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Immunotherapy has emerged as a crucial advancement in pulmonary carcinoma treatment. Nevertheless, its unique side effects not only reduce patients’ quality of life but also affect treatment efficacy, with severe cases potentially endangering the patient’s life. This study uses bibliometric analysis to perform a comprehensive bibliometric analysis literature on IRAEs in lung cancer from 1991 to 2023, retrieved from the Web of Science database. The dataset was analyzed using VOSviewer and CiteSpace to identify trends, key contributors, and emerging research areas. A total of 124 publications were analyzed, revealing a notable increase in research activity post-2015, with China and the USA contributing over 50% of the studies. This research highlights the importance of understanding IRAEs and suggests future investigations into the pulmonary microbiota and tumor microenvironment.

Simple Summary: We investigated a new method for diagnosing and predicting outcomes in canine pulmonary carcinoma. We developed a deep learning-based algorithm that accurately detects tumor nuclei and subsequently measures size and shape parameters. The variation in nuclear size and shape (nuclear pleomorphism) is a crucial malignancy criterion used in the current grading system for canine pulmonary carcinoma. Pathologists currently evaluate it and classify it according to a three-tier system. Manual morphometry is a more objective approach where tumor nuclei are individually encircled and analyzed. This task can be easily performed by an algorithm. Our algorithm's accuracy in correctly detecting and segmenting tumor nuclei was considered good when compared to manual morphometry. By comparing automated morphometry with conventional prognostic tests, such as pathologists' estimates, mitotic count, histological grading, and clinical staging, we found that our approach was equally accurate in terms of prognostic value. The algorithm's advantage lies in its high reproducibility and efficiency. Automated evaluation of nuclear pleomorphism can enhance the efficiency and reliability of canine pulmonary carcinoma diagnosis and grading, effectively addressing issues of inter-observer reproducibility. However, further optimization of the algorithm and validation with a larger study group is necessary to confirm our findings. The integration of deep learning-based tools into diagnostic workflows is increasingly prevalent due to their efficiency and reproducibility in various settings. We investigated the utility of automated nuclear morphometry for assessing nuclear pleomorphism (NP), a criterion of malignancy in the current grading system in canine pulmonary carcinoma (cPC), and its prognostic implications. We developed a deep learning-based algorithm for evaluating NP (variation in size, i.e., anisokaryosis and/or shape) using a segmentation model. Its performance was evaluated on 46 cPC cases with comprehensive follow-up data regarding its accuracy in nuclear segmentation and its prognostic ability. Its assessment of NP was compared to manual morphometry and established prognostic tests (pathologists' NP estimates (n = 11), mitotic count, histological grading, and TNM-stage). The standard deviation (SD) of the nuclear area, indicative of anisokaryosis, exhibited good discriminatory ability for tumor-specific survival, with an area under the curve (AUC) of 0.80 and a hazard ratio (HR) of 3.38. The algorithm achieved values comparable to manual morphometry. In contrast, the pathologists' estimates of anisokaryosis resulted in HR values ranging from 0.86 to 34.8, with slight inter-observer reproducibility (k = 0.204). Other conventional tests had no significant prognostic value in our study cohort. Fully automated morphometry promises a time-efficient and reproducible assessment of NP with a high prognostic value. Further refinement of the algorithm, particularly to address undersegmentation, and application to a larger study population are required. [ABSTRACT FROM AUTHOR]

Management of postoperative pain is of vital importance for patients undergoing Video‐Assisted Thoracoscopic Surgery (VATS) for Pulmonary Carcinoma Resection. The study evaluates the impact of Paravertebral Nerve Blockade (PNB) in conjunction with general anaesthesia on postoperative pain relief, as compared with general anaesthesia alone. A retrospective analysis was carried out from May 2020 to May 2023, involving 100 patients with pathologically confirmed pulmonary carcinoma. The patients were divided into two groups: a control group that received general anaesthesia and an observation group that received a combination of general anaesthesia and PNB. The intensity of postoperative pain was assessed at various time intervals using the visual analogue scale (VAS), while the effectiveness of patient‐controlled analgesia was also evaluated. Additionally, the study examined the incidence rates of chronic pain in the postoperative period. Statistical analysis was performed using IBM SPSS version 27.0. Significant reductions in VAS scores for both resting and cough‐induced pain were observed in the observation group at 2 and 6 h post‐operation (p < 0.01). However, the difference diminished over time. The observation group had fewer patient‐controlled analgesia activations and required lower dosages of hydromorphone at both 24‐ and 48‐h post‐operation. The incidence of chronic pain was also significantly lower in the observation group (24.00%) compared with the control group (54.00%) (p < 0.01). PNB, when administered in combination with general anaesthesia, significantly reduces immediate postoperative pain and the requirement for additional analgesics in patients undergoing VATS for pulmonary carcinoma resection. The effect diminishes over time but has a lasting impact on reducing the incidence of chronic postoperative pain. [ABSTRACT FROM AUTHOR]

In recent years, information technology has vastly improved. The quality of the image has been degraded by noise, which defeats the purpose of the noisy images. The major purpose of this paper is to find out which filters provide a better outcome while preprocessing medical images using computer tomography scans. The purpose of this paper is to remove noise from any images, whether they are real-time datasets or online datasets. To enhance an image for preprocessing, we have compared various filters; these filters are already available, but the major purpose is to identify the best filter. We compared the different parameters to find the best and finally found that the modified bilateral filtering provided a better result. The noise has been removed by using a bilateral filter, and the image clarity has not changed when using this filter. We have discussed the advantages and drawbacks of each approach. The effectiveness of these filters is compared using the peak signal-to-noise ratio, structural similarity index, contrast-tonoise ratio, and mean square error. The proposed algorithm is tested on 5 sample lung images. The results show that the modified bilateral filter produces better results. [ABSTRACT FROM AUTHOR]

Micro-computed tomography (micro-CT) is a relatively new imaging modality and the three-dimensional (3D) images obtained via micro-CT allow researchers to collect both quantitative and qualitative information on various types of samples. Micro-CT could potentially be used to examine human diseases and several studies have been published on this topic in the last decade. In this study, the potential uses of micro-CT in understanding and evaluating lung carcinoma and the relevant studies conducted on lung and other tumors are summarized. Currently, the resolution of benchtop laboratory micro-CT units has not reached the levels that can be obtained with light microscopy, and it is not possible to detect the histopathological features (e.g., tumor type, adenocarcinoma pattern, spread through air spaces) required for lung cancer management. However, its ability to provide 3D images in any plane of section, without disturbing the integrity of the specimen, suggests that it can be used as an auxiliary technique, especially in surgical margin examination, the evaluation of tumor invasion in the entire specimen, and calculation of primary and metastatic tumor volume. Along with future developments in micro-CT technology, it can be expected that the image resolution will gradually improve, the examination time will decrease, and the relevant software will be more user friendly. As a result of these developments, micro-CT may enter pathology laboratories as an auxiliary method in the pathological evaluation of lung tumors. However, the safety, performance, and cost effectiveness of micro-CT in the areas of possible clinical application should be investigated. If micro-CT passes all these tests, it may lead to the convergence of radiology and pathology applications performed independently in separate units today, and the birth of a new type of diagnostician who has equal knowledge of the histological and radiological features of tumors. [ABSTRACT FROM AUTHOR]

Feline pulmonary carcinoma (FPC) is an uncommon neoplasm with unique morphological features. We describe the gross, histological, metastatic, and immunohistochemical aspects of FPC, based on postmortem examinations from an 11-year retrospective study. Thirty-nine cases were selected. Predispositions were observed in senior (P <.001) and Persian (P =.039) cats. There were three gross patterns of the pulmonary tumors: (a) a large nodule and additional smaller nodules, (b) a solitary nodule, and (c) small, multifocal to coalescent nodules. Extrapulmonary metastases were present in 22/39 cases (56.4%), mainly in the regional lymph nodes (17/39, 43.5%), skeletal muscles (9/39, 23%), kidneys (6/39, 15.3%), and parietal pleura (4/39, 10.2%). The primary tumor size was correlated with the occurrence of extrapulmonary metastases (P =.002). Histologically, the tumors were classified as papillary adenocarcinoma (19/39, 48.7%), adenosquamous carcinoma (ADS) (8/39, 20.5%), acinar adenocarcinoma (6/39, 15.3%), solid adenocarcinoma (3/39, 7.6%), lepidic adenocarcinoma (2/39, 5.1%), and micropapillary adenocarcinoma (1/39, 2.5%). By immunohistochemistry, 39/39 cases (100%) were positive for pancytokeratin, 34/39 (87.1%) for thyroid transcription factor-1, and 8/39 (20.5%) for vimentin. Immunoreactivity for p40 was detected in the squamous component of all ADSs (8/8, 100%) and occasionally in the glandular component of adenocarcinomas (10/31, 32.2%). Napsin A expression was absent in all feline tissue tested. The results indicate that a modified and simplified histological classification based on current human and domestic animal systems is appropriate for cats. Additionally, this study highlights the utility of p40 as an immunohistochemical marker for the diagnosis of FPC with squamous differentiation. [ABSTRACT FROM AUTHOR]

The prevalence of lung cancer in women currently merits our attentions. However, cigarette exposure alone does not tell the whole story that lung cancer is more prevalent among non-smoking women. Since female lung cancer is closely linked to estrogen levels, many of endocrine disrupting chemicals (EDCs), as the substances similar to estrogen, affect hormone levels and become a potential risk of female lung cancer. Additionally, the combined toxicity of EDCs in daily environment has only been discussed on a limited scale. Consequently, this study explored the cancer-promoting effect of two representative substances of EDCs namely Bisphenol A (BPA) and Di(2-Ethylhexyl) Phthalate (DEHP) after their exposure alone or in combination, using a rat pulmonary tumor model published previously, combining bioinformatics analysis based on The Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas (TCGA) databases. It demonstrated that BPA and DEHP enhanced the promotion of pulmonary tumor in female rats, either alone or in combination. Mechanistically, BPA and DEHP mainly directly bound and activated ESR2 protein, phosphorylated CREB protein, activated HDAC6 transcriptionally, induced the production of the proto-oncogene c-MYC, and accelerated the formation of pulmonary tumor in female rats. Remarkably, BPA, rather than DEHP, exhibited a much more critical effect in female lung cancer. Additionally, the transcription factor ESR2 was most affected in carcinogenesis, causing genetic disruption. Furthermore, the TCGA database revealed that ESR2 could enhance the promotion and progression of non-small cell lung cancer in females via activating the WNT/β-catenin pathway. Finally, our findings demonstrated that BPA and DEHP could enhance the promotion of pulmonary carcinoma via ESR2 in female rats and provide a potential and valuable insight into the causes and prevention of lung cancer in non-smoking women due to EDCs exposure.

Enhancing diagnostic bronchoscopy techniques is paramount for lung cancer detection; bronchial washing is one of those modalities. However, there is controversy regarding the optimum sequence of performing this procedure in relation to biopsy. The present study aimed to assess the most effective sequence of bronchial washing in relation to bronchial biopsy for diagnosing lung cancer. The present study was a single-center prospective study carried out over a period of 18 months. The study included patients >18 years of age with mass or suspected lesions on a chest computed tomography and an endoscopically visible mass. They were randomly assigned to a bronchial washing before the forceps biopsy group and a bronchial washing after the forceps biopsy group. Bronchial washing and forceps biopsy were performed under cytological and histopathological analysis, respectively. The present study included 50 patients with a mean age of 72 years. The males comprised 36 (72%) of the patients. The pre-biopsy bronchial wash (pre-BW) yielded positive results in 21 (42%) patients, and the post-biopsy bronchial wash (post-BW) yielded positive results in 23 (46%) patients. The biopsy results revealed that 22 (44%) of the cases were squamous cell carcinoma, 18 (36%) were adenocarcinoma, 8 (16%) were small cell lung carcinoma, 1 (2%) was acinar cell carcinoma, and 1 (2%) was not malignant. A comparison of pre-BW and post-BW revealed a statistically significant difference between them (P-value <0.001). Pre- and post-BW may affect the yield of diagnostic outcomes for endoscopically visible lung tumors. However, additional research, such as studies using larger sample sizes or meta-analyses, is required to determine the efficacy of this approach. [ABSTRACT FROM AUTHOR]

Abstract Background The occurrence of spontaneous pneumothorax in primary lung cancer patients is infrequent. No exact theory could explain its mechanism of association. It could be either a primary manifestation or a late complication of primary lung cancer. The aim of this study is to analyze the association of the spontaneous pneumothorax with the primary lung cancer. Results A retrospective revision of patients’ files that presented with spontaneous pneumothorax and admitted at the Cardiothoracic Surgery Department during the period between January 2000 and January 2018 was done. Twenty-three patients were included in this study. Seventy-four percent of them were males (n = 17). Age ranged between 48 and 77 years (62.3 ± 7.3 years). Twelve patients (52%) were known to have advanced primary lung cancer, while seven patients (30%) had SPnx as a primary presentation for the primary lung cancer that was discovered during radiological assessment for SPnx. The remaining four patients had SPnx and were treated via surgery. In three of them, bullectomy and pleurodesis was performed; the postoperative histo-pathological examination of excised bullae revealed a primary non-small cell lung cancer (NSCLC). While in one patient, who had bullectomy, the primary lung cancer was discovered accidently during surgery. Conclusion Pneumothorax as a first manifestation for lung cancer is infrequent. Its relation to the prognosis has not been yet clear. Recurrent spontaneous pneumothorax in old, heavy smoker patient, or emphysema patient should raise the suspicion for the possibility of association of lung carcinoma.

Paraneoplastic optic neuropathy is a relatively rare ocular manifestation. We report the case of a patient with bilateral papilledema revealing a pulmonary squamous cell carcinoma. Paraneoplastic neuropathy is linked to an immune reaction by the presence of autoantibodies against collapsin responsive mediator protein 5. Diagnosis is based on the determination of these autoantibodies and the search for occult cancer by PET scan.Treatment is often based on corticosteroid therapy and sometimes immunosuppressive treatment is necessary in the case of corticosteroid unresponsiveness. [ABSTRACT FROM AUTHOR]

The stage classification for canine primary pulmonary carcinomas (PPC) was last updated in 1980. In people, the human lung cancer stage classification (HLCSC) (currently in its eighth edition) plays an integral role in diagnostic and therapeutic decision‐making and is prognostic despite a heterogeneous population of tumours. The objective of this retrospective case study was to evaluate the prognostic significance of a canine lung carcinoma stage classification (CLCSC) adapted from the HLCSC by removal of substage for ease of application to canine PPC. A secondary objective was to evaluate the effect of adjuvant chemotherapy. Medical records of 71 dogs with histologically confirmed PPC were reviewed. All dogs underwent surgical excision of the primary lung tumour. Primary tumour features (referring to T1‐T4 stages) and TNM stages (1‐4) were assigned using the CLCSC. Canine lung carcinoma stage was I (n = 7), II (n = 32), III (n = 24) and IV (n = 8). Median survival time was 952, 658, 158 and 52 days for stages I‐IV, respectively. Primary tumour features (T1‐T4), incomplete surgical excision, presence of lymph node metastasis and tumour grade were independent prognostic indicators for overall survival. Twenty‐six dogs received adjuvant chemotherapy; however, no statistically significant benefit was found. The CLCSC primary tumour features and stage classification were highly prognostic for survival in dogs with PPC. We propose further application and evaluation of this update to canine PPC stage classification. Given the poor prognosis of advanced stage canine PPC, novel treatments are needed. [ABSTRACT FROM AUTHOR]

A captive, 22-year-old, intact male Sunda wrinkled hornbill (Aceros corrugatus) was presented for an acute onset of open-mouth breathing and bilaterally drooped wings. An external physical examination revealed a moderately thin body condition, marked respiratory effort, and a significant heart murmur. Diagnostic blood testing revealed moderate azotemia and persistent erythrocytosis, initially documented 2 years before this event. Radiographic imaging revealed a subjectively enlarged heart and a right dorsal coelomic cavity mass. Further diagnostic testing included an echocardiogram and ultrasound-guided fine-needle aspirate of the right coelomic cavity mass, with cytology consistent with a carcinoma. The bird was euthanatized because of the poor prognosis. Necropsy and histopathology identified right atrioventricular valve hypertrophy with severe hypertrophic and dilated cardiomyopathy of the right ventricular free wall, atherosclerosis of the great vessels and arteriosclerosis of myocardial vessels, severe hepatic extramedullary hematopoiesis, and pulmonary carcinoma of the right lung. In this case, erythrocytosis was considered a physiologic response to hypoxemia caused by the lung mass. [ABSTRACT FROM AUTHOR]

A 3‐year‐old Himalayan cat was presented with respiratory distress. Radiography showed multiple gas opacity foci, with the locations dependent on patient positioning, and severe pleural effusion with a contralateral mediastinal shift. A large volume of fluid and air was aspirated, and the fluid components were consistent with a nonseptic exudate. A pulmonary mass, pleural nodules, and an air–fluid interface with air bubbles trapped in fibrous septations were identified using thoracic ultrasonography and CT. The cat died 2 days after imaging studies. Necropsy revealed tension pyopneumothorax caused by pulmonary carcinoma and multiple pleural metastases. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPV) are a big group of infection agents with oncogenic potential, especially regarding squamous epithelium. Some high-risk variants are key in the development of squamous cell carcinomas (SCC) across multiple systems, the most affected of which is the female reproductive system, but also parts of the gastrointestinal tract, head, and neck SCC, and cutaneous and pulmonary (bronchogenic) SCCs. In cases where a patient develops two SCCs in different systems, often the main question is whether these tumors are synchronous, metachronous, or if one of the tumors is a metastasis from the other, with HPV testing and stereotype identification often being of aid in differentiating between these. Herein, we report the case of a female patient in her 50s, initially diagnosed with SCC of the uterine cervix. The patient remained stable for three calendar years after completing preoperative radiotherapy, surgical resection, and postoperative chemo-radiotherapy. At that point, she developed respiratory symptoms, and radiography suggested a pulmonary malignancy. After undergoing surgical resection of the pulmonary lesion, histological specimens were initially interpreted to be a metachronous pulmonary SCC. Immunohistochemical testing proved that both the cervical and pulmonary lesions were HPV-associated, with further testing proving that both lesions were associated with high-risk HPV (genotype 16). Based on the clinical history and aggregated data, the pulmonary lesion was interpreted as a metastatic and not a metachronous one, and the patient is currently undergoing treatment for metastatic disease., Competing Interests: The authors would like to disclose that one of the authors (George Stoyanov, MD, Ph.D.) was a member of the editorial approval board of the journal (Cureus Journal of Medical Science) at the time of the manuscript submission. The authors affirm that this in no way, shape, or form manipulated the reviewer selection process, reviews, or the initial or final editorial decision., (Copyright © 2024, Pavlov et al.)

Introduction: The tumoral immune milieu plays a crucial role for the development of non-small-cell lung cancer (NSCLC) and may influence individual prognosis. We analyzed the predictive role of immune cell infiltrates after curative lung cancer surgery., Materials and Methods: The tumoral immune-cell infiltrate from 174 patients with pN1 NSCLC and adjuvant chemotherapy was characterized using immunofluorescence staining. The density and distribution of specific immune cells in tumor center (TU), invasive front (IF) and normal tissue (NORM) were correlated with clinical parameters and survival data., Results: Tumor specific survival (TSS) of all patients was 69.9% at 5 years. The density of tumor infiltrating lymphocytes (TIL) was higher in TU and IF than in NORM. High TIL density in TU (low vs. high: 62.0% vs. 86.7%; p = .011) and the presence of cytotoxic T-Lymphocytes (CTLs) in TU and IF were associated with improved TSS (positive vs. negative: 90.6% vs. 64.7% p = .024). High TIL-density correlated with programmed death-ligand 1 expression levels ≥50% (p < .001). Multivariate analysis identified accumulation of TIL (p = .016) and low Treg density (p = .003) in TU as negative prognostic predictors in squamous cell carcinoma (p = .025), whereas M1-like tumor- associated macrophages (p = .019) and high programmed death-ligand 1 status (p = .038) were associated with better survival in adenocarcinoma., Conclusion: The assessment of specific intratumoral immune cells may serve as a prognostic predictor in pN1 NSCLC. However differences were observed related to adenocarcinoma or squamous cell carcinoma histology. Prospective assessment of the immune-cell infiltrate and further clarification of its prognostic relevance could assist patient selection for upcoming perioperative immunotherapies., Competing Interests: Disclosure Thomas Muley has received grants/contracts from Roche Diagnostics and Oncohost outside the submitted work. Petros Christopoulos has received research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, Roche, and Takeda, speaker's honoraria from AstraZeneca, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Daiichi Sankyo, Gilead, Novartis, Pfizer, Takeda, and personal fees for participating to advisory boards from Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche, all outside the submitted work. Hauke Winter has received received payment (lectures, presentations, speaker fee, manuscript writing, educational events) from MSD, AstraZeneca, Intuitive, Medtronic, Roche; expert testimony from Intuitive; support for attending meetings/travel from Roche, Intuitive, MSD and participation on Data Safety Monitoring/Advisory Board for AstraZeneca and Intuitive; all outside the submitted work. Florian Eichhorn, Andreas Weigert, Rajender Nandigama, Laura Klotz, Jochen Wilhelm, Mark Kriegsmann, Michael Allgäuer, Rajkumar Savai and Martin Eichhorn declare that they have no known conflict of interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acute arterial tumor embolism is a rare complication in cancer patients. Most of the previously reported cases of arterial tumor embolism have been associated with pulmonary malignancies and occurred during the intraoperative and postoperative periods. Very few cases occurred spontaneously. To our knowledge, there is no previous report of spontaneous and massive tumor embolism occluding the abdominal aorta in patients suffering from primary pulmonary carcinoma. We describe the case of 64-year-old man who presented with left homonymous hemianopsia and backache. Further evaluation revealed a mass in the right lung, severe coagulopathy, and cerebral hemorrhagic infarction in the right occipital lobe. He suddenly developed lower limb ischemia 4 weeks after his first clinical visit, and finally, died of multiple organ failure. Autopsy showed non-keratinizing squamous cell carcinoma in the right lung and massive tumor emboli in the abdominal aorta containing nests of squamous cell carcinoma. Infarct regions were found in the bilateral kidneys, spleen, liver, and brain; fibrin thrombi, but not tumor emboli, were found in these regions. This case suggested that tumor embolism should be considered when patients suffering from primary pulmonary malignancies develop arterial embolism and arterial tumor emboli could be massive enough to occlude the abdominal aorta. [ABSTRACT FROM AUTHOR]

Cancer is an uncommon event in pregnancy. The most common gestational cancers arise from the breast and cervix. Although lung cancer is the most common malignancy, its occurrence in pregnancy is a distinctly rare event. Diagnosing it during pregnancy is an additional challenge as the pregnancy, common respiratory ailments, and the lung cancer can have overlapping symptoms. We report an uncommon histological variant of lung cancer - giant cell carcinoma, which resulted in a fatal outcome in a 26-year-old pregnant woman. A high level of suspicion and vigilance should be exercised during pregnancy to diagnose such rarer entities. [ABSTRACT FROM AUTHOR]

Um caso de carcinoma bronquíolo-alveolar difuso do tipo misto foi diagnosticado em um leão-africano (Panthera leo), hospitalizado com sinais de dispnéia e emagrecimento progressivo. Em todos os lobos pulmonares havia múltiplos nódulos esbranquiçados, macios e homogêneos, de 0,2-0,5cm em diâmetro. Histologicamente, os nódulos eram constituídos por células neoplásicas arranjadas em alvéolos e papilas sustentados por moderado estroma fibrovascular, um padrão que lembrava a estrutura pulmonar pré-existente. Na reação pelo ácido periódico de Schiff (PAS) foi observada marcação positiva no citoplasma de numerosas células neoplásicas. Todas as células neoplásicas demonstraram forte e uniforme imunorreatividade citoplasmática para pancitoceratina. A marcação para o fator 1 de transcrição da tireóide (TTF-1) foi observada em focos nos núcleos das células neoplásicas das margens dos nódulos. Nas secções avaliadas para surfactante A, a marcação foi observada em múltiplas áreas focais, tanto no citoplasma como na membrana citoplasmática das células neoplásicas. O diagnóstico de carcinoma bronquíolo-alveolar difuso do tipo misto foi feito com base nos achados histológicos, histoquímicos e imuno-histoquímicos. Essa parece ser a primeira descrição de um neoplasma pulmonar primário maligno em leão-africano.A case of diffuse bronchioloalveolar carcinoma of the mixed type was diagnosed in the lung of an adult female African lion (Panthera leo) with presenting signs of progressive dyspnea and weight loss. In all pulmonary lobes there were multiple 0.2-0.5cm in diameter soft and homogenous white nodules. Histologically, these nodules consisted of neoplastic cells with an alveolar and papillary disposition, a pattern reminiscent of the preexistent pulmonary structure. The cytoplasms of numerous neoplastic cells were positive in the periodic acid-Schiff (PAS) stain. At immunohistochemistry examination, all neoplastic cells reacted strongly and uniformly to pancytokeratin; focal reactivity for thyroid transcription factor 1 (TTF-1) was observed in the nucleus of neoplastic cells mainly in those at the margins of the nodules. Positive reaction for surfactant A was observed in multifocal areas, both in the cytoplasm and plasma membranes of neoplastic cells. The diagnosis of diffuse bronchioloalveolar carcinoma of the mixed type was made based on histological, histochemistry and immunohistochemistry findings. This seems to be the first report of a primary malignant neoplasm in the lung of the African lion.

Background: Lung cancer is the most commonly diagnosed neoplasm in humans, however this does not apply to other animal species. Living in an aquatic environment the respiratory system of cetaceans had to undergo unique adaptations in order to them to survive and cope with totally different respiratory pathogens and potentially carcinogens from those affecting humans. Case presentation: This article discusses not only macroscopical, histopathological and immunohistochemical features of a pulmonary carcinoma with disseminated metastases in a long-finned pilot whale (Globicephala melas), as well as the immunohistochemical analysis performed on various tissues of cetaceans belonging to the genus Globicephala. On the necropsy examination of the carcass, multiple pulmonary nodules and generalised thoracic lymphadenomegaly were noted. Histologically, a malignant epithelial neoplasia was identified in the lung, thoracic lymph nodes, and adrenal gland. Immunohistochemical analysis revealed a pulmonary carcinoma. Vasculogenic mimicry and epithelial-to-mesenchymal transition phenotype, as suggested by cytomorphological and immunohistochemical characteristics, were observed. Conclusions: A diagnosis of metastatic pulmonary carcinoma was determined, which to the author's knowledge, appears to be not previously recorded in long-finned pilot whale species. This is also the first report of vasculogenic mimicry and epithelial-to-mesenchymal transition event in a spontaneous cancer from a cetacean species. [ABSTRACT FROM AUTHOR]

The Papanicolaou Society of Cytopathology has formulated guidelines for respiratory cytology which include a classification scheme. The recommended classification scheme is based on the expertise of the committee members, extensive review of the literature and feedback from presentations at national and international meetings. Each category of the classification system is closely defined and link to a known risk for malignancy. The classification contains six categories designated as: 1) Non-diagnostic; 2) Negative for Malignancy; 3) Atypical; 4) Neoplastic (Benign and low grade cancer); 5) Suspicious for Malignancy; and 6) Malignant. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Conventional treatment options have limited efficacy because most cases are in the advanced stage at the time of diagnosis. In recent years, gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown its good antitumor activities in treating NSCLC in a number of studies. This paper reviews its role in the targeted treatment of NSCLC in Chinese patients. [ABSTRACT FROM AUTHOR]

Metastatic disease to muscle is rare and may be misdiagnosed when it is the presenting symptom, particularly in the absence of a known primary tumor. Skeletal muscle metastasis as a mode of presentation of primary lung cancer is an unusual phenomenon. Here, we report a case of ileo-psoas muscle metastasis from lung cancer as the initial clinical manifestation in a 58 year-old male with a personal history of heavy smoking. Excisional biopsy of the mass in the ileo-psoas muscle revealed metastatic adenocarcinoma. Computed tomography scan of the chest for a primary search was done and found to be pulmonary carcinoma. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6033 JPN 2012; 2(3): 251-253

The prevalence of lung cancer in women currently merits our attentions. However, cigarette exposure alone does not tell the whole story that lung cancer is more prevalent among non-smoking women. Since female lung cancer is closely linked to estrogen levels, many of endocrine disrupting chemicals (EDCs), as the substances similar to estrogen, affect hormone levels and become a potential risk of female lung cancer. Additionally, the combined toxicity of EDCs in daily environment has only been discussed on a limited scale. Consequently, this study explored the cancer-promoting effect of two representative substances of EDCs namely Bisphenol A (BPA) and Di(2-Ethylhexyl) Phthalate (DEHP) after their exposure alone or in combination, using a rat pulmonary tumor model published previously, combining bioinformatics analysis based on The Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas (TCGA) databases. It demonstrated that BPA and DEHP enhanced the promotion of pulmonary tumor in female rats, either alone or in combination. Mechanistically, BPA and DEHP mainly directly bound and activated ESR2 protein, phosphorylated CREB protein, activated HDAC6 transcriptionally, induced the production of the proto-oncogene c-MYC, and accelerated the formation of pulmonary tumor in female rats. Remarkably, BPA, rather than DEHP, exhibited a much more critical effect in female lung cancer. Additionally, the transcription factor ESR2 was most affected in carcinogenesis, causing genetic disruption. Furthermore, the TCGA database revealed that ESR2 could enhance the promotion and progression of non-small cell lung cancer in females via activating the WNT/β-catenin pathway. Finally, our findings demonstrated that BPA and DEHP could enhance the promotion of pulmonary carcinoma via ESR2 in female rats and provide a potential and valuable insight into the causes and prevention of lung cancer in non-smoking women due to EDCs exposure. • Combined exposure to BPA and DEHP promotes pulmonary carcinoma in female rats. • BPA and DEHP can directly bind and activate ESR2 in vivo and in silico. • Genetic perturbations induced by BPA and DEHP are mainly caused by ESR2, not ESR1. • BPA is the main effect in the combined exposure to BPA and DEHP. • ESR2 is related to multiple lung cancer pathways in female lung cancer. [ABSTRACT FROM AUTHOR]

Background: Lung cancer poses a severe threat to human life. Biomarkers of cancers are helpful in the diagnosis and treatment of patients with cancers. Biomarkers of lung cancers are rare, and thus deserve further research. Objective: The objective of the present study was to explore the expression of Fascin-1 in human lung cancer and paracarcinoma tissue, its correlation with clinicopathological characteristics in patients with lung cancer, and study the possible relationship between Fascin-1 expression and clinical-biological behavior of lung cancer. Method: This study used the MaxVision two-step immunohistochemical detection method to detect Fascin-1 expression in 84 of lung cancer and paracarcinoma tissues. This study set the expression of Fascin-1 in vascular endothelial cells as the positive control, and used phosphate buffered saline (replacing the primary antibodies) as negative control. Result: Of all the 84 lung cancer tissues and paracarcinoma tissues, positive expression of the Fascin-1 protein were detected in 78 cases (92.9%) and 27 cases (32.1%), respectively, and the difference was statistically significant (P<0.05). Differences in Fascin-1 expression between different age groups, clinical stages, and lymph node metastases were statistically significant (P<0.05), while differences in Fascin-1 expression between sexes, tumor stages, and pathological types demonstrated no statistical significance (P>0.05). The survival times of the patients with different Fascin-1 protein-positive expressions in lung cancer tissues were statistically significant (P<0.05), while the survival times of the patients with different Fascin-1 protein-positive expressions in paracarcinoma tissues were not statistically significant (P>0.05). Conclusion: In lung cancer, Fascin-1 expression was closely related to tumor invasion and metastasis, and the difference in expression of Fascin-1 had a significant effect on the survival time of the lung cancer patients. Therefore, Fascin-1 might be expected to serve as a possible potential biomarker of lung cancer. [ABSTRACT FROM AUTHOR]

Objective Myricetin, a common dietary flavonoid is widely distributed in fruits and vegetables, and is used as a health food supplement based on its immune function, anti-oxidation, anti-tumor, and anti-inflammatory properties. The aim of this study was to investigate the effects of myricetin on combination with radiotherapy enhance radiosensitivity of lung cancer A549 and H1299 cells. Methods A549 cells and H1299 cells were exposed to X-ray with or without myricetin treatment. Colony formation assays, CCK-8 assay, flow cytometry and Caspase-3 level detection were used to evaluate the radiosensitization activity of myricetin on cell proliferation and apoptosis in vitro. Nude mouse tumor xenograft model was built to assessed radiosensitization effect of myricetin in vivo. Results Compared with the exposed group without myricetin treatment, the groups treated with myricetin showed significantly suppressed cell surviving fraction and proliferation, increased the cell apoptosis and increased Caspase-3 protein expression after X-ray exposure in vitro. And in vivo assay, growth speed of tumor xenografts was significantly decreased in irradiated mice treated with myricetin. Conclusions The study demonstrated both in vitro and in vivo evidence that combination of myricetin with radiotherapy can enhance tumor radiosensitivity of pulmonary carcinoma A549 and H1299 cells, and myricetin could be a potential radiosensitizer for lung cancer therapy. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/5791518001210633 [ABSTRACT FROM AUTHOR]

Aims To evaluate thyroid transcription factor-1 (TTF-1) expression in a large cohort of invasive breast carcinomas (IBCs) using two commercially available monoclonal antibody clones (8G7G3/1 and SPT24). Methods and results Nuclear and cytoplasmic TTF-1 expression was evaluated in 1132 primary IBCs and 208 primary pulmonary carcinomas using tissue microarray (TMA) sections. TTF-1 nuclear expression was detected in one of 1132 (0.09%) IBCs by 8G7G3/1. In pulmonary carcinoma, TTF-1 expression was detected in 149 (71.6%) and 147 (70.6%) cases by 8G7G3/1 and SPT24, respectively, with no significant difference being seen between the two clones ( P = 0.839), and there was good consistency between these two antibodies in differentiating breast and pulmonary carcinomas (kappa value 0.905; P < 0.001). Both clones showed high specificity but relatively low sensitivity. Cytoplasmic TTF-1 expression was detected in 44 IBCs by 8G7G3/1, and this particular expression pattern was an independent adverse prognostic factor. Conclusions Both TTF-1 antibodies (clones 8G7G3/1 and SPT24) were useful in differentiating breast from pulmonary carcinomas. Nuclear expression of TTF-1 was detected in IBCs by 8G7G3/1, but not by SPT24. Cytoplasmic expression of 8G7G3/1 was seen in IBC for the first time, and was an independent unfavourable prognostic factor. [ABSTRACT FROM AUTHOR]

Metastatic tumors to the jaws and oral tissues are rarely encountered, accounting for less than 1% of all malignant tumors affecting the mouth. Although, metastasis to the mandible from a pulmonary carcinoma is extremely rare, when it does occur it mimics more common pathoses such as odontogenic cysts, osteomyelitis, space infections making its diagnosis even more challenging. Metastasis should be taken into account especially in patients with chronic history of smoking and sudden onset of paresthesia. The rarity of such cases has also resulted in there being no definitive consensus on managing them. [ABSTRACT FROM AUTHOR]

Background: Pulmonary carcinoma is the main cause of malignant pleural effusions (MPEs). However, there is no satisfactory marker for diagnosing MPEs caused by pulmonary carcinoma. The purpose of this study is to assess the clinical significance of Lunx mRNA detection in diagnosing MPEs caused by pulmonary carcinoma. Methods: A total of 209 patients with pleural effusions were recruited. The patients were diagnosed by cast-off cells, bronchoscopy, and pleural biopsy. The levels of Lunx mRNA in the pleural effusions were determined by real-time PCR. The levels of PH, LDH, glucose, albumin, and CEA were also determined. Patients who accepted chemotherapy underwent Lunx mRNA detection before and after the first chemotherapy session. The patients were divided into four groups according the effect of chemotherapy: complete remission (CR), partial remission (PR), no change (NC), and progressive disease (PD). The patients were also divided into two groups according the change in direction of Lunx mRNA expression after chemotherapy: increased group and decreased group. The patients were followed up to determine survival. Results: Lunx mRNA was positive in 89 of 106 patients with pleural effusions caused by pulmonary carcinoma. The specificity and sensitivity were 95.9% and 84.9%. The area under the ROC curve was 0.922. Lunx mRNA detection was better than detection using cast-off cells and CEA. All of the Lunx-positive patients with MPEs were diagnosed with pulmonary carcinoma, and all extrapulmonary carcinoma patients were Lunx-negative. The positive predictive value of Lunx mRNA for the source of tumor cells was 100%. Lunx mRNA expression decreased after the first session of chemotherapy in the CR and PR groups, increased in the PD group, there was no change in the NC group. Further analysis indicated the change in direction of Lunx mRNA expression was associated with the overall survival of patients. The patients in the increased group had longer overall survival times than those in the decreased group. Conclusion: Lunx mRNA is a specific tumor gene that is highly expressed in MPEs caused by pulmonary carcinoma. The changes in Lunx mRNA levels after chemotherapy can predict the prognosis of patients with MPEs caused by pulmonary carcinoma. [ABSTRACT FROM AUTHOR]

Background: Most intraocular metastatic tumors occur in the uveal tract, while isolated metastasis to the optic nerve is rarely found. We report a case of metastasis to the optic disc from primary lung cancer, diagnosed from biopsy findings obtained during a vitrectomy. Patient and methods: A 69-year-old male presented with gradual visual impairment due to a milky white tumour that extended from the optic disc into the vitreous cavity. A systemic examination revealed primary squamous cell lung cancer. Results: A biopsy specimen was obtained from the optic disc tumor during a vitrectomy, which led to a diagnosis of metastasis from lung cancer. Despite courses of chemotherapy and radiotherapy, the patient died of brain metastasis. Discussion: There are few reports of secondary optic disc tumors and pathological biopsy findings are rare. When a milky white tumor is observed extending from the optic disc, a possible differential diagnosis is metastatic neoplasm. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Radiofrequency ablation (RFA) has been recently applied as an alternative option of pulmonary surgery in the treatment of pulmonary malignancies. In this study, we assessed the risk associated with percutaneous RFA, and discussed its safety and efficacy. Methods: The clinical data of 329 consecutive patients with primary (n =237) and metastatic (n =92) lung tumor treated with RFA from 1999 to 2006 in this hospital were considered for this study, and the character and clinical data of these patients were analyzed. Complications, local progression, and overall survival at 1, 2 and 5 years of these patients were evaluated. Results: Following the procedure 63 (19.1%) patients presented with pneumothorax, 14 (4.2%) with hemoptysis (one death), 10 (3.0%) hemothorax, 15 (4.5%) pneumonia, and three (0.9%) pericardial tamponade (one death); the 30-day mortality after the procedure was 0.6%. Needle-track implantation was observed in six (1.8%) patients. Median progression-free interval was 21.6 months. The overall survival at 1, 2 and 5 years was 68.2%, 35.3%, and 20.1%, respectively. A total of 78 (23.7%) patients developed local progression during the follow-up. Significant difference in the risk of local progression was found in tumors more than 4cm; however, no significant difference was found in tumors less than 3cm and 3–4cm in our group. Conclusion: RAF is a safe and well-tolerated procedure with satisfied efficacy in the treatment of malignant lung nodules. To avoid complications with potential fatal outcome, adequate training and careful patient selection by a multidisciplinary team might be helpful. [Copyright &y& Elsevier]

Abstract: Secretoglobin (SCGB) 3A2, also called uteroglobin-related protein (UGRP) 1, is a downstream target for a homeodomain transcription factor NKX2-1, which is critical for the development of lung, thyroid and ventral forebrain. Both SCGB3A2 and NKX2-1 are expressed in airway epithelial cells and the latter also in alveolar Type II cells. NKX2-1 has been used clinically for diagnosis of human pulmonary tumors. Recently, the expression of SCGB3A2 was reported in human carcinomas, suggesting the use of this protein as a tumor marker. In this study, 28 lung tumors from aging B6;129 mice and nine lung adenocarcinomas from CC10TAg transgenic mice that express SV40 large T antigen under the mouse Scgb1a1 (CC10) gene promoter, were subjected to histopathological and immunohistochemical analyses for the expression of NKX2-1 and SCGB3A2. NKX2-1 was expressed in all types of tumors albeit more focally in carcinomas. In contrast, SCGB3A2 normally expressed in Clara cells, was negative in Type II cell hyperplasias and adenomas. However, it was expressed in alveolar Type II cell carcinomas and Clara cell adenocarcinomas. In these carcinomas, SCGB3A2 expression was observed in the portion of the tumor where NKX2-1 expression was reduced or almost abolished. As a comparison, the expression of SCGB3A2 and NKX2-1 from 23 human non-small cell lung carcinoma specimens was also examined. The results demonstrate that SCGB3A2 is a useful marker for diagnosis of pulmonary tumors both in mice and humans. [Copyright &y& Elsevier]

The aim of the study is to investigate the survival of patients treated surgically for lung cancer. 151cases treated during the years 2000-03 are reviewed. The average age was 56.6 ± 9.9 years (from 19 to 83 years old). The histological type was: 80 (53%) Squamous-cell carcinoma, 27 (17.9%) adenocarcinoma, 10 (6.6%) bronchioalveolar carcinoma, 5 (3.3%) small-cell carcinoma, and others - 29 (19.2%). The post-surgical stage was often advanced; 92 (63%) of the patients were at stage IIIA. With 5 (3.3% of total operated cases) of the patients had limited disease of SCLC. Most of the patients had lobectomy (64.9%) and pneumonectomy (16.6%) Performed. Neoadjuvant treatment was carried out on 37 (24.5%) of the patients. Only half of the patients were alive after 1 year, and 11.9% after 2 years of the postoperative period. Survival was highly significantly better in patients with an early stage of the disease. Survival resulted decreasingly with the extent of the surgical intervention; lower survival resulted in the patients treated with pneumonectomy, but this was not statistically significant. Significantly better results of survival were seen in correlation with higher values of pre-surgical FEV1. There are significant differences in survival (p < 0.05) in relation to diagnosis, group-age, histology, and highly significant differences (p < 0.01) regarding definition N, M, stage of disease, FEV1. There were no significant differences in the survival of patients according to sex, type of intervention, site of intervention, FVC, definition T. [ABSTRACT FROM AUTHOR]

Summary: We report a case of α-fetoprotein (AFP)–producing pulmonary carcinoma with studies for messenger RNA (mRNA) expression of hepatocyte nuclear factor (HNF)-4α, which is a transcription factor that is highly expressed in the process of liver development. The patient was a 64-year-old man with a pulmonary tumor in his left lower lobe. Serum AFP was 673 ng/mL. The microscopic analysis of the surgical specimen revealed a large cell neuroendocrine carcinoma with occasional hepatoid foci. The competitive reverse transcriptase polymerase chain reaction analysis revealed that HNF-4α mRNA was expressed on the order of 102- to 103-fold more abundantly than control pulmonary carcinomas and normal lung tissues. In addition, AFP and HNF-4α expression was restricted in hepatoid foci. Two previously reported cases of AFP-producing pulmonary carcinoma were also positive, whereas all 18 control pulmonary carcinomas were negative for HNF-4α. These findings suggest that aberrant expression of HNF-4α is implicated in the emergence or maintenance of hepatoid foci in AFP-producing pulmonary carcinomas. [Copyright &y& Elsevier]

Summary: Adenoid cystic carcinoma (ACC) is a common head and neck tumor originating from salivary glands but that can also exceptionally develop in the trachea and major bronchi. ACC is generally considered as a slow-growing, low-grade malignancy with prolonged clinical course. Metastases are very unusual and recurrences are more often local. Treatment for localized ACC is surgery. We here report for the first time a case of lung ACC with a synchronous liver metastasis proved by biopsy. Moreover, we report the interest of performing a 18FDG PET–CT as both primary tumor and liver metastasis presented an intense FDG uptake. The specificity of the liver 18FDG uptake was confirmed by Glut-1 positive immunostaining. We propose that 18FDG PET–CT should be considered in the initial staging of lung ACC in selected patients. [Copyright &y& Elsevier]

We present a 54-year-old man, a heavy smoker, with clinical and laboratory evidence of familial hypercholesterolemia and an asymptomatic solitary pulmonary nodule (SPN) increasing in size on follow-up chest X–ray. Laboratory work-up revealed high titers of rheumatoid factor and the presence of acute phase reactants. Because of the patient’s age and history of smoking, open lung biopsy was performed to rule out malignancy. The biopsy showed histological features compatible with a rheumatoid nodule. Identical features were noted in the histological examination of the subcutaneous nodule. Usually, rheumatoid nodules occur in patients with active, long-standing rheumatoid arthritis (RA) with other extra-articular manifestations. The presence of a single pulmonary rheumatoid nodule as the first manifestation of RA is extremely rare. Histologic proof is often required since pulmonary carcinoma can present an identical clinical and radiological pattern. The diagnostic work-up and the differential diagnosis of an SPN, particularly in a heavy smoker, is a common clinical request and remains a diagnostic challenge. [ABSTRACT FROM AUTHOR]

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Forty-three consecutive patients with solitary pulmonary nodules (SPNs) on chest radiographs were studied scintigraphically after administration of the somatostatin analogue 99mTc-EDDA/HYNIC-TOC. The objective of the study was to assess the usefulness of the procedure for differentiation of SPNs as malignant or benign. The administered activity was 740–925 MBq, and a single-photon emission computed tomography imaging technique was employed. Verification of the nodule aetiology was based on histology or cytology and bacteriology. A stable tumour size on chest radiography for at least 3 years was accepted as an additional criterion of benignity. In 29 patients, nodules were found to be malignant. The diagnoses included ten adenocarcinomas, five squamous cell carcinomas, two large cell carcinomas, six non-small cell lung cancers without specification of the more detailed morphology, two small cell lung cancers, two typical carcinoids and two metastatic tumours (leiomyosarcoma and malignant melanoma). In 14 patients the following benign tumours were diagnosed: four tuberculomas, one other granuloma, three hamartomas, one non-specific inflammatory infiltrate, one abscess, one peripheral carcinoid with the morphological characteristics of a benign tumour, one ectopic lesion of thyroid tissue and two benign tumours of unspecified aetiology with a stable size over 3 and 5 years respectively. Positive scintigraphic results were obtained in 26 of the 29 patients (90%) with malignant SPNs; among these, 24 of the 25 (96%) cases of primary pulmonary carcinoma yielded positive results. The remaining two false negative cases were the metastatic tumours, liposarcoma and melanoma. Of the 14 benign lesions, ten (71%) did not accumulate the radiopharmaceutical. The remaining four benign tumours that were visible on scintigrams comprised one tuberculoma, one hamartoma, one abscess and one case in which the diagnosis could not be established (the tumour had a stable size over 3 years). In conclusion, scintigraphy with 99mTc-EDDA/HYNIC-TOC appears to be an effective procedure for differentiation between malignant and benign SPNs. A fully credible assessment of the clinical efficacy of this procedure requires further study in a larger number of patients. [ABSTRACT FROM AUTHOR]

Enhanced local control of disease in lung cancer has been shown to improve survival, and controlled clinical trials of hyperthermia adjunctive to radiotherapy in other cancers have shown improved disease control and survival over radiotherapy alone. The challenge of lung hyperthermia, however, persists. This investigation sought to demonstrate the feasibility of localized lung hyperthermia at depth via therapeutic ultrasound. The method is based on using breathable perfluorochemical liquids as acoustic coupling media in the lung, liquids that have also been shown to enable controlled liquid-filled lung convective hyperthermia (LCHT). The ability to use both lung convective hyperthermia and liquid-filled lung ultrasound hyperthermia (LUHT) provides potential flexibility in heating patterns for the hyperthermic treatment of lung cancer with concurrent radiotherapy and/or chemotherapy. Using custom ultrasound transducers designed and built for these studies, the acoustic properties of three candidate perfluorochemicals were characterized over a range of temperatures, gas contents and ultrasound frequencies and acoustic intensities. Both sound speed and attenuation were measured in the neat liquids and in isolated lungs filled with the perfluorochemicals. Successful ultrasound hyperthermia at depth was demonstrated in vivo in sheep lung lobes in intraoperative conditions. In addition, the use of ultrasound diagnostic imaging was explored as a tool for use in conjunction with lung ultrasound hyperthermia. [ABSTRACT FROM AUTHOR]

Clinical studies have shown that hyperthermia in combination with radiotherapy and/or chemotherapy may be effective in the treatment of advanced cancer. No method of lung hyperthermia, however, has been accepted as standard or superior. This investigation sought to demonstrate in animals the thermal and physiologic feasibility of lung hyperthermia induced using heated breathable perfluorochemical (PFC) liquids, a method termed liquid-filled lung convective hyperthermia (LCHT). The ability to use LCHT is rooted in the development of both PFC liquid ventilation, now in clinical development with the PFC perflubron (LiquiVent®), and a PFC blood substitute also in late Phase III trials (Oxygent™). As LCHT background, the PFC technologies and biology are first reviewed. The physical properties of a variety of PFCs were evaluated for LCHT and it was concluded that more than one liquid is suitable based on such properties. Using total liquid ventilation type devices, LCHT was shown to deliver successfully localized (lobar) lung heating in sheep, and bilateral whole lung heating and whole-body hyperthermia in rabbits, cats and lambs. During LCHT, lung parenchymal temperatures were uniform (<1°C) across heated regions. In addition, based on patterns relating lung tissue temperatures to inspiratory and expiratory PFC liquid temperatures in the endotracheal tube, LCHT may minimize invasive thermometry requirements in the lung. Based on acute experiments, it was concluded that LCHT appears feasible and may simplify lung hyperthermia. It was recommended that potentially synergistic combinations of LCHT with other whole-body hyperthermia or local heating modalities, and with chemotherapeutic lung drug delivery, also be explored in the future. [ABSTRACT FROM AUTHOR]

After a left pneumonectomy, thoracoscopic closure with fibrin glue was performed for a fistula on the bronchial stump and the postoperative state progressed favorably thereafter. In this paper, we report on this successful case. Case: A 61 year-old male, who underwent a left pneumonectomy on January 17, 1996 for pulmonary carcinoma (T 3 N 1M 0 stage III A). The bronchial stump was covered with anterior serratus muscle flap. On April 1 (the 76th postoperative day), after two courses of Carboplatin and Vindesine treatment, the patient suddenly developed a fistula on the bronchial stump. Bronchofiberscopic closure with fibrin glue was attempted, but failed to close the fistula. Thoracoscopic surgery was then performed on May 15 (the 45th day after the onset of the fistula). After the intrathoracic opening of the fistula was found with a contrast medium, fibrin glue was injected to fill up to the bronchial stump, and communication with the thoracic cavity was blocked. Owing to coverage with a myocutaneous flap, the patient's general postoperative state remained relatively stable. Thoracoscopic surgery is useful as a treatment for some cases of bronchial stump fistula after pneumonectomy. [ABSTRACT FROM AUTHOR]

Primary sarcomas of the lungs occur at frequencies of 1:100, as compared with carcinomas reported in our retrospective studies covering 394 cases reported in the literature from 1957 to 1972 and 41 cases from 1957 to 1974. The average age was 45 years, the disease usually occurred between the ages of 35 and 65, the peak being between 45 and 60 years. Distribution between sexes was much the same as that seen in general. X-ray with rapid thoractomy provided the best clinical results. The literature showed a postoperative survival time of 5 years in 19% and 44% of our own cases. The general metastasis, haematologenous and lymphogenous were more or less equal and recidive tendency in 7% essentially varied, as related to the single histological forms. Lymphosarcomas (28.6%) were the most frequent, the group of spindle-celled sarcomas, inclusive of leiomyosarcomas, occurred in 40%. Histological maturity of the tissues and the prognosis according to active therapy were in parallel. A comparison of 41 primary sarcomas of the lung with the 192 cases of carcinomas seen in our clinic showed no connection between sarcomas of the lungs and smoking of cigarettes, pollution of the environment, industrial toxins or chronic bronchitis. These findings relate to the peripheral localization as well as to the lack, of incidence among men, with regard to pulmonary adenocarcinomas. An overall view of the characteristics led to the assumption of a probable endogenous tumour. A summarization of the characteristics of pulmonary sarcomas and carcinomas revealed the role of primary sarcomas in the total complex of malignant tumours of the lungs. [ABSTRACT FROM AUTHOR]

Cyclin D3, a cell cycle regulator, is encoded in the 6q21 chromosome region. Abnormalities of this gene and its protein product have not been found in normal tissues or in malignancies from human subjects. The expression of cyclin D3 was studied immunohistochemically in archival formalin-fixed, paraffin-embedded specimens from normal organs obtained from three autopsy cases and 237 human primary pulmonary carcinomas. In normal organs, nuclear positivity for cyclin D3 was observed in reactive type-2 pneumocytes, islets of Langerhans, lymphocytes from lymph nodes, superficial cells of transitional epithelium, epithelium of oesophagus, stomach, small intestine and gallbladder, endothelium, smooth muscles, and brain. Proliferating cells such as lymphocytes in the germinal centres and non-proliferating cells such as neurons both demonstrated cyclin D3 immunoreactivity. Cyclin D3 showed obvious nuclear immunoreactivity in 168 pulmonary carcinomas (71%). The proportion of tumour cells that were cyclin D3-positive ranged from 1% to 73% (median, 16%). There was no relationship between cyclin D3 immunoreactivity and histological typing, tumour differentiation, or pathological TNM staging. In pulmonary carcinomas, distinct expression of the cyclin D3 protein is unlikely to be implicated in tumorigenesis, because of its expression in only a small fraction of cancer cells. It may relate to cancer progression. The distribution of cyclin D3 reactivity in the normal tissues suggests that cyclin D3 affects other processes than cell cycle regulation in a lineage-specific manner. [ABSTRACT FROM AUTHOR]

Cytochrome P450 2E1 (CYP2E1) is a major xenobiotic-metabolizing enzyme but data concerning its extrahepatic expression are few. CYP2E1 can metabolically activate many procarcinogens and therefore its presence in the lung might play a role in bioactivation of procarcinogens, so we studied the expression and localization of CYP2E1 in primary pulmonary carcinomas and surrounding normal bronchial tissue from 28 patients. Seromucous glands showed expression of CYP2E1 in 19 and bronchial epithelium in 18 of the 28 samples of normal bronchial tissue. Thirteen of the corresponding cases of primary pulmonary carcinoma showed staining for CYP2E1. In 11 of these 13 cases, CYP2E1 was also present in normal bronchial tissue. There was no statistically significant difference in the expression of CYP2E1 between adenocarcinomas and squamous cell carcinomas. No association was observed between the expression of CYP2E1 in tumour tissue and normal bronchial tissue. However, there was a significant correlation between the expression of CYP2E1 in seromucous glands and bronchial epithelium (r = 0.61, P < 0.01) of normal tissue. We conclude that CYP2E1 can be present in both normal and neoplastic bronchial tissue. [ABSTRACT FROM AUTHOR]

With the aid of specific monoclonal antibodies, tumor tissues from 68 patients with lung cancer were examined for their expression of two small cell lung carcinoma (SCLC) antigens, Fuc-GMl (fucosyl GM1; IV2FucII3NeuAc GgOse4) and neural-cell adhesion molecule (NCAM), and two broader tumor antigens, carcinoembryonic antigen (CEA) and carbohydrate cancer-associated antigen CA 50. Expression of Fuc-GMl was seen in 75% and NCAM in 78% of the SCLC specimens, but also in 12 and 20% of non-SCLC. Either or both of these antigens were expressed in more than 90% of SCLC and in 25% of non-SCLC. CEA was found in more than 80% of SCLC and non-SCLC. Expression of CA 50 was seen in 65-68% of non-SCLC and SCLC, showing preference for SCLC and lung adenocarcinoma. In SCLC, cellular expression of Fuc-GM1 was generally seen together with NCAM and CA 50, but rarely with CEA. There was considerable inter- and intratumor heterogeneity in the expression of all four antigens. The results suggest that CEA is the antigen of choice for the detection of lung cancer regardless of histotype. In combined analysis of CEA, CA 50, Fuc-GM1 and NCAM, two patterns of antigen expression were recognized that appear to discriminate between SCLC and non-SCLC tumors, respectively. A considerable fraction of SCLC and non-SCLC tumors, however, exhibited similar patterns of antigen expression. The biological and clinical significance of these observations remains to be investigated. Copyright © 1992 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The occurrence and coexpression of the cytoskeletal proteins vimentin and cytokeratins were studied in malignant mesotheliomas and pulmonary carcinomas. For this purpose a double immunoenzyme staining with monoclonal antibodies was developed which made it possible to visualize vimentin and cytokeratins simultaneously within the same cell. A clear distinction between stromal cells (vimentin only) and tumour cells was also obtained. A total of 12 mesotheliomas (six mixed type and six epithelioid type) and 13 carcinomas (eight adenocarcinomas and five large cell undifferentiated carcinomas) were studied. The results revealed a clear difference between mesotheliomas and adenocarcinomas: 11 of 12 mesotheliomas showed coexpression of vimentin and cytokeratins in at least 50% of the tumour cells, while in seven of the eight adenocarcinomas none or only a few cells could be seen with this coexpression. In the undifferentiated large cell carcinomas three of five expressed both components, but in less than 25% of the cells. It is concluded that a reliable double immunoenzyme staining of vimentin and cytokeratins can be used as an additional means to distinguish malignant mesothelioma from pulmonary adenocarcinoma. [ABSTRACT FROM AUTHOR]

In this necropsy-based case-control study, there was no relationship between pancreatic carcinoma and previous gastric resection. Based on the association between lung cancer and gastric resection, it is suggested that the relationship between pancreatic carcinoma and gastric resection shown in other studies may have been confounded by smoking. This case-control study was designed to assess whether in patients dying from pancreatic carcinoma, there is a relationship to previous gastric resection for peptic ulcer disease. By linking the autopsy data base in Malmö with the national Cause of Death Register, we identified 439 autopsied individuals who had died of pancreatic carcinoma between 1970 and 1982. The 21,660 individuals in the data base represent 64% of all deaths during that time period. For each of these individuals who died of pancreatic carcinoma, we randomly chose three controls who were matched for age at death, gender, and year of death. In order to assess the specificity of the assumed relationship, we also used as a control group the 1337 autopsied individuals who had died of lung cancer. The prevalence of previous gastric resections was 3.4% in patients dying from pancreatic carcinoma, 7.6% in patients dying from lung cancer, and 4.4% in the age-and sex-matched control group. The odds for previous gastric resection in patients dying from pancreatic carcinoma was 0.9 [95% confidence interval (CI) 0.5–1.7] in comparison with this age- and sex-matched control group. The lower odds for previous gastric resection in patients dying of pancreatic carcinoma than in patients dying of lung cancer remained in the logistic regression analysis after controlling for age at death, gender, and year of death (odds ratio [OR] 0.5; 95% CI 0.3–0.9). [ABSTRACT FROM AUTHOR]