Spread Of Malignant Cells Research Articles

Metallic-based phthalocyanine nanoemulsions for photodynamic purging of ovarian tissue in leukemia patients

For cancer patients with a high risk of ovarian tissue metastasis, ovarian autotransplantation is not advised due to the potential spread of malignant cells. Ex vivo purging of ovarian fragments may offer a more suitable alternative for fertility restoration. Eradicating malignant cells should be done selectively without affecting follicles or ovarian stromal cells (SCs). As a clinically licensed method, photodynamic therapy (PDT) is a minimally invasive treatment to destroy cancer cells. This study evaluates the effectiveness of nanoemulsions (NE) containing two phthalocyanine photosensitizers; aluminum (III) phthalocyanine (AlPc) and zinc (II) phthalocyanine (ZnPc) in eliminating cancer cells. Human leukemic malignant (HL-60) and ovarian stromal cells (SCs) were treated with AlPc/ZnPc loaded NEs with or without diode laser irradiation. HL-60 leukemia cells in 2D culture were eliminated by treatment with 10nM AlPc-NE or 0.1µM ZnPc-NE, while no toxicity was observed in SCs. In 3D culture models, although the cells showed more resistance to the NEs as a result of limited oxygen and photosensitizer penetration, the treatment remained selective for cancer cells. These approaches have the potential to eliminate malignant cells from ovarian tissue fragments.

Extracellular vesicles derived from melanoma cells induce carcinoma-associated fibroblasts via miR-92b-3p mediated downregulation of PTEN.

In melanoma, carcinoma-associated fibroblasts (CAFs) are important cellular components in the tumour microenvironment due to their potential to promote tumour growth and metastatic spread of malignant cells. Melanoma cells have the ability to affect non-tumour cells in the microenvironment by releasing extracellular vesicles (EVs). The mechanisms responsible for reprogramming normal dermal fibroblasts (NHDFs) into CAFs remain incompletely understood. However, it is likely thought to be mediated by melanoma-specific miRNAs, which are transported by EVs derived from melanoma cells. Therefore, we wondered if one of the most enriched miRNAs in EVs secreted by melanoma cells, miR-92b-3p, is involved in the conversion of normal fibroblasts into CAFs. We observed that melanoma cell-derived EVs indeed delivered miR-92b-3p into NHDFs and that its accumulation correlated with CAF formation, as demonstrated by enhanced expression of CAF marker genes and increased proliferation and migration. Overexpression of miR-92b-3p in NHDFs revealed similar results, while EVs deficient of miR-92b-3p did not induce a CAF phenotype. As a target we identified PTEN, whose repression led to increased expression of CAF markers. We thus provide a novel pathway of intercellular communication by which melanoma cells control the transformation of CAFs by virtue of EV-transported miRNAs.

SNORD99 promotes endometrial cancer development by inhibiting GSDMD-mediated pyroptosis through 2'-O-methylation modification.

Eukaryotic cells possess multiple mechanisms of self-destruction, including pyroptosis and necroptosis. Pyroptosis is a type of programmed cell death characterized by cellular rupture and linked to inflammation. SnoRNA, a small non-coding RNA in the nucleolus, can dysregulate specific RNAs through 2'-O-methylation, contributing to tumorigenesis. Our StarBase and qRT-PCR analysis revealed SNORD99 upregulation in endometrial cancer (EC) tissue compared to normal tissue, suggesting its role in pathogenesis. SNORD99 overexpression enhanced migration and proliferation of EC cells, while ASO-mediated suppression reduced malignant cell spread and division. RNA-seq and base-comparing analysis identified GSDMD's differential expression upon SNORD99 overexpression, forming the SNORD99-FBL RNP complex. RTL-P experiments showed SNORD99 increased GSDMD's 2'-O-methylation. SNORD99 reduced GSDMD, caspase-1, and NLRP3 protein levels, implicating its role in pyroptosis. Optical and electron microscopy confirmed enhanced pyroptosis features. In summary, SNORD99 modifies GSDMD via 2'-O-methylation, suppressing pyroptosis and promoting EC progression. Developing pyroptosis-inducing drugs may offer new cancer treatment avenues.

Jejunojejunal intussusception induced by a gastrointestinal stromal tumor: a case report and literature review.

Intussusception is defined as the invagination of a proximal segment of the bowel into the adjoining or distal segment. In most adults with intussusception, there is a demonstrable lead point with a definite pathologic abnormality. The clinical features of intussusception include chronic intermittent abdominal pain, nausea and vomiting, constipation, and a palpable abdominal mass. The present case report describes a 62-year-old woman with a 2-week history of abdominal pain and 9-day history of vomiting. Clinical, imaging, and histologic evaluations revealed a jejunojejunal intussusception with a gastrointestinal stromal tumor as the lead point. A gastrointestinal stromal tumor should be considered as a possible lead point in adult patients with intussusception. The implication of reducing the intussusception prior to tumor resection requires further evaluation in view of the risk of venous embolism, including direct spread of malignant cells, in cases involving a large polypoid mass with a necrotic surface that extends to the serosa as shown by intraoperative examination. Accordingly, the rationale for adjuvant therapy with imatinib also requires further evaluation.

Extracellular Vesicles from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients Deliver MiR-21 and Induce Methotrexate Resistance in Lung Cancer Cells.

Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood. Here, we confirm, in 36 patients with NSCLC-LM, that elevated miR-21 expression prior to treatment correlates with poor prognosis. MiR-21 overexpression or sponging results in a corresponding increase or decrease in MTX resistance, demonstrating that cellular miR-21 expression correlates with drug resistance. MiR-21-monitoring sensor and fluorescent extracellular vesicle (EV) staining revealed that EV-mediated delivery of miR-21 could modulate MTX resistance. Moreover, EVs isolated from the CSF of LM patients containing miR-21 could enhance the cell proliferation and MTX resistance of recipient cells. These results indicate that miR-21 can be transferred from cell-to-cell via EVs and potentially modulate MTX sensitivity, suggesting that miR-21 in CSF EVs may be a prognostic and therapeutic target for overcoming MTX resistance in patients with NSCLC-LM.

Spectrum of Cutaneous Metastasis in Visceral and Haematolymphoid Malignancies: A Cross-sectional Study at a Tertiary Care Centre in Kolkata, West Bengal, India

Introduction: Cutaneous Metastasis (CM) is the spread of malignant cells from a primary site of malignancy to the skin. The incidence of CM ranges from 0.5% to 9% of all patients with cancer. CM may be the first sign of clinically silent visceral cancer or can even be a clue to tumour recurrence and heralds a poor prognosis requiring intense chemoradiotherapy. Aim: To study the spectrum of CM of internal malignancies, including haematolymphoid neoplasms. Materials and Methods: This cross-sectional study was conducted at Department of Pathology, Command Hospital Kolkata, West Bengal, India, over a period of two years from April 2020 to March 2022 and data was analysed over the next six months. A total of 16 patients who developed CM secondary to underlying solid organ or haematological malignancy were analysed. Categorical variables were summarised as percentages. Data in tables were presented as the frequency of variables (categories) or as absolute numbers. Results: The parameters studied included the primary site of malignancies, the frequency of various histological types at the primary site, and the common cutaneous metastatic regions. The mean patient age was 55.25 years (ranges 24- 72 years) with no gender predilection (M:F=1:1). The most common primary cancer site was the kidney and the oral cavity 4 each (25%), followed by breast, lung, and haematolymphoid malignancy, 2 each (12.5%), and 1 each of thyroid and gallbladder (6.25%). The most common site of CM was the head, abdomen, and epigastric wall 07/16 each (43.75%). The majority of the CM were identified as adenocarcinoma on histopathology. Conclusion: The CM occurs rarely and can be the initial presentation of an occult internal malignancy or may suggest recurrence if diagnosed later. Renal cell carcinomas and squamous cell carcinomas of the oral cavity are the tumours that have a high predisposition for CM, and hence these patients require close follow-up and surveillance.

High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis

Single-cell and spatial technologies that profile gene expression across a whole tissue are revolutionizing the resolution of molecular states in clinical samples. Current commercially available technologies provide whole transcriptome single-cell, whole transcriptome spatial, or targeted in situ gene expression analysis. Here, we combine these technologies to explore tissue heterogeneity in large, FFPE human breast cancer sections. This integrative approach allowed us to explore molecular differences that exist between distinct tumor regions and to identify biomarkers involved in the progression towards invasive carcinoma. Further, we study cell neighborhoods and identify rare boundary cells that sit at the critical myoepithelial border confining the spread of malignant cells. Here, we demonstrate that each technology alone provides information about molecular signatures relevant to understanding cancer heterogeneity; however, it is the integration of these technologies that leads to deeper insights, ushering in discoveries that will progress oncology research and the development of diagnostics and therapeutics.

Assessment of immunohistochemical expression of claudin-1 in oral squamous cell carcinoma and its clinicopathological correlation

Oral carcinogenesis is complex and multi-step process, which results from various deleterious habits, multiple environmental factors and genetic susceptibility. CLDN-1 expression is regulated oncogenic Wnt/B-catenin transduction pathway. They recruit matrix metalloproteinases (MMPs) on the cell surface to achieve elevated focal concentrations and eventual activations of proMMP2. These collagenases are responsible for the breakdown of extracellular matrix proteins and thus facilitate invasion and spread of malignant cells. Reduced cell-cell adhesion is associated with loss of contact inhibition of proliferation. This allows escape from growth control signals and triggers carcinogenesis. Significant correlation was observed between histopathological grade of the tumor with the localization and immunostaining intensity of CLDN-1. Determination of localization of CLDN-1 for a particular patient may be important to decide site (cytoplasmic or nuclear) for targeting CLDN-1. This targeted drug therapy for CLDN-1 may prevent worsening of the disease in the patient, resulting in better prognosis.

DTBV: A Deep Transfer-Based Bone Cancer Diagnosis System Using VGG16 Feature Extraction

Among the many different types of cancer, bone cancer is the most lethal and least prevalent. More cases are reported each year. Early diagnosis of bone cancer is crucial since it helps limit the spread of malignant cells and reduce mortality. The manual method of detection of bone cancer is cumbersome and requires specialized knowledge. A deep transfer-based bone cancer diagnosis (DTBV) system using VGG16 feature extraction is proposed to address these issues. The proposed DTBV system uses a transfer learning (TL) approach in which a pre-trained convolutional neural network (CNN) model is used to extract features from the pre-processed input image and a support vector machine (SVM) model is used to train using these features to distinguish between cancerous and healthy bone. The CNN is applied to the image datasets as it provides better image recognition with high accuracy when the layers in neural network feature extraction increase. In the proposed DTBV system, the VGG16 model extracts the features from the input X-ray image. A mutual information statistic that measures the dependency between the different features is then used to select the best features. This is the first time this method has been used for detecting bone cancer. Once selected features are selected, they are fed into the SVM classifier. The SVM model classifies the given testing dataset into malignant and benign categories. A comprehensive performance evaluation has demonstrated that the proposed DTBV system is highly efficient in detecting bone cancer, with an accuracy of 93.9%, which is more accurate than other existing systems.

Natural killer cells suppress cancer metastasis by eliminating circulating cancer cells.

Despite significant advances in cancer treatment, the metastatic spread of malignant cells to distant organs remains a major cause of cancer-related deaths. Natural killer (NK) cells play a crucial role in controlling tumor metastasis; however, the dynamics of NK cell-mediated clearance of metastatic tumors are not entirely understood. Herein, we demonstrate the cooperative role of NK and T cells in the surveillance of melanoma metastasis. We found that NK cells effectively limited the pulmonary seeding of B16 melanoma cells, while T cells played a primary role in restricting metastatic foci growth in the lungs. Although the metastatic foci in the lungs at the endpoint were largely devoid of NK cells, they played a prominent role in promoting T cell recruitment into the metastatic foci. Our data suggested that the most productive interaction between NK cells and metastatic cancer cells occurred when cancer cells were in circulation. Modifying the route of administration so that intravenously injected melanoma cells bypass the first liver passage resulted in significantly more melanoma metastasis to the lung. This finding indicated the liver as a prominent site where NK cells cleared melanoma cells to regulate their seeding in the lungs. Consistent with this notion, the liver and the lungs of the tumor-bearing mice showed dominance of NK and T cell activation, respectively. Thus, NK cells and T cells control pulmonary metastasis of melanoma cells by distinct mechanisms where NK cells play a critical function in shaping T cell-mediated in situ control of lung-seeded cancer cells. A precise understanding of the cooperative role of NK and T cells in controlling tumor metastasis will enable the development of the next generation of cancer immunotherapies.

Low-intensity continuous ultrasound to inhibit cancer cell migration.

In recent years, it has been verified that collective cell migration is a fundamental step in tumor spreading and metastatic processes. In this paper, we demonstrate for the first time how low-intensity ultrasound produces long-term inhibition of collective migration of epithelial cancer cells in wound healing processes. In particular, we show how pancreatic tumor cells, PANC-1, grown as monolayers in vitro respond to these waves at frequencies close to 1MHz and low intensities (<100mWcm-2) for 48-72h of culture after some minutes of a single ultrasound irradiation. This new strategy opens a new line of action to block the spread of malignant cells in cancer processes. Despite relevant spatial variations of the acoustic pressure amplitude induced in the assay, the cells behave as a whole, showing a collective dynamic response to acoustic performance. Experiments carried out with samples without previous starving showed remarkable effects of the LICUs from the first hours of culture, more prominent than those with experiments with monolayers subjected to fasting prior to the experiments. This new strategy to control cell migration demonstrating the effectiveness of LICUS on not starved cells opens a new line of action to study effects of in vivo ultrasonic actuation on tumor tissues with malignant cells. This is a proof-of-concept study to demonstrate the physical effects of ultrasound stimulation on tumor cell migration. An in-depth biological study of the effects of ultrasounds and underlying biological mechanisms is on-going but out of the scope of this article.

Visualization of the effect of TR100 anti-cancer compound on membrane nanotubes with SR-SIM microscopy

AbstractOne of the most dangerous diseases is cancer, nearly 2 million new cancer types are diagnosed each year, worldwide, causing most of the death. Therefore, cancer is in the focus of many types of research. To prevent the proliferation and spreading of malignant cells, several compounds have been developed in chemotherapy, however, a significant proportion of these have serious side effects, and resistance is commonly emerging early after administration. Tumor cells require tropomyosin-containing actin network for their growth and survival. The tropomyosin profile is considerably changed in cancers resulting in the dramatic rearrangements of the actin cytoskeleton structure, therefore anti-tropomyosin compounds can be a new perspective in cancer therapy, such as TR100 which was reported to be capable of destroying cancer cells in a highly tumor-specific manner by increasing the depolymerization of the actin filament. On the other hand tumor cells can commonly communicate with each other via membrane nanotubes (NTs) for which actin is essential for growth. Tumor cell NTs may transport not only signal molecules, or cell organelles, but resistance factors against chemotherapeutic agents to help to survive. Immune cells also frequently use membrane nanotubes for communication, therefore, in this study we focused on the visualization of the effect of TR100 on the morphology and formation of B lymphoma cell NTs with superresolution structured illumination microscopy. TR100 treatment caused spectacular changes on the NT forming capability and the morphology of B cells in a concentration dependent manner, while low concentration of the agent significantly promoted NT formation, and at the same time produced shorter and thicker tubes in the early stage of their formation, in higher concentration it affected mainly only the cells, causing the rounding and finally the death of them. We were not able to detect any significant change on cells with extended nanotubular network, suggesting that TR100 is a less potent candidate in anti-cancer therapy.

Contribution of Stemness-Linked Transcription Regulators to the Progression of Breast Cancer.

Although there are currently several factors that allow measuring the risk of having breast cancer or predicting its progression, the underlying causes of this malignancy have remained unknown. Several molecular studies have described some mechanisms involved in the progress of breast cancer. These have helped in identifying new targets with therapeutic potential. However, despite the therapeutic strategies implemented from the advances achieved in breast cancer research, a large percentage of patients with breast cancer die due to the spread of malignant cells to other tissues or organs, such as bones and lungs. Therefore, determining the processes that promote the migration of malignant cells remains one of the greatest challenges for oncological research. Several research groups have reported evidence on how the dedifferentiation of tumor cells leads to the acquisition of stemness characteristics, such as invasion, metastasis, the capability to evade the immunological response, and resistance to several cytotoxic drugs. These phenotypic changes have been associated with a complex reprogramming of gene expression in tumor cells during the Epithelial- Mesenchymal Transition (EMT). Considering the determining role that the transcriptional regulation plays in the expression of the specific characteristics and attributes of breast cancer during ETM, in the present work, we reviewed and analyzed several transcriptional mechanisms that support the mesenchymal phenotype. In the same way, we established the importance of transcription factors with a therapeutic perspective in the progress of breast cancer.

Abstract 709: Metabolomic differences between pulmonary metastasis of Lewis lung carcinoma and normal lungs from C57BL/6 mice fed an obesogenic high-fat diet

Abstract Metastasis, the spread of malignant cells from a primary tumor to distant organs, is the most devastating aspect of cancer. To understand the metabolism of metastases, we compared the metabolomes of pulmonary metastases of Lewis lung carcinoma (LLC) with that of normal lung tissues from mice fed an obesogenic high-fat diet. In a 2x2 design, male C57BL/6 mice, with or without a subcutaneous LLC inoculation, were fed the standard AIN93G diet or a high-fat diet (HFD), which provided 16% or 45% of energy from soybean oil, for 12 weeks. At the end of the study, lung metastases from injected mice and the lungs from non-injected mice were harvested for untargeted metabolomic analysis of primary metabolism by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We identified 91 metabolites, 70 of which differed among the four groups. Pathway and network analyses along with the discriminant analysis showed that amino acid and carbohydrate metabolism were altered the most in metastases compared to the normal lung tissue (e.g., aminoacyl-tRNA biosynthesis pathways and the citric cycle). A 60% decrease in glutamine and a 25-fold elevation in sorbitol were observed in metastases. Cholesterol and its metabolite dihydrocholesterol were 50% lower in metastases than in the lungs. The HFD elevated arachidonic acid and its precursor linoleic acid in the lungs from non-LLC-bearing mice, which reflected dietary fatty acid composition of the HFD. However, such elevation did not occur in metastases from HFD-fed LLC-bearing mice, suggesting alterations in fatty acid metabolism during LLC metastatic progression. Differences in metabolomes between LLC pulmonary metastases and the normal healthy lungs identified in the present study can be useful in designing targeted studies for prevention and treatment of metastasis using this spontaneous metastasis model. Citation Format: Lin Yan, Sneha Sundaram, Bret M. Rust, Matthew J. Picklo, Michael R. Bukowski. Metabolomic differences between pulmonary metastasis of Lewis lung carcinoma and normal lungs from C57BL/6 mice fed an obesogenic high-fat diet [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 709.

Does Gas Insufflation during Gynecologic or Urologic Oncologic Laparoscopy Cause Dissemination of Malignant Cells

<h3>Study Objective</h3> To investigate whether benign or malignant cells are found in evacuated gas during laparoscopy for gynecological or urological malignancies. <h3>Design</h3> Observational prospective study. <h3>Setting</h3> Academic, tertiary medical center. <h3>Patients or Participants</h3> A total of 30 patients were included; 15 underwent laparoscopic staging due to uterine adenocarcinoma and 15 had laparoscopic nephrectomy due to suspected renal cell carcinoma. <h3>Interventions</h3> All gas evacuated during laparoscopy was passed through a filter in order to capture any aerosolized cells formed during surgery. After surgery, the filter was rinsed backwards with 50 CC of normal saline. The fluid was collected, centrifuged and sent for cytological evaluation. Filter ability to capture malignant cells was proved by filtering ascites fluid of an ovarian cancer patient through the filter. The primary outcome was the rate laparoscopic surgeries in which the filtered sample was positive for malignant or benign cells. <h3>Measurements and Main Results</h3> No benign or malignant cells were identified in evacuated gas during laparoscopic surgeries in all but one case. This case of malignant adenocarcinoma had a clear, macroscopic extra-uterine pelvic spread and malignant adenocarcinoma cells were identified in the cytology examination of the fluid collected. <h3>Conclusion</h3> In contrast to previous concerns, in all cases where the tumor was confined to its' organ, we found no evidence of benign or malignant cell spread in the gas evacuated from the abdominal or retroperitoneal cavity during laparoscopy. The single event of malignant cells from aerosolized gas was in a case with a macroscopic, extra-organ involvement. Our study confirms the safety of performing laparoscopic surgery for gynecologic and urologic malignancies with regard to aerosolized gas. The explanation for malignant cells found in evacuated gas could be both aerosolization of cells or cells that adhered to surgical instruments. The clinical significance of this finding in the setting of macroscopic, extra-organ tumor spread is unclear.

Transcriptome analysis of heterogeneity in mouse model of metastatic breast cancer

BackgroundCancer metastasis is a complex process involving the spread of malignant cells from a primary tumor to distal organs. Understanding this cascade at a mechanistic level could provide critical new insights into the disease and potentially reveal new avenues for treatment. Transcriptome profiling of spontaneous cancer models is an attractive method to examine the dynamic changes accompanying tumor cell spread. However, such studies are complicated by the underlying heterogeneity of the cell types involved. The purpose of this study was to examine the transcriptomes of metastatic breast cancer cells using the well-established MMTV-PyMT mouse model.MethodsOrgan-derived metastatic cell lines were harvested from 10 female MMTV-PyMT mice. Cancer cells were isolated and sorted based on the expression of CD44low/EpCAMhigh or CD44high/EpCAMhigh surface markers. RNA from each cell line was extracted and sequenced using the NextSeq 500 Illumina platform. Tissue-specific genes were compared across the different metastatic and primary tumor samples. Reads were mapped to the mouse genome using STAR, and gene expression was quantified using RSEM. Single-cell RNA-seq (scRNA-seq) was performed on select samples using the ddSeq platform by BioRad and analyzed using Seurat v3.2.3. Monocle2 was used to infer pseudo-time progression.ResultsComparison of RNA sequencing data across all cell populations produced distinct gene clusters. Differential gene expression patterns related to CD44 expression, organ tropism, and immunomodulatory signatures were observed. scRNA-seq identified expression profiles based on tissue-dependent niches and clonal heterogeneity. These cohorts of data were narrowed down to identify subsets of genes with high expression and known metastatic propensity. Dot plot analyses further revealed clusters expressing cancer stem cell and cancer dormancy markers. Changes in relevant genes were investigated across pseudo-time and tissue origin using Monocle2. These data revealed transcriptomes that may contribute to sub-clonal evolution and treatment evasion during cancer progression.ConclusionsWe performed a comprehensive transcriptome analysis of tumor heterogeneity and organ tropism during breast cancer metastasis. These data add to our understanding of metastatic progression and highlight targets for breast cancer treatment. These markers could also be used to image the impact of tumor heterogeneity on metastases.

Etiopathogenesis of malignant pleural effusion

: Malignant pleural effusion (MPE) is featured by containing malignant cells. It is a frequent finding in patients with metastatic disease and it develops in 15% of patients with malignant disease. Two-thirds of all cases have a pleural effusion as one or sole initial manifestation of malignant disease. Primary tumors that most frequently develop MPE are lung, breast cancer, and lymphoma accounting for 75% of all cases. A MPE can develop in primary or metastatic malignancies of the pleura by spreading of malignant cells within the intrapleural cavity and into lymphatics causing their obstruction. The otherwise physiologic balance between the secretion of fluids into the pleural space and its reabsorption is largely disturbed by the occurrence of a MPE. Malignant cells can enter the pleural space via the hematogenous, direct or lymphatic spread. Direct tumor involvement of pleura can lead to a pleural fluid accumulation by increasingly producing the liquid and thus influencing the normal parietal pleural lymphatic functioning. Tumor may extensively infiltrate pleural capillaries, leading to increased filtration, or may produce different cytokines that increase capillary permeability, while decreased plasma osmotic pressure or decreased pleural pressure can contribute to the enhanced entry of liquid as well. On the other hand, tumor growth infiltrating the draining lymphatics or lymph nodes may block the lymphatic drainage thus decreasing the absorbtion rate of pleural fluid, with the subsequent accumulation of fluid in the pleural space, while different extrinsic factors including limited respiratory mobility, mechanical compression of lymphatics with blockage of their stomata, may be responsible in the cases when lymphatics activity is significantly disturbed, but not due to direct damage of the vessels. With the advancements in molecular medicine, the impact of tumor-host cell interactions has been recognized as an important pathogenesis mechanism in development of MPE.

Hemostatic Biomarkers and Cancer Prognosis: Where Do We Stand?

Cancer patients are characterized by hypercoagulable state and an increased rate of thrombotic events, the most common being venous thromboembolism. Several hemostatic pathways that are significantly implicated in mechanisms of thromboembolic disease are also involved in growth, invasion, and metastatic spread of malignant cells as well in tumor-induced neo-angiogenesis. This close connection between cancer and the hemostatic system has prompted numerous studies on the role of alterations in the level plasma biomarkers of the different compartments of hemostasis in predicting cancer prognosis. In this review, we collect the results of several exemplificative studies that have evaluated clotting activation biomarkers in relation to different cancer outcomes with a final emphasis on current research and forthcoming directions in this field.

Extramammary Paget's Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments.

Extramammary Paget’s disease (EMPD) is a rare neoplasm that usually develops in apocrine gland-bearing areas, such as the vulva, scrotum, and penis. EMPD may present with a focal, multifocal, or an ectopic lesion. Clinically, EMPD lesions often exhibit infiltrative erythema, which is sometimes similar to other skin disorders such as eczema. While primary EMPD arises as intraepithelial neoplasm of the epidermis, EMPD-like lesions may occur from epidermotropic spread of malignant cells or direct extension from an underlying internal neoplasm, known as secondary EMPD. Because treatment strategies differ for primary EMPD and secondary EMPD, accurate diagnosis based on detailed histopathological evaluation is required. In the early stages, EMPD usually shows indolent growth, and most cases are diagnosed as carcinoma in situ. However, invasive lesions may result in metastases, and deep invasion is associated with high incidence of metastases. Conventional chemotherapies have been used for EMPD treatment in patients with distant metastases, but the efficacy is not satisfactory, and the prognosis for such patients remains poor. Recent studies have provided various insights into the molecular pathogenesis of the development and advancement of EMPD, which may lead to novel treatment approaches for metastatic EMPD. This review addresses the diagnosis, pathogenesis, and treatment of EMPD with focus on recent progress in understanding this disease.

Port site metastases a year after initial laparoscopic cholecystectomy. Should the use of retrieval bags during laparoscopic cholecystectomy be the new gold standard?

Port site metastases a year after initial laparoscopic cholecystectomy. Should the use of retrieval bags during laparoscopic cholecystectomy be the new gold standard?