Estimated plasma volume status in COVID-19 patients and its relation to comorbidities and clinical outcomes.

Blood plasma is a large reservoir of circulating mediators of inflammation and its expansion has been associated with unfavorable outcomes in patients with inflammatory and cardiovascular diseases. The aim of this study was to determine clinical and prognostic value of estimated plasma volume status (ePVS) in hospitalized patients with COVID-19. We retrospectively investigated 5871 consecutive COVID-19 patient hospitalized in our tertiary-level institution in period 3/2020-6/2021. ePVS was determined using the Strauss-derived Duarte formula and was correlated with clinical characteristics and unwanted outcomes. Median ePVS was 4.77 dl/g with interquartile range 4.11-5.74. Higher ePVS was significantly associated with older age, female sex, higher comorbidity burden, worse functional status, less severe COVID-19 clinical presentation with lower severity and longer duration of symptoms, but more pronounced inflammatory profile with higher C-reactive protein, interleukin-6 and D-dimer levels (P < 0.05 for all analyses). In the multivariate regression analysis U shaped relationship of ePVS with mortality was revealed, present independently of age, sex, COVID-19 severity and comorbidity burden. In addition, higher ePVS was independently associated with higher tendency for mechanical ventilation, intensive care unit treatment, venous thromboembolism, major bleeding and bacteriemia and lower ePVS was independently associated with tendency for arterial thrombotic events. Higher ePVS, indicative of plasma volume expansion and inflammatory cytokine accumulation, may predispose respiratory deterioration and venous thromboembolism, despite less severe initial clinical presentation. Lower ePVS, indicative of hemoconcentration, may predispose arterial thrombotic events. Both may be associated with higher mortality in hospitalized COVID-19 patients.

Pathogenesis and Therapy of Oral Carcinogenesis.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck with an extremely poor five-year survival rate of approximately 50 to 55%, despite significant advances in diagnostic and therapeutic procedures over the past three decades [...].

The performance of the WHO COVID-19 severity classification, COVID-GRAM, VACO Index, 4C Mortality, and CURB-65 prognostic scores in hospitalized COVID-19 patients: data on 4014 patients from a tertiary center registry.

AIM: To evaluate the predictive properties of several common prognostic scores regarding survival outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively reviewed the medical records of 4014 consecutive COVID-19 patients hospitalized in our tertiary level institution from March 2020 to March 2021. Prognostic properties of the WHO COVID-19 severity classification, COVID-GRAM, Veterans Health Administration COVID-19 (VACO) Index, 4C Mortality Score, and CURB-65 score regarding 30-day mortality, in-hospital mortality, presence of severe or critical disease on admission, need for an intensive care unit treatment, and mechanical ventilation during hospitalization were evaluated. RESULTS: All of the investigated prognostic scores significantly distinguished between groups of patients with different 30-day mortality. The CURB-65 and 4C Mortality Score had the best prognostic properties for prediction of 30-day mortality (area under the curve [AUC] 0.761 for both) and in-hospital mortality (AUC 0.757 and 0.762, respectively). The 4C Mortality Score and COVID-GRAM best predicted the presence of severe or critical disease (AUC 0.785 and 0.717, respectively). In the multivariate analysis evaluating 30-day mortality, all scores mutually independently provided additional prognostic information, except the VACO Index, whose prognostic properties were redundant. CONCLUSION: Complex prognostic scores based on many parameters and comorbid conditions did not have better prognostic properties regarding survival outcomes than a simple CURB-65 prognostic score. CURB-65 also provides the largest number of prognostic categories (five), allowing more precise risk stratification than other prognostic scores.

Nuclear Epidermal Growth Factor Receptor Overexpression as a Survival Predictor in Oral Squamous Cell Carcinoma.

The aim of this study was to determine, by immunohistochemical methods, the expression of nEGFR and markers of cell proliferation (Ki-67), cell cycle (mEGFR, p53, cyclin D1), and tumor stem cells (ABCG2) in 59 pathohistological samples of healthy oral mucosa, 50 oral premalignant changes (leukoplakia and erythroplakia), and 52 oral squamous cell carcinomas (OSCC). An increase in the expression of mEGFR and nEGFR was found with the development of the disease (p < 0.0001). In the group of patients with leukoplakia and erythroplakia, we found a positive correlation between nEGFR and Ki67, p53, cyclin D1, and mEGFR, whereas in the group of patients with OSCC, we found a positive correlation between nEGFR and Ki67, mEGFR (p < 0.05). Tumors without perineural (PNI) invasion had a higher expression of p53 protein than tumors with PNI (p = 0.02). Patients with OSCC and overexpression of nEGFR had shorter overall survival (p = 0.004). The results of this study suggest a potentially important independent role of nEGFR in oral carcinogenesis.

Necrotic Cells from Head and Neck Carcinomas Release Biomolecules That Are Activating Toll-like Receptor 3.

Tumor necrosis is a recurrent characteristic of head and neck squamous cell carcinomas (HNSCCs). There is a need for more investigations on the influence of biomolecules released by these necrotic foci in the HNSCC tumor microenvironment. It is suspected that a fraction of the biomolecules released by necrotic cells are damage-associated molecular patterns (DAMPs), which are known to be natural endogenous ligands of Toll-like receptors (TLRs), including, among others, proteins and nucleic acids. However, there has been no direct demonstration that biomolecules released by HNSCC necrotic cells can activate TLRs. Our aim was to investigate whether some of these molecules could behave as agonists of the TLR3, either in vitro or in vivo. We chose a functional approach based on reporter cell exhibiting artificial TLR3 expression and downstream release of secreted alkaline phosphatase. The production of biomolecules activating TLR3 was first investigated in vitro using three HNSCC cell lines subjected to various pronecrotic stimuli (external irradiation, serum starvation, hypoxia and oxidative stress). TLR3 agonists were also investigated in necrotic tumor fluids from five oral cancer patients and three mouse tumor grafts. The release of biomolecules activating TLR3 was demonstrated for all three HNSCC cell lines. External irradiation was the most consistently efficient stimulus, and corresponding TLR3 agonists were conveyed in extracellular vesicles. TLR3-stimulating activity was detected in the fluids from all five patients and three mouse tumor grafts. In most cases, this activity was greatly reduced by RNAse pretreatment or TLR3 blocking antibodies. Our data indicate that TLR3 agonists are consistently present in necrotic fluids from HNSCC cells and mainly made of dsRNA fragments. These endogenous agonists may induce TLR3, which might lead to a protumorigenic effect. Regarding methodological aspects, our study demonstrates that direct investigations-including functional testing-can be performed on necrotic fluids from patient tumors.

Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients.

The aim of this study was to evaluate selected parameters of redox signaling and inflammation in the granulocytes of COVID-19 patients who recovered and those who died. Upon admission, the patients did not differ in terms of any relevant clinical parameter apart from the percentage of granulocytes, which was 6% higher on average in those patients who died. Granulocytes were isolated from the blood of 15 healthy people and survivors and 15 patients who died within a week, and who were selected post hoc for analysis according to their matching gender and age. They differed only in the lethal outcome, which could not be predicted upon arrival at the hospital. The proteins level (respective ELISA), antioxidant activity (spectrophotometry), and lipid mediators (UPUPLC-MS) were measured in the peripheral blood granulocytes obtained via gradient centrifugation. The levels of Nrf2, HO-1, NFκB, and IL-6 were higher in the granulocytes of COVID-19 patients who died within a week, while the activity of cytoplasmic Cu,Zn-SOD and mitochondrial Mn-SOD and IL-2/IL-10 were lower in comparison to the levels observed in survivors. Furthermore, in the granulocytes of those patients who died, an increase in pro-inflammatory eicosanoids (PGE2 and TXB2), together with elevated cannabinoid receptors 1 and 2 (associated with a decrease in the anti-inflammatory 15d-PGJ2), were found. Hence, this study suggests that by triggering transcription factors, granulocytes activate inflammatory and redox signaling, leading to the production of pro-inflammatory eicosanoids while reducing cellular antioxidant capacity through SOD, thus expressing an altered response to COVID-19, which may result in the onset of systemic oxidative stress, ARDS, and the death of the patient.

Vaccination provides protection from respiratory deterioration and death among hospitalized COVID-19 patients: Differences between vector and mRNA vaccines.

Outcomes of 109 hospitalized COVID-19 patients who received at least one vaccine dose 14 or more days prior the disease onset were retrospectively compared to control cohort of 109 age, sex, and Charlson comorbidity index-matched patients chosen among 2990 total hospitalized patients in our tertiary-level institution in a period from January to June 2021. Among 109 vaccinated patients, 84 patients were partially and 25 fully vaccinated. Vaccinated patients experienced significantly lower 30 days mortality (30% vs. 49%; hazard ratio [HR]: 0.56 [0.37-0.85]; p = 0.008), less frequently required high flow oxygen therapy (17% vs. 34%; HR: 0.45 [0.26-0.76]; p = 0.005), and mechanical ventilation (8% vs. 18%; HR: 0.41 [0.20-0.88]; p = 0.027) in comparison to the matched cohort of unvaccinated patients. More favorable survival was observed in patients receiving vector in comparison to messenger RNA (mRNA) vaccine types in unadjusted analysis (30 days mortality 18% vs. 40%; HR: 0.45 [0.25-0.79]; p = 0.034). In the multivariable Cox regression analysis model both mRNA (HR: 0.59 [0.36-0.98]; p = 0.041) and vector vaccine types (HR: 0.30 [0.15-0.60]; p < 0.001) were associated with improved survival in comparison to unvaccinated patients, independently of age (HR: 1.03 [1.01-1.06]; p = 0.011), male sex (HR: 1.78 [1.14-2.76]; p = 0.010), severity of illness (HR: 2.06 [1.36-3.10]; p < 0.001) and functional status on admission (HR: 1.42 [1.07-1.85]; p = 0.013).

Short-term outcomes of patients with chronic liver disease hospitalised with COVID-19.

BACKGROUND: Patients with chronic liver disease (CLD) might have an aggravated course after acquisition of coronavirus disease 2019 (COVID-19). AIMS: To analyse the outcomes of patients with CLD who were hospitalised due to COVID-19. METHODS: The medical records of 4014 patients hospitalised because of COVID-19 in a regional referral hospital over a 12-month period were analysed. Patients with CLD were identified based on discharge diagnoses according to the International Classification of Diseases-10th Revision. Patients were followed for 30 days from admission and their outcomes (intensive care unit (ICU) admission, mechanical ventilation (MV) or death) were analysed. RESULTS: Of the 4014 patients, 110 (2.7%) had CLD and 49 (1.2%) had cirrhosis. The median age of CLD patients was 67.5 years, 79 (71.8%) were males, 224 (23.5%) were obese, 56 (50.9%) reported alcohol abuse, 24 (21.8%) had non-alcoholic fatty liver disease, 11 (10%) had viral hepatitis and 98 (89.1%) had pneumonia. The median length of hospitalisation was 12 days; 32 (29.1%) patients required ICU admission and 23 (20.9%) patients required MV, while 43 (39.1%) died. In univariate analysis, patients with cirrhosis (45% vs 73%, hazard ratio (HR) = 2.95; P < 0.001), but not those with non-cirrhotic CLD (74% vs 73%; P > 0.05), experienced worse 30-day survival when compared with age, sex and COVID-19 duration-matched cohorts. In a logistic regression analysis conducted on the overall and matched cohorts, liver cirrhosis, but not CLD, predicted inferior survival independently of age, comorbidities and severity of COVID-19, with a fourfold higher adjusted risk of 30-day mortality. CONCLUSION: Cirrhosis is independently associated with higher 30-day mortality of hospitalised patients with COVID-19.

Incidence and risk factors for venous and arterial thromboses in hospitalized patients with coronavirus disease 2019: data on 4014 patients from a tertiary center registry.

AIM: To evaluate the burden and predictors of thromboembolic complications in a large real-life cohort of hospitalized patients with established coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the records of 4014 consecutive adult patients admitted to a tertiary-level institution because of COVID-19 from March 2020 to March 2021 for the presence of venous and arterial thrombotic events. RESULTS: Venous-thromboembolic (VTE) events were present in 5.3% and arterial thrombotic events in 5.8% patients. The majority of arterial thromboses occurred before or on the day of admission, while the majority of VTE events occurred during hospitalization. The majority of both types of events occurred before intensive care unit (ICU) admission, although both types of events were associated with a higher need for ICU use and prolonged immobilization. In multivariate logistic regression, VTE events were independently associated with metastatic malignancy, known thrombophilia, lower mean corpuscular hemoglobin concentration, higher D-dimer, lower lactate dehydrogenase, longer duration of disease on admission, bilateral pneumonia, longer duration of hospitalization, and immobilization for at least one day. Arterial thromboses were independently associated with less severe COVID-19, higher Charlson comorbidity index, coronary artery disease, peripheral artery disease, history of cerebrovascular insult, aspirin use, lower C reactive protein, better functional status on admission, ICU use, immobilization for at least one day, absence of hyperlipoproteinemia, and absence of metastatic malignancy. CONCLUSION: Among hospitalized COVID-19 patients, venous and arterial thromboses differ in timing of presentation, association with COVID-19 severity, and other clinical characteristics.

The associations of age, sex, and comorbidities with survival of hospitalized patients with coronavirus disease 2019: data from 4014 patients from a tertiary-center registry.

AIM: To investigate how age, sex, and comorbidities affect the survival of hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed the records of 4014 consecutive adults hospitalized for COVID-19 in a tertiary-level institution from March 2020 to March 2021. RESULTS: The median age was 74 years. A total of 2256 (56.2%) patients were men. The median Charlson-comorbidity-index (CCI) was 4 points; 3359 (82.7%) patients had severe or critical COVID-19. A significant interaction between age, sex, and survival (P<0.05) persisted after adjustment for CCI. In patients <57 years, male sex was related to a favorable (odds ration [OR] 0.50, 95% confidence interval [CI] 0.29-0.86), whereas in patients ≥57 years it was related to an unfavorable prognosis (OR 1.19, 95% CI 1.04-1.37). Comorbidities associated with inferior survival independently of age, sex, and severe/critical COVID-19 on admission were chronic heart failure, atrial fibrillation, acute myocardial infarction, acute cerebrovascular insult, history of venous thromboembolism, chronic kidney disease, major bleeding, liver cirrhosis, mental retardation, dementia, active malignant disease, metastatic malignant disease, autoimmune/rheumatic disease, bilateral pneumonia, and other infections on admission. CONCLUSION: Among younger patients, female sex might lead to an adverse prognosis due to undisclosed reasons (differences in fat tissue distribution, hormonal status, and other mechanisms). Patient subgroups with specific comorbidities require additional considerations during hospital stay for COVID-19. Future studies focusing on sex differences and potential interactions are warranted.

Red cell distribution width is a potent prognostic parameter for in-hospital and post-discharge mortality in hospitalized coronavirus disease 2019 patients: a registry-based cohort study on 3941 patients.

AIM: To investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission. RESULTS: The median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index). CONCLUSION: RDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.

Survival after hospital discharge in patients hospitalized for acute coronavirus disease 2019: data on 2586 patients from a tertiary center registry.

AIM: To assess the long-term survival after hospital discharge of patients hospitalized due to coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed data on post-discharge survival of 2586 COVID-19 patients hospitalized in our tertiary hospital from March 2020 to March 2021. RESULTS: Among 2586 patients, 1446 (55.9%) were men. The median age was 70 years, interquartile range (IQR, 60-80). The median Charlson comorbidity index was 4 points, IQR (2-5). The median length of hospital stay was 10 days, IQR (7-16). During a median follow-up of 4 months, 192 (7.4%) patients died. The median survival time after hospital discharge was not reached, and 3-month, 6-month, and 12-month survival rates were 93%, 92%, and 91%, respectively. In a multivariate analysis, mutually independent predictors of worse mortality after hospital discharge were age >75 years, Eastern Cooperative Oncology Group status 4, white blood cell count >7 ×109/L, red cell distribution width >14%, urea on admission >10.5 mmol/L, mechanical ventilation during hospital stay, readmission after discharge, absence of obesity, presence of chronic obstructive pulmonary disease, dementia, and metastatic malignancy (P<0.05 for all). CONCLUSION: Substantial risk of death persists after hospital admission due to COVID-19. Factors related to an increased risk are older age, higher functional impairment, need for mechanical ventilation during hospital admission, parameters indicating more pronounced inflammation, impaired renal function, and particular comorbidities. Interventions aimed at improving patients' functional capacity may be needed.

Real-life experience with remdesivir for treatment of hospitalized coronavirus disease 2019 patients: matched case-control study from a large tertiary hospital registry.

AIM: To evaluate the association of remdesivir use and the survival of hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the medical records of 5959 COVID-19 patients admitted to our tertiary-level hospital from March 2020 to June 2021. A total of 876 remdesivir-treated patients were matched with 876 control patients in terms of age, sex, Charlson comorbidity index (CCI), WHO-defined COVID-19 severity on admission, and oxygen requirement at the time of remdesivir use. RESULTS: Among 1752 COVID-19 patients (median age 66 years, 61.8% men), 1405 (80.2%) had severe and 311 (17.8%) had critically severe COVID-19 on admission. Remdesivir was given at a median of one day after hospital admission and at a median of eight days from the onset of symptoms. Overall, 645 (73.6%) patients received remdesivir before high-flow oxygen therapy (HFOT) or mechanical ventilation (MV), 198 (22.6%) after HFOT institution, and 83 (9.5%) after MV institution. Remdesivir use was associated with improved survival in the entire cohort (hazard ratio 0.79, P=0.006). Survival benefit was evident among patients receiving remdesivir during low-flow oxygen requirement (hazard ratio 0.61, P<0.001) but not among patients who received it after starting HFOT (P=0.499) or MV (P=0.380). CONCLUSION: Remdesivir, if given during low-flow oxygen therapy, might be associated with survival benefit in hospitalized COVID-19 patients.

Epidemiological characteristics, baseline clinical features, and outcomes of critically ill patients treated in a coronavirus disease 2019 tertiary center in continental Croatia.

AIM: To describe epidemiological characteristics and baseline clinical features, laboratory findings at intensive care unit (ICU) admission, and survival rates of critically ill coronavirus disease 2019 (COVID-19) patients treated at a tertiary institution specialized for COVID-19 patients. METHODS: This retrospective study recruited 692 patients (67.1% men). Baseline demographic data, major comorbidities, anthropometric measurements, clinical features, and laboratory findings at admission were compared between survivors and non-survivors. RESULTS: The median age was 72 (64-78) years. The median body mass index was 29.1 kg/m2. The most relevant comorbidities were diabetes mellitus (32.6%), arterial hypertension (71.2%), congestive heart failure (19.1%), chronic kidney disease (12.6%), and hematological disorders (10.3%). The median number of comorbidities was 3 and median Charlson Comorbidity Index (CCI) was 5. A total of 61.8% patients received high-flow nasal oxygen therapy (HFNO) and 80.5% received mechanical ventilation (MV). Median duration of HFNO was 3, and that of MV was 7 days. ICU mortality rate was 72.7%. Survivors had significantly lower age, number of comorbidities, CCI, sequential organ failure assessment score, serum ferritin, C-reactive protein, D-dimer, and procalcitonin, interleukin-6, lactate, white blood cell, and neutrophil counts. They also had higher lymphocyte counts, PaO2/FiO2 ratio, and glomerular filtration rate at admission. Length of ICU stay was 9 days. The median survival was 11 days for mechanically ventilated patients, and 24 days for patients who were not mechanically ventilated. CONCLUSION: The parameters that differentiate survivors from non-survivors are in agreement with published data. Further multivariate analyses are warranted to identify individual mortality risk factors.

Diversified Effects of COVID-19 as a Consequence of the Differential Metabolism of Phospholipids and Lipid Peroxidation Evaluated in the Plasma of Survivors and Deceased Patients upon Admission to the Hospital.

As a result of SARS-CoV-2 infection, inflammation develops, which promotes oxidative stress, leading to modification of phospholipid metabolism. Therefore, the aim of this study is to compare the effects of COVID-19 on the levels of phospholipid and free polyunsaturated fatty acids (PUFAs) and their metabolites produced in response to reactions with reactive oxygen species (ROS) and enzymes (cyclooxygenases-(COXs) and lipoxygenase-(LOX)) in the plasma of patients who either recovered or passed away within a week of hospitalization. In the plasma of COVID-19 patients, especially of the survivors, the actions of ROS and phospholipase A2 (PLA2) cause a decrease in phospholipid fatty acids level and an increase in free fatty acids (especially arachidonic acid) despite increased COXs and LOX activity. This is accompanied by an increased level in lipid peroxidation products (malondialdehyde and 8-isoprostaglandin F2α) and lipid mediators generated by enzymes. There is also an increase in eicosanoids, both pro-inflammatory as follows: thromboxane B2 and prostaglandin E2, and anti-inflammatory as follows: 15-deoxy-Δ-12,14-prostaglandin J2 and 12-hydroxyeicosatetraenoic acid, as well as endocannabinoids (anandamide-(AEA) and 2-arachidonylglycerol-(2-AG)) observed in the plasma of patients who recovered. Moreover, the expression of tumor necrosis factor α and interleukins (IL-6 and IL-10) is increased in patients who recovered. However, in the group of patients who died, elevated levels of N-oleoylethanolamine and N-palmitoylethanolamine are found. Since lipid mediators may have different functions depending on the onset of pathophysiological processes, a stronger pro-inflammatory response in patients who have recovered may be the result of the defensive response to SARS-CoV-2 in survivors associated with specific changes in the phospholipid metabolism, which could also be considered a prognostic factor.

The Impact of Severe COVID-19 on Plasma Antioxidants.

Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARS-CoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients.

Elective neck dissection in adenoid cystic carcinoma of head and neck: yes or no? A systematic review.

PURPOSE: Adenoid cystic carcinoma of head and neck (AdCCHN) is salivary gland malignancy known for its slow progression accompanied with perineural invasion, rare lymphatic spread to the neck, high rate of local recurrence and delayed onset of distant metastases. While local recurrence and distant metastases are most common patterns of relapse and cause of death in AdCCHN, it has been debated whether lymph node involvement affects the course of the disease. The aim of this systematic review was to address this important issue and to recommend guidelines on clinically node-negative neck management in patients with AdCCHN. METHODS: A systematic review of the published literature on cases of elective neck dissection (END) among patients with AdCCHN was performed. RESULTS: This analysis included a total of 5767 AdCCHN patients with 2450 ENDs, ranging from 10 to 1190. Elective lymphadenectomy was employed in 42.5% of patients with AdCCHN (range 9.2-100%). The overall rate of occult neck metastases in patients with AdCCHN was reported to range between 0 and 43.7%, the average being 13.9%. CONCLUSIONS: If performed, END should be limited to levels I-III of the ipsilateral neck since occult metastases are exclusively located within these neck regions. Although END is associated with a prolonged regional recurrence-free period, it influence on final outcome or survival is still controversial. This review strongly supports conduction of prospective trials on indications, prognostic significance and extent of END in AdCCHN.

Cisplatin-based chemoradiotherapy vs. cetuximab-based bioradiotherapy for p16-positive oropharyngeal cancer: an updated meta-analysis including trials RTOG 1016 and De-ESCALaTE.

PURPOSE: Human papilloma virus (HPV)-associated oropharyngeal cancer (OPC) is a special entity among head and neck squamous cell carcinomas (HNSCCs). Given its favorable prognosis, one of the de-escalating strategies in the treatment of OPC includes the introduction of cetuximab (C225) instead of cisplatin (CDDP) in conjunction with radiotherapy. An updated meta-analysis of published studies has been performed, which directly compared the efficacy of CDDP vs. C225 given concurrently with radiotherapy as definitive treatment of p16-positive OPC. METHODS: A systematic literature search was performed for studies published between 2006 and 2018. A total of 1490 citations were obtained and 8 studies met inclusion criteria, with a total of 1665 patients. RESULTS: The data from seven studies were available for the analysis of 2-year overall survival (OS). Calculated pooled OR for CDDP-based chemoradiotherapy vs. C225-based bioradiotherapy, was 0.45 (P < 0.0001). The data from eight studies were available for the analysis of 2-year locoregional recurrence (LRR). Calculated pooled OR for CDDP-based chemoradiotherapy vs. C225-based bioradiotherapy was 0.35 (P < 0.0001). Patients receiving CDDP with irradiation had 2.2- and 2.9-fold decreased risk for death from any cause and LRR, respectively. CONCLUSIONS: For patients with HPV-positive OPC, radiotherapy plus C225 showed inferior OS and higher LRR rates compared with radiotherapy plus CDDP. CDDP-based chemoradiotherapy should remain standard of definitive treatment of p16-positive OPC.