embolization material following portal vein embolization and hepatic resection: a cautionary tale Krishna Kotecha MBBS, Krishna Kotecha MBBS orcid.org/0000-0002-1558-8607 Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia Contribution: Formal analysis, Methodology, Writing - original draft, Writing - review & editingSearch for more papers by this authorAditya Bopanna MBBS, Aditya Bopanna MBBS Department of Upper Gastrointestinal Surgery, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: Data curation, ​Investigation, Resources, Writing - review & editingSearch for more papers by this authorMudassir Rashid MBBS, MD, FRANZCR, EBIR, Mudassir Rashid MBBS, MD, FRANZCR, EBIR Department of Radiology, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: Conceptualization, Formal analysis, ​Investigation, Resources, Supervision, Validation, Visualization, Writing - review & editingSearch for more papers by this authorRamesh Damodaran Prabha MBBS, MRCS, FRACS, Ramesh Damodaran Prabha MBBS, MRCS, FRACS Department of Upper Gastrointestinal Surgery, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: Conceptualization, Resources, Supervision, Validation, Visualization, Writing - review & editingSearch for more papers by this authorHarald Puhalla MD, PhD, FRACS, Harald Puhalla MD, PhD, FRACS Department of Upper Gastrointestinal Surgery, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: ​Investigation, Methodology, Supervision, Validation, Visualization, Writing - review & editingSearch for more papers by this author Krishna Kotecha MBBS, Krishna Kotecha MBBS orcid.org/0000-0002-1558-8607 Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia Contribution: Formal analysis, Methodology, Writing - original draft, Writing - review & editingSearch for more papers by this authorAditya Bopanna MBBS, Aditya Bopanna MBBS Department of Upper Gastrointestinal Surgery, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: Data curation, ​Investigation, Resources, Writing - review & editingSearch for more papers by this authorMudassir Rashid MBBS, MD, FRANZCR, EBIR, Mudassir Rashid MBBS, MD, FRANZCR, EBIR Department of Radiology, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: Conceptualization, Formal analysis, ​Investigation, Resources, Supervision, Validation, Visualization, Writing - review & editingSearch for more papers by this authorRamesh Damodaran Prabha MBBS, MRCS, FRACS, Ramesh Damodaran Prabha MBBS, MRCS, FRACS Department of Upper Gastrointestinal Surgery, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: Conceptualization, Resources, Supervision, Validation, Visualization, Writing - review & editingSearch for more papers by this authorHarald Puhalla MD, PhD, FRACS, Harald Puhalla MD, PhD, FRACS Department of Upper Gastrointestinal Surgery, Gold Coast University Hospital, Gold Coast, Queensland, Australia Contribution: ​Investigation, Methodology, Supervision, Validation, Visualization, Writing - review & editingSearch for more papers by this author First published: 18 March 2021 https://doi.org/10.1111/ans.16732Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume91, Issue11November 2021Pages 2527-2529 RelatedInformation

Pulmonary recurrence after radical hysterectomy for uterine cervical carcinoma

Pulmonary spread from carcinoma of the uterine cervix, though uncommon, has been reported in 2.2–9.1% of all cervical cancers. The aim of this study was to evaluate the surgical, clinical, pathological factors and clinical outcomes of cervical cancer patients with pulmonary recurrence (PR).This study included 17 cervical cancer patients with PR after radical hysterectomy. The entire cohort consisted of 413 patients whose surgeries (type III radical hysterectomy + pelvic ± para-aortic lymphadenectomy) had been performed in our Gynaecologic Oncology Clinic between 1993 and 2018. Tumour size, lymph node metastasis and receiving adjuvant therapy were found to be effective for PR on univariate analyses in the main cohort (p = .042, p < .001 and p = .001, respectively). Therefore, performing adjuvant therapy to reduce the PR must be assessed properly with the information of lymph node status and tumour size obtained from the final pathology reports.Impact StatementWhat is already known on this subject? Pulmonary spread from carcinoma of the uterine cervix has been reported in 2.2–9.1% of all cervical cancers. Data related to clinico-pathological features of patients with pulmonary recurrence (PR) is limited. Diagnosis of a PR is considered to worsen the prognosis.What do the results of this study add? Tumour size, lymph node metastasis and receiving adjuvant therapy were found to be effective for PR on univariate analyses.What are the implications of these findings for clinical practice and/or further research? Performing adjuvant therapy to reduce the PR must be assessed properly with the information of lymph node status and tumour size obtained from the final pathology reports in patients with uterine cervical carcinoma.

The histone deacetylases HDAC1 and HDAC2 are required for the growth and survival of renal carcinoma cells.

Novel therapies are required for the treatment of metastatic renal cell carcinoma (RCC), which is associated with inoperable disease and patient death. Histone deacetylases (HDACs) are epigenetic modifiers and potential drug targets. Additional information on molecular pathways that are altered by histone deacetylase inhibitors (HDACi) in RCC cells is warranted. It should equally be delineated further which individual members of the 18 mammalian HDACs determine the survival and tumor-associated gene expression programs of such cells. Most importantly, an ongoing dispute whether HDACi promote or suppress metastasis-associated epithelial-to-mesenchymal transition (EMT) has to be resolved before HDACi are considered further as clinically relevant drugs. Here we show how HDACi affect murine and primary human RCC cells. We find that these agents induce morphological alterations resembling the metastasis-associated EMT. However, individual and proteomics-based analyses of epithelial and mesenchymal marker proteins and of EMT-associated transcription factors (EMT-TFs) reveal that HDACi do not trigger EMT. Pathway deconvolution analysis identifies reduced proliferation and apoptosis induction as key effects of HDACi. Furthermore, these drugs lead to a reduction of the cell adhesion molecule E-cadherin and of the platelet-derived growth factor receptor-β (PDGFRβ), which is a key driver of RCC metastasis formation. Accordingly, HDACi reduce the pulmonary spread of syngeneic transplanted renal carcinoma cells in mice. Specific genetic elimination of the histone deacetylases HDAC1/HDAC2 reflects the effects of pharmacological HDAC inhibition regarding growth suppression, apoptosis, and the downregulation of E-cadherin and PDGFRβ. Thus, these epigenetic modifiers are non-redundant gatekeepers of cell fate and precise pharmacological targets.

PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer

ABSTRACTPulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before.53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study. Tissue samples of resected pulmonary metastases and available corresponding primary tumors were collected and assessed for PD-1, PD-L1 and PD-L2 expression by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression patterns were correlated with clinical outcome parameters.PD-1 and PD-L1 expression was commonly found in TILs and tumor cells. Expression levels significantly differed between metastases and primary tumors. High PD-1 expression by TILs was associated with impaired overall survival (low vs high expression (mean, 95% CI): 78 mo (60–96) vs 35 mo (25–44); p = 0.011). Additionally, the subgroup of patients, who experienced an upgrading in their TILs/PD1 status between primary and metastasis had a worse survival outcome compared with patients with the same grade or a downgrading (34 mo (26–42) vs 96 mo (72–120); p = 0.004).Thus, PD-1 expression by TILs is a strong prognostic marker in CRC patients with pulmonary spreading treated by PM. Moreover, this study provides a rationale for a therapeutic PD-1 pathway blockade in the treatment of CRC lung metastases. Future, large-scale studies are warranted to validate the findings of this single-center, retrospective analysis.

Pulmonary Spread of Juvenile Laryngeal Papillomatosis: A Case Report

Introduction: Recurrent respiratory papillomatosis (RRP) is usually a relatively benign disease but can have an aggressive clinical course. The primary treatment for laryngeal papillomatosis is endoscopic resection. However, there is no effective treatment for pulmonary spread of laryngeal papillomatosis. Case Presentation: We describe a rare case of a 19-year-old man with pulmonary spread of laryngeal papillomatosis. The treatment regimen was surgical resection under general anesthesia using suspension laryngoscopy and endoscopy. The patient had been diagnosed with laryngeal papillomatosis and had undergone a tracheotomy when he was 18 months old. He underwent 17 endoscopic resections for laryngeal papillomatosis at intervals of 3 months to 1 year. At follow-up, the patient continued to have tracheal intubation and was not extubated. CT scans revealed multiple nodular and cavitary lesions in both lungs. Laryngoscopy performed when the patient was 18 years showed diffuse papillomata in the glottis and left ventricular fold. Conclusions: This article presents a rare case of juvenile laryngeal papillomatosis associated with the human papilloma virus (HPV) HPV-11 and pulmonary spread. Intravenous cidofovir has oncogenic potential, but it has been used successfully to treat five patients with pulmonary spread of RRP. Intravenous cidofovir should be considered as salvage therapy.

Pediatric thyroid surgery and management of thyroid nodules - an institutional experience over a 10-year period.

BackgroundWe reviewed our institutional experience in the diagnosis and management of pediatric thyroid nodules and well-differentiated thyroid carcinoma (WDTC), highlighting the unique challenges in this population.MethodsIRB approved retrospective chart review was conducted on patients who underwent fine needle aspiration (FNA) or thyroid surgery from 1/1/2001 to 12/31/2010 at Rady Children’s Hospital San Diego, a tertiary referral center in Southern California. Patients thus identified who completed their initial treatment at our institution were included.ResultsTotal of 79 subjects qualified; 20 had FNA only, and 59 underwent thyroid surgery. Of the latter, 29 had benign histology and 30 had WDTC. Average age was 14.5 years with a female: male ratio of 4:1 for WDTC versus 1.6:1 for benign nodules. When compared to final pathology, malignancy rate was high in indeterminate FNA cytology at 60 %. Neck metastasis was noted in 40 % and pulmonary spread in 10 % of patients. There was a 2.75 fold increase in malignant cases (n = 22) treated during 2006–2010 compared to 2001–2005 (n = 8) with more advanced disease at initial presentation. Ninety percent of WDTC patients received adjuvant I-131 treatment with an initial average dose of 132.4 mCi. Despite aggressive initial presentation, 26/30 patients had no evidence of disease at last follow-up, with an average length of 40.3 months.ConclusionsIn recent years, we are managing significantly more WDTC cases at our institution with advanced disease at the onset. Malignancy rate on indeterminate cytology is higher than reported in adults with an overall high rate of malignancy in thyroid nodules removed in this cohort. Disease control and short-term outcome is still excellent. The recently published pediatric guidelines for WDTC will further standardize management.

Increased lymphangiogenesis in lung metastases from colorectal cancer is associated with early lymph node recurrence and decreased overall survival.

Pulmonary metastasectomy (PM) is an accepted treatment modality in colorectal cancer (CRC) patients with pulmonary tumor spread. Positive intrathoracic lymph nodes at the time of PM are associated with a poor prognosis and 5-year survival rates of <20%. Increased lymphangiogenesis in pulmonary metastases might represent an initial step for a subsequent lymphangiogenic spreading. We aimed to evaluate the presence of lymphangiogenesis in clinically lymph node negative patients undergoing PM and its impact on outcome parameters. 71 patients who underwent PM for CRC metastases were included in this dual-center study. Tissue specimens of pulmonary metastases and available corresponding primary tumors were assessed by immunohistochemistry for lymphatic microvessel density (LMVD) and lymphovascular invasion (LVI). Results were correlated with clinical outcome parameters. LMVD was 13.9±8.1 and 13.3±8.5 microvessels/field (mean±SD) in metastases and corresponding primary CRC; LVI was evident in 46.5 and 58.6% of metastases and corresponding primary CRC, respectively. Samples with high LMVD had a higher likelihood of LVI. LVI was associated with early tumor recurrence in intrathoracic lymph nodes and a decreased overall survival (p<0.001 and p=0.029). Herein, we present first evidence in a well-defined patient collective that increased lymphangiogenesis is already present in a subtype of pulmonary metastases of patients staged as N0 at the time of PM. This lymphangiogenic phenotype has a strong impact on patients' prognosis. Our findings may have impact on the post-surgical therapeutic management of CRC patients with pulmonary spreading.

Recurrent respiratory papillomatosis: current and future perspectives.

Although recurrent respiratory papillomatosis is a benign disease of the upper aerodigestive tract caused by infection with human papillomavirus, the disease process is unpredictable, ranging from mild disease and spontaneous remission to an aggressive disease with pulmonary spread and requirement for frequent surgical debulking procedures. It can present a protracted clinical course and cause potentially life-threatening compromise of the airways. Over recent decades, a number of alternative medical therapies to standard surgical treatment have been investigated, with modest outcomes overall. Currently, some additional therapies are being explored, together with novel surgical instrumentation that can help to avoid inevitable long-term stenotic complications, ultimately affecting quality of life. Hopefully, clinicians might soon be able to significantly improve the quality of treatment and outcomes for patients affected with recurrent respiratory papillomatosis, with human papillomavirus vaccination having a potentially important role.

Metastatic carotid body paraganglioma detected during evaluation for biliary stone disease

Carotid body paragangliomas are neuroendocrine cell tumors. Most invade locally to surrounding tissues with metastases being less commonly encountered than with other tumors: a minority of tumors metastasizes to distal sites. Spread is more unusual after surgical removal of the primary tumor. Hepatic spread is very rare but has been documented. We report a case of a clinically silent metastatic paraganglioma identified during an evaluation for choledocholithiasis. We describe a 70-year-old female presenting with symptoms of abdominal pain who was found to have cholelithiasis and choledocholithiasis. MRI imaging performed during evaluation revealed enhancing liver and lung lesions suspicious for metastasis. FNA of a hepatic lesion showed paraganglioma. She had a remote history of bilateral carotid body tumors, of which the left tumor was resected in 2005. This is a rare case of metastatic carotid body paraganglioma. Primary tumor source was a resected tumor or a smaller sized nodule that was managed with serial imaging. The subject's lack of symptoms and her disease extent with confirmed hepatic and presumed pulmonary spread is unique.

Carbonic anhydrase IX is associated with early pulmonary spreading of primary colorectal carcinoma and tobacco smoking

Pulmonary metastasectomy is performed routinely in selected patients with metastatic spreading to the lungs. According to current guidelines, the tumour biology should be taken into account when selecting patients for a resection. Carbonic anhydrase IX (CA9) expression has been shown to be a common feature in primary tumour growth and metastasis and it negatively affects the clinical outcome in various malignancies. Data on CA9 in pulmonary metastases are lacking. Forty-four patients with primary colorectal cancer (CRC) who underwent curative pulmonary metastasectomy were included in this study. We determined the expression of CA9 in pulmonary metastases and corresponding primaries by immunohistochemistry. The expression level was correlated with clinical parameters and patients' smoking habits. Furthermore, the impact of nicotine treatment on phosphorylation of STAT3, HIF-1α and CA9 expression was assessed in HT29 cells. High expression of CA9 in resected pulmonary metastases and corresponding primary tumours correlated with early spreading to the lung (both P < 0.001). Moreover, CA9 expression was affected by the smoking habits of the patients. Treating HT29 cells with nicotine resulted in an induction of CA9 in vitro. This induction was associated with STAT3 phosphorylation and was independent of HIF-1α. This study provides first evidence of CA9 expression in pulmonary metastases of CRC and suggests a role of CA9 as a prognostic marker. Moreover, our in vitro and in vivo data indicate an association between tobacco smoking and CA9 expression. Immunohistochemical assessment of CA9 expression might serve as an additional tool in decision-making for selecting patients for pulmonary metastasectomy.

EGFR, BRAF and KRAS Status in Patients Undergoing Pulmonary Metastasectomy from Primary Colorectal Carcinoma: A Prospective Follow-Up Study

Pulmonary metastasectomy is an integral part of the interdisciplinary treatment of patients with pulmonary metastases (PMs) from colorectal carcinoma (CRC). Although alterations in the epidermal growth factor receptor (EGFR) pathway are common in CRC, there is still insufficient data regarding PM. We hypothesized that EGFR expression and Kirsten rat sarcoma viral oncogene homolog (KRAS)/BRAF mutations (Mts) might be associated with clinicopathological variables and the outcome in patients undergoing pulmonary metastasectomy. In this single-center study, 44 patients undergoing pulmonary metastasectomy from primary CRC were included and prospectively followed up. Tissue specimens of resected PMs were assessed. Restriction fragment length analysis was used for BRAF V600E and KRAS codons 12 and 13 Mt analyses. EGFR expression was evaluated by immunohistochemistry. Patients were followed up in 3-6-month intervals. EGFR expression was evident in 49 % of the PMs, whereas Mts in KRAS and BRAF were detected in 48 and 0 %, respectively. Time to lung-specific recurrence after metastasectomy was significantly decreased in patients with KRAS mutated PMs in univariate (p = 0.013) and multivariate analysis (p = 0.035), whereas EGFR expression had no impact on recurrence free survival. Moreover, KRAS Mts were associated with the number of PMs (p = 0.037) and with the lung as first site of recurrence after metastasectomy (p = 0.047). This is the first evaluation of EGFR pathway alterations in the setting of pulmonary metastasectomy. Our data suggest that patients with KRAS Mts are at high risk for early pulmonary recurrence and have a more diffuse pattern of metastasis. These findings may have impact on the therapeutic management of CRC patients with pulmonary spreading.

Complete pathological response of NSCLC

Methods In a 64y o. male a squamous cell lung cancer was diagnosed in his left upper lobe by bronchoscopic brush biopsy cytology. Stage III.A cT2N2MO. He underwent the neoadjuvant treatment: received six cycles of cisplatin etoposid combination. After the restaging (Stage IBycT2NOMO) we performed a pneumonectomy and the mediastinal blockdissection, because of the involvement of the pulmonary artery and spreading to the lower lobe. The pathologist found only pulmonary fibrosis, but no tumor. In 50 y.o. male an adenocarcinoma of the right upper lobe was diagnosed by bronchoscopic brush cytology. Stage IIIA cT3N2MO. He received the same induction therapy regimen. After restaging (Stage IBycT2NOMO) he underwent a right upper lobectomy. At the operation we have not found any abnormal or enlarged N2 lymphonodes. The hystopathological examination showed only necrotic tissues and haemorrhages, but no tumour. Both patients are alive without any complications and tumourfree.

Clinical colorectal cancer (CRC) subsets in advanced disease: Patterns of metastatic spread to predict survival.

e14703 Background: Advanced CRC is a heterogeneous disease. Some patients exhibit diffuse metastatic spread while others show selective organ involvement. We aimed to investigate the frequency and survival implications of initial pattern of metastatic spread in a Mexican cohort. Methods: We retrospectively reviewed charts and radiologic images of patients with advanced CRC at our institution from 2004 to 2011. The initial pattern of spread was recorded. Categories depending on the predominant site of involvement were: 1) Locally advanced, 2) Hepatic, 3) Pulmonary, 4) Peritoneal or 5) Diffuse. Survival was estimated by the Kaplan Meier method and Log rank test used to determine survival differences among categories. Results: 179 patients with advanced CRC were identified. Median age was 60yo, 56% were male. Primary tumor location was 50.3% colon, 27.9% rectum, 17.9% recto-sigmoid and 3.4% had synchronous disease. 66% of patients had advanced disease at diagnosis and 34% were recurrent cases. Metastasis at diagnosis involved the liver in 105 (58.7%), peritoneum in 49 (27.4%), lung in 56 (31.3%) and non regional lymph nodes in 36 (20.1%) patients. Notably, 101 (56%) patients had a predominant site of metastatic involvement: locally advanced in 3 (1.7%), hepatic in 51 (28.5%), peritoneal in 21 (11.7%), pulmonary 21 (11.7%) while 78 patients (44%) had disseminated disease. Median overall survival was 15 months (n= 179) and differed according to predefined CRC subsets: 9, 13, 22, 23, and 52 months for peritoneal, disseminated, hepatic, locally advanced and pulmonary spread respectively p=.018 (significant after multivariate analysis). Other factors associated with better survival were female gender p=.040, absence of morbidity from primary tumor p=.27, resection of primary tumor p=.004, recurrent presentation p=.039, and access to 1stline chemotherapy p=.00. Conclusions: Over 50% of patients exhibited selective metastatic spread. Clinically defined subsets correlate with better (pulmonary) or worse (peritoneal/disseminated) survival. This finding might have implications in patient selection for regional therapies and encourage research to find the molecular determinants of this biologic behavior.

Carpal Tunnel Syndrome with Paracoccidioidomycosis

Carpal Tunnel Syndrome with Paracoccidioidomycosis

Relapsed breast adenorcarcinoma presenting as pulmonary lymphangitic carcinomatosis

Pulmonary lymphagitic carcinomatosis is an entity referring to diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by a tumour. The most common malignancies involved are the breasts, lung, colon and stomach. Previous studies have shown that at autopsy up to 24% of patients who died of metastatic breast cancer had pulmonary lymphagitic spread. However the diagnosis of lymphangitic carcimatosis can be challenging due to its non-specific symptoms which include dypsnoea and cough, which occur in a variety of lung diseases.

Abstract 5701: Targeting KRAS lung cancer in vivo by pulmonary surfactant-mediated gene transfer

Abstract Pulmonary surfactant has been used as a carrier to deliver a therapeutic virus to dysfunctional lung cells that reside within an intricate lung structure. To investigate whether pulmonary surfactant enhances the efficacy of intratracheal instillation of a therapeutic virus to target KRAS lung cancer in vivo, we developed a recombinant adenovirus that induces cell death only in lung cancer cells and injected the adenovirus into a KRAS lung cancer model mouse intratracheally with or without surfactant. A therapeutic adenovirus that induces cell death only in lung cancer cells was constructed by combining a cancer specific hTERT promoter fused to CEBPα with a modified lung specific CC10 promoter fused to cytotoxic E1A. CEBPα is induced only in cancer cells and activates the CC10 promoter, which in turn induces cytotoxic E1A, and causes cell death only in lung cancer cells in vitro. This adenovirus was intratracheally injected into the KRAS lung cancer model mice (CCSP-rtTA/Tet-op-K-Ras4bG12D bitransgenic mice) in the presence/absence of pulmonary surfactant. Intratracheally-injected therapeutic adenovirus with pulmonary surfactant spread to airways as well as to the alveolar region of the lung and caused reduction of lung tumors developed in the KRAS lung cancer model mouse. The therapeutic adenovirus without pulmonary surfactant spread only to airways and had ten times less effectiveness in tumor reduction. Here, we demonstrate that pulmonary surfactant is an efficient tool to intratracheally deliver a therapeutic virus to treat KRAS lung cancer in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5701. doi:1538-7445.AM2012-5701

Upper aerodigestive tract cancer and the lung

Patients with upper aerodigestive epithelial cancers frequently develop second primary cancers due to common risk factors or develop distant metastases depending on the locoregional status of the primary tumor. In most instances, the organ affected is the lung. Pulmonary spread usually occurs due to hematogenous or lymphatic dissemination. The following is a report of two patients with upper aerodigestive tract squamous cell carcinomas who developed lung metastases due to aspiration, a route not well documented in recent literature.

In vivo pulmonary metastatic profile of breast cancer cell lines expressing hormonal receptors versus triple negative

Breast cancer metastized to lungs is a challenge considering clinical management and molecular processes. The interaction between tumor cells and lung environment as well as the influence of hormonal receptor (HR) are a question of debate. The aim of this study is the characterization of pulmonary metastatic spread in vivo of breast cancer cell lines that express HR comparing with triple negative (TN) after injection in the tail vein. It was performed injection in the tail vein of female mice Balb/c nude with 1.5×106 cells of each breast cancer cell line (MCF7 and HCC1806) previously labeled with 99mTc-HMPAO. Imagiological studies with 99mTc-HMDP and 99mTc-MIBI were performed between 7th and 8th weeks and then sacrificed. The lungs were submitted to histological image analysis focusing on regions of interest (ROI), in order to obtain lesion areas. Tumor cells injected labeled with 99mTc-HMPAO showed a preference embolization to the lungs. The ROI analysis of imagiological studies with 99mTc-HMDP and 99mTc- MIBI did not reveal significant differences according to each cell type. Histology showed metastatic lung foci in all animals injected. On one hand, the number of lung foci was not significantly different considering MCF7 and HCC1806 injection. On the other hand, the mean area of lung metastasis in MCF7 cases were significantly higher than in HCC1806 (p = 0.023). The mice injected with HR positive breast cancer cells in the tail vein were associated with higher lung metastatic areas than TN cells. This emphasizes the influence of HR in the expression of growth factors and pulmonary neovascularization that is not still delineated.