Current practice in assessment and management of malnutrition in surgical oncology practice - An ESSO-EYSAC snapshot analysis.

INTRODUCTION: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments. MATERIAL AND METHODS: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team. RESULTS: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation. CONCLUSIONS: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening.

The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy.

Background and Objectives: Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best characterize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting drug resistance. We aimed to assess the association of miR-375-3p, miR-210-3p and let-7e-5p in breast cancer tissues with pathological response to neoadjuvant therapy (NAT) and clinicopathological data. Material and methods: Sixty female patients diagnosed with invasive breast cancer at The Oncology Institute "Ion Chiricuța", Cluj-Napoca, Romania (IOCN) were included in this study. Before patients received any treatment, fresh breast tissue biopsies were collected through core biopsy under echographic guidance and processed for total RNA extraction and miRNA quantification. The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) database was used as an independent external validation cohort. Results: miR-375-3p expression was associated with more differentiated tumours, hormone receptor presence and lymphatic invasion. According to the Miller-Payne system, a higher miR-375-3p expression was calculated for patients that presented with intermediate versus (vs.) no pathological response. Higher miR-210-3p expression was associated with an improved response to NAT in both Miller-Payne and RCB evaluation systems. Several druggable mRNA targets were correlated with miR-375-3p and miR-210-3p expression, with upstream analysis using the IPA knowledge base revealing a list of possible chemical and biological targeting drugs. Regarding let-7e-5p, no significant association was noticed with any of the analysed clinicopathological data. Conclusions: Our results suggest that tumours with higher levels of miR-375-3p are more sensitive to neoadjuvant therapy compared to resistant tumours and that higher miR-210-3p expression in responsive tumours could indicate an excellent pathological response.

Prognostic factors for in-transit metastasis in patients with malignant melanoma.

Background and aims: Malignant melanoma represents an aggressive and unpredictable malignancy, with high locoregional recurrence rates, regardless of tumor stage and therapeutic management. This study aims to identify the main histopathological prognostic factors involved in the development of in-transit metastasis in patients with malignant melanoma. Methods: The study includes only patients that were diagnosed with malignant melanoma and with histologically confirmed in-transit metastasis who were treated in a comprehensive cancer center between 2010-2021. Histopathological parameters were investigated, univariate and multivariate analysis was performed. Results: A total of 26 patients were included in the analysis. On univariate and multivariate analysis, only primary cutaneous melanomas located on the thorax correlated with the risk of developing in-transit metastasis, whereas clinicopathological factors such as an increased Breslow thickness and Clark level, the presence of ulceration, positive lymph nodes, a non-brisk TIL density, a high mitotic rate, a nodular subtype, and age >50 years may represent risk factors, even though we could not find any correlations. Conclusions: Primary cutaneous melanomas that arise on the thorax present a high risk for the occurrence of locoregional disease, whereas other clinicopathological characteristics could not be used to predict local recurrence. However, prospective and more extensive cohort studies are needed in order to validate these important prognostic factors.

Axillary surgery after neoadjuvant therapy in initially node-positive breast cancer: international EUBREAST survey.

BACKGROUND: There is no consensus on axillary management after neoadjuvant therapy (NAT) in patients with clinically node-positive (cN+) breast cancer. To investigate current clinical practice, an international survey was conducted among breast surgeons and radiation oncologists. The aim of the first part of the survey was to provide a snapshot of international discrepancies regarding axillary surgery in this context. METHODS: The European Breast Cancer Research Association of Surgical Trialists (EUBREAST) developed a web-based survey containing 39 questions describing clinical scenarios in the setting of axillary management in patients with cN1 disease converting to ycN0 after NAT. The survey was then distributed to breast surgeons and radiation oncologists via 14 breast cancer societies between April and October 2021. RESULTS: Responses from 349 physicians in 45 countries were recorded. The most common post-NAT axillary surgery in patients with cN1 disease converting to ycN0 was targeted axillary dissection (54.2 per cent), followed by sentinel lymph node biopsy (SLNB) alone (20.9 per cent), level 1-2 axillary lymph node dissection (ALND) (18.4 per cent), level 1-3 ALND (4 per cent), and targeted lymph node biopsy (2.5 per cent). For SLNB alone, dual tracers were most commonly used (62.3 per cent). Management varied widely in patients with ambiguous axillary status before initiation of treatment or a residual metastatic burden in the axilla after NAT. In patients with ycN+ tumours, ALND was the preferred surgical approach for 66.8 per cent of respondents. CONCLUSION: These results highlight the wide heterogeneity in surgical approaches to the axilla after NAT. To standardize the guidelines, further data from clinical research are urgently needed, which underlines the importance of the ongoing AXSANA (EUBREAST-3) study.

The Role of Circulating Tumor Cells in the Prognosis of Metastatic Triple-Negative Breast Cancers: A Systematic Review of the Literature.

Breast cancer is one of the leading causes of death in women worldwide. One subtype of breast cancer is the triple-negative, which accounts for 15% of total breast cancer cases and is known for its poor prognosis. The main cause of death is due to metastasis. Circulating tumor cells (CTCs) play a key role in the metastatic process. CTCs arise either by detaching from the primary tumor or from cancer stem cells undergoing an epithelial-to-mesenchymal transition (EMT). This review aims to present up-to-date data concerning the role of CTC numbers in relation to the prognostic and treatment response in metastatic triple-negative breast cancer (mTNBC) patients, and also to discuss the methods used for CTCs' identification. A search in the MEDLINE database was performed. A total of 234 articles were identified. The results of the 24 eligible studies showed that positive CTC status is associated with shorter overall survival (OS) and progression-free survival (PFS) in mTNBC patients. Furthermore, a decrease in number of CTCs during therapy seems to be a favorable prognostic factor, making CTCs' detection an important prognostic tool before and during therapy in mTNBC patients. The methods used for CTC detection are still developing and need further improvement.

Treatment and Prevention of Periprosthetic Capsular Contracture in Breast Surgery With Prosthesis Using Leukotriene Receptor Antagonists: A Meta-Analysis.

BACKGROUND: Capsular contracture (CC) is the most common long-term complication of breast surgery with prosthesis. Leukotriene receptor antagonists (LRAs) have been tested as a potential treatment; however, mixed results have been observed. OBJECTIVES: The aim of this study was to undertake a meta-analysis to clarify the treatment and prophylactic capabilities of LRAs in the management of CC. METHODS: A systematic literature search of the most popular English-language databases was performed to identify relevant primary publications. We included all studies that used the Baker scale to evaluate the treatment and preventive capabilities of LRAs. RESULTS: Six eligible studies were included based on predefined inclusion and exclusion criteria, totalling 2276 breasts, of which 775 did not receive LRAs and 1501 did. Final pooled results showed that LRAs could help manage CC with a risk difference (RD) of -0.38 with a corresponding 95% CI of -0.69 to -0.08, showing statistical significance at a Z value of 2.48, P = 0.01. Subgroup analysis based on the type of drug showed that only montelukast yielded statistical significance (RD = -0.27, 95% CI = -0.51 to -0.03, Z = 2.20, P = 0.03). Zafirlukast did not seem to influence CC. Further subgroup analysis based on treatment timing showed that prophylaxis was ineffective and only treatment for ongoing CC yielded statistically significant improvements. CONCLUSIONS: The current meta-analysis proved that LRAs could be used in the management of CC. Only treatment for ongoing CC showed statistically significant improvements. Montelukast seemed to be more efficient with a safer profile for adverse effects, whereas zafirlukast yielded no statistically significant results.

Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation.

Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute ovalbumin-induced (OVA-induced) asthmatic inflammation. The experimental prevention group received a long-term daily dose of 50 µg/kg (total dose of 1300 µg/kg), whereas the rescue group underwent a short-term daily dose of 100 µg/kg (total dose of 400 µg/kg). The following oxidative stress parameters were analyzed in serum, bronchoalveolar lavage fluid (BALF) and lung tissue homogenate (LTH): total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde and total thiols. Results showed that VD significantly reduced oxidative forces and increased the antioxidant capacity in the serum and LTH of treated mice. There was no statistically significant difference between the two types of VD supplementation. VD also exhibited an anti-inflammatory effect in all treated mice, reducing nitric oxide formation in serum and the expression of nuclear factor kappa B p65 in the lung. In conclusion, VD supplementation seems to exhibit a protective role in oxidative stress processes related to OVA-induced acute airway inflammation.

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

Does Surgical Margin Width Remain a Challenge for Triple-Negative Breast Cancer? A Retrospective Analysis.

Background and Objectives: Local and distant relapse (LR, DR) in breast cancer vary according to its molecular subtypes, with triple-negative breast cancer (TNBC) being the most aggressive. The surgical resection margin width (SRMW) for breast-conserving surgery (BCS) has been intensely debated, especially for the aforementioned subtype. The aim of this study was to examine the impact of SRMW on LR following BCS in TNBC patients. Materials and Methods: We conducted a retrospective study including all patients with TNBC for whom BCS was performed between 2005 and 2014. Results: Final analysis included a total of 92 patients, with a median tumor size of 2.5 cm (range 0-5 cm) and no distant metastasis at the time of diagnosis. A total of 87 patients had received neoadjuvant and/or adjuvant chemotherapy, and all patients had received adjuvant whole-breast radiotherapy. After a median follow-up of 110.7 months (95% CI, 95.23-126.166), there were 5 local recurrences and 8 regional/distant recurrences with an overall LR rate of 5.4%. The risk of LR and DR was similar between groups of patients with several SRMW cut-off values. Conclusions: Our study supports a safe "no ink on tumor" approach for TNBC patients treated with BCS.

The Role of Circulating Tumor Cells in Chemoresistant Metastatic Breast Cancer.

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor.

What we learned in axillary management of breast cancer patients at the American society of clinical oncology (ASCO) 2020 virtual meeting? The EUBREAST point of view.

In 2020, the American Society of Clinical Oncology (ASCO) annual meeting was held as a virtual conference. Overall, 461 abstracts focused on breast cancer management. As European Breast Cancer Association of Surgical Trialists (EUBREAST) we summarize and comment the results of these abstracts dealing with axillary management in breast cancer patients and offer an interpretation on how these findings may be incorporated into clinical practice and further research.

MicroRNA in Papillary Thyroid Carcinoma: A Systematic Review from 2018 to June 2020.

The involvement of micro-ribonucleic acid (microRNAs) in metabolic pathways such as regulation, signal transduction, cell maintenance, and differentiation make them possible biomarkers and therapeutic targets. The purpose of this review is to summarize the information published in the last two and a half years about the involvement of microRNAs in papillary thyroid carcinoma (PTC). Another goal is to understand the perspective offered by the new findings. Main microRNA features such as origin, regulation, targeted genes, and metabolic pathways will be presented in this paper. We interrogated the PubMed database using several keywords: "microRNA" + "thyroid" + "papillary" + "carcinoma". After applying search filters and inclusion criteria, a selection of 137 articles published between January 2018-June 2020 was made. Data regarding microRNA, metabolic pathways, gene/protein, and study utility were selected and included in the table and later discussed regarding the matter at hand. We found that most microRNAs regularly expressed in the normal thyroid gland are downregulated in PTC, indicating an important tumor-suppressor action by those microRNAs. Moreover, we showed that one gene can be targeted by several microRNAs and have nominally described these interactions. We have revealed which microRNAs can target several genes at once.

Suboptimal Serum 25-Hydroxy-Vitamin D Is Associated with a History of Recent Disease Exacerbation in Pediatric Patients with Bronchial Asthma or Asthma-Suggestive Recurrent Wheezing.

Even though vitamin D is widely acknowledged as having a potential immunomodulatory role in asthma, its exact beneficial mechanisms are yet to be clarified. An optimal serum 25-hydroxy-vitamin D (25-OH-VitD) level in pediatric asthma patients might not rely solely on the effect of dose-dependent vitamin D3 intake, but might also be influenced by factors related to insufficient asthma control. We aimed to survey the prevalence of serum 25-OH-VitD deficiency and analyze whether suboptimal levels were associated with asthma severity factors. The current cross-sectional study enrolled 131 pediatric asthma or asthma-suggestive recurrent wheezing patients, for whom serum 25-OH-VitD, IgE, and eosinophil count were assessed. The prevalence of suboptimal serum 25-OH-VitD was 58.8%. A suboptimal vitamin D status was associated with asthma exacerbation in the previous month (p = 0.02). Even under seasonal oral vitamin D3 supplementation, patients with a positive history of asthma attack in the previous four weeks presented significantly lower serum 25-OH-VitD concentrations, compared to their peers with no disease exacerbation. In conclusion, sequential measurements of serum 25-OH-VitD might prove useful for future studies evaluating the dynamic changes in vitamin D3 status in regard to asthma, especially in symptomatic patients.

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Post-Treatment Thyroid Diseases in Children with Brain Tumors: A Single-Center Experience at "Prof. Dr. Ion Chiricuța" Institute of Oncology, Cluj-Napoca.

AIM OF STUDY: The purpose of the study was to evaluate the association of thyroid dysfunction occurring in pediatric patients treated for brain tumors. PATIENTS AND METHODS: A total of 255 patients with brain tumors were treated between 2001 and 2018 at the "Prof. Dr. Ion Chiricuța" Institute of Oncology, Cluj-Napoca. Due to a minimum follow-up of 4 years, we studied 184 out of the 255 patients. The cohort included 69 girls (37.5%) and 109 boys (62.5%), with a median age of 8.4 years. The evaluated tumors included medulloblastomas (47 patients), astrocytomas (44 patients), ependymomas (22 patients), gliomas (20 patients), germ cell tumors (12 patients), primitive neuroectodermal tumors (4 patients), as well as other types of tumors (15 patients); in 20 of the cases, biopsy could not be performed. RESULTS: There was a 60% overall survival rate; among the 120 surviving patients, 11 (9.1%) were diagnosed with iatrogenic thyroid disease. We observed an important number of iatrogenic thyroid disease cases in this group of patients, thus revealing the importance of long-term thyroid function evaluation in all children who finalized their treatment for brain tumors. Through this study, we aimed to provide an accurate image of the methodology of monitoring for thyroid dysfunction in childhood brain tumor survivors. CONCLUSION: Given the fact that the probability of developing thyroid dysfunction in the pediatric population treated for brain tumors is not rare, we recommend that childhood brain tumor survivors be monitored for iatrogenic thyroid disease, in order to provide early diagnosis and treatment.

Skeletal Muscle Metastasis in Papillary Thyroid Microcarcinoma Evaluated by F18-FDG PET/CT.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy and is characterized by slow growth and an indolent biological behavior. Papillary thyroid microcarcinoma is the PTC with the maximum size of the tumor <1cm, considered the most indolent form of thyroid cancer. PTC is usually metastasizes in cervical lymph nodes, lungs and bones and, less commonly, in brain or liver. Skeletal muscle metastases from PTC are extremely rare, a retrospective review of the literature revealed only 13 case reports. Among them, six cases are solitary skeletal muscle metastases, and seven are multiple metastases, most of them being associated with lung lesions. It seems that PTC is prone to metastasizing to the erector spinae and thigh muscles groups with unique cases located in trapezoid, biceps, deltoid, gastrocnemius and rectus abdominis muscles. Although extremely rare, one must bear in mind the fact that muscle metastasis from PTC is possible, and that is the reason we would like to discuss the existing clinical cases and to add a unique case of solitary skeletal muscle metastasis from papillary microcarcinoma.

The value of tumor infiltrating lymphocytes as prognostic factor for lymph node status and survival amongst patients with cutaneous malignant melanoma.

PURPOSE: Tumor infiltrating lymphocytes (TILs) in cutaneous malignant melanoma are classified as brisk, non-brisk or absent. Numerous studies suggest the presence of TILs, especially brisk, are associated with a lower rate of lymph node metastasis and with an improved overall survival (OS). Our purpose was to assess the value of TILs as a prognostic factor for the lymph node metastasis and survival in completely resected pT3 stage malignant melanoma patients. METHODS: We included a number of 114 patients with pathological pT3 cutaneous malignant melanoma, treated exclusively in our institution, between 2000-2015. Correlations of clinical and pathological factors with lymph node status and OS were analyzed. RESULTS: A brisk infiltrate was present in 60% of the patients, whereas 40% presented a non-brisk infiltrate or absent TILs. In univariate analysis, the presence of ulceration was correlated with a non-brisk infiltrate, whereas in multivariate analysis, lymph node invasion and a non-brisk infiltrate were associated with a higher risk of death. CONCLUSIONS: TILs density grade represents an independent prognostic factor for the OS. Therefore, we conclude that an accurate prognosis may be provided by TILs status in patients with pT3 malignant melanoma.

A review on immunohistochemical and histopathologic validation in PET-CT findings with consideration to microRNAs.

PURPOSE: This review provides an overview of some of the most recent clinical trials which investigated various types of cancer and other diseases, through the use of PET-CT imaging, highlighting the use of immunohistochemical stains or conventional histopathology for the validation or contradiction of their hypothesis. Furthermore, we investigate a potential new direction of research by analyzing the upcoming role of microRNAs in disease confirmation. METHODS: An extensive search of MEDLINE/PubMed and SCOPUS electronic databases was made, using the MeSH terms "positron emission tomography computed tomography" and "immunohistochemistry" as well as "SUV" and "immunohistochemistry", restricting the search by clinical trials and time period. Further searches were made for articles regarding Ki-67 and microRNAs in correlation with metabolic PET-CT uptake. RESULTS: Out of all 389 initial search results, 27 original articles were found relevant to the topic. Their contents were synthesized and discussed regarding the matter at hand. No relevant clinical trials involving microRNAs were found. CONCLUSIONS: Immunohistochemical and histopathologic results remain widely used and indispensable in modern research, concerning PET-CT validation. Possible candidates for diagnosis confirmation, in future research, may reside in the further development of microRNAs.

Radiation induced thyroid carcinoma in Romania - effects of the Chernobyl fallout, a systematic review of observational studies.

INTRODUCTION: The development of thyroid carcinoma is a complex process, in which both genetic and environmental factors play an important role. The rising incidence of thyroid neoplasm determines researchers to investigate factors implicated in this phenomenon. This article aims to elucidate the effects of the Chernobyl nuclear disaster on the Romanian population, studying the existing literature on radiation induced thyroid carcinoma. We analyzed the main studies published on this matter. METHODS: We used the PubMed and Google Scholar databases to search for articles upon the effects of the Chernobyl nuclear disaster on the incidence of thyroid carcinoma in the Romanian population. After a careful review of the existing literature, we selected the relevant and accessible studies, the first observation being that data on thyroid related effects of the Chernobyl nuclear disaster are scarce. RESULTS: From the selected studies, results show that there is a possible link between the Chernobyl fallout and the incidence of thyroid carcinoma. Multiple factors have been studied that play an important role in the increasing number of thyroid carcinoma cases, such as: better diagnostic techniques, incidentalomas, microcarcinomas and radiation exposure. In consequence it is difficult to measure the influence that the Chernobyl nuclear fallout has on thyroid carcinoma incidence. CONCLUSION: Especially in pediatric patients, there seems to be a convincing evidence of radiation related thyroid carcinoma, while in adult patients the rising incidence due exclusively to nuclear fallout is not that clear. Further studies must be done on this matter to clearly see the influence radiation has on the incidence of thyroid cancer.