Staging with computed tomography of patients with colon cancer.

PURPOSE: Accurate staging of colonic cancer is important for patient stratification. We aimed to correlate the diagnostic accuracy of preoperative computed tomography (CT) with final histopathology as reference standard. METHODS: Data was collected retrospectively on 615 consecutive patients operated for colonic cancer. Evaluation was based upon T-stage. Patients were stratified into high-risk and low-risk groups, based on the extent of tumor invasion beyond the proper muscle layer of more or less than 5 mm. The Kendall tau correlation coefficient was used to calculate concordance between radiological (r)T-stage obtained at CT imaging and pathological (p)T-stage from the final pathology. RESULTS: In total, 501 patients were included. We found no significant differences in the Kendall tau values for diagnostic measures between the groups at the 95% confidence interval (CI) level: 49% (95% CI, 43-55) for all individuals, 48% (95% CI, 40-56) for screened individuals, and 47% (95% CI, 37-56) for non-screened individuals. The overall sensitivity and specificity for all individuals in identifying high-risk tumors on CT was 65% (95% CI, 56-73) and 89% (95% CI, 85-92). The risk of ending up in the high-risk group due to overstaging among all individuals was calculated as the number needed to harm 11.7 (95% CI, 9-16). CONCLUSIONS: There is basis for improvement of CT-based preoperative staging of patients with colorectal cancer. Supplementary modalities may be needed for correct staging of patients preoperatively, especially in relation to stratification of patients into neoadjuvant treatments or tailored therapy in patients with early cancers.

Endoscopic ultrasonography and computed tomography scanning for preoperative staging of colonic cancer.

PURPOSE: With an increasing demand for more accurate preoperative staging methods for colon cancer, we aimed to compare preoperative tumour (T)- and nodal (N)-stage in patients with left-sided colon cancer by endoscopic ultrasonography (EUS) and computed tomography (CT) with post-operative histology as gold standard. METHODS: A total of 44 patients were prospectively recruited at Herlev and Roskilde University Hospitals during November 2014-January 2016. Thirty-five patients were included in the final analysis and underwent EUS, CT and surgery within 2 weeks. Diagnostic values were evaluated for "low risk" (T1+T2+T3 with ≤5 mm extramural invasion) and "high risk" (T3 with >5 mm of extramural spread + T4) colonic cancer. RESULTS: Sensitivity and specificity in "low risk" colonic cancer evaluated with EUS was 0.90 [0.74;0.98] and 0.75 [0.19;0.99] and with CT 0.96 [0.80;0.99] and 0.25 [<0.01;0.81]. EUS and CT were poor in predicting N0 or N+ disease. CONCLUSIONS: The sensitivity of EUS and CT were good and comparable regarding T-stage evaluation, while EUS had a significantly higher specificity in the evaluation of "low risk" tumours. The results obtained for "high risk" colonic cancer were difficult to evaluate due to small patient numbers. EUS could be considered as a supplement to CT scans in selecting patients for neoadjuvant therapies, or local transmural treatment, in the future. TRIAL REGISTRATION: NCT02324023.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided interventions: General Aspects and EUS-guided Sampling (Short Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided Interventions: General aspects and EUS-guided sampling (Long Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V.

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation in clinical practice (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V - EUS-Guided Therapeutic Interventions (short version).

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Short Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version/ short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Long Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version).

Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions - a prospective multicenter study of its usefulness in clinical practice.

PURPOSE: To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. MATERIAL AND METHODS: CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patient's informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. RESULTS: A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. CONCLUSION: CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology.

The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided on optimisation of scanning technique, image display, image interpretation and some of the known image artefacts.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 2: Clinical applications.

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.

Feasibility study of EUS-NOTES as a novel approach for peroral cholecysto-gastrostomy.

BACKGROUND: EUS-guided cholecysto-gastrostomy might be a useful minimally invasive procedure used for salvage drainage in advanced pancreaticobiliary cancers, but also for drainage of the gallbladder in acute cholecystitis in patients deemed unfit for laparoscopic surgery. OBJECTIVE: Direct EUS-guided cholecysto-gastrostomy with placement of a double flanged expandable metal stents. DESIGN/SETTING: This was an animal pilot/feasibility study. INTERVENTIONS: The feasibility of EUS-guided cholecysto-gastrostomy through a transgastric approach was tested in five pigs. Specially designed EUS-guided devices for initial access in the gallbladder and a double flanged expandable metal stent were used in this study. RESULT: The results showed the feasibility of EUS-guided cholecysto-gastrostomy based on prototype devices for access in the gallbladder and transgastric stent placement. LIMITATIONS: Survival feasibility study with prototype devices in a small number of animals. CONCLUSIONS: EUS guided cholecysto-gastrostomy in a porcine model is feasible but technically demanding due to anatomical limitations of the pig and/or complexity of the procedure and the preliminary stage of development of the accessory devices. ABBREVIATIONS: NOTES - Natural Orifice Translumenal Endoscopic Surgery; EUS - Endoscopic Ultrasound; EUSFNA - Endoscopic Ultrasound Fine Needle Aspiration.

Nutritional risk screening and prevalence of malnutrition on admission to gastroenterology departments: a multicentric study.

BACKGROUND AND AIMS: There is little awareness and a lack of data on the prevalence of hospital malnutrition in gastro-enterology departments. Since part of these patients are referred for surgical treatment and poor nutritional status is a known risk factor for perioperative morbidity, we conducted a prospective study aimed to screen for the nutritional risk and assess the prevalence and risk factors of malnutrition in gastro-enterology departments in Romania. METHODS: We included patients consecutively admitted to 8 gastroenterology units over a period of three months in our study. Nutritional risk was evaluated using NRS 2002. Malnutrition was defined using BMI ( 20 kg m2) or and 10% weight loss in the last six months. RESULTS: 3198 patients were evaluated, 51.6% males and 48.4% females, with the mean age of 54.5 Â+- 14.3 years. Overall percentage of patients at nutritional risk was 17.1%, with the highest risk for patients with advanced liver diseases (49.8%), oncologic (31.3%), inflammatory bowel diseases (20.2%), and pancreatic diseases (18.9%). The overall prevalence of malnutrition was of 20.4%, higher for advanced liver diseases (39.4%), inflammatory bowed diseases (30.6%), oncologic (26.8%) and pancreatic diseases (23%). Independent risk factors for malnutrition were younger age (p 0.0001), female gender (p 0.0001), a higher (A ≥ 3) NRS (p 0.0001), presence of neoplasm (p 0.0001), of advanced liver disease (p=0.0003) and a reduction of 25% of dietary intake (p 0.0001). CONCLUSIONS: One in five patients admitted to gastroenterology units could benefit from prompt nutritional intervention. Correction of nutritional status is mandatory before any surgical procedure. Emphasis on nutritional evaluation at admission and beginning of nutritional therapy where needed are particularly required in patients with advanced liver diseases, digestive neoplasms, inflammatory bowel diseases and pancreatic diseases. ABBREVIATIONS: NRS= nutritional risk score, BMI = body mass index, IBD = inflammatory bowel diseases.

Technical performance of colonoscopy -- multicenter study in university and non-university centers of Romania.

UNLABELLED: The aim of the paper was to evaluate the national availability of colonoscopy and the quality parameters of this procedure in our country. MATERIAL AND METHOD: During a 6 months period (01.07- 31.12.2009), we performed a prospective multicenter study in which 76 centers were invited to respond to a questionnaire regarding colonoscopy, 39 centers agreeing to participate. We assessed: the number of colonoscopies, the number of total colonoscopies and the causes of incomplete colonoscopies. RESULTS: During the study period, 16,083 colonoscopies were performed, 12,294 (76.4%) of them total colonoscopies. In 1,191 cases, stenosis was the cause of incomplete colonoscopy. If we consider this an objective reason for an incomplete colonoscopy, there were 12,294 total colonoscopies (82.4%). Comparing university centers with non-university ones, the proportion of total colonoscopies was 10,400/12,475 (83.4%) vs. 1,894/2,417 (78.4%) (p less then 0.0001). However, comparing the present study with previous ones, performed in 2003 and 2007, the proportion of total colonoscopies increased from 70.5% to 76.9% and 82.4% respectively (2003 vs. 2007 p less then 0.0001; 2007 vs. 2009 p less then 0.0001), while the quality difference between university and non-university hospitals persisted. CONCLUSIONS: the quality of colonoscopy in Romania increased in the last 5 years, while the quality difference between university and non-university hospitals persisted.

Contrast-enhanced harmonic endoscopic ultrasound.

Second-generation intravenous blood-pool ultrasound contrast agents are increasingly used in endoscopic ultrasound (EUS) for characterization of microvascularization, differential diagnosis of benign and malignant focal lesions, and improving staging and guidance of therapeutic procedures. Although initially used as Doppler signal enhancers, second-generation microbubble contrast agents are now used with specific contrast harmonic imaging techniques, which benefit from the highly nonlinear behavior of the microbubbles. Contrast-specific modes based on multi-pulse technology are used to perform contrast-enhanced harmonic EUS based on a very low mechanical index (0.08 - 0.12). Quantification techniques based on dynamic contrast-enhanced ultrasound have been recommended for perfusion imaging and monitoring of anti-angiogenic treatment, mainly based on time-intensity curve analysis. Most of the clinical applications include the differential diagnosis of focal pancreatic masses, with adenocarcinoma having a distinct hypovascular (hypo-enhanced) appearance compared with neuroendocrine tumors, which are hypervascular (with strong arterial hyper-enhancement). However, pseudotumoral chronic pancreatitis and autoimmune pancreatitis also have an iso- or hypervascular appearance, making the differential diagnosis difficult. Even more promising is the use of dynamic contrast-enhanced harmonic EUS for the longitudinal monitoring of the effects of chemotherapy and/or anti-angiogenic therapy in advanced digestive cancers, which are difficult to examine by conventional cross-sectional imaging techniques.

Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) elastography represents a new imaging procedure that might characterize the differences of hardness and strain between diseased tissue and normal tissue. The aim of this study was to assess the efficiency of EUS elastography for the differentiation of focal masses in chronic pancreatitis and pancreatic cancer. PATIENTS AND METHODS: The study group comprised 258 patients with focal pancreatic masses included prospectively at 13 participating centers. Qualitative analysis of the diagnoses made by two expert doctors using all recorded video clips was performed in order to test the interobserver variability. A post-processing software analysis was used to examine the EUS elastography videos by calculating average-hue histograms of individual elastography images. The quantitative information was used to calculate intra-observer variability and the accuracy of the method. RESULTS: Qualitative analysis of the recorded videos revealed a kappa value of 0.72. Intra-observer variability analysis revealed that the single measure intraclass correlation ranged between 0.86 and 0.94. The average-hue histogram analysis of the data indicated a sensitivity of 93.4 %, a specificity of 66.0 %, a positive predictive value of 92.5 %, a negative predictive value of 68.9 %, and an overall accuracy of 85.4 %, based on a cut-off value of 175. Area under the receiver operating characteristic curve (AUROC) was 0.854 ( P < 0.0001) with a confidence interval of 0.804 - 0.894. CONCLUSION: The value of quantitative analysis of EUS elastography recordings was proven by good reproducibility of the videos, as well as good parameters of the AUROC analysis. (Clinical Trials.gov identifier: CT00909103).

[Correlation of adenomatous polyps and early colorectal cancer. Diagnostic and therapeutic implications]. / Relatia polip adenomatos--cancer colorectal precoce. Implicatii diagnostice si terapeutice.

AIM: To detect the patients with colorectal adenomatous polyps or those with adenocarcinoma areas with a view to prevent and to treat the malignant disease. MATERIAL AND METHOD: A prospective study including 309 patients hospitalized between 2000-2005 diagnosed with isolated adenomatous polyps after repeated colonoscopies. The research method was selective screening with identification of risk factors regarding the evolution of colorectal polyps in early cancer, using colonoscopy and histopathological examination. RESULTS: We identified 464 single or multiple isolated polyps of which 399 were adenomas, 59 hyperplastic polyps and 6 other types of lesions. Histologically we recorded 41 (13.27%) polyps with a low grade of dysplasia, 56 (18.12%) with severe dysplasia and 30 (9.7%) intramucosal adenocarcinoma with submucosal invasion. TREATMENT: Colonoscopic polypectomy was used for benign polyps and in situ carcinoma. In case of adenocarcinoma is probable the invasion of submucosal lymphatics being shown a colorectal resection as appropriate. We performed 279 colonoscopic polypectomies and 30 conventional resections. CONCLUSIONS: High grade of dysplasia, the number of polyps, ulceration, bleeding, intraepithelial areas of neoplastic transformation are predictive factors for early colorectal cancer. Depth of submucosal invasion of malignant transformed polyps are important pathological factors to predict lymphatic metastasis and to select the therapeutic procedure.

No Interval Cancers in Endoscopic Practice.

Colonoscopy is long time the most preferred method for CRC screening along with diagnosis and treatment for a range of colon diseases. Based on its difficulty in visualizing precursor CRC lesions, mostly those located on the right colon, this method can be subject of improvement. The colonoscopy quality can be influenced by many factors such as colon preparation, retraction time, the colonoscopists medical training and knowledges as well as the performance of endoscopy equipment. The bad quality of colonoscopy will result in the emergence of interval cancers defined, based on the author, as cancers that appear at 3-5 years up to 10 years from the colonoscopy procedure. Interval cancers have predominantly incriminated both the colonoscopy quality and the clinician competences and less the tumor biology. Subsequently there were set quality indicators of colonoscopy in order to raise the quality of the exploration. Among the important indicators, proving their utility in studies, the ADR (adenoma detection rate) is most commonly used along with PDR (polyp detection rate) and APC (adenoma per colonoscopy). Following the purpose of obtaining a higher colonoscopy quality the medical units should keep in check all indicators. Furthermore, there should be an active involvement in an additional training of non-conforming medical personnel or even restrain of practice, given the medical legal actions that have interval cancers as a main cause.

Assessment of the Quality of Outpatient Endoscopic Procedures by Using a Patient Satisfaction Questionnaire.

INTRODUCTION: Endoscopic procedures represent an important part of daily practice, both for gastroenterologists and nurses, enabling diagnosis and treatment of digestive diseases. An optimal level of quality needs to be obtained for endoscopic procedures to be efficient, which is reflected directly by patient satisfaction. The Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ) has already been validated in a multicenter trial as an efficient method for measuring patient satisfaction. Aim The aim of our study was to evaluate the quality of endoscopic procedures and patient satisfaction by applying a modified version of the GESQ in an outpatient facility, with or without deep sedation performed under the supervision of an anesthesiologist. MATERIAL AND METHODS: Our study included 552 patients undergoing diagnostic and therapeutic upper and lower GI endoscopies, including endoscopic ultrasound procedures (EUS) performed under propofol sedation, from September 2015 to February 2016. Consecutive patients examined during these 6 months received the questionnaire which was handed by the endoscopy nurse two hours after procedure. The GESQ was modified to include different sections for: 1) communication skills with questions regarding the quantity and clarity of the information delivered to the patient before and after the procedures; 2) pain and discomfort related to the examination with an added question about the specific procedure the patient had undergone; 3) staff manners; 4) physician's technical skills; 5) facility organization (waiting time, comfort in the recovery room, good facilities and equipment) and 6) overall satisfaction. The questionnaire did not include personal data, while answers were analyzed in a confidential manner. RESULTS: A total number of 552 patients agreed to answer our questionnaire, 192 (34,7%) underwent gastroscopies, 288 (52,1%) colonoscopies and 72 (13,2%) EUS examinations. Regarding the overall level of satisfaction (assessed on a five-point scale), 476 (86,2%) were very satisfied or satisfied, 69 (12,5%) dissatisfied and the remainder 7 (1,3%) were indifferently. For the communication section 16 (3%) patients were not satisfied with the explanations received before the procedure or with the answers to their questions. Pain and discomfort were mentioned by 29 (5,2%) of the patients, usually related to colonoscopies or EUS examinations. 13 (2,3%) of the patients considered the comfort or intimacy of the recovery room to be poor, and 11 (2%) patients were not satisfied with the waiting time before the procedure. CONCLUSION: Our modified questionnaire showed good overall patient satisfaction with our endoscopy unit, while also suggesting some areas in need of improvement, such as staff communication skills, better time management and reorganization of the recovery area. Our study demonstrates the importance of such questionnaires in providing feedback information meant to improve standards in endoscopy, including staff skills and organization.

Molecular Profiling of EGFR Status to Identify Skin Toxicity in Colorectal Cancer: A Clinicopathological Review.

Colorectal cancer (CRC) represents an important health problem, being the third most common type of cancer. In Romania, the CRC incidence has doubled over the years. Both environmental factors and genetic susceptibility are very important for the pathogenesis of CRC. The epidermal growth factor receptor (EGFR) plays an extremely important role in CRC tumorigenesis. Overexpression or dysregulation of EGFR pathway molecules are frequently associated with tumor aggressiveness and patient response to treatment. Based on these considerations, EGFR became one of the first targets of molecular therapies used in CRC. At present, cetuximab and panitumumab are considered to be essential in the treatment of patients with metastatic colorectal cancer expressing the KRAS wild-type gene and EGFR. The main adverse effect for both cetuximab and panitumumab is skin toxicity, present in approximately 80% of patients. The risk of secondary infections, in particular of bacterial infections, is also increased. Cases of staphylococcal infection associated with skin peeling, cellulite, erysipelas, and even Staphylococcus sepsis, were reported. For a long time cutaneous toxicity has been a positive predictor in the efficacy of anti-EGFR treatment, but compliance with treatment and the quality of life of patients with metastatic CRC decreases in the presence of these skin reactions. That is why we emphasize the necessity and importance of using a modern method (molecular analysis of gene polymorphisms possibly supplemented by targeted confocal laser endomicroscopy) to identify a molecular diagnosis, in order to foresee and prevent the appearance of skin reactions and to manage skin toxicity.