Optimized procedure for high-throughput transcriptome profiling of small extracellular vesicles isolated from low volume serum samples.

OBJECTIVES: Small extracellular vesicles (EVs) contain various signaling molecules, thus playing a crucial role in cell-to-cell communication and emerging as a promising source of biomarkers. However, the lack of standardized procedures impedes their translation to clinical practice. Thus, we compared different approaches for high-throughput analysis of small EVs transcriptome. METHODS: Small EVs were isolated from 150 µL of serum. Quality and quantity were assessed by dynamic light scattering, transmission electron microscopy, and Western blot. Comparison of RNA extraction efficiency was performed, and expression of selected genes was analyzed by RT-qPCR. Whole transcriptome analysis was done using microarrays. RESULTS: Obtained data confirmed the suitability of size exclusion chromatography for isolation of small EVs. Analyses of gene expression showed the best results in case of samples isolated by Monarch Total RNA Miniprep Kit. Totally, 7,182 transcripts were identified to be deregulated between colorectal cancer patients and healthy controls. The majority of them were non-coding RNAs with more than 70 % being lncRNAs, while protein-coding genes represented the second most common gene biotype. CONCLUSIONS: We have optimized the protocol for isolation of small EVs and their RNA from low volume of sera and confirmed the suitability of Clariom D Pico Assays for transcriptome profiling.

MicroRNA Biogenesis Pathway Genes Are Deregulated in Colorectal Cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Each step of their production and maturation has to be strictly regulated, as any disruption of control mechanisms may lead to cancer. Thus, we have measured the expression of 19 genes involved in miRNAs biogenesis pathway in tumor tissues of 239 colorectal cancer (CRC) patients, 17 CRC patients with liver metastases and 239 adjacent tissues using real-time PCR. Subsequently, the expression of analyzed genes was correlated with the clinical-pathological features as well as with the survival of patients. In total, significant over-expression of all analyzed genes was observed in tumor tissues as well as in liver metastases except for LIN28A/B. Furthermore, it was shown that the deregulated levels of some of the analyzed genes significantly correlate with tumor stage, grade, location, size and lymph node positivity. Finally, high levels of DROSHA and TARBP2 were associated with shorter disease-free survival, while the over-expression of XPO5, TNRC6A and DDX17 was detected in tissues of patients with shorter overall survival and poor prognosis. Our data indicate that changed levels of miRNA biogenesis genes may contribute to origin as well as progression of CRC; thus, these molecules could serve as potential therapeutic targets.

Communication with cancer patient.

The oncological patients meet the diverse physicians in the different stages of their illness. It is important for other physicians to know a basic rules of supportive effective communication. There are big differences between patients in the communication style and type of information they accept. Patient´s information requirements may also change at various stages of the disease. Providing bad news is a frequent and important communication challenge for physicians. Internationally recognized and proven recommendation for communication is the six steps known as the SPIKES. Prolonging survival of cancer patients means not only communicating disease information but also information about irreversible and potentially irreversible side effects of treatment, disease complications, and limited prognosis. The communication skills are not inborn and do not necessarily improve with the clinical experience, this skill should be learned through structured communication training. Its the effective communication that lets talk sensitively about serious facts in the time-limited consultation.

Efficacy of bevacizumab and chemotherapy in the first-line treatment of metastatic colorectal cancer: broadening KRAS-focused clinical view.

BACKGROUND: The aim of the present retrospective study was to analyze clinical outcome and risk factors associated with treatment outcomes according to KRAS status in patient with metastatic colorectal cancer (mCRC) treated with bevacizumab (bev) plus chemotherapy in the first-line setting. METHODS: We performed observational study on 1622 patients with mCRC treated with bev plus oxaliplatin- or irinotecan-based chemotherapy, and correlated treatment outcomes with KRAS mutation status. The primary endpoint was progression-free survival (PFS) and additionally overall survival (OS). Adverse events of bevacizumab and risk factors including location of metastases were evaluated. RESULTS: Mutation in KRAS was present in 40.6% of mCRC cases. The median PFS in patients with wild-type KRAS (wtKRAS) vs mutant KRAS was 11.5 vs 11.4 months, respectively. The median OS was 30.7 vs 28.4 months (p = 0.312). Patients with KRAS mutation had lung metastases more frequently than wtKRAS individuals (32.0% vs 23.8%; p = 0.001). We observed no difference in clinical outcome between hepatic and extrahepatic metastatic disease. CONCLUSION: KRAS mutation does not interfere with clinical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC patients.

Enhancing patient well-being in oncology waiting rooms: a pilot field experiment on the emotional impact of virtual forest therapy.

Introduction: This study explores the emotional impact of virtual forest therapy delivered through audio-visual recordings shown to patients in the oncology waiting rooms, focusing on whether simulated forest walks can positively influence patients' emotional states compared to traditional waiting room stimuli. Methods: The study involved 117 participants from a diverse group of oncology patients in the outpatient clinic waiting room at the Masaryk Memorial Cancer Institute. Using a partially randomized controlled trial design, the study assessed basic emotional dimensions-valence and arousal-as well as specific psychological states such as thought control, sadness, anxiety, and pain. This assessment used the Self-Assessment Manikin and the modified Emotional Thermometer before and after participants watched three video types (forest, sea, news). Baseline stress levels were measured using the Kessler Psychological Distress Scale (K6). Results: Participants exposed to forest and sea videos reported significant improvements in emotional valence and reduced arousal, suggesting a calming and uplifting effect. No significant changes were observed in the control and news groups. Secondary outcomes related to anxiety, sadness, and pain showed no significant interaction effects, though small but significant main effects of time on these variables were noted. Discussion: The findings suggest that videos of forest and sea can be a beneficial intervention in the oncology waiting rooms by enhancing patients' emotional well-being. This pilot study underscores the potential for integrating virtual mental health support elements into healthcare settings to improve patient care experience.

N-glycan profiling of tissue samples to aid breast cancer subtyping.

Breast cancer is a highly heterogeneous disease. Its intrinsic subtype classification for diagnosis and choice of therapy traditionally relies on the presence of characteristic receptors. Unfortunately, this classification is often not sufficient for precise prediction of disease prognosis and treatment efficacy. The N-glycan profiles of 145 tumors and 10 healthy breast tissues were determined using Matrix-Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry. The tumor samples were classified into Mucinous, Lobular, No-Special-Type, Human Epidermal Growth Factor 2 + , and Triple-Negative Breast Cancer subtypes. Statistical analysis was conducted using the reproducibility-optimized test statistic software package in R, and the Wilcoxon rank sum test with continuity correction. In total, 92 N-glycans were detected and quantified, with 59 consistently observed in over half of the samples. Significant variations in N-glycan signals were found among subtypes. Mucinous tumor samples exhibited the most distinct changes, with 28 significantly altered N-glycan signals. Increased levels of tri- and tetra-antennary N-glycans were notably present in this subtype. Triple-Negative Breast Cancer showed more N-glycans with additional mannose units, a factor associated with cancer progression. Individual N-glycans differentiated Human Epidermal Growth Factor 2 + , No-Special-Type, and Lobular cancers, whereas lower fucosylation and branching levels were found in N-glycans significantly increased in Luminal subtypes (Lobular and No-Special-Type tumors). Clinically normal breast tissues featured a higher abundance of signals corresponding to N-glycans with bisecting moiety. This research confirms that histologically distinct breast cancer subtypes have a quantitatively unique set of N-glycans linked to clinical parameters like tumor size, proliferative rate, lymphovascular invasion, and metastases to lymph nodes. The presented results provide novel information that N-glycan profiling could accurately classify human breast cancer samples, offer stratification of patients, and ongoing disease monitoring.

Investigation of long non-coding RNAs in extracellular vesicles from low-volume blood serum specimens of colorectal cancer patients.

Colorectal cancer (CRC) is the second most prevalent cancer type worldwide, which highlights the urgent need for non-invasive biomarkers for its early detection and improved prognosis. We aimed to investigate the patterns of long non-coding RNAs (lncRNAs) in small extracellular vesicles (sEVs) collected from low-volume blood serum specimens of CRC patients, focusing on their potential as diagnostic biomarkers. Our research comprised two phases: an initial exploratory phase involving RNA sequencing of sEVs from 76 CRC patients and 29 healthy controls, and a subsequent validation phase with a larger cohort of 159 CRC patients and 138 healthy controls. Techniques such as dynamic light scattering, transmission electron microscopy, and Western blotting were utilized for sEV characterization. Optimized protocol for sEV purification, RNA isolation and preamplification was applied to successfully sequence the RNA content of sEVs and validate the results by RT-qPCR. We successfully isolated sEVs from blood serum and prepared sequencing libraries from a low amount of RNA. High-throughput sequencing identified differential levels of 460 transcripts between CRC patients and healthy controls, including mRNAs, lncRNAs, and pseudogenes, with approximately 20% being lncRNAs, highlighting several tumor-specific lncRNAs that have not been associated with CRC development and progression. The validation phase confirmed the upregulation of three lncRNAs (NALT1, AL096828, and LINC01637) in blood serum of CRC patients. This study not only identified lncRNA profiles in a population of sEVs from low-volume blood serum specimens of CRC patients but also highlights the value of innovative techniques in biomolecular research, particularly for the detection and analysis of low-abundance biomolecules in clinical samples. The identification of specific lncRNAs associated with CRC provides a foundation for future research into their functional roles in cancer development and potential clinical applications.

Extraction, Labeling, Clustering, and Semantic Mapping of Segments From Clinical Notes.

This work is motivated by the scarcity of tools for accurate, unsupervised information extraction from unstructured clinical notes in computationally underrepresented languages, such as Czech. We introduce a stepping stone to a broad array of downstream tasks such as summarisation or integration of individual patient records, extraction of structured information for national cancer registry reporting or building of semi-structured semantic patient representations that can be used for computing patient embeddings. More specifically, we present a method for unsupervised extraction of semantically-labeled textual segments from clinical notes and test it out on a dataset of Czech breast cancer patients, provided by Masaryk Memorial Cancer Institute (the largest Czech hospital specialising exclusively in oncology). Our goal was to extract, classify (i.e. label) and cluster segments of the free-text notes that correspond to specific clinical features (e.g., family background, comorbidities or toxicities). Finally, we propose a tool for computer-assisted semantic mapping of segment types to pre-defined ontologies and validate it on a downstream task of category-specific patient similarity. The presented results demonstrate the practical relevance of the proposed approach for building more sophisticated extraction and analytical pipelines deployed on Czech clinical notes.

The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers.

Calcium channel blockers are among the most commonly used agents in the treatment of cardiovascular diseases. There are several known side-effects associated with their long-term use, whereas other potential adverse effects are yet to be proven. This study aims to evaluate the association between calcium channel blockers exposure and the incidence of second primary malignancy. We established a cohort of 1401 patients with colorectal cancer diagnosed in our institution between January 2003 and December 2016. Patients were followed-up until December 2020. The tumor characteristics and basic clinical data including medication information were obtained from the hospital information system database. Second malignancy was detected in 301 patients (21.5%), and occurred in 27.8% of patients who used calcium channel blockers compared to only 19.9% among non-users. Their use was associated with an increased incidence of bladder cancer in particular. Subanalysis of patients with second malignancy displayed a higher proportion of right-sided colon cancer compared to rectal carcinoma in non-users. Survival analysis revealed significantly better outcomes in early-stage colorectal cancer patients without a history of calcium channel blockers treatment or second primary malignancy.

The effectiveness of three mobile-based psychological interventions in reducing psychological distress and preventing stress-related changes in the psycho-neuro-endocrine-immune network in breast cancer survivors: Study protocol for a randomised controlled trial.

Background: A growing body of literature shows that psychological distress is not only a major threat to psychological well-being but can also have a significant impact on physical health. In cancer patients, it can negatively affect prognosis and posttreatment recovery processes. Since face-to-face psychological interventions are often inaccessible to cancer patients, researchers have recently been focusing on the effectiveness of eHealth adaptations of well-established approaches. In this context, there has been a call for high-quality randomised controlled trials that would allow for a direct comparison of different approaches, potentially addressing different needs and preferences of patients, and also for more systematic research focusing on how psychological interventions affect not only psychological but also biological markers of stress. Both of these questions are addressed in the present study. Methods: A randomised controlled trial will be carried out to test and compare the effectiveness of three eight-week eHealth programmes for the mental health support of cancer patients. All programmes will be delivered through the same application for mobile devices MOU MindCare. N = 440 of breast cancer survivors will be recruited at the end of their adjuvant treatment (chemotherapy, radiotherapy, or both) and randomly assigned to one of the three interventions - Mindfulness-Based Cognitive Therapy for Cancer (MBCT-Ca), Positive Psychology (PP), or Autogenic Training (AT) - or the treatment-as-usual (TAU) control group. Psychological and biological markers of stress and adaptive functioning will be assessed at baseline (T0), post-treatment (T1), three-month follow-up (T2), and nine-month follow-up (T3). Primary outcomes will include heart-rate variability and self-report measures of depression, anxiety, perceived stress, general quality of life, and positive mental health. Secondary outcomes will include the levels of serum cortisol and immunomarkers, sleep quality, fatigue, common health symptoms, and several transdiagnostic psychological variables that are expected to be specifically affected by the MBCT-Ca and PP interventions, including dispositional mindfulness, emotion regulation, self-compassion, perceived hope, and gratitude. The data will be analysed using the mixed model repeated measures (MMRM) approach. Discussion: This trial is unique in comparing three different eHealth interventions for cancer patients based on three well-established approaches to mental health support delivered on the same platform. The study will allow us to examine whether different types of interventions affect different indicators of mental health. In addition, it will provide valuable data regarding the effects of stress-reducing psychological interventions on the biomarkers of stress playing an essential role in cancer recovery processes and general health.

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

INTRODUCTION: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). STUDY DESIGN: Registry-based cohort study including only people with rare head and neck cancers. OBJECTIVES: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. METHODS: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. RESULTS: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.

Use of Hypolipidemic Drugs and the Risk of Second Primary Malignancy in Colorectal Cancer Patients.

An increasing number of studies has brought evidence of the protective role of statin use against different types of cancer. However, data on their association with second primary malignancies (SPMs) are lacking. The purpose of this study was to determine the role of hypolipidemic treatment in the prevention of second primary cancer in colorectal cancer (CRC) survivors. We conducted a retrospective single-institution study of 1401 patients with newly diagnosed colorectal cancer from January 2003 to December 2016, with follow-up until December 2020. An SPM was detected in 301 patients (21%), and the incidence was significantly lower in patients with statin medication. However, stratification by cancer types revealed an increased incidence of bladder and gastric cancer in hypolipidemic users. A Kaplan-Meier analysis of early-stage CRC survivors with an SPM showed a significant survival benefit in patients without a history of hypolipidemic treatment. Despite the protective role of statins on overall second cancer incidence, these data indicate that CRC survivors treated with hypolipidemic drugs should be screened more cautiously for SPMs, especially for gastric and bladder cancer.

Clinical relevance of uPA, uPAR, PAI 1 and PAI 2 tissue expression and plasma PAI 1 level in colorectal carcinoma patients.

BACKGROUND/AIMS: Urokinase (uPA) is a serine protease, which together with uPAR, tPA, PAI 1 and PAI 2 forms the plasminogen activator system, a component of metastatic cascade contributing to the invasive growth and angiogenesis of malignant tumours. METHODOLOGY: Both preceding therapy and after 6-8 weeks of the treatment, plasma PAI 1 levels (photometric microplate method on the ELISA) and uPA, uPAR, PAI 1 and PAI 2 tissue expression (immunohistochemical reaction) were analysed from 80 colorectal carcinoma patients. RESULTS: Analysis showed higher pre-treatment plasma levels of PAI 1 in patients with advanced tumours, which decreased after surgery or the start of therapy (p=0.004); Patients with higher plasma level PAI 1 before (0.013) and after therapy (0.004) had significantly shorter survival. There was a higher expression of uPA (p<0.001), uPAR (p<0.001), PAI 1 (p=0.042) and PAI 2 (p<0.001) in advanced colorectal carcinoma. A relationship between PAI 2 (p=0.010) and uPAR (p=0.019) expression and survival was demonstrated. There is a correlation between pre-treatment plasma PAI 1 levels and PAI 2 (p=0.028) and uPAR (p=0.043) expression. CONCLUSIONS: Immunohistochemical analysis of PAS in tumour tissue and plasma PAI 1 levels was found to be a useful prognostic factor in colorectal carcinoma patients. Plasma PAI 1 could be advantageous in evaluating the effectiveness of a mode of treatment.

Significant current epidemiological trend: Haematological malignancies as subsequent primary tumours in cancer patients.

BACKGROUND: Numbers of patients who develop subsequent primary tumours have markedly increased recently. This study aimed to carry out a comprehensive analysis documenting the risk of incidence of subsequent haematological malignancies. METHODS: The Czech National Cancer Registry was the main data source, containing records of 126,822 haematological malignancies diagnosed in the period 1977-2016. Subsequent haematological malignancies were identified according to IACR rules. Joinpoint regression was employed to assess the time trends. The risk of development of subsequent haematological malignancy was evaluated by the standardised incidence ratio. The Kaplan-Meier curves were used to assess the differences in survival. RESULTS: Age-standardised incidence of subsequent haematological malignancies increased from 0.5 in 1977 to 9.1 in 2016. In 1992, there was a significant change in the trend: a sharp increase by 7.7 % annually was revealed thereafter. The risk of development of a haematological malignancy was approximately 1.5 times higher in persons with history of any cancer than in the general Czech population. Patients with haematological malignancies - mainly myelodysplastic syndromes, polycythaemia vera and non-Hodgkin lymphoma - were shown to be at the highest risk of developing a subsequent haematological malignancy. While the median survival following a first haematological malignancy was 2.3 years, it was only 1.1 years for subsequent haematological malignancies (p < 0.001). CONCLUSIONS: Our study identified the highest-risk diagnoses in terms of development of subsequent haematological malignancy. The results might be useful to set up correctly follow-up procedures from which cancer patients could benefit.

Penis as a primary site of an extraskeletal Ewing sarcoma: A case report.

RATIONALE: The Ewing sarcoma family of malignant tumors is a group of tumors characterized by morphologically similar round-cell neoplasms and by the presence of a common chromosomal translocation; Ewing sarcoma family of tumors typically occur in children and young adults between 4 to 15 years of age. The primary tumor usually originates in the bone, extraskeletal localization is rare. PATIENT CONCERN: We present a case report concerning a 32-year-old male patient with a primary involvement of the penis. DIAGNOSIS: The histopathology from the first penile biopsy showed a small-cell neuroendocrine carcinoma; however, that result was based on a sample obtained at a different facility than the Sarcoma Center, where the investigating pathologist did not have the adequate expertise. The patient then underwent a radical penectomy and a second reading of the histology was demanded after a radical penile amputation when Ewing sarcoma with R1 resection was confirmed. INTERVENTIONS: The patient was referred to the national Sarcoma Center, where - using a multidisciplinary approach - the treatment was started with curative intent. However, it was preceded by a non-standard initiation of the therapy due to the poor primary diagnosis. OUTCOMES: The non-standard therapy at the onset of the disease caused a poor prognosis of an otherwise curable diagnosis. Despite all that, the patient survived for a relatively long time. LESSONS: The treatment of sarcomas with atypical localizations should be conducted by an experienced multidisciplinary team in a center with experience in sarcoma treatment.

Effect of Acupuncture in Pain Management of Head and Neck Cancer Radiotherapy: Prospective Randomized Unicentric Study.

This prospective randomized open-label trial aimed to evaluate the role of acupuncture in the treatment of pain related to curative and adjuvant (chemo)radiotherapy of head and neck cancer. Patients in two arms (30 patients in each arm) underwent standard oncology therapy and standard supportive care with or without acupuncture. The stratification factors were the type of treatment and chemotherapy indication. The toxicity assessed was represented by pain rated on a 10-point pain scale and analgesic use. Average pain (AP) and the worst pain during the day (WP) were significantly lower in the acupuncture arm during radiotherapy (AP median 0.16 vs. 1.36, p < 0.001; WP median 0.90 vs. 1.96, p < 0.001) and three months after radiotherapy (AP median 0.07 vs. 0.50, p < 0.001; WP median 0.30 vs. 0.83, p = 0.002). The analgesic consumption between arms was statistically significantly different. A median of the proportion of days when the patients used analgesics was 8% and 32.5% during radiotherapy (p = 0.047) and 0% and 20.8% during three months after radiotherapy (p = 0.006) for the acupuncture and control arm, respectively. Results point out lower analgesic consumption and milder pain in acupuncture arm. Acupuncture consequently offers another alternative to standard treatment leading to a reduction in the toxicity of oncological treatment.

Second primary malignancies in colorectal cancer patients.

The prevalence of second primary malignancies (SPMs) in the western world is continually increasing with the risk of a new primary cancer in patients with previously diagnosed carcinoma at about 20%. The aim of this retrospective analysis is to identify SPMs in colorectal cancer patients in a single-institution cohort, describe the most frequent SPMs in colorectal cancer patients, and discover the time period to occurrence of second primary tumors. We identified 1174 patients diagnosed with colorectal cancer in the period 2003-2013, with follow-up till 31.12.2018, and median follow-up of 10.1 years, (median age 63 years, 724 men). A second primary neoplasm was diagnosed in 234 patients (19.9%). Older age patients, those with early-stage disease and those with no relapse have a higher risk of secondary cancer development. The median time from cancer diagnosis to development of CRC was 8.9 years for breast cancer and 3.4 years for prostate cancer. For the most common cancer diagnosis after primary CRC, the median time to development was 0-5.2 years, depending on the type of malignancy. Patients with a diagnosis of breast, prostate, or kidney cancer, or melanoma should be regularly screened for CRC. CRC patients should also be screened for additional CRC as well as cancers of the breast, prostate, kidney, and bladder. The screening of cancer patients for the most frequent malignancies along with systematic patient education in this field should be the standard of surveillance for colorectal cancer patients.

Everolimus-related unilateral abdominal lymphedema in a renal cancer patient: A case report.

RATIONALE: Unilateral manifestation of lymphedema during everolimus therapy has been described only rarely, mostly in transplant recipients. PATIENT CONCERNS: We report the first case of a patient who developed unilateral abdominal lymphedema, during a short period of everolimus treatment for renal cancer. DIAGNOSIS: The abdominal asymmetry occurred only on the right side of the abdomen, neither ultrasound nor CT scan detected ascites but showed enlargement of the abdominal wall. The Naranjo Adverse Drug Reaction Probability scale was evaluated, in this case, a score of 6 indicated a probable adverse reaction to everolimus. INTERVENTIONS: Discontinuation of everolimus therapy led to immediate alleviation and reduction of the lymphedema, with worsening once again after initiating retreatment with everolimus at a reduced dose. OUTCOMES: The patient's lymphedema recovered after discontinuation of everolimus. LESSONS: This rare case demonstrates the importance of the selection of mammalian target of rapamycin inhibitors using caution, especially for patients with a high risk of developing lymphedema.

The Impact of Diabetes Mellitus on the Second Primary Malignancies in Colorectal Cancer Patients.

INTRODUCTION: All colorectal cancer (CRC) survivors have an increased risk of developing second primary malignancies (SPMs). The association between diabetes mellitus (DM) and the risk of cancer is well known. However, the role of DM and its therapy in the development of SPMs in CRC patients is not well described. METHODS: In this single-institutional retrospective analysis we identified 1,174 colorectal carcinoma patients, median follow-up 10.1 years, (median age 63 years, 724 men). All patients over 18 years with histologically confirmed CRC who were admitted in the period 1.1. 2003- 31.12.2013 and followed-up till 31.12. 2018 at the Masaryk Memorial Cancer Institute (MMCI) were screened for eligibility. The exclusion criteria were CRC diagnosed at autopsy, lost to follow-up and high risk of development of SPMs due to hereditary cancer syndrome. Tumours are considered multiple primary malignancies if arising in different sites and/or are of a different histology or morphology group. Comparisons of the basic characteristics between the patients with SPM and the patients without SPM were performed as well as comparison of the occurrence of SPMs by the site of diagnosis between the DM and non-DM cohorts and survival analyses. RESULTS: A SPM was diagnosed in 234 (20%) patients, DM in 183 (15%) patients. DM was diagnosed in 22.6% of those with SPM vs. in 13.8% of those without SPM (p=0.001). The most common types of SPMs in DM patients were other CRC, kidney, lung, bladder and nonmelanoma skin cancer, but only carcinoma of the liver and bile duct tracts was significantly more common than in the group without DM. Although breast cancer was the second most common in the group with DM, its incidence was lower than in the group without DM, as well as prostate cancer. A significantly higher incidence of SPMs was found in older CRC patients (≥ 65 years) and in those with lower stage colon cancer and DM. No significant difference in DM treatment between those with and without a SPM was observed including analysis of type of insulin. CONCLUSION: CRC patients with diabetes mellitus, especially those with older age, and early stages of colon cancer, should be screened for second primary malignancies more often than the standard population. Patients without DM have longer survival. According to the occurrence of the most common second malignancies, a clinical examination, blood count, and ultrasound of the abdomen is appropriate, together with standard breast and colorectal cancer screening, and lung cancer screening under certain conditions, and should be recommended in CRC survivors especially in patients with intercurrent DM, however the necessary frequency of screening remains unclear.

MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9.

Growing evidence suggests that microRNAs are involved in the development and progression of colorectal cancer (CRC). In the present study, deregulation and functioning of tumor-suppressive miR-215-5p was evaluated in CRC. In total, 448 tumor tissues and 325 paired adjacent healthy tissues collected from Czech and Spain cohorts of CRC patients have been used for miR-215-5p expression analyses. A series of in vitro experiments have been performed using transient transfection of miR-215-5p mimics into four CRC cell lines to identify specific cellular processes affected by miR-215-5p. Further, the effects of miR-215-5p on tumor growth were evaluated in vivo using NSG mice and stable cell line overexpressing miR-215-5p. Target mRNAs of miR-215-5p were tested using luciferase assay and western blot analyses. We found that miR-215-5p is significantly downregulated in tumor tissues compared with non-tumor adjacent tissues and its decreased levels correlate with the presence of lymph node metastases, tumor stage, and shorter overall survival in CRC patients. Overexpression of miR-215-5p significantly reduced proliferation, clonogenicity, and migration of CRC cells, lead to cell cycle arrest in G2/M phase and p53-dependent induction of apoptosis. The ability of miR-215-5p to inhibit tumor growth was confirmed in vivo. Finally, we confirmed epiregulin and HOXB9 to be the direct targets of miR-215-5p. As epiregulin is EGFR ligand and HOXB9 is its transcriptional inducer, we suggest that the main molecular link between miR-215-5p and CRC cells phenotypes presents the EGFR signaling pathway, which is one of the canonical pathogenic pathways in CRC.