Comprehensive Glycoprofiling of Oral Tumors Associates N-Glycosylation With Lymph Node Metastasis and Patient Survival.

While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), the heterogeneous and dynamic glycoproteome of tumor tissues from OSCC patients remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a cohort of resected primary tumor tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumor tissues displayed relatively uniform N-glycome profiles suggesting overall stable global N-glycosylation during disease progression, altered expression of six sialylated N-glycans was found to correlate with lymph node metastasis. Notably, glycoproteomics and advanced statistical analyses uncovered altered site-specific N-glycosylation revealing previously unknown associations with several clinicopathological features. Importantly, the glycomics and glycoproteomics data unveiled that comparatively high abundance of two core-fucosylated and sialylated N-glycans (Glycan 40a and Glycan 46a) and one N-glycopeptide from fibronectin were associated with low patient survival, while a relatively low abundance of N-glycopeptides from both afamin and CD59 were also associated with poor survival. This study provides insight into the complex OSCC tissue N-glycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC.

Management of Stage III Oral Cavity Squamous Cell Carcinoma in Light of the New Staging System: a Critical Review.

PURPOSE OF REVIEW: Oral squamous cell carcinoma (OSCC) patients have a poor prognosis, especially in advanced stages. AJCC/UICC staging system 8th edition (TNM8) included depth of invasion (DOI) as part of T staging and stage III has become a heterogeneous group of lesions, composed of patients with larger DOI and/or width. Additionally, stage III includes N1, regardless of the primary tumor width or DOI. The real prognostic value of each of these characteristics and the need for adjuvant treatment for stage III patients is not well established. RECENT FINDINGS: TNM8 stratified OSCC into prognostic groups based on overall survival. Extranodal extension, positive or close margins, pT3 or pT4 tumors, pN2 or pN3 nodal disease, nodal disease in levels IV or V, perineural invasion, vascular invasion, and lymphatic invasion are the main adverse features for OSCC, and adjuvant treatment is largely recommended for these patients. Stage III patients should be addressed with caution. So far, there is no significant evidence for recommending or excluding adjuvant treatment for stage III OSCC without adverse features. The authors largely recommend adjuvant radiotherapy for these cases, especially because pT3 without adverse features is rare. Further studies on this topic are necessary.

Medical students' and residents' views on euthanasia.

BACKGROUND: Doctors are increasingly faced with end-of-life decisions. Little is known about how medical students approach euthanasia. The objective of this study was to evaluate, among medical students and residents, the view on euthanasia and its variants; correlate such a view with empathy and religiosity/spiritualism; and with the stages of medical training in Brazil. METHODS: This is an exploratory cross-sectional study using an online questionnaire to be filled out on a voluntary basis among medical students and residents, consisting of: socio-demographic data, an empathy questionnaire and questions with elaborate clinical cases that typify situations of the variants of euthanasia. RESULTS: From 1550 invitations, 273 volunteer participants responded (17.6%). The percentages of strong agreement/agreement on the concepts were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%). Passive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. Religious belief and degree of empathy did not significantly influence the opinion about the concepts. Strong agreement/agreement were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%). CONCLUSIONS: Passive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. The external validation of our findings relies on the distinct legal, cultural, and religious frameworks found across various countries.

Congenital Midline Cervical Cleft and Thyroglossal Duct Fibrous Cord-Like, is There a Mixed Presentation?

INTRODUCTION: Congenital midline cervical cleft is a rare condition and is frequently misdiagnosed as thyroglossal duct cyst. Otherwise, the combination of congenital midline cervical cleft and thyroglossal duct fibrosis in the same patient is as rare as important to be registered with the intention to inform and offer specific managements details for the literature. CASE PRESENTATION: Eight-year-old boy with simultaneous congenital midline cervical cleft and a thyroglossal duct fibrosis. The anatomic, clinical, radiologic, and pathologic characteristics of the congenital midline cervical cleft are described as well as surgical technique for removal and repair with Z-plasty. CONCLUSION: Congenital midline cervical cleft is a rare condition and when diagnosed must be surgically treated as early as possible. Its differential diagnosis is a clinical challenge.

Active Surveillance of Thyroid Microcarcinomas: a Critical View.

PURPOSE OF THE REVIEW: There has been an increasing interest on active surveillance for papillary thyroid microcarcinomas (PTMC) in the literature. We will analyze the contributions of those authors who support this approach in most patients with low-risk tumors. RECENT FINDINGS: The development of molecular methods to effectively detect aggressive PTMC at the fine-needle aspiration biopsy will enable the sound indication of immediate surgery in those patients, assuring the other individuals with the far more frequent indolent PTMC will undergo active surveillance with less anxiety. Several studies compared the quality of life between patients with PTMC who underwent active surveillance with immediate total thyroidectomy. However, thyroid lobectomy is a quite acceptable intermediate alternative for most patients with PTMC, with less surgical morbidity. It is important to wait for worldwide validation, with reports from low- and middle-income areas, before recommending the routine adoption of active surveillance for patients with PTMC, due to difficult logistic obstacles in those environments.

Tumor volume as a prognostic factor of locally advanced laryngeal cancer.

PURPOSE: The TNM tumor staging system is the most widely used for laryngeal cancer. However, in the same T stage, lesions with different primary tumor volumes (TV) can be found, impacting treatment outcomes. METHODS: 145 patients with T3 and T4a laryngeal cancer, according to Union for International Cancer Control, who underwent surgical treatment from 2008 to 2017, were analyzed. TV measurements were collected and compared to different outcomes. RESULTS: The mean TV was 23.0 ± 16.4 cm3. A cutoff point for TV of 14.2 cm3 was established. Cumulative sample 5-year overall survival (OS) was 62.1%, while 5-years disease-free survival (DFS) was 65.5%. In univariate analysis, TV ≥ 14.2 cm3 was associated with a higher risk of distant metastases (p = 0.045), and worse rates of OS (p = 0.009) and DFS (p = 0.035). In multivariate analysis, TV was not an independent risk factor of worse DFS (p = 0.569) or OS (p = 0.094). CONCLUSION: Primary lesion TV showed significant association, in univariate analysis, with worse rates of recurrence and survival in advanced laryngeal cancer undergoing surgical treatment and can be a promising prognostic for these patients.

Oral Squamous Cell Carcinoma Bone Invasion: Possible Roles of E-Cadherin in Osteoclastogenesis and Bone Infiltration.

INTRODUCTION: Squamous cell carcinoma is the most common cancer of the oral cavity. When the tumor invades the bone tissue, the prognostic and survival rates decrease a lot, and the treatment becomes more aggressive, with several damages to the patient and health system. Many of the molecular mechanisms of bone invasion process are not understood yet, but it is already known that one of central processes of tumor evolution - adjacent tissues invasion and metastasis - is a large spectrum of phenotypic changes in epithelial cells to mesenchymal, in a process named as epithelial-mesenchymal transition (EMT). Loss of E-cadherin, an important epithelial cell adhesion protein, is a hallmark of this phenomenon. The objective of this retrospective study is to evaluate the expression of E-cadherin protein, comparing its distribution with clinical characteristics of the patients and possibly relation to EMT. METHODS: Sixty-two cases with respective clinical data were analyzed by comparing immunohistochemical, H and E staining, and clinical data, observing the tumor-bone interface (TBI) and the surrounding tumor that had no direct contact with the bone surface (ST). RESULTS: Forty cases were positive for E-cadherin (64%) with a heterogeneous pattern. Statistical analysis showed a significant difference between the presence of E-cadherin expression and tobacco smokers. Also, the equal or weaker protein expression in the ST than TBI is related to a worse overall survival. No statistically significant difference in other prognostic factors was observed. CONCLUSION: Our results suggest that the tumor cells that interact with the bone tissue could gain molecular changes, like partial EMT and osteoclastogenesis induction, which facilitate their migration and increase the bone resorption, resulting in a worse patient's prognosis.

Cervicofacial and Pharyngolaryngeal Lymphedema and Deglutition After Head and Neck Cancer Treatment.

One of the sequelae of head and neck cancer treatment is secondary lymphedema, with important impact on breathing, swallowing and vocal functions. The aim of the study was to assess the presence, staging characteristics and relationship of external and internal lymphedema and dysphagia after head and neck cancer treatment. The MDACC Lymphedema Rating Scale in Head and Neck Cancer was employed for the assessment and staging of face and neck lymphedema; the Radiotherapy Edema Scale for internal lymphedema; and a fiberoptic endoscopic evaluation of swallowing (FEES) for swallowing. The sample consisted of 46 patients with a diagnosis of head and neck cancer. Lymphedema was detected in 97.8% (45) of the evaluations with predominance of the composite type (73.9%-34). A high percentage of external lymphedema of the neck (71.7%-33) and submandibular (63%-29) were detected, with predominance of the more advanced levels. Internal edema was found in almost all structures and spaces at moderate/severe level. At FEES, residue (higher percentage in valleculae and pyriform sinus), penetration and aspirations were observed. The residue was detected in higher occurrence in patients with composite lymphedema (p = 0.012). The combined treatment with radiotherapy was related to submandibular external lymphedema (p = 0.009), altered pharyngolaryngeal sensitivity (0.040), presence of residue (p = 0.001) and penetration to pasty (p = 0.007) and internal edema in almost all structures. There was also a higher percentage of residue in cases with internal altered pharyngolaryngeal sensitivity, residue, penetration and aspiration. Combined treatment with radiotherapy is an associated factor of edema. Cervicofacial and pharyngolaryngeal lymphedema is a frequent event after treatment for HNC, with important impact on swallowing performance characterised by altered pharyngolaryngeal sensitivity, residue, penetration and aspiration. Combined treatment with radiotherapy is an associated factor.

Correction to: Cervicofacial and Pharyngolaryngeal Lymphedema and Deglutition After Head and Neck Cancer Treatment.

The original version of this article unfortunately contained a mistake. Figure 2 was repeated in Figure 3.

Patient Perception of Swallowing after Thyroidectomy in the Absence of Laryngeal Nerve Injury.

INTRODUCTION: Swallowing and voice alterations may manifest in patients with thyroid disease, especially after thyroidectomy. OBJECTIVE: To identify the prevalence of patients with complaints of swallowing disorders after thyroidectomy and to evaluate patients' perceptions regarding swallowing before and after the procedure. METHODS: A prospective longitudinal study was performed with 26 consecutive patients undergoing a private service thyroidectomy, in which the presence of swallowing dysfunction was evaluated using validated questionnaires that addressed the perception of swallowing by patients before (on the day of surgery) and after the surgery (on the first postoperative day). RESULTS: Of the 26 patients, 18 (69.2%) were subjected to total thyroidectomy and 8 to partial thyroidectomy. Analysis of the domains of the Swallowing Handicap Index questionnaire showed higher scores when evaluated on the first postoperative day, demonstrating a significant worsening in swallowing after the procedure. The same result was demonstrated for the final score of swallowing perception, with 15.3 and 30.8% of patients reporting moderate alterations before and after the thyroidectomy, respectively, and 11.5% reporting the alterations as severe. Swallowing and vocal symptoms on the first postoperative day were more prevalent in the procedure than previously mentioned. Eight patients (30.8%) noted swallowing alterations before the procedure, compared with 80.8% (21 cases) after thyroidectomy. CONCLUSION: There was a prevalence of 42.3% in swallowing complaints on the first postoperative day, regardless of the lesion in the laryngeal innervation, and this prevalence was significantly higher than that prior to the procedure.

Crosstalk between tumor cells and lymphocytes modulates heparanase expression.

BACKGROUND: Heparanase (HPSE) is an endo-beta-glucuronidase that degrades heparan sulfate (HS) chains on proteoglycans. The oligosaccharides generated by HPSE promote angiogenesis, tumor growth and metastasis. Heparanase-2 (HPSE2), a close homolog of HPSE, does not exhibit catalytic activity. Previous studies have demonstrated that serum or plasma from breast cancer patients showed increased expression of both heparanases in circulating lymphocytes. The aim of this study was to better understand the mechanisms involved in the upregulation of heparanases in circulating lymphocytes. METHODS: Lymphocytes collected from healthy women were incubated in the presence of MCF-7 breast cancer cells (co-culture) to stimulate HPSE and HPSE2 overexpression. The protein level of heparanases was evaluated by immunocytochemistry, while mRNA expression was determined by quantitative RT-PCR. RESULTS: The medium obtained from co-culture of MCF-7 cells and circulating lymphocytes stimulated the expression of HPSE and HPSE2. Previous treatment of the co-culture medium with an anti-heparan sulfate proteoglycan antibody or heparitinase II inhibited the upregulation of heparanases in circulating lymphocytes. The addition of exogenous heparan sulfate (HS) enhanced the expression of both heparanases. Moreover, the co-cultured cells, as well as MCF-7 cells, secreted a higher number of exosomes expressing an increased level of HS compared to that of the exosomes secreted by circulating lymphocytes from women who were not affected by cancer. CONCLUSIONS: The results revealed that HS is likely responsible for mediating the expression of heparanases in circulating lymphocytes. HS secreted by tumor cells might be carried by exosome particles, confirming the key role of tumor cells, as well as secreted HS, in upregulating the expression of heparanases, suggesting a possible mechanism of crosstalk between tumor cells and circulating lymphocytes.

Oral Cancer Treatment: Still an Indication for Elective Neck Dissection?

INTRODUCTION: Oral squamous cell carcinoma has a high incidence and, although elective neck dissection is recommended, the removed nodes frequently present without metastasis. This surgical approach causes disabilities and increases possible surgical complications. OBJECTIVE: To evaluate the possibility of a watchful waiting approach in oral cancer. METHODS: We compared 78 patients with clinical and pathological node metastases and their counterparts with pathological node metastases but without evident clinical neck disease. Therefore, we provided a theoretical comparison between the patients who had an elective neck dissection and those who waited until a clinically positive node was evident. RESULTS: The prognostic factor rates were similar between the groups. Their regional recurrence and mortality rates had no statistical differences. CONCLUSION: A watchful waiting policy could be applied to selected oral cancer patients who can undergo a very close follow-up. This option would be more cost-effective and less harmful than elective neck dissection.

Morphological Evaluation of Thyroid Cartilage Invasion in Early Glottic Tumors Involving the Anterior Commissure.

INTRODUCTION: The anterior commissure is an area of glottic cancer infiltration, even in early stages. OBJECTIVE: To evaluate the invasion by tumors into the anterior commissure cartilage in surgical specimens of frontolateral laryngectomy. METHODS: Forty-eight patients who had undergone frontolateral laryngectomy for T1b/T2 squamous cell carcinoma were included. Epidemiological and clinical aspects as well as morphological histopathological analysis were evaluated. RESULTS: Of the 48 patients, 42 (87.5%) had T1b lesions and 6 (12.5%) had T2. Thirty-four cases (70.8%) showed healthy tissue between the tumor and the thyroid cartilage, 10 cases (20.8%) had a tumor in close proximity to the cartilage, and in 4 cases (8.3%) there was cartilage invasion. There was no major risk of adverse outcome in the groups with infiltration or tumor adjacent to the cartilage. Level of differentiation, mitotic index, nuclear irregularity, and the presence of nucleolus and tumor necrosis were not related to cartilage invasion. CONCLUSION: The infiltration of thyroid cartilage occurred in 8.3% of tumors and did not change the outcome in patients submitted to frontolateral laryngectomy. The morphological characteristics did not present any statistical significance.

DEATH RELATED TO PULMONARY METASTASIS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

OBJECTIVE: The purpose of the present study was to investigate the predictive factors for shorter disease-specific survival in patients with pulmonary disease secondary to differentiated thyroid cancer (DTC). METHODS: This was a retrospective cohort study conducted over a 5-year period that included 54 patients with pulmonary disease secondary to DTC during the follow-up. Among these patients, 13 (24.1%) died from the disease. Dedifferentiation characteristics were identified at pathological examination of the metastatic disease (lymph node or distant metastases) and was defined as the abrupt transformation of a well-differentiated tumor into high-grade morphology lacking the original distinct histologic characteristics. RESULTS: Tumor dedifferentiation marked by cellular aberrations and radioiodine (RAI) therapy resistance occurred in 5 (9.3%) patients. Four of them died due to pulmonary progression (80.0%), and the median survival of this group was 30 months compared to 279 months in the patients without dedifferentiation. The cumulative disease-specific survival was 20.0% in the patients with dedifferentiation during the follow-up versus 46.1% among the cases without this condition (P = .003, log-rank test). Moreover, dedifferentiation was independently associated with shorter disease-specific survival (hazard ratio [HR] = 31.607; 95% confidence interval [CI]: 4.815-207.478; P<.0001, Cox regression model) as were age over 45 years (HR = 10.904; 95% CI: 1.145-103.853; P = .038) and male sex (HR = 4.210; 95% CI: 1.056-16.783; P = .042). CONCLUSION: DTC patients with pulmonary disease exhibited shorter disease-specific survival, particularly those who developed tumor dedifferentiation, and these patients require special attention during follow-up. ABBREVIATIONS: CI = confidence interval DTC = differentiated thyroid cancer FTC = follicular thyroid carcinoma HR = hazard ratio IQR = interquartile range LN = lymph node LR = likelihood ratio PTC = papillary thyroid carcinoma RAI = radioiodine pTNM = pathologic tumor-node-metastasis stage system.

Treatment delays among women with breast cancer in a low socio-economic status region in Brazil.

BACKGROUND: Considering the inequalities and the areas of low socioeconomic status in Brazil, access to health services is a challenge and the delay between diagnosis and treatment represents an important factor of worse prognosis in patients with breast cancer. Herein, we describe the clinical and epidemiological profiles of women with breast cancer and evaluate their access to health services, as well as treatment delays, at a reference centre of the Cariri region, Ceará, Brazil. METHODS: This is a retrospective study that included 473 women treated with breast cancer between 2009 and 2011 at the Oncology Centre of the Cariri. RESULTS: The majority of these patients were aged between 40 and 69 years old (65.7%), without a completed high school degree (89.2%). They were married (62.9%) and were already diagnosed but had not yet been subjected to any previous treatment (77.8%). It was observed that 91.8% were referred from the public health service, and treatment was paid for by the public health service in 92.9% of the cases. The patients whose source of referral was the public system waited longer between diagnosis and the treatment initiation (p = 0.031; Mann-Whitney's test), with a median waiting time of 71.5 days versus 39 days for those receiving referrals from private services. In addition, those with public referrals prior to diagnosis also experienced a longer waiting time between the first medical visit and treatment initiation (77 days vs. 37 days; p = 0.036; Mann-Whitney's test), with the waiting time for the biopsy being an important factor in this delay. CONCLUSIONS: Late diagnosis was often the result of inefficiency of the prevention policies coupled with difficulty accessing the public health network. It was commonly observed that, even after diagnosis, the patients needed to wait too long before entering the Oncology Service because of long waiting queues in the public health system.

Comparison between Primary and Secondary Tracheoesophageal Puncture Prosthesis: A Systematic Review.

INTRODUCTION: Since the introduction of tracheoesophageal puncture (TEP) and placement of voice prosthesis, this has become the method of choice to achieve speech rehabilitation after total laryngectomy. OBJECTIVE: To compare the complications and success in speech rehabilitation of patients undergoing rehabilitation after primary and secondary TEP (TEP1 and TEP2) through a systematic review. METHODS: The literature survey included research in MedLine, Scielo, Lilacs, Cochrane and Websco until June 2016. RESULTS: The rate of leakage around the prosthesis was higher in TEP1 (22.5 vs. 6.9%, p = 0.03). There were higher rates of wound infection (9.1 vs. 3.9%) and tracheal stenosis (8.5 vs. 4.5%) in the TEP1 group compared to TEP2, however with no statistical significance. The evaluation of speech quality was not possible due to the heterogeneity of the studies. CONCLUSION: There is a reduction in the risk of leakage around the prosthesis among TEP2 patients.

Risk Factors for Distant Metastasis in Patients with Oral Cavity Squamous Cell Carcinoma Undergoing Surgical Treatment.

OBJECTIVE: The aim of this study is to investigate the clinical and pathological factors related to distant metastasis in patients with oral cavity squamous cell carcinoma (OCSCC) undergoing surgery. STUDY DESIGN: A retrospective data review was conducted on patients who underwent primary surgery for OCSCC at the Instituto do Cancer do Estado de São Paulo (ICESP) between 2009 and 2015. Distant metastasis rates were calculated and predictive factors were determined by the Cox proportional-hazards model. RESULTS: There was a total of 274 patients, including 210 (76.6%) men and 64 (23.4%) women, with a mean age of 59.9 ± 10.9 years. The incidence of distant metastasis was 9.6%, with the lung being the most common site. The mean time interval between surgical treatment and the diagnosis of distant metastasis was 12 months (range 2-40 months). In the multivariate analysis, angiolymphatic invasion (HR = 2,87; p = 0.023), contralateral cervical metastasis (HR = 3.3; p = 0,007), tumor thickness >25 mm (HR = 3.50; p = 0.009), and locoregional recurrence (HR = 6.59; p < 0.0001) were the only independent risk factors for distant metastasis. CONCLUSION: Patients with OCSCC who have contralateral lymph node metastasis, tumors with a thickness >25 mm, angiolymphatic invasion, or locoregional recurrence after surgical treatment have a greater risk of developing distant metastasis.

Meta-analysis of adjunctive non-NK1 receptor antagonist medications for the control of acute and delayed chemotherapy-induced nausea and vomiting.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a distressing chemotherapy-induced symptom that may adversely impact the quality of life of cancer patients. METHODS: We conducted a systematic search of the Pubmed, Bireme, and Cochrane databases for randomized clinical trials that were published in English and that evaluated the combination of adjunctive non-neurokinin 1 (NK1) antagonist drugs (i.e., neuroleptics, anticonvulsants, benzodiazepines, and cannabinoids) with 5-hydroxytryptamine 3 (5-HT3) antagonists for adult cancer patients who were scheduled to receive moderate or highly emetogenic chemotherapy. We employed the Review Manager (RevMan) Computer program Version 5.2 for statistical calculations. RESULTS: We included 13 studies with a total of 1,669 patients. We observed a higher complete protection for acute CINV with adjunctive medications (risk ratio (RR) = 0.55; 95% confidence interval (CI) 0.30-1.01; p = 0.05; I2 = 47%), which was not the case for the delayed period (RR = 0.89; 95% CI 0.73-1.10, p = 0.29, I2 = 15%). We also observed that these adjunctive medications significantly increased the complete control of nausea (RR = 0.72; 95% CI 0.55-0.95; p = 0.02, I2 = 83%) and vomiting (RR = 0.61; 95% CI 0.50-0.75; p < 0.00001; I2 = 60%). There was no subgroup analysis evidence of the superiority of any single group of adjunctive medications. CONCLUSIONS: We conclude that adjunctive non-NK1 antagonist medications may be useful for CINV control. Prospective randomized studies incorporating these low-cost medications into new regimens combining 5-HT3 and NK1 antagonists may be warranted.