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Background/Objectives : Positive margins are associated with locoregional recurrence in early laryngeal cancer. The aim of this study was to evaluate the impacts of specimen-driven (ex vivo) positive margins on patients with early-stage laryngeal cancer whose tumor bed (defect-driven) margins had been negative. Methods : A retrospective study was performed on 60 consecutive T1b/T2 glottic cancer patients who underwent open frontolateral laryngectomy. The intraoperative margins were obtained from the tumor bed. Their recurrence and disease-free survival were evaluated. In all cases, negative margins were obtained from the surgical bed. The impact of positive margins from the specimen was evaluated in a paraffin study. Results : Among 10 patients with positive margins in the specimen, six experienced local relapse, and among 50 patients with negative margins in the specimen, three developed recurrence. The 5-year disease-free survival rates were 37.5% and 93.9%, respectively ( p < 0.001; log-rank). Even with negative margins in the surgical bed, patients with positive margins in the specimen at the final histopathological examination had a 3.5-fold higher chance of developing local recurrence than those with negative margins (HR = 13.993; 95% CI: 3.479-56.281; p < 0.001; univariate Cox regression). Conclusions : Specimen-driven positive margins represent a significant risk factor for local recurrence, even under negative margins at the tumor bed.

Introduction  The harmonic scalpel (HS) is a technique introduced to reduce blood loss and intraoperative time during neck dissection (ND). Objective  To compare the results of HS with traditional hemostasis in ND through a systematic review and metanalysis. Methods  A computer-based strategy of systematic literature survey included research in the MEDLINE, EMBASE, and Cochrane Library databases from January 2007 up to August 2022. The survey strategy employed was [harmonic scalpel OR ultrasonic scalpel] AND neck dissection. Results  There were 61 articles identified that addressed the use of HS in patients undergoing ND. From those, 10 randomized clinical trials were selected, comprising 264 cases of ND using HS and 262 cases of ND without HS. Conclusion  The use of HS for ND significantly reduces the operative time, intraoperative bleeding, volume of draining fluid, and the number of ligatures., Competing Interests: Conflict of Interest The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

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., (© 2023. The Author(s).)

Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours., Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186., Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039)., Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: We performed a systematic review dedicated to pooling evidence for the associations of clinical features with malignant transformation (MT) and recurrence of 3 oral potentially malignant disorders (OPMDs) (actinic cheilitis [AC], oral leukoplakia [OL], and proliferative verrucous leukoplakia [PVL])., Study Design: We selected studies that included clinical features and risk factors (age, sex, site, size, appearance, alcohol intake, tobacco use, and sun exposure) of OL, PVL, and AC associated with recurrence and/or MT., Results: Based on the meta-analysis results, non-homogeneous OL appears to have a 4.53 times higher chance of recurrence after treatment. We also found 6.52 higher chances of MT of non-homogeneous OL. Another clinical feature related to higher MT chances is the location (floor of the mouth and tongue has 4.48 higher chances) and the size (OL with >200 mm 2 in size has 4.10 higher chances of MT). Regarding habits, nonsmoking patients with OL have a 3.20 higher chance of MT. The only clinical feature related to higher chances of MT in patients with PVL was sex (females have a 2.50 higher chance of MT)., Conclusions: Our study showed that some clinical features may indicate greater chances of recurrence after treatment and MT of OPMD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Bone invasion is an important prognostic factor in oral squamous cell carcinoma, leading to a lower survival rate and the use of aggressive treatment approaches. Epithelial-mesenchymal transition (EMT) is possibly involved in this process, because it is often related to mechanisms of cell motility and invasiveness. This study examined whether a panel of epithelial-mesenchymal markers are present in cases of oral squamous cell carcinoma with bone invasion and whether these proteins have any relationship with patients' clinical-pathological parameters and prognostic factors., Methods: Immunohistochemical analysis of E-cadherin, twist , vimentin, TGFβ1, and periostin was performed in paraffin-embedded samples of 62 oral squamous cell carcinoma cases., Results: The analysis revealed that most cases (66%) presented with a dominant tumor infiltrative pattern in bone tissue, associated with lower survival rates, when compared with cases with a dominant erosive invasion pattern (P = 0.048). Twenty-seven cases (43%) expressed markers that were compatible with total or partial EMT at the tumor-bone interface. There was no association between evidence of total or partial EMT and other demographic or prognostic features. E-cadherin-positive cases were associated with tobacco smoking (P = 0.022); vimentin-positive cases correlated with tumors under 4 cm (P = 0.043). Twist expression was observed in tumors with a dominant infiltrative pattern (P = 0.041) and was associated with the absence of periostin (P = 0.031)., Conclusion: We observed evidence of total or partial EMT in oral squamous cell carcinoma bone invasion. The transcription factor twist appears to be involved in bone invasion and disease progression., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: The AJCC/UICC TNM staging system evaluates the risk of death from cancer. Its 8th edition aimed to increase its accuracy. In turn, the American Thyroid Association proposed an initial risk stratification system (IRSS) focusing on the risk of recurrence in differentiated thyroid carcinoma. The present study intended to analyze their prediction abilities., Methods: Six hundred and eighty-five consecutive surgical patients (mean follow-up 71.6 months) were staged. Correlations with disease-free survival (DFS) and overall survival (OS) were carried out., Results: IRSS was discriminative for DFS but not for OS. Applying TNM 8th, 36.9% of the cohort was downstaged. Their DFS was shorter, compared with other patients in the same stage, but with no impact on OS. However, all those who died of the disease had been downstaged., Conclusions: IRSS was more effective to predict DFS, but not OS. TNM 8th was more appropriate for OS analysis than TNM 7th and IRSS., (© 2021 Wiley Periodicals LLC.)

Background: We evaluated microRNAs and extracellular matrix component profiles in squamous cell carcinoma of the oral cavity (OSCC) in comparison to healthy mucosa., Methods: Retrospective study investigating 64 microRNAs related to oncogenic process and to constituents of the extracellular matrix. We also performed immunohistochemical assays for molecules involved in the same biological processes., Results: High expression of miR-21-5p (p < 0.001) and miR-106-5p (p < 0.001) and low expression of miR-320a (p = 0.001) and miR-222-3p (p = 0.001) were predictors of malignancy. Individually, miR-21-5p exhibited the best statistical performance (area under the curve = 0.972; 95% confidence interval: 0.911-1.000) in the differentiation between tumor tissue and healthy mucosa. Moreover, tumor sample showed increased expression of MMP-2, MMP-9, α-laminin, and β-laminin in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane., Conclusion: The present study demonstrates the biological effects of microRNAs on the carcinogenesis of OSCC as well as the intense modification of the tumor microenvironment., (© 2021 Wiley Periodicals LLC.)

Background: Sphingolipids are bioactive lipids that play a role in cancer development. However, the clinical role of sphingolipid (SPL)-related genes in oral cancer (OC) remains not fully understood., Objective: This study, aimed to examine the mRNA expression of 14 sphingolipid-related genes in oral cancer patients and their implication with clinicopathological features and prognosis., Methods: qPCR analysis was performed in 50 OC tissues and their matched surgical margins. Next, Kaplan-Meier, Cox regression, and Receiver operating characteristics (ROC) analysis were applied to evaluate the impact of sphingolipid-related genes expression on the prognosis of OC., Results: The genes SET, ACER3, SK1 and S1PR5 were predominantly up-regulated, while ABCG2, S1PR1, ABCB1 and SPNS2 were down-regulated in OC patients. Analyzing the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) data, which are predominantly composed of OC samples, these genes displayed a similar profile. In OC patients, high levels of SK1 were associated with lymph node metastasis, extracapsular invasion, desmoplasia, locoregional relapse, and disease status. Low levels of SPNS2 were associated with lymph node metastasis, perineural invasion, and disease status. Furthermore, OC and HNSC patients with higher SK1 expression demonstrated shorter disease-free survival (p= 0.0037; p= 0.0087), whereas those with lower SPNS2 expression exhibited shorter overall survival (p= 0.051; p= 0.0012). High levels of ACER3 and low levels of S1PR1 were associated with shorter disease-free and overall survival in HNSC patients., Conclusion: Several sphingolipid-related genes are deregulated in OC at the mRNA level and are associated with clinicopathological features and presented potencial for the prediction of poor prognosis in OC patients.

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.

Objective: This study aimed to evaluate the effect of the delay to initiate postoperative radiation therapy (RT) on locoregional control to head and neck squamous cell carcinoma patients., Methods: Retrospective cohort study that included patients submitted to surgery followed by adjuvant RT (with/without chemotherapy). The time interval between surgery and RT was dichotomized by the receiver operating characteristics curve method at 92 days. Other possible sources of heterogeneity with potential impact on locoregional control were explored by regressive analysis., Results: A total of 168 patients were evaluated. The median time for locoregional recurrence (LRR) was 29.7 months. The relapse-free survival rates were 66.4% and 75.4% for patients who initiated RT more than and within 92 postoperative days (p=0.377), respectively. Doses lower than 60Gy were associated with worse rates of locoregional control (HR=6.523; 95%CI:2.266-18.777, p=0.001). Patients whose total treatment time (TTT) was longer than 150 days had LRR rate of 41.8%; no patient with TTT inferior to 150 days had relapses (p=0.001)., Conclusions: The interval between surgery and RT did not show influence on locoregional control rates. However, doses <60Gy and the total treatment time >150 days were associated with lower locoregional control rates.

Epithelial cadherins with catenins form the E-cadherin-catenin complex that acts on cell-to-cell adhesion. The loss of these complex lead to the reduction or absence of epithelial cadherin expression in the cell membrane, cytoplasmic accumulation of β-catenin and its translocation to the nucleus, contributing to carcinogenic events. The objective of this study was to evaluate the expression of epithelial cadherin and β-catenin in patients with laryngeal tumor. A retrospective study of 52 patients with glottic or supraglottic squamous cell carcinoma was conducted and evaluated according to the tumor site, histological differentiation, TNM stage, survival analysis and compared with the immunohistochemical expression of epithelial cadherin and β-catenin. We observed statistically significant association between the epithelial cadherin expression reduction and supraglottic localization of the lesion, the presence of cervical metastasis, poorly differentiated tumors and locally advanced tumors when in glottic topography. Related to the expression of β-catenin, statistical significance was also found to the presence of cervical metastasis and tumor of low differentiation with the decreased expression of this marker. Regarding survival analysis, the low expression of β-catenin is related to worse overall survival and the reduction of expression of both markers to worse disease-free survival. We concluded that the reduction in expression of the markers studied leads to a prognostic impact as they are related to tumors with greater local aggressiveness and presence of cervical metastasis., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Background: The purpose of the present study was to investigate the role of tumor volume in the prognosis of patients with oral cavity squamous cell carcinoma (SCC)., Methods: One hundred twenty-three patients with T4a oral cavity SCCs underwent surgical treatment. The volumes of the primary cancer were calculated by the multiplication of 3 macroscopic dimensions of the surgical specimen and related to recurrence and death., Results: There were 54 recurrences (43.9%) and 75 deaths (60.9%). The mean tumor volume among the patients living without disease during the follow-up period was 28.2 cc, compared to 88.2 cc for patients living with disease, and to 78.9 cc for patients who died of the disease (p < .001). Multivariate analyses showed that volume and perineural invasion were independent factors for recurrence, whereas volume and lymph node metastasis were independent factors for death., Conclusion: Among patients who already have advanced cancers, tumor volume can significantly impact their prognoses. © 2017 Wiley Periodicals, Inc. Head Neck 39: 960-964, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: Human papillomavirus (HPV) prevalence in head and neck squamous cell carcinomas (HNSCC) diverges geographically. The reliability of using p16(INK4a) expression as a marker of viral infection is controversial in HNSCC. We evaluated HPV types and HPV-16 variants prevalence, and p16(INK4a) expression in HNSCC specimens provided by two different Institutions in São Paulo., Methods: HPV DNA from formalin-fixed specimens was accessed by Inno-LiPA, HPV-16 variants by PCR-sequencing, and p16(INK4a) protein levels by immunohistochemistry., Results: Overall, HPV DNA was detected among 19.4 % of the specimens (36/186). Viral prevalence was higher in the oral cavity (25.0 %, 23/92) then in other anatomical sites (oropharynx 14,3 %, larynx 13.7 %) when samples from both Institutions were analyzed together. HPV prevalence was also higher in the oral cavity when samples from both Institutions were analyzed separately. HPV-16 was the most prevalent type identified in 69.5 % of the HPV positive smaples and specimens were assigned into Asian-American (57.2 %) or European (42.8 %) phylogenetic branches. High expression of p16(INK4a) was more common among HPV positive tumors., Conclusion: Our results support a role for HPV-16 in a subset of HNSCC.

The pectoralis major myocutaneous flap (PMMF) is a safe and versatile flap used widely for head and neck cancer reconstructions, but one of the major and most feared complications is oro- or pharyngocutaneous fistula. Herein, we attempt to establish risk factors for fistula formation in reconstructions of mucosal defects in the head and neck using PMMF through retrospective analysis of PMMF performed during 3 years at a single institution, with a total of 84 procedures. There were 69 men and 15 women, with a mean age of 59.5 years. There were 15 cases of partial flap loss, two total flap losses and 31 fistulas. The independent risk factors for fistula formation were preoperative serum hemoglobin < 13 g/dl, preoperative serum albumin < 3.4 g/dl and hypopharynx reconstruction. The PMMF is still a very useful flap and this is the first multivariate analysis analysing risk factors for fistula formation. These findings are helpful in selecting patients with elevated risk of fistula formation, and therefore preventive measures can be undertaken to avoid potentially serious complications.

The aim is to determine if tumor thickness is a risk factor related to the development of early recurrences in surgically treated oral cavity squamous cell carcinoma (SCC). Retrospective cohort study conducted at Instituto do Câncer do Estado de São Paulo (ICESP). Fifty-seven patients with oral cavity SCC (excluding lip tumors and patients previously submitted to any treatment) were analyzed regarding the occurrence of an early disease progression (locoregional or distant metastasis) within the first 12 months after initial treatment. Tumor thickness and other histological characteristics related to the development of recurrence up to 1 year after treatment were tested. Results demonstrated that tumor thickness greater than 10 mm (P = 0.034), as well as angiolymphatic invasion (P = 0.001), perineural invasion (P = 0.041) and lymph-node metastasis (P = 0.021) was associated with a worse 12-month disease-free survival (Log-Rank test). In multivariate analysis, tumor thickness greater than 10 mm emerged as an independent risk factor for early recurrence in oral cavity tumors (HR = 3.4, 95% CI: 1.005-11.690; P = 0.049--Cox regression). Post-operative radiotherapy seems to be a protective factor for early recurrences in patients with tumor thickness greater than 10 mm (P = 0.017--Log-Rank test; HR = 0.32, 95% CI: 0.12-0.87, P = 0.026--Cox regression). The results of the present research suggest that tumor thickness greater than 10 mm may be an independent adverse factor for early progression of surgically treated oral cavity SCC. Adjuvant therapies, in particular post-operative radiotherapy, should be advocated in this group of patients, regardless of the co-existence of other well-described histological risk factors.

Objective: To assess psychiatric symptoms, substance use, quality of life and eating behavior of patients undergoing bariatric surgery before and after the procedure., Methods: We conducted a prospective longitudinal study of 32 women undergoing bariatric surgery. To obtain data, the patients answered specific, self-administered questionnaires., Results: We observed a reduction in depressive and anxious symptoms and also in bulimic behavior, as well as an improved quality of life in the physical, psychological and environmental domains. There was also a decrease in use of antidepressants and appetite suppressants, but the surgery was not a cessation factor in smoking and / or alcoholism., Conclusion: a decrease in psychiatric symptoms was observed after bariatric surgery, as well as the reduction in the use of psychoactive substances. In addition, there was an improvement in quality of life after surgical treatment of obesity.

Purpose: Paullinia cupana (guaraná) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue (CRF) in patients with breast cancer. We aimed to evaluate the efficacy of a purified dry extract of P. cupana (PC-18) in patients with various solid tumors treated with chemotherapy., Methods: We included 40 patients with solid tumors who showed increases in their Brief Fatigue Inventory (BFI) questionnaire scores after 1 week of systemic chemotherapy. PC-18 was administered at 37.5 mg by mouth two times per day (PO bid), starting after 1 week of chemotherapy, for 3 weeks (induction phase). Patients who had an improvement in or stabilization of their BFI scores were randomized to receive either PC-18 at the same dose or placebo for the following 3 weeks (maintenance phase)., Results: After PC-18 treatment, the BFI fatigue scores improved or stabilized in 36 out of the 40 patients (mean BFI score difference = 2.503; 95% confidence interval: 1.716-3.375, p = .0002). Three weeks after randomization (16 patients on PC-18 and 17 on placebo), we observed no significant differences in the BFI, Functional Assessment of Chronic Illness Therapy, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores between patients randomized to PC-18 versus placebo., Conclusions: We conclude that the PC-18 extract may be effective for the treatment of CRF in patients with a variety of solid tumors. A conditioning effect, which was observed in patients who had a beneficial effect of PC-18 on CRF, may explain the better than expected fatigue scores of the placebo-treated patients.

Background: To distinguish between malignant and benign lesions of the thyroid gland histological demonstration is often required since the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers using immunocytochemistry and immunohistochemistry techniques have been studied, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions., Methods: A systematic review of published articles on MEDLINE and The Cochrane Library was performed. After establishing inclusion and exclusion criteria, 66 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed and global values of sensitivity, specificity, area under the summary ROC curve, and diagnostic odds ratio (dOR) were calculated., Results: For the immunohistochemistry technique, the positivity of CK-19 for the diagnosis of malignant thyroid lesions demonstrated global sensitivity of 81% and specificity of 73%; for Gal-3, sensitivity of 82% and specificity of 81%; and for HBME-1, sensitivity of 77% and specificity of 83%. The association of the three markers determined sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Similar results were also found for the immunocytochemistry assay., Conclusion: This meta-analysis demonstrated that the three immunomarkers studied are accurate in pre- and postoperative diagnosis of benign and malignant thyroid lesions. Nevertheless, the search for other molecular markers must continue in order to enhance this diagnostic accuracy since the results found still show a persistency of false-negative and false-positive tests., Virtual Slides: Http://www.diagnosticpathology.diagnomx.eu/vs/3436263067345159.

Introduction: The reconstruction of complex cervicofacial defects arising from surgical treatment for cancer is a real challenge for head and neck surgeons, especially in salvage reconstruction surgery and/or failed previous reconstruction. The pectoralis major myocutaneous flap (PMMF) has been widely used in these specific situations due to its reliability and low rate of failure or complications., Objectives: Identify factors that determine complications and influence the final outcome of the reconstructions with PMMF in salvage cancer surgery or in salvage reconstruction., Methods: A cross-sectional study design was used to evaluate a sample including 17 surgical patients treated over a period of ten years that met the inclusion criteria., Results: Reconstruction was successful in 13 cases (76.5%), with two cases of partial flap loss and no case of total loss. Complications occurred in 13 cases (76.5%) and were specifically related to the flap in nine instances (52.9%). An association was identified between the development of major complications and reconstruction of the hypopharynx (P = 0.013) as well as in patients submitted to surgery in association with radiation therapy as a previous cancer treatment (P = 0.002). The former condition is also associated with major reconstruction failure (P = 0.018). An even lower incidence of major complications was noted in patients under the age of 53 (P = 0.044)., Conclusion: Older patients, with hypopharyngeal defects and submitted to previous surgery plus radiation therapy, presented a higher risk of complications and reconstruction failure with PMMF.

Background: Atrial fibrillation (AF) is the most commonly sustained cardiac rhythm disturbance. Surgical ablation techniques were developed involving the left atrium only and modifications of the maze procedure in ablating both atria., Objective: The aim of this study was to compare, in patients with permanent AF, the efficacy of uniatrial versus biatrial radiofrequency ablation procedure in the treatment of chronic atrial fibrillation in patients with associated cardiac disease., Method: Between September 2003 and May 2009, 30 patients were submitted to the radiofrequency ablation procedure for AF associated with concomitant cardiac surgery; 15 patients underwent a uniatrial procedure, and 15 patients underwent biatrial ablation. The mean age was 47.73 ± 9.85 years, and 53.4% were men. The average followup time was 12.16 ± 10.89 months for the uniatrial group and 7.0 ± 4.0 months for the biatrial group., Results: Neither hospital mortality nor complications related to radiofrequency ablation were was registered. At the time of hospital discharge, 9 patients (60%) were in a state of sinus rhythm in both groups. However, patients undergoing biatrial ablation (range 73.3% versus 46.7%) demonstrated complete freedom from atrial fibrillation at all times., Conclusion: Biatrial ablation surgical procedures were more effective in controlling atrial fibrillation than procedures limited to the left atrium.

The aim of this paper was to determine if the subclavicular route of rotation improved the pectoralis major myocutaneous flap's ability to reach head and neck sites in comparison to the traditional supraclavicular rotation. We dissected 50 flaps in 25 fresh adult male cadavers. The length of the pedicle and the flap's ability to reach five anatomical head and neck sites (laryngeal prominence of thyroid cartilage, mentum, angle of the mandible, external auditory canal, and orbit) were tested by supraclavicular and subclavicular rotation. Although the average length of the flap's pedicle was higher when the subclavicular rotation was employed, there was no statistical difference between the two techniques concerning the flap's ability to reach the studied sites. Our results suggest that the subclavicular route apparently adds little to the reconstruction of head and neck defects using the pectoralis major myocutaneous flap. We believe that the indication of this technique should be evaluated on a case-by-case basis before it is recommended to keep from unnecessarily increasing the potential morbidity of the reparative procedure.

Introduction: Studies have highlighted the changes that take place in the environment between the cell and the extracellular matrix during the process of neoplastic expansion. Several papers have associated the expression of heparanase 1 with various malignant tumors. Heparanase 2 is probably related to loss of cell adhesion., Objective: The aim of this study was to evaluate the expression of heparanase 2 in epithelial neoplasia of the ovaries and in samples of normal ovarian tissue., Methods: Seventy-five ovary specimens were analyzed and divided into 3 groups: 23 malignant and 35 benign epithelial ovarian neoplasia and 17 without ovarian disease. We used 2 methodological techniques for evaluating the immunoexpression of heparanase 2. The first followed the qualitative criterion of positive or negative in relation to enzymatic expression, and the second involved computerized quantification of this expression, performed on the same slides., Results: In the quantitative analysis, we found positivity indices for heparanase 2 expression of 72.2% and 87.3% in the samples of benign and malignant neoplasias, respectively. In these, the intensity of expression and the expression index were 147.2 and 121.2, respectively, for the benign neoplasia and 134.1 and 118.0 for the malignant neoplasia. Qualitatively, its expression was strong or moderate in 44.2% of the benign and 78.2% of the malignant tumors; its expression in all of the nonneoplastic samples was negative, with the exception of one that was weakly positive., Conclusions: Heparanase 2 is involved in neoplastic proliferation, but it was not exclusively associated with the malignant process. Furthermore, there was no difference in its expression between benign and malignant ovarian epithelial neoplasia.

Heparanase is an endo-beta-glucuronidase that is capable of degrading heparan sulfate chains of proteoglycans, generating a variety of bioactive molecules such as growth factors and chemotactic and angiogenic agents. The expression of heparanase was investigated in the peripheral blood mononuclear cell fraction (PBMC) of 30 patients with breast cancer and 20 healthy control women by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. PBMC samples from all breast cancer patients at study entry showed the expression of heparanase, whereas no expression was observed for healthy women. Immunocytochemistry analysis demonstrated that heparanase was expressed in lymphocytes of breast cancer PBMC. Throughout follow-up, heparanase expression by RTPCR decreased significantly after surgery in patients treated with neoadjuvant chemotherapy (P = .002) and after tamoxifen treatment (P = .040), whereas it increased significantly with the advent of systemic metastasis (P = .027). In vitro, either serum from breast cancer patients or a medium originated from coculture experiments of MCF-7 cells and lymphocytes from healthy women stimulated heparanase expression in normal lymphocytes. The results suggest that there is a tumor-inducing effect on heparanase expression by lymphocytes present in the PBMCs of breast cancer patients, which depends, in turn, on the interaction between a tumor and normal lymphocytes.

The interactions between growth factors and sulphated glycosaminoglycans (GAG) have been extensively studied. The aim of this study is to investigate if growth factors would show specificity of action on the synthesis and shedding of sulphated GAG, using two different cell lines: endothelial and smooth muscle cells. The cells were grown in the presence or absence of growth factors: EGF, FGF2, VEGF121, VEGF165. Transfection assays were also performed using recombinant pcDNA3.1, containing VEGF165 cDNA. In order to analyse the different types of GAG the cells were metabolically labelled with [(35)S]-sulphate. At low doses, VEGF121 was the only growth factor able to increase both the synthesis and secretion of heparan sulphate (HS) in endothelial cells. Over expression of VEGF165 stimulated HS synthesis in both cells. The combined results showed that growth factors affect GAG synthesis in a cell specific and dose dependent manner.

Bronchopulmonary typical carcinoid tumors (BTCT) are neuroendocrine neoplasms with histologic low grade characteristics considered benign. However, despite reassuring histologic classification, some of them demonstrate an aggressive nature and metastatic behavior. During a not yet concluded study aiming at establishing criteria to predict this metastatic behavior, three uncommon cases were observed. Metastasis occurred despite typical carcinoid microscopic features in 3 female patients of African origin presenting at macroscopic examination as ramifying bronchopulmonary typical carcinoid tumors following the bronchial tree. We suggest that clinical ramifying presentation may be related to metastatic behavior, even for bronchopulmonary typical carcinoid tumors not displaying histologic criteria for atypical carcinoid tumors.

Bronchopulmonary carcinoid tumors have been associated with a variety of endocrine disorders including Cushing's syndrome (CS), which is caused by ectopic adrenocorticotrophic hormone (ACTH) secretion. We report two cases of CS secondary to bronchopulmonary carcinoid tumors. The first patient, a 29-year-old woman, presented hypokalemia, high serum ACTH level and high free-urinary cortisol, raising suspicion of an ectopic ACTH syndrome. Chest computed tomography and Octreoscan showed a peripheral nodule in the left-superior lobe of the lung. After lobectomy, a typical bronchopulmonary carcinoid was diagnosed. The second patient, a 16-year-old boy, presented "moon face" and progressive asthenia, high serum ACTH level and high free-urinary cortisol, raising the same hypothesis. Chest computed tomography and Octreoscan showed a peripheral nodule in the middle lobe. After lobectomy, an atypical bronchopulmonary carcinoid was diagnosed. Both cases had IA stage (T1N0M0), positively immunostaining for chromogranin and ACTH. Neither of these patients had hypophysary microadenomas, adrenal adenomas or recurrence of CS after surgical treatment, demonstrating that CS was caused solely by the presence of the bronchopulmonary carcinoid tumors.

Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.

Unlabelled: Angiogenesis is new blood vessel formation, a process that can lead to tumor development. Microvessel count has been correlated to metastasis in some neoplasias., Purpose: To determine if measurement of microvessel density is useful in predicting metastasis to the cervical lymph node and prognosis in patients with papillary thyroid carcinoma., Methods: A retrospective analysis was performed in 30 patients that had undergone total thyroidectomy. They were divided in 2 groups of 15 patients--with and without metastatic disease. Immunohistochemistry was used to detect expression of CD34 in archival paraffin-embedded papillary thyroid tumors, and microvessel density was calculated based on it. Association between microvessel density and the presence of metastasis, according to histological subtype, disease recurrence, and AMES prognostic index groups was determined through statistical analysis., Results: The median microvessel density for the patient group without metastasis (200.0 microvessels/mm2) was apparently, but not significantly, less than that observed among metastatic disease patients (254.4 microvessels/mm2) (P=.20). When papillary carcinoma subtypes were analyzed, this difference became significant (P=02). The follicular variant exhibited a greater microvessel density than the other subtypes, independent of metastasis presence. There was an apparent, but not significant, tendency for a larger median microvessel density in the group of patients that presented recurrence (294.4 microvessels/mm2 vs 249.6 microvessels/mm2, P=.11). There was no relationship between risk level and microvessel density: in the low- and high-risk groups, the median MVD was 304.0 microvessels/mm2 and 229.6 microvessels/mm2, respectively (P=.27)., Conclusions: The results suggest that angiogenesis is more intense among metastatic tumors in the classic and the tall cell variants, indicating that microvessel count can be an indicator of the potential for metastasis in these subtypes of papillary thyroid carcinoma. Patients that developed recurrent disease had a tendency to exhibit higher angiogenesis; however, there was no association between microvessel density and the AMES prognostic index.