Web-based prognostic tools for oral tongue cancer: An analysis of online predictors.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) often presents with aggressive clinical behaviour that may require multimodality treatment based on reliable prognostication. We aimed to evaluate the prognostic ability of five online web-based tools to predict the clinical behaviour of OTSCC resection and biopsy samples. METHODS: A total of 135 OTSCC resection cases and 33 OTSCC biopsies were included to predict recurrence and survival. Area under the receiver operating characteristic curves (AUC), χ2 tests, and calibration plots constructed to estimate the prognostic power of each tool. RESULTS: The tool entitled 'Prediction of risk of Locoregional Recurrences in Early OTSCC' presented an accuracy of 82%. The tool, 'Head & Neck Cancer Outcome Calculator' for 10-year cancer-related mortality had an accuracy 77% and AUC 0.858. The other tool entitled 'Cancer Survival Rates' for 5-year mortality showed an accuracy of 74% and AUC of 0.723. For biopsy samples, 'Cancer Survival Prediction Calculators' predicted the recurrence free survival with an accuracy of 70%. CONCLUSIONS: Web-based tools can aid in clinical decision making of OTSCC. Three of five online web-based tools could predict recurrence risk and cancer-related mortality in resected OTSCC and one tool could help in clinical decision making for biopsy samples.

Reconstruction of oral mucosal defects with regenerative dermal matrix after T1-T2 squamocellular carcinoma resection.

OBJECTIVE: Resection of tumors of oral cavity usually causes short- or long-term sequelae such as chewing, speech and swallowing impairment. To preserve this function it is necessary to maintain the lining of the oral cavity, the mobility and sensitivity of the tongue. Reconstructive options for oral mucosal defects resulting from tumor resection included primary closure, mucosal and skin grafts, pedicle and microvascular free flaps, and dermal matrix. STUDY DESIGN: Retrospective study on patients undergoing reconstruction of intraoral defects, after removal of T1, T2 malignant tumors, by placement of bilayer dermal matrix. METHODS: From 2021 to 2022, 47 patients with oral mucosa defects after removal of squamous cell carcinoma were treated. All patients were affected by a T1-T2 squamous cell carcinoma. For each patient, data were collected regarding the site of the disease, the initial staging, the size of the surgical defect, the complications and the outcome months after the operation. RESULTS: In all treated cases the surgical defect involved the mucosa of the cheek, the oral floor or the tongue with an average size of 5.45cm2. Patients who underwent this type of reconstruction benefited from excellent healing of intraoral wounds and good restoration of oral function 6 months after surgery. Out of the total number of patients, membrane attachment failure was reported in only two cases. CONCLUSION: As emerges from the data reported in our study, the dermal matrix represents a valid alternative in oncological reconstructive surgery for small/medium-sized intraoral mucosal defects because it allows re-epithelialization of the wound.

Promising Role of Alkaloids in the Prevention and Treatment of Thyroid Cancer and Autoimmune Thyroid Disease: A Comprehensive Review of the Current Evidence.

Thyroid cancer (TC) and thyroid autoimmune disorders (AITD) are among the most common diseases in the general population, with higher incidence in women. Chronic inflammation and autoimmunity play a pivotal role in carcinogenesis. Some studies, indeed, have pointed out the presence of AITD as a risk factor for TC, although this issue remains controversial. Prevention of autoimmune disease and cancer is the ultimate goal for clinicians and scientists, but it is not always feasible. Thus, new treatments, that overcome the current barriers to prevention and treatment of TC and AITD are needed. Alkaloids are secondary plant metabolites endowed with several biological activities including anticancer and immunomodulatory properties. In this perspective, alkaloids may represent a promising source of prophylactic and therapeutic agents for TC and AITD. This review encompasses the current published literature on alkaloids effects on TC and AITD, with a specific focus on the pathways involved in TC and AITD development and progression.

Tumor budding is a prognostic factor in head and neck squamous cell carcinoma: A comprehensive meta-analysis and trial sequential analysis.

BACKGROUND: Mortality is linked to tumor budding (TB) in certain neoplasms. TB as a relevant histopathological feature is conditioned by tumor site, a specific study on head and neck squamous cell carcinoma (HNSCC) is needed. METHODS: A comprehensive meta-analysis was undertaken to investigate the relationship between TB and HNSCC-related outcomes. RESULTS: Overall 42 studies were included. Patients harboring high TB reported an Overall Survival (OS) Hazard Ratio (HR) of 2.63 (95% confidential interval (CI) 2.04-3.39; p-value < 0.001), Disease-free Survival (DFS) HR of 1.88 (95%CI 1.57-2.24; p-value <0.001) and Disease-specific Survival (DSS) HR of 2.14 (95%CI 1.81-2.52; p-value <0.001). Lymph Node Metastasis (LNM) studies harbored null heterogeneity and marked association with TB (Odds Ratio (OR) = 4.48, 95%CI 2.97-6.76; p-value < 0.001). Trial Sequential Analysis (TSA) supported definitive results for DSS. CONCLUSION: The study has provided compelling evidence that there is a significant association between TB and a worse prognosis for HNSCC.

LGALS3BP is a potential target of antibody-drug conjugates in oral squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody-drug conjugate (ADC) therapy. METHODS: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT-PCR, Western Blot analysis, and ELISA. RESULTS: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer-derived extracellular vesicles. Moreover, LGALS3BP high-expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC-payload DM4, with an IC50 around 0.3 nM. CONCLUSIONS: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC-based therapy.

High-risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes. MATERIALS AND METHODS: Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes. RESULTS: Cases harbouring high-risk-of-death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild-type cases, while no significant difference in treatment outcomes was found between cases with low-risk-of-death mutations and wild-type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease. CONCLUSIONS: This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients.

Cost/effectiveness analysis of treatment options for the rehabilitation of the total edentulous mandible.

BACKGROUND: Several solutions are available for the rehabilitation of edentulous jaws. Each treatment option is characterised by specific advantages and drawbacks. OBJECTIVE: The aim of this research was to perform a cost-effectiveness (CE) analysis of the main rehabilitative solutions of totally edentulous mandibles. METHODS: Decision tree models were built using TreeAge Pro Healthcare 2021 software to compare the following strategies: Conventional Denture (CD), Overdenture retained by two implants (OD-2), Overdenture retained by a bar on two implants (ODbar), Overdenture retained by 4 mini-implants (ODmini) and Fixed denture supported by 4 implants (FD). Costs were estimated using data from public rate tables. Effectiveness measures were obtained from a meta-analysis of literature data, normalising the different scales in 0-1 range. A value of 30 000€ per 1 normalised utility points was set as threshold of willingness to pay (WTP). Probabilistic sensitivity analysis (PSA) with 1000 Monte Carlo Simulations was performed to characterise uncertainty. RESULTS: Total costs ranged between 1804,40€ for CD and 10 008,80€ for FD rehabilitations, with an effectiveness of 0,69 and 0,95 normalised points (0-1 scale) for the two solutions. The ODbar resulted to be the most CE strategy at the established WTP value, with the highest Net Monetary Benefit (22 001,20€), followed by the OD-2 rehabilitation (21 866,80€). PSA analysis confirmed the dominance of OD-2 and ODbar strategies, confirming a net separation from the other alternatives. CONCLUSION: OD stabilised by 2 implants could represent a good rehabilitative solution for patients with edentulous mandible, being a good trade-off in terms of costs and effectiveness. Nevertheless, a standardised measure of oral health-related quality of life is needed to obtain more reliable results.

Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma.

BACKGROUND: Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor-Node-Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. METHODS: About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. RESULTS: Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph-node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value = 0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p-value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. CONCLUSIONS: Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

Prognostic significance of tumor budding thresholds in oral tongue squamous cell carcinoma.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) represents the most common malignancy of the oral cavity. Tumor budding (TB) is a reliable prognostic factor in OTSCC; however, a standardized scoring system is not still validated. AIMS: The study aims to evaluate the prognostic role of TB in 211 OTSCC patients treated between 1997 and 2018. MATERIALS & METHODS: TB was evaluated on hematoxylin and eosin-stained sections in the hotspot area of the infiltrative front (×200-magnification). It was scored using a two-tier system, a three-tier system, and according to BD-model and revised-Grading system. Univariate and multivariate Cox regression analyses of disease-specific survival (DSS) and disease-free survival (DFS) were performed. A p < 0.05 was considered as statistically significant. RESULTS: The two-tier and three-tier systems resulted an independent prognostic factor of DSS. High-risk patients had a 2.21 and 3.08 times increased probability of poor DSS compared with low-risk group. It is significantly increased even for intermediate-risk group. No significant differences emerged classifying patients according to BD-model and revised-Grading system. DISCUSSION: These data confirm the prognostic value of TB in predicting DSS in OTSCC. Classifying patients into two groups using the 5-bud cutoff significantly discriminates their outcomes. CONCLUSION: Since the established role of DOI and the poor prognostic value of grading, TB could be considered an independent prognostic marker.

Factors influencing survival in metastatic castration-resistant prostate cancer therapy.

INTRODUCTION: The number of patients with metastatic castration-resistant prostate cancer (mCRPC) is expected to increase due to the long life expectancy of those with advanced disease who are also more commonly diagnosed today because of stage migration. Several compounds are available for treating these patients. AREAS COVERED: We reviewed currently available treatments for mCRPC, their mechanism of action and resistance, and we explored possible predictors of treatment success useful to predict survival in mCRPC patients. EXPERT OPINION: A combination of molecular, clinical, pathological, and imaging features is necessary to correctly estimate patients' risk of death. The combination of these biomarkers may allow clinicians to tailor treatments based on cancer history and patients' features. The search of predictive biomarkers remains an unmet medical need for most patients with mCRPC.

Potential benefit of lymph node dissection during radical nephrectomy for kidney cancer: A review and critical analysis of current literature.

Objective: The role of lymph node dissection (LND) is still controversial in patients with renal cell carcinoma undergoing surgery. We aimed to provide a comprehensive review of the literature about the effect of LND on survival, prognosis, surgical outcomes, as well as patient selection and available LND templates. Methods: Recent literature (from January 2011 to December 2021) was assessed through PubMed and MEDLINE databases. A narrative review of most relevant articles was provided. Results: The frequencies in which LNDs are being carried out are decreasing due to an increase in minimally invasive and nephron sparing surgery. Moreover, randomized clinical trials and meta-analyses failed to show any survival advantage of LND versus no LND. However, retrospective studies suggest a survival benefit of LND in high-risk patients (bulky tumors, T3-4 stage, and cN1 patients). Moreover, extended LND might provide important staging information, which could be of interest for adjuvant treatment planning. Conclusion: No level 1 evidence of any survival advantage deriving from LND is currently available in literature. Thus, the role of LND is limited to staging purposes. However, low grade evidence suggests a possible role of LND in high-risk patients. Randomized clinical trials are warranted to corroborate these findings.

The Emerging Impact of Tumor Budding in Oral Squamous Cell Carcinoma: Main Issues and Clinical Relevance of a New Prognostic Marker.

Tumor Budding (TB) represents a single cancer cell or a small cluster of less than five cancer cells on the infiltrative tumor front. Accumulating evidence suggests TB is an independent prognostic factor in oral squamous cell carcinoma (OSCC). However, its exact role is not yet elucidated, and a standardized scoring system is still necessary. The study aims to extensively review the literature data regarding the prognostic role of TB in OSCC. The results of TB are an independent prognostic factor of poor survival outcomes in OSCC. To date, the manual detection of hematoxylin and eosin-staining or pancytokeratin-immunostaining sections are the most commonly used methods. Between the several cut-offs, the two-tier system with five buds/field cut-offs provides better risk stratification. The prognostic role of the BD model in predicting survival outcomes was extensively validated; however, the inclusion of DOI, which is already a staging parameter, encouraged other authors to propose other models, integrating TB count with other adverse risk factors, such as the tumor-stroma ratio and tumor-infiltrated lymphocytes. The prognostic relevance of TB in OSCC highlights its evaluation in daily pathological practice. Therefore, the TB detection method and the TB scoring system should be validated based on tumor stage and site.

Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis.

Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80-90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.

Role Played by Paraoxonase-2 Enzyme in Cell Viability, Proliferation and Sensitivity to Chemotherapy of Oral Squamous Cell Carcinoma Cell Lines.

Oral squamous cell carcinoma represents the most aggressive and frequent form of head and neck cancer. Due to drug resistance, the 5-year survival rate of patients with advanced disease is less than 50%. In order to identify molecular targets for effective oral cancer treatment, we focused on paraoxonase-2 enzyme. Indeed, based on data previously obtained from preliminary immunohistochemistry and Western blot analyses performed on tissue specimens, the enzyme was found to be upregulated in tumor compared with normal oral mucosa. Therefore, paraoxonase-2 gene silencing was achieved in HSC-3 and HOC621 oral cancer cell lines, and the effect on cell proliferation, viability, apoptosis induction and sensitivity to cisplatin and 5-fluorouracil treatment was evaluated. Fourier Transform InfraRed Microspectroscopy analyzed alterations of cellular macromolecules upon treatment. Enzyme level and cell proliferation were also determined in cisplatin-resistant clones obtained from HOC621 cell line, as well as in parental cells. Reported data showed that paraoxonase-2 knockdown led to a reduction of cell proliferation and viability, as well as to an enhancement of sensitivity to cisplatin, together with the activation of apoptosis pathway. Spectroscopical data demonstrated that, under treatment with cisplatin, oxidative damage exerted on lipids and proteins was markedly more evident in cells down-regulating paraoxonase-2 compared to controls. Interestingly, enzyme expression, as well as cell proliferation were significantly higher in cisplatin-resistant compared with control HOC621 cells. Taken together these results seem to candidate the enzyme as a promising target for molecular treatment of this neoplasm.

Prognostic assessment of different methods for eosinophils detection in oral tongue cancer.

BACKGROUND: TATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature. METHODS: Clinic-pathological data of 204 patients treated at "Ospedali Riuniti" Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin-and-eosin-stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE-1) and classical (TATE-2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature. RESULTS: Regardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease-specific survival. The density method (TATE-1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2 , two cutoffs of 10 and 100 eosinophils/mm2 , or two cutoffs of 50 and 120 eosinophils/mm2 . CONCLUSION: The evaluation of TATE is simple, cost-effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE-1) method as the standard approach to evaluate TATE in future studies, enhancing replicability.

Nicotinamide N-Methyltransferase in Head and Neck Tumors: A Comprehensive Review.

The head and neck tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of nicotinamide N-methyltransferase (NNMT). However, its biological effects have not been completely disclosed and the role of NNMT in cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT. NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with cancer cell migration and adverse clinical outcomes, such as high-pathological stage, lymph node metastasis, and locoregional recurrences. However, in oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of NNMT. The shRNA-mediated gene silencing efficiently suppressed the NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related proteins and modulating the cell cycle. NNMT could represent a new molecular biomarker and a new target of molecular-based therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT.

Treatment-Related Dysgeusia in Oral and Oropharyngeal Cancer: A Comprehensive Review.

Oral cancer is the most common tumor of the head and neck region. Its management is based on surgical and systemic therapies. Taste disorders represent the most common side effect of these treatments; indeed, dysgeusia is noted by 70% of oral cancer patients. Despite survival remaining the primary endpoint of cancer patients, taste impairments can cause psychological distress. This comprehensive review describes the last decade's knowledge from the literature regarding taste alterations in patients with oral and oropharyngeal squamous cell carcinoma. A total of 26 articles in English, including prospective, cross-sectional, and case-control studies, and clinical trials were evaluated. Literature analysis shows that anti-cancer treatments can destroy taste cells, decrease and alter their receptors, and interrupt nerve transmission. Furthermore, the tumour itself can destroy the oral mucosal lining, which encloses the taste buds. Dysgeusia typically occurs in 3-4 weeks of treatments, and usually taste sensation is recovered within 3-12 months. However, some patients exhibit incomplete or no recovery, even several years later. Thus, dysgeusia can become a chronic issue and negatively influence patients' quality of life, worsening their dysphagia and their nutritional status. Physicians should be focused on preventing oncological treatment-related symptoms, offering the most suitable personalized support during therapy.

Therapeutic Potential of Antibody-Drug Conjugate-Based Therapy in Head and Neck Cancer: A Systematic Review.

BACKGROUND: Antibody-drug conjugates (ADCs) are designed to deliver potent cytotoxic agents into tumor tissues. During the last two decades, a plethora of ADCs have been successfully developed and used for several indications, including hematologic and solid tumors. In this work, we systematically reviewed the progress in ADC development for the treatment of HNC. METHODS: This review was registered in PROSPERO database. A comprehensive search was conducted following PRISMA guidelines and using PubMed, Scopus and Web of Science database. RESULTS: In total, 19 studies were included. Due to the significant heterogeneity of the outcome measures, meta-analysis was not performed, and data were summarized in tables. HNC results are poorly represented in the cohorts of completed clinical trials; published data are mostly focused on safety evaluation rather than efficacy of ADCs. CONCLUSIONS: Although several novel agents against a wide range of different antigens were investigated, showing promising results at a preclinical level, most of the targets reported in this review are not specific for HNC; hence, the development of ADCs tailored for the HNC phenotype could open up new therapeutic perspectives. Moreover, the results from the present systematic review call attention to how limited is the application of current clinical trials in HNC.

Tumour-associated tissue eosinophilia (TATE) in oral squamous cell carcinoma: a comprehensive review.

Oral squamous cell carcinoma is the most common head and neck malignancy, characterised by high invasive capacity, lymph node metastasis, and high recurrence rate. Among the morphological features of oral cancer, the tumour-associated tissue eosinophilia has gained growing interest in the last years. Eosinophils are a minor subpopulation of leukocytes, representing 1-3% of all circulating white blood cells. The presence of high levels of eosinophils is associated with several diseases, but their role in cancer pathophysiology is controversial. In particular, an uncertain and contradictory relationship exists between the exact role of tumour-associated tissue eosinophilia and oral cancer development. Many studies have shown that tumour-associated tissue eosinophilia increases both in the progression of oral potentially malignant disorders as well as in the grade and stage progression of oral cancer. Despite this, both negative and positive prognostic outcomes have been associated with eosinophil infiltration. The heterogeneous results may be partially due both to several methodological inconsistencies and to an incorrect interpretation of the physiological role of eosinophils. Therefore, further studies to elucidate the contribution of eosinophil infiltration are needed, focusing on the existence of eosinophil subpopulations regulated by the cancer immune microenvironment. Furthermore, the correct reporting of prognostic marker research is encouraged, in order to ensure the reproducibility and the comparability of the results from different studies.