Paragangliomas of the Head and Neck: A Review of the Latest Diagnostic and Treatment Methods.

Background and objectives: Paragangliomas of the head and neck are rare, slow-growing neuroendocrine tumors, benign in their vast majority, but with a possibility of developing distant metastases. They show great inheritable character, and their behavior has proven to be unpredictable; therefore, they are considered malignant. Material and methods: This article aims to offer a more comprehensive presentation of the pathogenesis, epidemiology, diagnostic methods, imaging development, and treatment guidelines. We tried to bring together all the necessary data that, in our opinion, a head and neck practitioner should know when managing this type of tumor. Our main focus is on the most recent studies, with the purpose of a homogenous presentation of all current guidelines and approaches to this pathology. Results: Paragangliomas of the head and neck are still a disputed topic. One of the main reasons for that is their low incidence of 0.3 to 1 per 100,000 every year. The most frequent locations are the carotid body, the temporal bone, the jugular and mastoid foramen, and the vagal nerve. Their clinical presentation usually involves a painless lateral mass associated with symptoms such as hoarseness, hearing loss, tinnitus, and cranial nerve deficits. Up to 40% of them are inherited, mostly linked with mutations of succinate dehydrogenase complex. Imaging evaluation consists of CT and MRI, and new functional explorations such as 18F-FDA and 18F-FDG PET/CT, 18F-DOPA PET, 123I-MIBG, and 68Ga-DOTATE PET/CT. Measuring the catecholamine levels in the plasma and urine is mandatory, even though paragangliomas of the head and neck rarely display secretory behavior. Treatment mainly consists of surgery, with different approaches and techniques, but conservative management methods such as wait and scan, radiotherapy, proton therapy, and chemotherapy have proven their efficiency. The therapeutical decision lacks consensus, and current studies tend to recommend an individualized approach. Guidelines regarding long-term follow-up are still a matter of debate.

Laryngeal Paraganglioma-A Case Report.

Background and Objectives: Paragangliomas of the head and neck are rare neuroendocrine tumors originating from the paraganglia, which might be sympathetic or parasympathetic. Laryngeal paragangliomas are the rarest subtype of these tumors, with only 1.41% of all paragangliomas, arising from the supraglottic or subglottic paraganglia of the larynx. The vast majority of them are benign, but there are some cases in which they turn out to be malignant, and the only way to know with certainty the difference between them is when we identify distant metastases. The aim of this article is to share our experience with a rare case of laryngeal paraganglioma and review the clinical characteristics, methods of diagnostic, necessary investigation prior to the operation, and surgical management of this type of tumor. Materials and Methods: We present the case of a 68-year-old female patient, a non-smoker, who accused dysphagia, dysphonia, foreign body sensation, chronic cough, and hoarseness for six months. We performed a tracheostomy prior to biopsy to secure the airways in case of bleeding and then took a few biopsy samples. The histopathological exam revealed the presence of a laryngeal paraganglioma. An enhanced CT scan was performed in order to describe the localization, size, and invasion of the tumor. We also measured the vanillylmandelic acid from the urine to determine if the tumor produced catecholamines alongside a full cardiology and endocrinology examinations. In order to prevent massive bleeding during the operation, chemoembolization was attempted before surgery, but it was unsuccessful due to an anatomical variation of the left superior thyroid artery. She underwent surgery, first through transoral endoscopic microsurgery; however, we decided to undertake an external approach because of poor bleeding control, even though we had ligated both the superior thyroid artery and the external carotid artery, with a thyrotomy and laryngofissure achieving the complete resection of the tumor. Results: The patient was discharged 10 postoperative days later, with the recommendation of introducing food step-by-step from liquids to solids. She was decannulated after 30 days, with no complications regarding breathing, phonation, or deglutition. Twelve months after the surgery, we did not identify any local relapses of distant metastases. Conclusions: Laryngeal paragangliomas are rare neuroendocrine tumors that arise from the laryngeal paraganglia. Surgery is the best treatment option available, and it can be done by either an external approach or by transoral endoscopy. Enhanced CT or MRI, as well as full cardiological and endocrinological evaluation are mandatory prior to the operation. Measuring the catecholamines levels show the if the tumor is secretory. Controlling the bleeding poses the biggest challenge in performing the resection of the tumor, especially when a transoral endoscopic approach is chosen. Further standardized follow-up guidelines are required in the future.

Efficacy of Continuous Suctioning in Adenoidectomy Haemostasis-Clinical Study.

Introduction: Adenoidectomy is often the first major surgical challenge for the child's haemostatic system, and controlling intraoperative bleeding can be a challenge for the surgeon. Different methods have been used intraoperatively by surgeons in order to enhance haemostasis. The cold air effect (continuous suctioning) has been used by some surgeons during adenoidectomy; however, no documentation of its haemostatic effect has been made. Objectives: Our prospective randomised controlled study enrolled a sample of 140 children undergoing adenoidectomy, and we studied the effect of continuous suctioning on the duration of haemostasis in paediatric adenoidectomy. Materials and Methods: We evaluated the effect of using continuous suctioning during haemostasis at the end of adenoidectomy procedures, comparing variables such as total surgery time, total haemostasis time, and intraoperative blood loss, between two groups: 70 adenoidectomy procedures where no continuous suctioning was used to enhance haemostasis versus the other 70 patients where continuous suctioning was the haemostatic method employed. RESULTS: After statistical analysis of the recorded data, we found that the total duration of adenoidectomy, the duration of haemostasis in adenoidectomy, and the intraoperative blood loss were significantly lower in patients in whom cold air was used for haemostasis. Intraoperative haemostasis failure (and consequent use of electrocautery for haemostasis) was more frequent in patients in whom no suctioning was used; as for the rates of postoperative primary bleeding after adenoidectomy, they were similar in both groups of patients, regardless of the technique used for haemostasis. Conclusions: The use of continuous suctioning during adenoidectomy haemostasis significantly shortens total surgical and haemostasis time, reduces intraoperative blood loss, and reduces the incidence of haemostasis failure (with the consequent need for bipolar electrocautery haemostasis).

The present and the future of benzydamine: expert opinion paper.

Objectives: Benzydamine is a compound indicated in the treatment of symptoms of irritation/inflammation of the oropharyngeal cavity, including those associated with pain. Objectives of this expert opinion narrative review is to summarize current indicated benzydamine applications and elicit further ones to be explored. Materials and methods: In this expert opinion paper, evidences underlying the mechanism of action and clinical application of benzydamine are reviewed. Insights are also provided on possible new clinical applications of the drug and new formulations. Results: Current recognized indications of benzydamine include: relief of symptoms associated with inflammatory conditions of the mouth and oropharynx, symptomatic treatment of gingivitis and stomatitis, oral mucositis induced by chemotherapy and/or radiotherapy and post operative sore throat. In addition, among new applications that need to be explored experts embed: oral lichen planus, burning mouth syndrome, post intubation sore throat, antifungal action and new anticancer target agents induced mucositis. Conclusions: Benzydamine is a very versatile compound able to play an auxiliary and adjuvant role in the prevention and treatment of oral cavity/oropharynx disorders. According to experts' opinion there is the need to design clinical trials to highlight novel possible applications of benzydamine and implemented translational analyses to fine-tune patients' selection and open future research scenarios.

Postoperative Outcomes of Endoscopic versus Microscopic Myringoplasty in Patients with Chronic Otitis Media-A Systematic Review.

Endoscopes are increasingly being used in middle ear surgery as an adjunct to or replacement for the operative microscope. The superior visualization of hidden areas and a minimally invasive transcanal approach to the pathology are some of the endoscope's advantages. The aim of this review is to compare the surgical outcomes of a totally endoscopic transcanal approach with a conventional microscopic approach for type 1 tympanoplasty in patients with chronic otitis media (COM) in order to establish if endoscopic myringoplasty (EM) could be a better alternative to microscopic myringoplasty (MM). A literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. The selected articles were identified by searching PubMed Central, PubMed, MEDLINE and Embase databases for the relevant publications. Only studies where the same surgeon in the department performed both endoscopic and microscopic myringoplasty have been included in the review. The results suggest that with an endoscopic approach, minimally invasive myringoplasty can be achieved with a similar graft success rate and postoperative air-bone gap (ABG) improvement, a shorter operative time and less postoperative complications compared to a microscopic approach.

Comparative Efficacy of Velopharyngeal Surgery Techniques for Obstructive Sleep Apnea: A Systematic Review.

Background: In recent years, surgical interventions for obstructive sleep apnea (OSA) have evolved rapidly, with numerous techniques described in the literature. The approach to velopharyngeal surgery for obstructive sleep apnea has transformed over time, shifting from an aggressive removal of redundant excess soft tissue to less invasive reconstruction techniques that aim to preserve pharyngeal function while effectively managing sleep apnea. This review aims to evaluate and compare the efficacy of the surgical techniques utilized for OSA at the level of the palate and pharynx. It will cover both traditional and novel procedures. Methods: A comprehensive search of the major databases, such as PubMed/MEDLINE, Web of Science, and Scopus, was conducted to identify the relevant literature. We included articles written in English that analyzed the outcomes of adult patients who received velopharyngeal surgery for sleep apnea. Only comparative studies that examined at least two techniques were considered. Results: In all of the studies combined, the total number of patients who underwent velopharyngeal surgery was 614 in eight studies. All surgical procedures resulted in improvements in the apnea-hypopnea index (AHI). The highest success rates and best outcomes were achieved by barbed reposition pharyngoplasty (BRP) in most studies, ranging from 64.29% to 86.6%. BRP also demonstrated the most significant improvements in both objective and subjective parameters closely followed by ESP that obtained similar efficiency in some studies, especially when combined with anterior palatoplasty (AP), but with a higher incidence of complications. While LP showed moderate efficiency compared with BRP or ESP, the UPPP techniques exhibited greater outcome variability among studies, with a success rate ranging from 38.71% to 59.26%, and the best results observed in a multilevel context. Conclusions: In our review, BRP was the most preferred, effective, and safe among all velopharyngeal techniques, closely followed by ESP. However, older described techniques also showed good results in well-selected patients. Larger-scale studies, preferably prospective, that rigorously incorporate DISE-based strict inclusion criteria might be needed to assess the efficacy of different techniques and generalize the findings.

Management of Capillary Hemangioma of the Sphenoid Sinus.

Background and objectives: Capillary hemangiomas are rare, benign vascular tumors that mainly affect the skin and soft tissue, with scarce appearance within the nasal cavities and paranasal sinuses. Materials and methods: We present a case report of capillary hemangioma of the sphenoid sinus and a review of the literature in the last ten years. Results: Clinical and endoscopic examination of the nose, radiologic assessment and particular histologic features contribute to the correct diagnosis of capillary hemangioma of the nose and paranasal sinuses. Conclusions: Transnasal endoscopic resection of capillary hemangioma located in the nose and paranasal sinuses is a valuable treatment method with good outcomes.

Use and Abuse of Electrocautery in Adenoidectomy Hemostasis.

Background and objectives: Bipolar electrocautery is commonly used to control bleeding after cold-instrument pediatric adenoidectomy, but the surgeon should be aware of the possible side effects. OBJECTIVE: The aim of our study is to investigate the effects of bipolar electrocautery when used for bleeding control at the end of an adenoidectomy procedure. Materials and Methods: We evaluated the effect of electrocautery on postoperative pain, velopharyngeal insufficiency symptoms, postoperative nasal obstruction, and rhinorrhea in a group of 90 children undergoing adenoidectomy in our ENT department over a period of 3 months. Results: After statistically analyzing the data, we found that the duration of postoperative pain, the duration of rhinorrhea and nasal obstruction, and the duration of painkiller administration, as well as the velopharyngeal insufficiency symptoms, were significantly longer in patients in whom electrocautery was used for hemostasis. A significantly higher incidence of posterior neck pain and halitosis (oral malodor) was noted in the patients in whom electrocautery was used for adenoidectomy hemostasis. Conclusions: Bipolar electrocautery use should be limited during pediatric adenoidectomy hemostasis because of the possible side effects: longer postoperative pain, prolonged nasal obstruction, rhinorrhea and velopharyngeal insufficiency, and halitosis. We noted some side effects that were specific to electrocautery use during adenoidectomy: posterior neck pain and oral malodor. Acknowledging the risk for these symptoms can help to alleviate the anxiety of both the parents and the patients regarding the expected postoperative outcomes.

The Role of Inverted Papilloma Surgical Removal for Sleep Apnea Treatment Success-A Case Report.

In recent years, increased attention has been directed to sleep apnea syndrome due to its high prevalence and preventable severe health consequences. Besides enhancing the risk of cardiovascular, cerebrovascular, and metabolic disorders, it determines increased daytime somnolence, cognitive impairment, and delayed reaction time. These symptoms, determined by sleep fragmentation and chronic hypoxemia, can result in a decrease in professional performance and, moreover, could have tragic implications, especially in patients with high-risk professions. We present the case of a 58-year-old male-truck driver, known to suffer from uncontrolled OSA and chronic obstructive pulmonary disease, who presented to our ENT department for incapacitating daytime somnolence and severe nasal obstruction. These symptoms were caused by a voluminous sinonasal inverted papilloma, occupying the entire left cavity with extension in the nasopharynx. Following nose permeabilization, the patients' APAP compliance grew substantially, with a dramatic decrease in daytime sleepiness and improvement in polysomnographic parameters. Due to the overlap syndrome of OSA and COPD, an oxygen supplementation was added to PAP therapy by a pulmonologist, improving pulse-oximetry parameters and resulting in the best outcome for the patient. Through this case report, we aim to emphasize the importance of multimodal, personalized treatment of sleep apnea with a focus on nasal surgical permeabilization. At the same time, we sustain a multidisciplinary approach, especially in patients with sleep apnea and associated pathologies, to obtain therapeutic success. We propose increased attention to the early recognition and proper treatment of sleep apnea in patients with high-risk professions as it prevents catastrophes.

Multidisciplinary Therapeutic Management in Complex Cervical Trauma.

Background and Objectives: In the current literature, mandatory surgical exploration is a controversial topic, with some advocating for it and others against it, proposing a selective conservative management. This multidisciplinary therapeutic approach is based on clinical examination and serial paraclinical explorations associated with supportive drug treatment. Materials and Methods: The study group consisted of 103 patients with complex cervical trauma pathology produced by various mechanisms such as car or domestic accidents, aggression, ballistic trauma, self-inflicted attempts, hanging or strangulation hospitalized in the Ear, Nose and Throat (E.N.T.) Clinic, at "St. Spiridon" Iași Hospital, between 2012 and 2016. Results: The universal clinical indication for urgent surgical exploration of the patient with complex cervical trauma is the presence of the following symptoms: unstable vital signs, significant pulsatile bleeding, hematoma with a substantial increase in size, shock, airway obstruction, open airway wound, hematemesis, or hemoptysis. In this context, we considered it worthwhile to research the management of complex cervical trauma in a reference university medical center, alongside the analysis of the patient's characteristics under different aspects (demographic, pathological aspects, therapeutic). Conclusions: Complex cervical trauma has a variety of clinical aspects, with a variable evolution, which involves multidisciplinary therapeutic management. The increasing trauma rate is one of the main public health problems, requiring epidemiological studies, and the implementation of control strategies.

Multicenter Epidemiological Study of Nosebleeds Requiring Hospitalization.

Epistaxis is a common presenting symptom either emergency condition or ambulatory in Otorhinolaryngology, affecting people of all ages. A multicentric retrospective descriptive study of 380 patients who were hospitalized with epistaxis over a 3.8 year period was carried out. Data collected was analyzed using IBM SPSS Statistics 25 and illustrated using Microsoft Office/Word 2016. The current study showed that male adults after 60 years old are most affected by nasal bleeding. More than half of hospitalized patients have severe epistaxis at the time of hospitalization. However, further studies are necessary to be done in order to fully elucidate the epidemiology of nosebleeds requiring hospitalization.

Etiological Profile of Epistaxis: Pre-Pandemic Versus Pandemic.

Nosebleed or epistaxis is one of the most common forms of presenting an emergency in the ENT field. Since March 11, 2020, the World Health Organisation has proclaimed COVID-19 a global pandemic, and the world has been closed down. The main objective of the study is to analyse and compare the dynamics of epistaxis aetiology among the cases that required hospitalisation in the pre-pandemic period and the period of the COVID 19 pandemic. The study is multicenter retrospective from October 2018 to May 2022, including 380 cases of hospitalised epistaxis, with the mention that March 2020 is considered the beginning of the pandemic period. 60.8% of the patients enrolled in the study in the pre-pandemic period (60.8%) and 39.2% in the pandemic period. Differences between groups were not statistically significant between study entries (pre-pandemic vs. pandemic) and age (p=0.331), gender (p=0.916) or existence of local causes for epistaxis (p=0.895). Patients with general causes for epistaxis were more frequently enrolled in the pandemic period, while patients without general causes for epistaxis were more frequently enrolled in the pre-pandemic period. Patients with a hospitalisation period of more than 5 days were more frequently enrolled in the pre-pandemic period while patients with a hospitalisation period of 3 to 5 days were more frequently enrolled in the pandemic period. Also, patients with idiopathic epistaxis were more frequently enrolled in the pre-pandemic period. Based on the results presented in our study, the period of the Covid 19 pandemic directly influenced both the number of patients and the period of hospitalisation.

Current approach of juvenile nasopharyngeal angiofibroma: a case series.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor that affects predominantly males and is known by its highly vascular character. We have performed a 3-year retrospective study of patients with JNA surgically treated within the third ENT Department of Prof. Dr. Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania. In all the cases, the patients were investigated both clinically and through medical imaging before surgery and all tumors were embolized. Our study comprised of eight cases, of which seven were solved by endoscopic endonasal approach and one case was treated through a combined endonasal-external approach. JNA should always be managed through a multidisciplinary team (MDT) approach in centers with adequate experience, to gain favorable results.

Liquid Biopsy in Squamous Cell Carcinoma of the Esophagus and of the Head and Neck.

Squamous cell carcinomas of the esophagus (ESCC) and of the head and neck (HNSCC) are two neoplasms that share common risk factors and have the same embryological origin, but a very different prognosis, the 5-year survival of HNSCC being almost double (40-50%) compared to the 5-year survival of ESCC (20%). Current guidelines emphasize the importance of screening for ESCC in patients diagnosed with head and neck cancers. A liquid biopsy is a novel tool for diagnosis, prognostic stratification, and personalized therapy. Liquid biopsy biomarkers for these two malignancies could help both their early detection, facilitate residual disease identification, and provide prognosis information. The present systematic review of the literature was aimed at describing the liquid biopsy biomarkers present in these two malignancies, with an emphasis on potential clinical applications.

Reconstructive challenges of sinonasal tumors: A case report.

Sinonasal tumors are an uncommon pathological entity and applying the optimal treatment may represent a challenge, even for experienced physicians. A various number of techniques and materials may be used in the reconstruction of craniofacial defects following surgery for extensive sinonasal cancer. The aim of the present study was to present the case of a 33-year-old male patient diagnosed with a large sinonasal tumor and discuss the challenges faced while selecting the most suitable rehabilitation technique. In the present case, it was decided that the optimal solution was to use a craniofacial prosthesis in order to cover the entire defect, as well as a temporoparietal flap. In summary, reconstructive interventions must always be adapted to each individual patient and a multimodal approach may lead to a highly satisfactory outcome, for both the patient and the surgical team. All the reconstructive solutions available must always be kept in mind and adapted to the individual requirements of each case, taking into consideration both the extent of the tumor and the comorbidities of the patient, as there is no one solution that is considered as optimal for all patients.

Endoscopic assessment of sinonasal mucormycosis with SPIES: The 'battlefield' sign.

Sinonasal mucormycosis is an extremely challenging pathology for the ear, nose and throat (ENT) surgeon from a therapeutic point of view. The disease affects immunocompromised patients and exhibits lethal potential. Although the diagnosis is relatively easy to suspect due to the distinctive clinical aspects which consists of black crusting present in the nasal fossae able to be confirmed by biopsy, the treatment requires resection of all affected tissue with safety limits. Due to the tendency of invasion associated with this fungal infection and taking into account the location involved (the sinonasal area) and the grave condition of these patients, it is extremely important to perform only the minimal resection necessary, but that includes all tissue infected by the fungus. This article presents a minimally invasive method of evaluation that can be performed during endoscopic surgical intervention and that aids the surgeon to better evaluate the affected area. It is associated with no additional risks for the patients, but it helps the surgeon to perform the intervention efficiently while not damaging healthy tissue. The authors consider that the method presented will aid the surgeon during the endoscopic surgical intervention in evaluating the lesion and resecting all the affected tissue while preserving healthy areas.

Clinical significance of serum matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in the first phase of burn trauma evolution.

No prospective study has specifically examined the serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the early shock phase of burn-injured patients. Thus, we aimed to detect early changes, activity dynamics, and the predictive value of MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio to better understand the early repair mechanisms for the development of future therapies for patients with thermal burns. Twenty-five patients with a total body surface area (TBSA) affected by burn <25%, and 30 healthy subjects were enrolled in the study. Serum levels of MMP-9 and TIMP-1 were determined by the ELISA method. Our results showed that MMP-9 concentrations increased immediately after injury and remained on a plateau. In contrast, TIMP-1 showed an upward trend throughout the 7-day study period, and the time course of the MMP-9/TIMP-1 ratio followed the inverse dynamics of TIMP-1. Analysis of the areas under the receiver operating characteristic (ROC) curves (AUC) showed that patients with burn wounds tended to have a MMP-9 value higher than 421.5 ng/ml (AUC=0.979), TIMP-1 value higher than 231.6 ng/ml (AUC=0.908), and MMP-9/TIMP-1 ratio higher than 2.31 (AUC=0.959) (P<0.001). Our findings suggest that although the variations in the two biomarkers were different regarding the time of the initial insult, their ratio is a specific and sensitive indicator of burn evolutivity in patients with a TBSA affected by a burn <25%.

Role and dynamics of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in burn patients.

Burn injuries can trigger tissue changes that can explain the variation in the level of different biochemical markers that can be recorded both locally or systemically. Some events observed in burn wounds such as vascular hyperpermeability have been associated with the release of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after trauma. Because it is unknown whether the serum levels of MMP-9 and TIMP-1 are a consequence of these destructions or a local response to thermal damage, we decided to follow their dynamics. Twenty-five patients (mean age 49.40±17.55 years) with a total body surface area (TBSA) affected by a thermal burn of <25% and 30 healthy subjects (mean age 49.70±8.04 years) were enrolled in the present study. Enzyme immunoassays were used to measure the serum levels of MMP-9 and TIMP-1. Our results showed that MMP-9 was increased 6.25-fold immediately after injury compared to the controls and remained on a plateau throughout the 7-day monitoring period. TIMP-1 showed an upward trend with an increase of 49.52% on the seventh day after triggering insult. The time-course of the MMP-9/TIMP-1 ratio followed the inverse dynamics of TIMP-1 starting from a ratio value measured at admission 3.82-fold higher than the one observed in the healthy volunteers and a highly statistically significant correlation between the values measured at different time-points during the monitoring period (P<0.001). The results of this retrospective study indicate that the MMP-9/TIMP-1 ratio may provide information on local changes over time, starting from the triggering insult, and may be considered as a predictive biomarker of burn evolutivity.

Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines.

In head and neck cancers, the effectiveness of cisplatin (CisPt) treatment is limited by its toxicity, especially when higher doses are necessary, and the possible occurrence of cisplatin resistance. This study evaluated the effects of resveratrol (RSV) on the expression of different genes involved in the response of human tumor cells (FaDu, PE/CA-PJ49) to cisplatin therapy. Our results revealed that RSV induced apoptosis amplification in both FaDu and PE/CA-PJ49 cells and modulated the expression of specific genes differently than in normal HaCaT cells. In FaDu cells, combined CisPt + RSV treatment induced an increase in apoptosis, which was associated with an increase in c-MYC and TP53 and a decrease in BCL-2 expression. While CisPt + RSV treatment induced apoptosis in PE/CA-PJ49 cells by inhibition of BCL-2 associated with high levels of MDM-2 and subsequently led to inhibition of TP53 gene expression. Decreased c-MYC expression in PE/CA-PJ49 treated with CisPt + RSV was accompanied by cell cycle blockage in G0/G1 phase. In conclusion, RSV influences tumor cell response to CisPt by inducing apoptosis and modulating gene expression. In addition, in normal HaCaT cells, RSV was able to reduce the harmful effects of CisPt.

Possible Influence of Weight Gain and Creatinine Levels in Predicting Response to Nivolumab: A Multicenter Analysis.

BACKGROUND: Literature suggests that high body mass index can be correlated with better response to immune checkpoint inhibitors. On the other hand, sarcopenia seems to be a negative predictive marker. Materials and methods: The present analysis is a retrospective, multicenter trial that included patients with metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma treated with nivolumab between 2018 and 2020. Patients were stratified by creatinine levels both at treatment initiation and at first follow-up (at three months) and by BMI for the same intervals, as recorded in the patients' charts. Creatinine was considered a surrogate marker for sarcopenia. IBM SPSS version 20 was used for statistical analysis. Results: A total of 57 (n = 57) patients were included in the trial. Overall response rate (ORR) for the entire population was 38.59% (p = 0.02). Patients with BMI lower than 25 had an ORR of 28.5% (p = 0.003), whereas patients with BMI higher than 25 had an ORR of 42.3% (p = 0.002). Patients who gained weight during treatment had a lower probability of having progressive disease (OR = 0.4 [95% CI; 0.4-1.2]), as did patients with creatinine higher than 0.9 (OR = 0.39 [95% CI: 0.13-1.14]). No superiority was found in progression-free survival (PFS) when patients were dichotomized for BMI = 25 or BMI = 18.5. Mean PFS in the BMI under 18.5 group was 10.2 months [95% CI: 5.8-23.1], versus 11.2 for BMI over 18.5 [95% CI: 5.3-25.3], p < 0.03. Mean PFS for the BMI under 25 was 11.2 months [95% CI: 7.2-20.1], vs. 13.3 months [95% CI: 6.4-22] for the BMI over 25, p < 0.001. There were also differences in PFS in the patients with baseline creatinine over 0.9 when compared with under 0.9 values. Mean PFS in the first group was 19.78 months [95% CI: 16.23-22.9] vs. 16.1 [95% CI: 12.2-20.3], p < 0.001. Conclusion: Patients treated with nivolumab who have weight gain during treatment have a better PFS than the ones who do not. Creatinine levels of over 0.9 at treatment initiation also have positive predictive value.