Spiritual Beliefs and Hastened Death: A Study on Medical Students.

This study focuses on the impact of common spiritual beliefs regarding metaphysical questions in agreeability with the practice of hastened death. A sample of 497 Portuguese medical students was collected. Differences between genders and religions, predictors for agreeability with hastened death and the association between spiritual beliefs and opinion towards hastened death cases were assessed. Respondents were mostly favourable to the practice of hastened death. Formal religious affiliation and higher levels of religiosity significantly associated with lesser agreeability with hastened death. Statistically significant association was found between every hastened death scenario and multiple of the spiritual beliefs used. A number of spiritual beliefs were predictors of agreeability. We discuss the implications of religion and spirituality in agreeability with hastened death. Further research is required to better understand the true weight of spirituality in one's opinion towards this ethical dilemma.

The arrival of COVID-19 in Brazil and the impact on coronary artery bypass surgery.

BACKGROUND AND AIM OF THE STUDY: This study analyzed the arrival of coronavirus disease 2019 (COVID-19) in Brazil and its impact on coronary artery bypass grafting (CABG) surgery. METHODS: Patients undergoing isolated CABG in six hospitals in Brazil were divided into two periods: pre-COVID-19 (March-May 2019, N = 468) and COVID-19 era (March-May 2020, N = 182). Perioperative data were included on a dedicated REDCap platform. Patients with clinical and tomographic criteria and/or PCR (+) for severe acute respiratory syndrome coronavirus 2 infection were considered COVID-19 (+). Logistic regression analysis was performed to create a multiple predictive model for mortality after CABG in COVID-19 era. RESULTS: Compared to 2019, in 2020, CABG surgeries had a 2.8-fold increased mortality risk (95% confidence interval [CI]: 1-7.6, p = .041), patients who evolved with COVID-19 had a 11-fold increased mortality risk (95% CI: 2.2-54.9, p < .003), rates of morbidities and readmission to the intensive care unit. The surgical volume was decreased by 60%. The model to predict mortality after CABG in the COVID-19 era was validated with good calibration (Hosmer-Lemeshow = 1.43) and discrimination (receiver operating characteristic = 0.78). CONCLUSION: The COVID-19 pandemic had an adverse impact on mortality, morbidity and volume of patients undergoing CABG.

Immunophenotype of neutrophils in oral squamous cell carcinoma patients.

BACKGROUND: The aim was to explore the immunophenotype of neutrophils and lymphocytes and the inflammatory mediators in patients with oral squamous cell carcinoma, comparing with controls; and to associate with clinicopathological data. METHODS: Blood was collected from 13 patients and 13 controls. The immunophenotype of neutrophils (CD66b, CD16, CD11a, arginase-1), T lymphocytes (CD4, CD8) and the intracellular cytokine production (IL-10, TNF, IFN-γ) was evaluated by flow cytometry. Plasma concentration of sVCAM-1, sTNF-RI, sTNF-RII, and IL-1ß was measured by ELISA. MPO, Lipocalin-2/NGAL, sICAM-1, and p-selectin were quantified by Luminex assay. The excised tumors were submitted to immunohistochemistry for neutrophils (CD66b) and lymphocytes (CD3, CD4, CD8). Association with clinical data was explored. P values <.05 were considered significant. RESULTS: Patients presented higher percentage of neutrophils and lower lymphocytes, resulting a higher neutrophil/lymphocyte ratio than controls. They also presented higher percentage of neutrophils expressing CD66b+ , CD66b+ Arginase-1+ , CD66b+ IL10+ , CD66b+ TNF+ , CD66b+ Arginase-1+ IL-10+ , and lower CD66b+ CD16+ CD11a+ and CD66b+ Arginase-1+ TNF+ . CD66b+ neutrophils were detected in all tumors, with a CD66b+ /CD3+ ratio of 0.40. Patients showed higher concentration of plasmatic sVCAM-1 and lower Lipocalin-2/NGAL. Patients with good outcome presented lower percentage of neutrophils, higher percentage of lymphocytes, and lower NLR than patients who died. CONCLUSION: The amount and immunophenotype of neutrophils and lymphocytes differ between patients and healthy individuals, with a pro-tumorigenic profile of neutrophils. As these cells also get within tumor microenvironment, they possibly exert systemic and local functions in cancer pathogenesis. The association of neutrophil count with outcome corroborates recent studies and this merits further investigation for applicability as a prognosticator.

[Arterial hypertension and associated factors in patients submitted to myocardial revascularization]. / Hipertensão arterial e fatores associados em pessoas submetidas à cirurgia de revascularização do miocárdio.

OBJECTIVE To identify the prevalence of arterial hypertension and associated factors in patients submitted to myocardial revascularization. METHOD Cross-sectional study using the database of a hospital in São Paulo (SP, Brazil) containing 3010 patients with coronary artery disease submitted to myocardial revascularization. A multiple logistic regression was performed to identify variables independently associated with hypertension (statistical significance: p<0.05). RESULTS Prevalence of hypertension was 82.8%. After the variables were adjusted, the associated factors were as follows: age, odds ratio (OR): OR=1.01; 95% confidence interval (CI): CI:1.00-1.02; female gender: (OR=1.77;CI:1.39-2.25); brown-skin race: (OR=1.53;CI:1.07-2.19); obesity: (OR=1.53;CI:1.13-2.06); diabetes: (OR=1.90;CI:1.52-2.39); dyslipidemia: (OR=1.51;CI:1.23-1.85); and creatinine>1.3: (OR=1.37;CI:1.09-1.72). CONCLUSION A high prevalence of arterial hypertension and association with both non-modifiable and modifiable factors was observed.

Unexpected pancreatic mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN)-reflection on a case report.

The authors present a case involving a 51-year-old male who was diagnosed with a 4-cm mass in the body of the pancreas, initially suspected to be a ductal adenocarcinoma due to an elevated Ca 19.9 during routine analysis. Subsequent imaging studies confirmed a resectable disease without suspicious lymph nodes or distant metastasis, leading to the proposal of surgery. The patient underwent a laparoscopic distal splenopancreatectomy, which was uneventful. The histopathological examination revealed a 3.7-cm pancreatic mixed neuroendocrine neoplasia (MiNEN) with a predominant high-grade ductal adenocarcinoma component and a concurrent high-grade neuroendocrine carcinoma, with negative margins. Two lymph node metastases were identified, each representing metastasis of one of the components. The tumor was classified as pT2N1M0. Currently, the patient is undergoing chemotherapy with FOLFIRINOX. This case prompts reflection on the optimal treatment strategy for pancreatic MiNEN and raises the question of how the preoperative diagnosis could influence the patient's outcome.

Clinical factors influencing long-term survival in a real-life cohort of early stage non-small-cell lung cancer patients in Spain.

Background: Current prognosis in oncology is reduced to the tumour stage and performance status, leaving out many other factors that may impact the patient´s management. Prognostic stratification of early stage non-small-cell lung cancer (NSCLC) patients with poor prognosis after surgery is of considerable clinical relevance. The objective of this study was to identify clinical factors associated with long-term overall survival in a real-life cohort of patients with stage I-II NSCLC and develop a prognostic model that identifies features associated with poor prognosis and stratifies patients by risk. Methods: This is a cohort study including 505 patients, diagnosed with stage I-II NSCLC, who underwent curative surgical procedures at a tertiary hospital in Madrid, Spain. Results: Median OS (in months) was 63.7 (95% CI, 58.7-68.7) for the whole cohort, 62.4 in patients submitted to surgery and 65 in patients submitted to surgery and adjuvant treatment. The univariate analysis estimated that a female diagnosed with NSCLC has a 0.967 (95% CI 0.936 - 0.999) probability of survival one year after diagnosis and a 0.784 (95% CI 0.712 - 0.863) five years after diagnosis. For males, these probabilities drop to 0.904 (95% CI 0.875 - 0.934) and 0.613 (95% CI 0.566 - 0.665), respectively. Multivariable analysis shows that sex, age at diagnosis, type of treatment, ECOG-PS, and stage are statistically significant variables (p<0.10). According to the Cox regression model, age over 50, ECOG-PS 1 or 2, and stage ll are risk factors for survival (HR>1) while adjuvant chemotherapy is a good prognostic variable (HR<1). The prognostic model identified a high-risk profile defined by males over 71 years old, former smokers, treated with surgery, ECOG-PS 2. Conclusions: The results of the present study found that, overall, adjuvant chemotherapy was associated with the best long-term OS in patients with resected NSCLC. Age, stage and ECOG-PS were also significant factors to take into account when making decisions regarding adjuvant therapy.

Microcapsules based on alginate and guar gum for co-delivery of hydrophobic antitumor bioactives.

The main goal was the development of a polysaccharide microcapsule for anticancer application based on guar gum and sodium alginate for the controlled release of hesperidin and betulinic acid by spray drying technique. The microcapsule showed an Encapsulation Efficiency of 98.15 ± 0.34 % for hesperidin and 99.76 ± 0.22 % for betulinic acid. In the release study, the Korsmeyer-Peppas mathematical model was identified as the most adequate to explain the observed release mechanism. In vivo tests were performed in zebrafish model, revealing that the microcapsules did not alter the locomotor activity and were not toxic within 96 h by oral administration, suggesting their biological safety. In vitro cytotoxic activity against HL-60 cells confirmed an IC50 value of 2.52 ± 0.23 µg mL-1 in 72 h. Additionally, a decrease in the cytotoxic activity of betulinic acid against L-929 (non-tumor) cells was evidenced. Therefore, the microcapsules synthesized in this work represent a promising formulation for anticancer applications.

Oral and oropharyngeal cancer: time from first symptoms to treatment initiation and associated factors.

The aim of this study was to evaluate the time elapsed from first symptoms to the treatment of oral and oropharyngeal cancer (OOC) and to identify variables associated with treatment delay. This is an observational study with retrospective and prospective data collection. Patients with a diagnosis of OOC seen at the Head and Neck Surgery outpatient clinic of a Brazilian public hospital were included and followed up to treatment initiation. Participants answered a questionnaire for the collection of socioeconomic, demographic, cultural, and clinical information, as well as information about the time elapsed from first symptoms to the first appointment with a head and neck surgeon. Time to treatment was classified into four intervals: 1- first symptoms to first medical appointment; 2- first medical appointment to specialized medical care; 3- specialized medical care to preparation for treatment; and 4- preparation for treatment to treatment initiation. Bivariate statistics were computed. Out of 100 participants, nine died before treatment. Mean time to treatment was 217 days. Highest mean time was observed for interval 2 (94 days), followed by interval 1 (63 days), interval 4 (39 days), and interval 3 (21 days). At interval 1, a longer time was associated with severe alcohol consumption, severe smoking, and family history of cancer. At interval 2, the delay was associated with appointment with a general practitioner, clinical diagnosis of disease other than cancer, and antibiotic prescription. At interval 4, delay in treatment was associated with surgical treatment. Patients with OOC experience delays from symptom onset to treatment initiation. The longest interval was associated with professional delay, followed by patient delay in help-seeking.

Light-emitting diode stimulates radiodermatitis recovery.

PURPOSE: To evaluate the effect of light-emitting diode (LED) in an experimental model of radiodermatitis. METHODS: Ten male Wistar rats weighing 200-250 g were analyzed. Radiation was delivered in a single dose (20 Gy with Strontium-90 dermatological plaques), two areas per animal. After 15 days, they were divided into two groups: control group (n = 5) and LED group (n = 5), which was treated during 21 days later (LED 660 nm, 10 min in alternate days). The endpoints were radiodermatitis scale, histological analysis HE, Picrius Sirius and the gene expression of interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9). RESULTS: The LED group showed a higher number of dermal appendages (p = 0.04) and angiogenesis(p = 0.007), a tendency towards higher IL-10 (p = 0.06) and an increase in MMP-9 (p = 0.004) when compared to the control group. CONCLUSIONS: This study suggested that the use of LED for radiodermatitis increased skin regeneration.

Xyloglucan-based hybrid nanocomposite with potential for biomedical applications.

Natural polymer-based hybrid nanocomposites have been proposed as one of the most promising tools for biomedical applications, including disease treatment and diagnosis procedures. Xyloglucan nanocapsules can simultaneously load magnetic iron oxide nanoparticles and bioactive for a specific tissue, reducing the processes of degradation and metabolic inactivation of molecules with biological activity. In this work, magnetic nanocapsules of xyloglucan loaded with hydrophilic sulfated quercetin (MNXQ_SO3) were successfully synthesized by inverse miniemulsion process through interfacial polymerization. The polymeric shell formation of nanocapsules was evidenced by Fourier Transform Infrared spectroscopy and Transmission Electron Microscopy. The ferrofluid (Fe3O4@PAAS) incorporated into the xyloglucan nanocapsules was synthesized by hydrothermal method, using polyacrylic acid sodium salt as coating. Dynamic Light Scattering technique confirmed the nanomeric dimensions (202.3 nm) and the good colloidal stability (-40.2 mV) of MNXQ_SO3. The saturation magnetization analyses pointed out the superparamagnetic behavior of Fe3O4@PAAS (48 emu/g) and MNXQ_SO3 (4.2 emu/g). MNXQ_SO3 was able to modify the release profile of sulfated quercetin (67%) when compared to the free bioactive (100%), exhibiting a release profile compatible with the zero-order kinetic model. The results showed that the development of MNXQ_SO3 presents a new perspective for biomedical applications, including studies of targeted drug delivery.

Survival analysis of recurrent squamous cell carcinoma of the lower oral cavity treated by surgery.

The aim of the present study was to investigate the survival of individuals with squamous cell carcinoma of the lower oral cavity who underwent surgical treatment and experienced recurrence, considering the site of the recurrent disease. A retrospective longitudinal study was conducted, comparing the survival rates of patients with and without recurrence and considering the site of recurrence (local, regional, distant). Statistical analysis was performed with SPSS and a p-value ≤ 0.05 was considered significant. The sample comprised 150 patients, 59 (39.3%) of whom experienced recurrence. Local recurrence occurred in 35 patients (23.4%), regional recurrence in 17 (11.3%), and distant recurrence in seven (4.6%). The average survival of participants with local, regional, and distant recurrence was 12, five, and two months, respectively. Patients with recurrent disease had worse survival than those who did not (P < 0.001). Patients with local recurrence had better survival than those with regional/distant recurrence (P = 0.011). All patients with regional and distant recurrence had deceased by the last follow-up. In conclusion, patients with local recurrence of squamous cell carcinoma of the lower oral cavity treated by surgery have a better survival rate than those with regional and distant recurrence. Local recurrence poses the possibility of curative salvage therapy.

Most deaths in low-risk cardiac surgery could be avoidable.

It is observed that death rates in cardiac surgery has decreased, however, root causes that behave like triggers of potentially avoidable deaths (AD), especially in low-risk patients (less bias) are often unknown and underexplored, Phase of Care Mortality Analysis (POCMA) can be a valuable tool to identify seminal events (SE), providing valuable information where it is possible to make improvements in the quality and safety of future procedures. Our results show that in São Paul State, only one third of AD in low-risk cardiac surgery was related to specific surgical problems. After a revisited analysis, 75% of deaths could have been avoided, which in the pre-operative phase, the SE was related judgment, patient evaluation and preparation. In the intra-operative phase, most occurrences could have been avoided if other surgical technique had been used. Sepsis was responsible for 75% of AD in the intensive care unit. In the ward phase, the recognition/management of clinical decompensations and sepsis were the contributing factors. Logistic regression model identified age, previous coronary stent implantation, coronary artery bypass grafting + heart valve surgery, ≥ 2 combined heart valve surgery and hospital-acquired infection as independent predictors of AD.

Mortality risk prediction in high-risk patients undergoing coronary artery bypass grafting: Are traditional risk scores accurate?

BACKGROUND: The performance of traditional scores is significantly limited to predict mortality in high-risk cardiac surgery. The aim of this study was to compare the performance of STS, ESII and HiriSCORE models in predicting mortality in high-risk patients undergoing CABG. METHODS: Cross-sectional analysis in the international prospective database of high-risk patients: HiriSCORE project. We evaluated 248 patients with STS or ESII (5-10%) undergoing CABG in 8 hospitals in Brazil and China. The main outcome was mortality, defined as all deaths occurred during the hospitalization in which the operation was performed, even after 30 days. Five variables were selected as predictors of mortality in this cohort of patients. The model's performance was evaluated through the calibration-in-the-large and the receiver operating curve (ROC) tests. RESULTS: The mean age was 69.90±9.45, with 52.02% being female, 25% of the patients were on New York Heart Association (NYHA) class IV and 49.6% had Canadian Cardiovascular Society (CCS) class 4 angina, and 85.5% had urgency or emergency status. The mortality observed in the sample was 13.31%. The HiriSCORE model showed better calibration (15.0%) compared to ESII (6.6%) and the STS model (2.0%). In the ROC curve, the HiriSCORE model showed better accuracy (ROC = 0.74) than the traditional models STS (ROC = 0.67) and ESII (ROC = 0.50). CONCLUSION: Traditional models were inadequate to predict mortality of high-risk patients undergoing CABG. However, the HiriSCORE model was simple and accurate to predict mortality in high-risk patients.

Correction: Mortality risk prediction in high-risk patients undergoing coronary artery bypass grafting: Are traditional risk scores accurate?

[This corrects the article DOI: 10.1371/journal.pone.0255662.].

Starch-based magnetic nanocomposite for targeted delivery of hydrophilic bioactives as anticancer strategy.

Magnetic nanocomposites were synthesized for the targeted delivery of hydrophilic bioactives through guidance generated by a magnetic field. Superparamagnetic iron oxide nanoparticles (SPIONs) were used to generate hydroxyethyl starch magnetic nanocapsules (HES MNCs). This synthesis allowed the co-encapsulation of oncocalyxone A (onco A) and surface-modified magnetite nanoparticles (Fe3O4@citrate) into the same nanostructure. The synthesized nanocapsules exhibited a core-shell morphology, with an average diameter of 143 nm. This nanocomposite showed potential anticancer activity (IC50) against four human tumor cell lines: glioblastoma SNB-19 (1.010 µgmL-1), colon carcinoma HCT-116 (2.675 µgmL-1), prostate PC3 (4.868 µgmL-1), and leukemia HL-60 (2.166 µgmL-1). Additionally, in vivo toxicity and locomotor activity were evaluated in a zebrafish (Danio rerio) model. The nanocomposite exhibited in vitro cytotoxicity, prolonged drug release profile and also responded to an applied magnetic field, representing a versatile compound with perspectives for highest concentration of different hydrophilic bioactives in a target tissue through magnetic vectorization.

Course of ionized calcium after thyroidectomy.

BACKGROUND: The goal of the present study was to investigate the course of ionized calcium after thyroidectomy and to define a cut-off value that indicates symptoms of hypocalcemia. METHODS: The sample included 333 patients undergoing thyroidectomy at the University Hospital of UFMG between September 2000 and December 2005. Ionized calcium was determined before and after surgery (days 1, 2, and 30) in all patients and on postoperative days 90 and 180 in those with hypocalcemia. Asymptomatic patients received no calcium replacement therapy, irrespective of calcium concentration. Patients with clinical manifestation of hypocalcemia were treated after laboratory confirmation. The presence or absence of postoperative hypocalcemia was associated with ionized calcium concentration measured on the reported days. RESULTS: Ionized calcium declined on the first two days after surgery in all patients when compared to preoperative levels (P = 0.000). Forty-seven (34.6%) of the 136 (40.8%) patients with postoperative hypocalcemia had symptoms. Patients with symptomatic hypocalcemia had significantly lower ionized calcium levels than those with asymptomatic hypocalcemia (P = 0.001). Fourteen (4.2%) patients progressed to definitive hypoparathyroidism by the end of 6 months. CONCLUSIONS: Measurement of ionized calcium on postoperative days 1 and 2 is sufficient for the evaluation of post-thyroidectomy hypocalcemia. Ionized calcium concentrations <1.03 mmol/l on postoperative day 1 are indicative of the presence of symptoms and the need for treatment.

[Prothrombotic events after percutaneous closure of an atrial septal defect]. / Complicações pró-trombóticas após o encerramento percutâneo de comunicação interauricular.

We describe the case of a 66 years-old patient, submitted to percutaneous closure of an ostium secundum atrial septal defect ( ASD ), with an " Amplatzer ASO 20 mm " ( Medical AGA Corp., MN (. There were no immediate complications and no residual leak. Eleven days after the procedure, atrial fibrillation ( AF ) ensued, followed by an acute myocardial infarction ( distal occlusion of the circumflex artery ). Three days later, this patient had also a transitory ischemic accident. Percutaneous closure of ASD is a procedure that can be associated with a few complications, namely AF and thromboembolic events. Although common, the use of dual antiplatelet therapy doesn't have an established efficacy to prevent these cases.

A non-inferiority study to compare daily fast-acting insulin versus twice a week slow-acting insulin-moderate diabetes mode.

Purpose Given the high prevalence of diabetes (D), several animal models have been analyzed. In the literature, most of the animal models have studied severe D. However, in clinical practice, most patients have moderate disease. Therefore, the present study aimed to describe a moderate D condition. Methods We analyzed 20 Wistar rats, age eight-weeks, weight between 200g-250g. All animals received an intravenous injection of Streptozotocin (55mg/kg weight). On the 15th day after D induction, the animals were divided into two groups: Group I - animals receiving a single daily dose of fast-acting insulin (FAIG) NPH (1UI,SC) for partial glycemic control, and Group II - animals receiving slow-acting insulin(SAIG) twice a week. We measured glycemia, weight, and adverse events every week during two months. Results Of the total of animals analyzed in the study, three animals died in the FAIG and two animals died in the SAIG. Regarding the glycemic level, results were 339.5 ± 125.4mg/dL (95CI 302.3402 to 376.6842) in the FAIG, and 367.8 ± 66.1mg/dL (95IC 333.7607 to 401.8978) in the SAIG. There was no difference between groups as to weight during the study. Conclusion The use of slow-acting-insulin is not inferior to the use of fast-acting-insulin in the management of partially insulin-controlled moderate diabetes in rats.

Does Prior Percutaneous Coronary Intervention Influence the Outcomes of Coronary Artery Bypass Surgery?

INTRODUCTION: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. METHODS AND RESULTS: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. CONCLUSION: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.

Impact of the 8th edition of the AJCC TNM classification on gastric cancer prognosis-study of a western cohort.

INTRODUCTION: The 8th edition of the American Joint Committee on Cancer (AJCC) TNM classification for gastric cancer introduced changes, mainly in stage III, with the incorporation of the pN3 sub-classification in the final staging group. The goal was to compare the 7th and 8th editions to evaluate the discriminative capacity of the new edition. METHODS: This study was a retrospective review of patients with gastric cancer treated with surgery in 2013 and 2014. RESULTS: We analysed 310 patients, with a median age of 66 years and out of which 55.5% were male. The most commonly performed surgery was subtotal gastrectomy (n = 158; 51%), with a median of 30 lymph nodes removed. With a median follow-up of 39.5 months, the 1- and 3-year overall survival (OS) was 82% and 59%, respectively. In stage III (n = 115), there was stage migration in 40 cases (34.8%), with upstage in 11 cases and downstage in 29 cases. In this group, there was a statistically significant difference in OS between N3a and N3b patients (p = 0.002), as well as a statistically significant difference in OS between stages IIIA, IIIB and IIIC when the 8th edition was applied (p = 0.001), which was not verified with the 7th edition (p = 0.057). In multivariate analysis, both extracapsular extension and N classification from TNM were independent prognostic factors (p = 0.033 and p = 0.024, respectively). CONCLUSION: The 8th edition of the AJCC TNM classification allows for a better prognostic refinement, namely in the new stage III groups after the stratification of lymph node disease in N3a and N3b. Factors that evaluate the biological behaviour of the disease remain excluded from this edition, such as extracapsular extension, which had a prognostic impact in our series.