Advanced Cancer Disease Research Articles

Patients with major medical illness seek cosmetic procedures to preserve a healthy appearance and avoid looking ill

Patients with major medical illness seek cosmetic procedures to preserve a healthy appearance and avoid looking ill

Novel Combinatorial Approaches to Tackle the Immunosuppressive Microenvironment of Prostate Cancer.

Simple SummaryThe mainstay of treatment for advanced prostate cancer (PCa) is androgen deprivation therapy (ADT), and although patients initially respond, almost all will eventually develop progressive and metastatic disease. Metastatic, hormone-resistant prostate cancer is essentially incurable. A key problem with ADT is that it is not effective in the long term, partly due to the fact that prostate cancers can switch from requiring androgen to grow to surviving without it and these new tumor cells are more sensitive to stress hormones released by the brain as a consequence of chronic stress/depression. Moreover, both extensive treatment with ADT and chronic stress/depression lead to the recruitment of immature myeloid-derived suppressor cells (MDSCs) which are known to suppress immune responses against tumors. The future of prostate cancer treatments will most certainly include a combination of vaccine with beta-blockers (to interfere with signals from stress hormones) and/or the use of histone deacetylase (HDAC) inhibitors which prevent the function/recruitment of MDSC where timing will be of critical importance.Prostate cancer (PCa) is the second-most common cancer in men worldwide and treatment options for patients with advanced or aggressive prostate cancer or recurrent disease continue to be of limited success and are rarely curative. Despite immune checkpoint blockade (ICB) efficacy in some melanoma, lung, kidney and breast cancers, immunotherapy efforts have been remarkably unsuccessful in PCa. One hypothesis behind this lack of efficacy is the generation of a distinctly immunosuppressive prostate tumor microenvironment (TME) by regulatory T cells, MDSCs, and type 2 macrophages which have been implicated in a variety of pathological conditions including solid cancers. In PCa, Tregs and MDSCs are attracted to TME by low-grade chronic inflammatory signals, while tissue-resident type 2 macrophages are induced by cytokines such as IL4, IL10, IL13, transforming growth factor beta (TGFβ) or prostaglandin E2 (PGE2) produced by Th2 cells. These then drive tumor progression, therapy resistance and the generation of castration resistance, ultimately conferring a poor prognosis. The biology of MDSC and Treg is highly complex and the development, proliferation, maturation or function can each be pharmacologically mediated to counteract the immunosuppressive effects of these cells. Herein, we present a critical review of Treg, MDSC and M2 involvement in PCa progression but also investigate a newly recognized type of immune suppression induced by the chronic stimulation of the sympathetic adrenergic signaling pathway and propose targeted strategies to be used in a combinatorial modality with immunotherapy interventions such as ICB, Sipuleucel-T or antitumor vaccines for an enhanced anti-PCa tumor immune response. We conclude that a strategic sequence of therapeutic interventions in combination with additional holistic measures will be necessary to achieve maximum benefit for PCa patients.

Total neoadjuvant treatment in locally advanced rectal cancer

Locally advanced rectal cancer requires a multidisciplinary management, traditionally based on neo-adjuvant (chemo) radiotherapy, conservative surgery with total mesorectal excision and adjuvant chemotherapy. Despite effective in term of local control, this strategy is linked to a high risk of distant metastasis (up to 30%). In this context, recent published randomized phase III clinical trials have tested the potential benefits with a different sequencing and/or intensification of the standard components of the trimodal therapy.Here, we briefly assess the efficacy and discuss the clinical relevance of total neoadjuvant treatment with a focus on indications and results in the short-course radiotherapy followed by chemotherapy use for this setting of patients. Long term results and additional prospective studies are necessary to more accurately estimate the clinical benefit and further establish the role of total neoadjuvant therapy in locally advanced rectal cancer disease.

Midazolam and hydroxymidazolam plasma concentrations can be monitored with selected biochemical and physiological parameters of palliative care patients

Rationale & objectiveMidazolam is one of top three drugs used in palliative care. Its use increases in the last days of hospice patients’ lives while safe dosage can be challenging. Equations currently used to estimate glomerular filtration rate, e.g: the Cockroft-Gault (eGFRCR) and the Modification of Diet in Renal Disease (eGFRMDRD) ones, do not generate precise calculations, especially in palliative patients exhibiting variations in body parameters. Our aim was to seek new relationships between mean midazolam (Mavg) and alfahydroxymidazolam (OH-Mavg) concentrations in plasma, and selected biochemical and physiological parameters of palliative patients, to enable optimal midazolam pharmacotherapy. Study design, participants and interventionsThe pilot study included 11 Caucasians, aged 42–95, with advanced cancer disease, receiving midazolam in a hospice in-patient unit. We tested correlations among Mavg, BMI, eGFRMDRD, midazolam clearance (CL), OH-Mavg, bilirubin (Bil) and blood creatinine concentration (Cr). F test and leave-one out (LOO) validation was applied to verify the correlations’ significance and predictive ability. ResultsWe found ten statistically significant (p < 0.05) correlations related to midazolam pharmacokinetics and physiological factors. We formulated two equations with high degree of predictive ability, based on the eGFRMDRD→CL and the (Bil + BMI × Ln(Cr))→Mavg-(OH-Mavg) correlations.The limitations of the study mainly revolve around its pilot nature and the need to continue testing the results on a bigger population.No funding to disclose. ConclusionsThe significance of correlations corresponding to the arithmetic expressions confirms that Bil, BMI, Ln(Cr) analyzed simultaneously report a series of processes on which midazolam metabolism depends. Two of ten correlations proposed came close to meet all LOO validation criteria. Current findings can help optimize midazolam treatment in palliative therapy.

Macrophage-mediated vascular permeability via VLA4/VCAM1 pathway dictates ascites development in ovarian cancer.

The development of ascites correlates with advanced stage disease and poor prognosis in ovarian cancer. Vascular permeability is the key pathophysiological change involved in ascites development. Previously, we provided evidence that perivascular M2-like macrophages protect the vascular barrier through direct contact with endothelial cells (ECs). Here, we investigated the molecular mechanism and its clinical significance in the ovarian cancer setting. We found that upon direct coculture with the endothelium, M2 macrophages tuned down their VLA4 and reduced the levels of VCAM1 in ECs. On the other hand, ectopically overexpressing VLA4 in macrophages or VCAM1 in ECs induced hyperpermeability. Mechanistically, downregulation of VLA4 or VCAM1 led to reduced levels of RAC1 and ROS, which resulted in decreased phosphorylation of PYK2 (p-PYK2) and VE-cadherin (p-VE-cad), hence enhancing cell adhesion. Furthermore, targeting the VLA4/VCAM1 axis augmented vascular integrity and abrogated ascites formation in vivo. Finally, VLA4 expression on the macrophages isolated from ascites dictated permeability ex vivo. Importantly, VLA4 antibody acted synergistically with bevacizumab to further enhance the vascular barrier. Taking these data together, we reveal here that M2 macrophages regulate the vascular barrier though the VCAM1/RAC1/ROS/p-PYK2/p-VE-cad cascade, which provides specific therapeutic targets for the treatment of malignant ascites.

The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment.

Simple SummaryImmunotherapy improved the therapeutic landscape for patients with advanced cancer diseases. However, many patients do not benefit from immunotherapy. The bidirectional crosstalk between myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) contributes to immune evasion, limiting the success of immunotherapy by checkpoint inhibitors. This review aims to outline the current knowledge of the role and the immunosuppressive properties of MDSC and Treg within the tumor microenvironment (TME). Furthermore, we will discuss the importance of the functional crosstalk between MDSC and Treg for immunosuppression, issuing particularly the role of cell adhesion molecules. Lastly, we will depict the impact of this interaction for cancer research and discuss several strategies aimed to target these pathways for tumor therapy.Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many patients still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within the tumor microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), contributes to the development of immune resistance. MDSC and Treg expand systematically in tumor patients and inhibit T cell activation and T effector cell function. Numerous studies have shown that the immunosuppressive mechanisms exerted by those inhibitory cell populations comprise soluble immunomodulatory mediators and receptor interactions. The latter are also required for the crosstalk of MDSC and Treg, raising questions about the relevance of cell–cell contacts for the establishment of their inhibitory properties. This review aims to outline the current knowledge on the crosstalk between these two cell populations, issuing particularly the potential role of cell adhesion molecules. In this regard, we further discuss the relevance of β2 integrins, which are essential for the differentiation and function of leukocytes as well as for MDSC–Treg interaction. Lastly, we aim to describe the impact of such bidirectional crosstalk for basic and applied cancer research and discuss how the targeting of these pathways might pave the way for future approaches in immunotherapy.

The expression of Galectin-3 in breast cancer and its association with metastatic disease: a systematic review of the literature.

Breast cancer is the most common form of cancer and the second highest cause of cancer mortality in female patients. The significance of the expression of Galectin-3 has been correlated with various malignancy types and in data from several research papers, the expression of Galectin-3 has been associated with the progression and metastasis of breast cancer. In the present study, the authors' goal is to identify whether the expression of Galectin-3 in breast cancer can be associated with the presence and/or recurrence of a metastatic disease. Both Scopus and PubMed databases were utilized, by inputting the following combination of keywords: (((Breast) AND Metastasis)) AND ((Galectin 3) OR Galectin-3). The time of publication and text availability were not considered when searching the databases and all relevant articles in English were initially accepted. We included one case-control study, three retrospective case studies and one retrospective cohort study. In two of the included studies, the levels in concentration of Galectin-3 were not correlated with a significant difference in prognosis. In two studies, the lacking in expression of Galectin-3 was associated with a worse prognosis and in one of the studies selected, the elevated levels of Galectin-3 were correlated with recurrence of disease in triple negative breast cancer cases. For most of the studies selected for this review, the results were contradictory in regard to the role of Galectin-3 for prognosis and metastatic potential in female breast cancer patients. It is still unclear, whether Galectin-3 can be used as a prognostic marker for advanced breast cancer disease.

Forkhead box P3 and indoleamine 2,3-dioxygenase co-expression in Pakistani triple negative breast cancer patients.

BACKGROUNDForkhead box P3 (FOXP3) is a specific marker for immunosuppressive regulatory T (T-reg) cells. T-regs and an immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO), are associated with advanced disease in cancer. AIMTo evaluate the co-expression of FOXP3 and IDO in triple negative breast cancer (TNBC) with respect to hormone-positive breast cancer patients from Pakistan. METHODSImmunohistochemistry was performed to analyze the expression of FOXP3, IDO, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor on tissues of breast cancer patients (n = 100): Hormone-positive breast cancer (n = 51) and TNBC (n = 49). A total of 100 patients were characterized as FOXP3 negative vs positive and further categorized based on low, medium, and high IDO expression score. Univariate and multivariate logistic regression models were used.RESULTSOut of 100 breast tumors, 25% expressed FOXP3 positive T-regs. A significant co-expression of FOXP3 and IDO was observed among patients with TNBC (P = 0.01) compared to those with hormone-positive breast cancer. Two variables were identified as significant independent risk factors for FOXP3 positive: IDO expression high (adjusted odds ratio (AOR) 5.90; 95% confidence interval (CI): 1.22-28.64; P = 0.03) and TNBC (AOR 2.80; 95%CI: 0.96-7.95; P = 0.05). CONCLUSIONOur data showed that FOXP3 positive cells might be associated with high expression of IDO in TNBC patients. FOXP3 and IDO co-expression may also suggest its involvement in disease, and evaluation of FOXP3 and IDO expression in TNBC patients may offer a new therapeutic option.

Cardiovascular Complications of Prostate Cancer Treatment.

Treatment of prostate cancer (PC) is a rapidly evolving field of pharmacology research. In recent years, numerous novel therapeutics that improve survival and ameliorate disease control have been approved. Currently, the systemic treatment for prostate neoplasm consists of hormonal therapy, chemotherapy, immunotherapy, radiopharmaceuticals, targeted therapy, and supportive agents (e.g., related to bone health). Unfortunately, many of them carry a risk of cardiovascular complications, which occasionally pose a higher mortality threat than cancer itself. This article provides a unique and comprehensive overview of the prevalence and possible mechanisms of cardiovascular toxicities of all PC therapies, including state-of-the-art antineoplastic agents. Additionally, this article summarizes available recommendations regarding screening and prevention of the most common cardiac complications among patients with advanced cancer disease.

Need for palliative care in patients admitted to emergency departments of three tertiary hospitals: evidence from a Latin-American city

Background: Emergency departments (ED) serve as a contact point for critically ill patients. According to experience, a fraction of patients visiting ED present with symptoms and require palliative care; however, the prevalence of these patients has not been determined in Peru so far. Objectives: To estimate the prevalence of advanced disease in patients admitted to ED and identify among them the need for palliative care. Patients and methods: In the ED of 3 tertiary hospitals in Lima all adult patients had an evaluation of the medical history and an interview with patients or caregivers. The presence of multiple metastases was considered advanced cancer, and dementia, neurological, respiratory, hepatic or cardiac disease with functional dependence or severe deterioration for non-oncological illness. The screening tool was a validated and adapted palliative care questionnaire. Results: The prevalence of advanced illness was 7.5% (60 of 797 admissions). The age of patients was 19–96 (median 73.1) years of which 48.3% were females, 23 (39%) patients had oncological and 37 (61%) patients non-oncological diagnoses. The most frequent symptoms upon admission were dyspnoea, drowsiness, and pain. A total of 13 (21.7%) of patients with advanced disease were already receiving palliative care and 8 (13.3%) had controlled symptoms. Conclusions: Nearly 1 in 13 patients attending ED of tertiary hospitals has advanced disease, of which 80% reported the need for palliative care with less than a quarter of them having received it.

Value of preoperative HE4 as predictor of advanced disease in endometrioid endometrial cancer.

To explore the predictive value of serum human epididymis protein 4 (HE4) marker in the preoperative prediction of the risk of advanced disease in the endometrioid subtype of endometrial cancer, and its association with poor prognostic factors. In addition, a cut-off value of HE4 was defined to classify patients according to these results. Prospective and multicenter cohort analytical pilot study of patients operated for endometrial cancer at the Miguel Servet University Hospital of Zaragoza (Spain) and the Complejo Universitario of León (Spain) from January 2017 to May 2019. Preoperative serum levels of HE4 were analyzed by clinical and pathologic characteristics. In all, 126 patients were included. A statistically significant association was found between the preoperative HE4 value and node involvement (P=0.008), late-stage disease (P=0.003), high histologic grade (P=0.007), deep myometrial invasion (P=0.001), lymphovascular space invasion (P=0.001), and other pathologic factors. In addition, an HE4 cut-off value (156.4pmol/L) has been determined to predict, preoperatively, which patients will present with early stage disease. The preoperative marker HE4 is a useful tool in the preoperative study of patients with endometrial cancer as it relates to late-stage disease as well as other prognostic factors in the endometrioid subtype of endometrial cancer.

Immunostimulatory and anticancer effect of Reishi and Coriol extracts at the level of clinical studies and their implementation in practice

Background Mushrooms Reishi and Coriolus have been used for centuries in Asian countries to treat various diseases, mainly respiratory tract infections or pulmonary diseases, and more recently also cancers. Polysaccharides and triterpenes, which are found in these mushrooms, are their main bio-active components. Preclinical and clinical studies in humans presented their beneficial effects as immunomodulators; besides this, they possess a direct anticancer effect. In Asia, they are used after cancer treatment as single agents or in combination with chemotherapy or radiotherapy. Extracts from Coriolus have been approved for more than 30 years as an effective adjuvant addition to standard cancer treatment in Japan and China without obvious toxicity. Purpose In this review, clinical studies with Reishi and Coriolus in cancer patients and their meta-analyses are briefly summarized. Conclusion Both extracts from Reishi and Coriolus, if used in combination with standard therapy or as an adjuvant single agent, have shown benefits at immune function measures, tumor-related symptoms and performance status of cancer patients. Moreover, they have prolonged their disease-free interval and overall survival. They are well tolerated even in advanced cancer diseases and could be safely used continuously for long periods of time. Because of clinically approved efficacy and safety, they are applied mainly in some countries as a complementary therapy for various types of cancers.

Comorbidity Burden and Presence of Multiple Intracranial Lesions Are Associated with Adverse Events after Surgical Treatment of Patients with Brain Metastases.

Simple SummaryPatients with brain metastasis must face advanced cancer diseases, and neurosurgical resection is often considered an inevitable part of treatment. However, peri- and postoperative complications might further worsen the prognosis for these vulnerable patients. It is therefore important to investigate risk factors for such unfavorable events in order to recognize high-risk patients at the earliest possible stage of disease. For this purpose, we aimed to identify risk factors for early postoperative complications following surgical resection of brain metastases. Our results showed that the presence of multiple brain metastases in a single patient and a high rate of additional comorbidities were associated with elevated levels of postoperative complications. Furthermore, patients who suffered from such unfavorable postoperative events were significantly more likely to die during the initial hospital stay. The present study therefore might help to preoperatively select for critically ill patients who are in mandatory need of advanced treatment and care.Surgical resection is a key treatment modality for brain metastasis (BM). However, peri- and postoperative adverse events (PAEs) might be associated with a detrimental impact on postoperative outcome. We retrospectively analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSCs) as high-quality metric profiles for PAEs in patients who had undergone surgery for BM in our department between 2013 and 2018. The comorbidity burden was assessed by means of the Charlson comorbidity index (CCI). A multivariate analysis was performed to identify independent predictors for the development of PAEs after surgical resection of BM. In total, 33 patients (8.5%) suffered from PAEs after surgery for BM. Of those, 17 PSI, 5 HAC and 11 CSC events were identified. Multiple brain metastases (p = 0.02) and a higher comorbidity burden (CCI > 10; p = 0.003) were associated with PAEs. In-hospital mortality of patients suffering from a PAE was significantly higher than that of patients without a PAE (24% vs. 0.6%; p < 0.0001). Awareness of risk factors for postoperative complications enables future prevention and optimal response, particularly in vulnerable oncological patients. The present study identified the presence of multiple brain metastases and increased comorbidity burden associated with PAEs in patients suffering from BM.

Timing of Severe Toxicity from Chemotherapy in Patients With Lung Cancer.

The aim of this study was to investigate the timing of severe toxicity in lung cancer patients receiving chemotherapy. Patients with advanced non-small cell lung cancer or limited disease small cell lung cancer included in two randomized controlled trials were analysed. Severe toxicity was defined as grade 3-5 toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. We analysed 569 patients and 433 (76.1%) experienced severe toxicity. Of these, 249 (57.5%) experienced the first episode of severe toxicity after the first, 109 (25.2%) after the second, 54 (12.5%) after the third and 18 (4.2%) after the fourth course of chemotherapy. Performance status (PS 2 vs. 0-1; p=0.046) and treatment arm were independent predictive factors for severe toxicity. Severe toxicity was most frequent after the first chemotherapy course, but some patients did not experience severe toxicity until after the fourth course. Accounting for timing might be important when studying factors predicting severe toxicity.

The pharmacological basis for application of cannabidiol in cancer chemotherapy

Chemotherapy is one of the therapeutic approaches for cancer treatment and has demonstrated great success with the introduction of selectively acting molecules against specific biomarkers of some types of tumors. Despite this success there is a large unmet need for novel therapies that provide effective control on the progression of advanced or drug-resistant cancer diseases. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, as possible agents for cancer therapy. We analyzed the anticancer properties and mechanism of action of cannabidiol (CBD), the main non-psychoactive cannabinoid received from hemp of Cannabis plant. Despite of data for pleiotropic effects of CBD, we here present the results for the efficacy of CBD in the modulation of different stages of cancer development. The analysis of the anticancer properties of CBD is made in relation to the proposed or newly discovered molecular targets of action. Thereafter, we consider the specific effects of CBD on primary tumors, their invasiveness and metastases, whether the influence on identified tumor markers in different types of tumors reflect the therapeutic potential of CBD. The studies reviewed herein indicate that CBD elicit activity through the cannabinoid receptor dependent and independent pathways. The processes such as ceramide production, ER-stress, autophagy and apoptosis, angiogenesis and matrix remodeling also appear to regulate the anticancer activity of CBD. So, the pharmacological basis for therapeutic application of CBD is constructed on the scientific data for its antitumor activity, extensively provided studies in vitro and in vivo in animal tumor models, and available data on the safety profile of clinically approved CBD products. We also try to reduce the deficits of our understanding in relation of pharmacological synergistic interactions of CBD with cytostatic drugs, where data remains limited. It is recognized that more studies for defining the specific molecular and signaling mechanisms of anticancer action of cannabinoids, particularly CBD, requires further evaluation. We believe that the therapeutic advantages of CBD are associated not only with its non-psychoactive behavior, but also are related to its influence on the important biochemical pathways and signal molecules, defining the genome instability and specific changes of the malignant tumor cells.

Disability in Basic Activities of Daily Living Is Associated With Symptom Burden in Older People With Advanced Cancer or Chronic Obstructive Pulmonary Disease: A Secondary Data Analysis

ContextManaging activities of daily living is important to people with advanced cancer or chronic obstructive pulmonary disease (COPD). Understanding disability in activities of daily living may inform service planning. ObjectiveTo identify the prevalence of disability in activities of daily living, associations and change over time, in older people with advanced cancer or COPD. MethodsSecondary analysis of International Access, Rights and Empowerment (IARE) studies in adults aged ≥65 years with advanced disease in the United Kingdom, Ireland, and United States, using cross-sectional (IARE I & II) and longitudinal (IARE II, 3 timepoints over 6 months) data. Measures included disability in activities of daily living (Barthel Index), symptom severity (Palliative Outcome Scale), and assistive device use (self-reported). Logistic regression was used to identify relationships between disability and age, sex, living alone, diagnosis, and symptom burden; visual graphical analysis explores individual disability trajectories. ResultsOne hundred fifty-nine participants were included (140 cancer, 19 COPD). Sixty-five percent had difficulty climbing stairs, 48% bathing, 39% dressing, and 36% mobilizing. Increased disability was independently associated with increased symptom burden (odds ratio, 1.08 [95% CI:1.02–1.15], P = 0.01) and walking unaided (z = 2.35, P = 0.02), but not with primary diagnosis (z = −0.47, P = 0.64). Disability generally increased over time but with wide interindividual variation. ConclusionDisability in activities of daily living in advanced cancer or COPD is common, associated with increased symptom burden, and may be attenuated by use of assistive devices. Individual disability trajectories vary widely, with diverse disability profiles. Services should include rehabilitative interventions, guided by disability in individual activities of daily living.

A novel co-culture assay to assess anti-tumor CD8+ T cell cytotoxicity via luminescence and multicolor flow cytometry

T cell immunotherapies have shown great promise in patients with advanced cancer disease, revolutionizing treatment. T cell cytotoxicity is crucial in its efficacy, therefore developing ex vivo methods testing tumor and T cell interactions is pivotal. Increasing efforts have been made in developing co-culture assays with sophisticated materials and platforms aiming to mimic the tumor microenvironment (TME), but its complexity makes it difficult to develop the ideal model. In this study, we developed a simple co-culture assay, reproducible in any lab, but respecting the multicellular nature of the TME. Our goal is to combine in a single assay well-established techniques such as a luciferase assay for target cell viability analysis, a CD107a degranulation assay, and multicolor flow cytometry for the detection of cytokines and cytotoxicity markers. Cell suspensions of whole spleens and tumors containing splenic or tumor-infiltrating effector T cells of mice bearing Lewis lung carcinoma (LLC) or CT26 colon carcinoma tumors treated with radiation alone or in combination with immunotherapies were used for co-culture. LLC and CT26 cell lines transduced with the firefly luciferase gene were used as target cells. We demonstrated that splenocytes and tumor-infiltrating T cells derived from mice treated with combination therapy were able to kill approximately 50% of target cells after 48 h of co-culture. This effect was tumor cell-specific and dependent on CD8+ T cells evidenced by in vitro CD8+ T cell depletion. Flow cytometry demonstrated increased expression of CD107a and production of granzyme B, IFNγ, and TNFα by CD8+ T cells. Our co-culture assay is therefore suitable as proof of principle for in vivo therapeutic studies testing immunotherapies, and specifically to assess the involvement of cytotoxic CD8+ T cells in treatment response in LLC and CT26 tumor models. We also propose this assay as an ex vivo platform for high-throughput screening of immunomodulating agents to be tested in these two murine tumor models. This assay can be adapted to other tumor models after optimizations.

Italian Version of Cancer Dyspnea Scale: Cultural-Linguistic and Clinical Validation in Patients With Advanced Cancer Disease in Palliative Care Settings

ContextThe Cancer Dyspnea Scale (CDS) is a self-reported multidimensional tool used for the assessment of dyspnea, a subjective experience of breathing discomfort, in patients with cancer. The scale describes dyspnea using three distinct factors: physical, psychological, and discomfort at rest. ObjectivesTo crossculturally validate the Italian version of CDS (CDS-IT) and examine its content validity, feasibility, internal consistency, and construct validity in patients with advanced cancer. MethodsA cross-sectional study was conducted. CDS-IT was forward-backward translated, and its content was validated among a group of experts. Cronbach's α coefficients were used to assess the internal consistency. Construct validity was examined in terms of structural validity through confirmatory factor analysis, and convergent validity was examined with Visual Analogue Scale Dyspnea through the Pearson's correlation coefficient (r). Cancer Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care) and Italian Palliative Outcome Scale were also tested. ResultsThe CDS-IT was crossculturally validated and showed satisfactory content validity. A total of 101 patients (mean age = 76 [SD = 12]; 53% females) were recruited in palliative care settings. CDS-IT reported a good internal consistency in the total score and its factors (α = 0.74–0.83). The factor analysis corresponded acceptably but not completely with the original study. CDS-IT strongly correlated with Visual Analogue Scale Dyspnea (r = 0.68) and moderately with Italian Palliative Outcome Scale and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (r = 0.33–0.36, respectively). ConclusionThe study findings supported the crosscultural validity of the CDS-IT. Its feasibility, internal consistency, and construct validity are satisfactory for clinical practice. The CDS-IT is available to health care professionals as a useful tool to assess dyspnea in patients with cancer.

Robotic interval debulking surgery for advanced epithelial ovarian cancer: current challenge or future direction? A systematic review.

We evaluated the effectiveness, safety and efficacy of robotic interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NACT). We conducted a systematic review of the published relevant studies. Α total of 102 patients were evaluated. Mean operative time ranged from 164 to 312min (mean ± SD: 246 ± 61min) while mean estimated blood loss ranged from 106.9 to 262.5ml (mean ± SD: 168 ± 68ml) and postoperative blood transfusion rate was 19% (n = 19/98). Complete cytoreduction rate (R0 resection) was achieved in 75 patients (76.5%), whereas residual disease ≤ 1cm in 21 women (21.5%). Mean hospital stay was 2.4days. No intraoperative and six postoperative (14.6%) complications were reported. Laparotomy conversion rate was 9.2% (9/98) mostly in the terms of achieving complete cytoreduction and 30-day mortality rate was 9.2% (n = 9/98). The median overall survival varied from 39.7 to 47.2months, while the progression-free survival ranged from 20.6 to 21.2months during a median follow-up period from 2 to 86months (median 25.3months). A total of 60 women (61%) developed disease recurrence. One of the studies reported significantly improved OS and PFS in patients who underwent robotic IDS when compared to those who had laparotomy either during or before the addition of robotic surgery in the management of advanced ovarian cancer disease (47.2 vs 37.8 vs 37.9, p = 0.004 for OS and 20.6 vs 13.9 vs 11.9, p = 0.005 for PFS, respectively). The same was also observed when controlling the parameters of age and stage for patients in the robotic arm (p = 0.02). Robotic interval debulking surgerycan be considered in the management of advanced ovarian cancer patients after receiving neoadjuvant chemotherapy. Larger meta-analyses including multicenter randomized control trials are necessary to specify the exact profile of the patients that could benefit from this treatment strategy.

Local Endoscopic Treatment of Locally Advanced Pancreatic Cancer

Pancreatic adenocarcinoma is one of the cancers with the poorest prognosis, and its incidence has gradually increased to become the 9th most common cancer in Korea in 2016. Surgical resection is the only treatment option to improve the cure and longterm survival rate. Unfortunately, only 10% to 20% of all pancreatic cancer patients present with resectable disease, because of common symptoms are rarely noticeable in its early stages and disease progress very quickly. Unresectable pancreatic cancer can be divided into locally advanced pancreatic cancer (LAPC) and metastatic disease. Pancreatic cancer with distant metastasis accounts for about 40–60% of the total pancreatic cancer and systemic chemotherapy is considered as standard treatment. LAPC is observed in 30–40%, defined as the tumor surrounding major blood vessels (especially, celiac artery and superior mesenteric artery) more than 180° without distant metastasis which cannot be completely removed by surgery. Standard treatment for LAPC has not yet been established, and chemotherapy and radiotherapy have mainly been used, but in most cases, response to these therapeutic options has been limited. As imaging techniques, endoscopic devices and procedures have recently been developed and the role of local endoscopic therapies for LAPC has expanded. This article provides an overview of local endoscopic treatment for LAPC such as injection therapy, radiofrequency ablation (RFA), irreversible electroporation (IRE), radiotherapy and drug-delivery stent insertion.