The impact of Hurricane Maria on Puerto Rico's health system: post-disaster perceptions and experiences of health care providers and administrators.

BACKGROUND: After its landfall in Puerto Rico in 2017, Hurricane Maria caused the longest blackout in United States history, producing cascading effects on a health care system that had already been weakened by decades of public sector austerity and neoliberal health reforms. This article addresses how health care professionals and administrators experienced the health care system's collapse and the strategies used by them to meet their communities' health needs. METHODS: Data were collected between September 2018 and February 2020. Ethnographic observations in health care facilities and semi-structured qualitative interviews with representatives of the health care system were conducted. This paper focuses on data from interviews with health care providers (n = 10) and administrators (n = 10), and an ethnographic visit to a pop-up community clinic. The analysis consisted of systematic thematic coding of the interview transcripts and ethnographic field notes. RESULTS: Results provide insight on how participants, who witnessed first-hand the collapse of Puerto Rico's health care system, responded to the crisis after Maria. The prolonged power outage and lack of a disaster management plan were partly responsible for the death of 3,052 individuals who experienced extended interruptions in access to medical care. Participants reported a sense of abandonment by the government and feelings of mistrust. They also described the health sector as chaotic and lacking clear guidelines on how to provide services or cope with personal crises while working under extreme conditions. In such circumstances, they developed resilient responses to meet communities' health needs (e.g., itinerant acupuncture services, re-locating physicians to local pharmacies). CONCLUSIONS: Participants' narratives emphasize that the management of Hurricane Maria was fraught with political and economic constraints affecting Puerto Rico. Ineffective planning and post-Maria responses of the local and federal governments were determinants of the disaster's impact. The findings contribute to a growing scientific literature indicating that Hurricane Maria revealed 'the collapse before the collapse,' alluding to the structural deficiencies that presaged the catastrophic event. In the context of governmental abandonment, the authors argue for the importance of developing alternative strategies in post-disaster health care provision among health professionals and administrators who work at the front lines of recovery.

Silicon Amendment Enhances Agronomic Efficiency of Nitrogen Fertilization in Maize and Wheat Crops under Tropical Conditions.

Sustainable management strategies are needed to improve agronomic efficiency and cereal yield production under harsh abiotic climatic conditions such as in tropical Savannah. Under these environments, field-grown crops are usually exposed to drought and high temperature conditions. Silicon (Si) application could be a useful and sustainable strategy to enhance agronomic N use efficiency, leading to better cereal development. This study was developed to explore the effect of Si application as a soil amendment source (Ca and Mg silicate) associated with N levels applied in a side-dressing (control, low, medium and high N levels) on maize and wheat development, N uptake, agronomic efficiency and grain yield. The field experiments were carried out during four cropping seasons, using two soil amendment sources (Ca and Mg silicate and dolomitic limestone) and four N levels (0, 50, 100 and 200 kg N ha-1). The following evaluations were performed in maize and wheat crops: the shoots and roots biomass, total N, N-NO3-, N-NH4+ and Si accumulation in the shoots, roots and grain tissue, leaf chlorophyll index, grain yield and agronomic efficiency. The silicon amendment application enhanced leaf chlorophyll index, agronomic efficiency and N-uptake in maize and wheat plants, benefiting shoots and roots development and leading to a higher grain yield (an increase of 5.2 and 7.6%, respectively). It would be possible to reduce N fertilization in maize from 185-180 to 100 kg N ha-1 while maintaining similar grain yield with Si application. Additionally, Si application would reduce N fertilization in wheat from 195-200 to 100 kg N ha-1. Silicon application could be a key technology for improving plant-soil N-management, especially in Si accumulator crops, leading to a more sustainable cereal production under tropical conditions.

Can silicon applied to correct soil acidity in combination with Azospirillum brasilense inoculation improve nitrogen use efficiency in maize?

Alternative management practices are needed to minimize the need for chemical fertilizer use in non-leguminous cropping systems. The use of biological agents that can fix atmospheric N has shown potential to improve nutrient availability in grass crops. This research was developed to investigate if inoculation with Azospirillum brasilense in combination with silicon (Si) can enhance N use efficiency (NUE) in maize. The study was set up in a Rhodic Hapludox under a no-till system, in a completely randomized block design with four replicates. Treatments were tested in a full factorial design and included: i) five side dress N rates (0 to 200 kg ha-1); ii) two liming sources (Ca and Mg silicate and dolomitic limestone); and iii) with and without seed inoculation with A. brasilense. Inoculation with A. brasilense was found to increase grain yield by 15% when N was omitted and up to 10% when N was applied. Inoculation also increased N accumulation in plant tissue. Inoculation and limestone application were found to increase leaf chlorophyll index, number of grains per ear, harvest index, and NUE. Inoculation increased harvest index and NUE by 9.5 and 19.3%, respectively, compared with non-inoculated plots. Silicon application increased leaf chlorophyll index and N-leaf concentration. The combination of Si and inoculation provided greater Si-shoot accumulation. This study showed positive improvements in maize growth production parameters as a result of inoculation, but the potential benefits of Si use were less evident. Further research should be conducted under growing conditions that provide some level of biotic or abiotic stress to study the true potential of Si application.

Total pharyngolaryngectomy in the elderly: The impact of age on postoperative complications and oncologic and functional outcomes.

OBJECTIVES: To evaluate the clinical outcomes of total pharyngolaryngectomy (TPL) in the elderly and to analyze the impact of age on postoperative complications and oncologic and functional outcomes. METHODS: We conducted a retrospective review of the medical records of all patients who underwent TPL for a laryngeal or hypopharyngeal squamous cell carcinoma, between 2000 and 2015. The impact of advanced age (>70 years) on clinical outcomes was assessed in univariate and multivariate analyses. RESULTS: A total of 245 patients (mean age = 66.4 years) were enrolled in this study including 91 (37%) patients aged over 70 years. In patients aged over 70 years, local and general complication rates were 36% and 10%, respectively. Five-year overall, cause-specific and recurrence-free survival rates were 36%, 52% and 31%, respectively. Satisfactory swallowing (swallowing score ≥ 1; i.e. no enteral feeding) and speech (speech score ≥ 1; i.e. intelligible speech) functions were recovered by 94% and 70% of elderly patients. In multivariate analysis, older age had no significant impact on postoperative complications, oncologic outcomes and swallowing function. Compared to younger patients, elderly patients achieved significantly lower speech scores (p = 0.05). CONCLUSION: TPL is associated with favorable clinical outcomes in patients aged over 70 years and can therefore be considered a reliable therapeutic option. However, compared to younger patients, a lower level of recovery regarding speech function is expected in the elderly, and particular attention should be paid to the postoperative speech rehabilitation program in this population of patients.

Depicting the physiological and ultrastructural responses of soybean plants to Al stress conditions.

Aluminium (Al) is a toxic element for plants living in soils with acidic pH values, and it causes reductions in the roots and shoots development. High Al concentrations can cause physiological and structural changes, leading to symptoms of toxicity in plant tissue. The aim of this study was to describe the Al toxicity in soybean plants through physiological, nutritional, and ultrastructure analyses. Plants were grown in nutrient solution containing increasing Al concentrations (0; 0.05; 0.1; 1.0, 2.0 and 4.0 mmol L-1). The Al toxicity in the soybean plants was characterized by nutritional, anatomical, physiological, and biochemical analyses. The carbon dioxide assimilation rates and stomatal conductance were not affected by the Al. However, the capacity for internal carbon use decreased, and the transpiration rate increased, resulting in increased root biomass at the lowest Al concentration in the nutrient solution. The soybean plants exposed to the highest Al concentration exhibited lower root and shoot biomass. The nitrate reductase and urease activities decreased with the increasing Al concentration, indicating that nitrogen metabolism was halted. The superoxide dismutase and peroxidase activities increased with the increasing Al availability in the nutrient solution, and they were higher in the roots, showing their role in Al detoxification. Despite presenting external lesions characterized by a damaged root cap, the root xylem and phloem diameters were not affected by the Al. However, the leaf xylem diameter showed ultrastructural alterations under higher Al concentrations in nutrient solution. These results have contributed to our understanding of several physiological, biochemical and histological mechanisms of Al toxicity in soybean plants.

Impact of HPV-associated p16-expression and other clinical factors on therapeutic decision-making in patients with oropharyngeal cancer: A GETTEC multicentric study.

OBJECTIVES: To analyze the impact of tumor p16 status and other clinical factors on the therapeutic decision-making process in patients with oropharyngeal squamous cell carcinoma (OPSCC). METHODS: We conducted a multicenter retrospective study (GETTEC collaborative study group) enrolling all OPSCC patients with a determined p16-status considered eligible for surgery between 2009 and 2014. The impact of p16-status and other clinical factors on the therapeutic decision was evaluated in multivariate analysis. RESULTS: A total of 476 patients were enrolled in the study, including 244 cases (51%) of p16-positive OPSCC. Overall, 223 (47%) patients underwent primary surgery, and 184 (83%) of them received postoperative radiotherapy ± chemotherapy. More patients with p16-positive OPSCC tended to undergo non-surgical treatment than did patients with p16-negative OPSCC (p = 0.10). Multivariate analysis showed that 5 factors significantly influenced therapeutic management of the patients: T-stage ≥ 3 (towards a non-surgical strategy; p < 0.001), N-stage ≥ 2a (non-surgical strategy; p = 0.02), tumor involvement of the glosso-tonsillar sulcus (surgical strategy; p = 0.002), tumor extension to the oral cavity (surgical strategy; p < 0.009) and the center of care (p < 0.001). The rate of patients directed towards a surgical strategy varied between 9% and 74% depending on the center. CONCLUSION: There was a non-significant trend to recommend patients with p16-positive OPSCC for non-surgical treatment. Center of care, tumor stage and tumor anatomical subsite and extensions were the main determinants of the treatment choice.

Long-term quality of life and psycho-social outcomes after oropharyngeal cancer surgery and radial forearm free-flap reconstruction: A GETTEC prospective multicentric study.

OBJECTIVE: To assess long-term quality of life (QoL) and psycho-social outcomes, and to determine their predictive factors after oropharyngeal cancer (OPC) surgery and radial forearm free-flap (RFFF) reconstruction. METHODS: Patients who had undergone OPC surgery and RFFF reconstruction who were still alive and disease-free at least 1 year after surgery were enrolled in this prospective multicentric study. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis. RESULTS: A total of 58 patients were included in this study. Long-term QoL and functioning scales scores were well-preserved (all superior to 70%). Main persistent symptoms were fatigue, reduced sexuality and oral function-related disorders (swallowing, teeth, salivary and mouth-opening problems). HADS anxiety and depression scores were 7.2 and 5.4, respectively. Twenty-one (36%) patients presented an anxiodepressive disorder (HADS global score ≥ 15). Among the 21 patients who were still working before surgery, 11 (52%) had returned to work at the time of our study. The HADS global score (p < 0.001) was the main predictor of QoL, VHI-10 and DOSS scores. CONCLUSIONS: Psychological distress is the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of OPC patients.

Physiological highlights of manganese toxicity symptoms in soybean plants: Mn toxicity responses.

Manganese (Mn) is an essential element for plants; however, high concentrations in certain soil conditions can cause toxicity symptoms in the plant tissue. Here, we describe Mn toxicity symptoms and Mn toxicity responses in soybean plants. Soybean plants exposed to excess Mn showed reductions in the CO2 assimilation rate and stomatal conductance, which in turn resulted in decreased shoot biomass. Furthermore, peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activity were higher in plants grown with the highest Mn concentration. The Mn doses increased the activity of antioxidant enzymes such as CAT, POD, and SOD. The toxicity symptoms presented by the leaves included hypertrophying of the adaxial epidermis and the formation of necrotic areas with purple-colored veins. Dramatic movement of calcium from the healthy region to the purple-colored necrotic region was observed, as was the exit of potassium from the necrotic area to the healthy region of the tissue. The high activities of POD and SOD in the presence of high Mn compartmented in the roots was the main physiological responses at high Mn uptake by soybean plants.

Primary radical ablative surgery and fibula free-flap reconstruction for T4 oral cavity squamous cell carcinoma with mandibular invasion: oncologic and functional results and their predictive factors.

The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score (p = 0.002), pathologic N-stage (p = 0.01), and close surgical margins (p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status.

Evaluation of the information given to patients undergoing head and neck cancer surgery using the EORTC QLQ-INFO25 questionnaire: A prospective multicentric study.

AIM: Providing head and neck cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate patient perceptions of the information received, the predictive factors of such perceptions and their potential correlation with patient quality of life (QoL). METHODS: We conducted a prospective multicentric study using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-INFO25 and QLQ-C30 questionnaires before and after surgery. RESULTS: This study enrolled 200 patients, 149 men and 51 women, mean age 63.5 ± 10.3 years. Before and after treatment, global QLQ-INFO25 scores were 39.3 and 42.5, respectively, whereas satisfaction with the information received scores were 69.9 and 58.1, respectively. Regarding EORTC QLQ-INFO25 scores, between the pre- and post-treatment periods, we observed a significant increase in three scales/items (information about other services, information about different places of care and information about things you can do to help yourself) and a significant decrease in two scales/items (satisfaction with the information received and overall the information has been helpful). Before and after treatment, global QoL scores were 62.7 and 61.0, respectively. Overall, we found low correlations between QLQ-INFO25 and QLQ-C30 scores. Patient age and education level, centre of care, tumour site and treatment characteristics had a significant impact on QLQ-INFO25 scores. CONCLUSION: Perceived information was satisfactory in the perioperative period for head and neck cancer patients. Several demographic and clinical factors were identified as significant predictors of QLQ-INFO25 scores.

MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.

In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib.Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.

Induction chemotherapy-based larynx preservation program for locally advanced hypopharyngeal cancer: oncologic and functional outcomes and prognostic factors.

To evaluate oncologic and functional outcomes and prognostic factors in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program in daily clinical practice. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngo-laryngectomy, treated by docetaxel (75 mg/m(2), day 1), cisplatin (75 mg/m(2), day 1) and 5-fluorouracil (750 mg/m(2)/day, day 1-5) (TPF)-ICT (2-3 cycles) for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Prognostic factors of oncologic (overall, cause-specific and recurrence-free survival: OS, SS and RFS) and functional (dysphagia outcome and severity scale, permanent enteral nutrition, larynx preservation) outcomes were assessed in univariate and multivariate analyses. A total of 53 patients (42 men and 11 women, mean age 58.6 ± 8.2 years) were included in this study. Grade 3-4 toxicities were experienced by 17 (32 %) patients during ICT. The rate of poor response (response <50 % without larynx remobilization) to ICT was 10 %. At 5 years, OS, SS and RFS rates were 56, 60 and 54 %, respectively. Four patients required definitive enteral nutrition (permanent enteral tube feeding). The rate of patients alive, disease-free and with a functional larynx at 2 years was 58 %. T4 tumor stage (p = 0.005) and response to ICT <50 % (p = 0.02) were independent prognostic factors of OS. Response to ICT was significantly associated with the risk of permanent enteral nutrition (p = 0.04) and larynx preservation (p = 0.01). In daily clinical practice, a TPF-ICT-based larynx preservation protocol can be used in patients with locally advanced hypopharyngeal cancer with satisfactory results in terms of tolerance, efficacy and oncologic and functional outcomes.

Nutritional status and feeding-tube placement in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy-based larynx preservation program.

The objective of the study is to evaluate the nutritional status and determine its impact on clinical outcomes in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program without prophylactic feeding-tube placement. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngolaryngectomy, treated by docetaxel, cisplatin and 5-fluorouracil (TPF)-ICT for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Patients' nutritional status was closely monitored. Enteral nutrition was used if and when a patient was unable to sustain per-oral nutrition and hydration. The impact of nutritional status on clinical outcomes was investigated in univariate and multivariate analysis. A total of 53 patients (42 men and 11 women, mean age = 58.6 ± 8.2 years) were included in this study. Six (11.3 %) patients had lost more than 10 % of their usual body weight before therapy. Compared with patients' usual weight, the mean maximum patient weight loss during therapeutic management was 8.7 ± 4.5 kg. Enteral nutrition was required in 17 patients (32 %). We found no influence of the tested nutritional status-related factors on response to ICT, toxicity of ICT, overall, cause-specific and recurrence-free survival, and on post-therapeutic swallowing outcome. Maximum weight loss was significantly associated with a higher risk of enteral tube feeding during therapy (p = 0.03) and of complications (grade ≥3, p = 0.006) during RT. Without prophylactic feeding-tube placement, approximately one-third of the patients required enteral nutrition. There was no significant impact of nutritional status on oncologic or functional outcomes.

Salvage surgery for recurrent oropharyngeal cancer: post-operative oncologic and functional outcomes.

CONCLUSION: Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (OPSCC) were acceptable. Pathologic overall, T- or N-stage and patient comorbidities were the main predictors of patient clinical outcomes. OBJECTIVES: To evaluate post-operative outcomes of salvage surgery in patients with recurrent OPSCC and to determine their predictive factors. MATERIALS AND METHODS: This study retrospectively reviewed the electronic medical records of all patients who underwent salvage surgery for recurrent OPSCC, between 2000-2013, in our institution. Overall survival (OS) and cause-specific survival (SS) were determined by Kaplan-Meier analysis. Predictive factors of post-operative outcomes were investigated by using univariate and multivariate analyses. RESULTS: A total of 34 patients were included in this study. Local and general post-operative complication rates were 26% and 27%, respectively. A high level of comorbidity (Kaplan Feinstein Index: KFI ≥ 2) was the only factor associated with a higher risk of local (p = 0.03) and general (p = 0.04) complications. OS and SS rates at 3 years were 48% and 61%, respectively. In multivariate analysis, pathologic overall stage ≥ III was a significant predictor of OS (p = 0.02) and pathologic T-stage ≥ 3 was a significant predictor of SS (p = 0.01). Mean pre-operative and post-operative DOSS (dysphagia outcome and severity scale) scores were 4.4 and 3.9, respectively.

Contemporary therapeutic management of locally advanced hypopharyngeal cancer: oncologic and functional outcomes - a report on 100 cases.

CONCLUSION: A significant proportion of patients with locally advanced hypopharyngeal cancer could not be managed by larynx-sparing therapy. T4 stage is one of the main predictive factors of oncologic and functional outcomes. OBJECTIVES: To analyze the therapeutic management of patients with locally advanced hypopharyngeal cancer in clinical practice and to report oncologic and functional outcomes. METHODS: This was a retrospective study of all patients treated for a locally advanced hypopharyngeal squamous cell carcinoma between 2001 and 2012 at our institution. RESULTS: A total of 100 patients were included in this study. Induction chemotherapy (CT) followed by radiotherapy (RT) ± CT, primary RT + CT, and primary total pharyngolaryngectomy (TPL) comprised the initial therapeutic management for 54, 24, and 20 patients, respectively. Two patients received only supportive care. Overall survival (OS) and cause-specific survival (SS) were 50% and 60% at 3 years, respectively. In the group of patients referred for induction CT, the 3-year OS and SS were 58% and 70%, respectively. In multivariate analysis, T stage (p = 0.05) and ASA score (p = 0.02) were significant predictive factors of OS. T4 tumor stage had a pejorative impact on swallowing function after therapy (p = 0.006). The rate of patients alive, disease-free, and with a functional larynx at 2 years was 23%.

Long-term functional outcomes and quality of life after oncologic surgery and microvascular reconstruction in patients with oral or oropharyngeal cancer.

CONCLUSIONS: Surgery for oral or oropharyngeal cancer with free-flap reconstruction is associated with moderate but persistent functional and quality of life (QoL) problems. Patient age, tumor stage, tumor site, and radiotherapy were the main predictors of functional outcome. OBJECTIVES: To evaluate long-term functional outcomes and QoL, and to determine their predictive factors in patients with oral or oropharyngeal cancer after oncologic surgery and free-flap reconstruction. METHODS: Patients who underwent surgery with free-flap reconstruction for oral or oropharyngeal cancer between 2000 and 2009 who were alive at least 1 year after therapy were included in this study. Patients completed the Voice Handicap Index (VHI-10) questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaires QLQ-C30 and H&N35. Swallowing was evaluated using the Dysphagia Outcome and Severity Scale (DOSS) and by flexible fiberoptic laryngoscopy. RESULTS: Sixty-four patients were included in the study. VHI-10 mean score was 11.2 ± 9 and its predictive factors were T stage (p = 0.005) and tumor involvement of the tongue base (p = 0.01). The mean DOSS score was 4 ± 0.8. Age (p = 0.008), gender (p = 0.04), and radiotherapy (p = 0.001) were the main predictive factors of the DOSS score.

Diagnostic value of immunohistochemistry for the detection of the BRAF(V600E) mutation in papillary thyroid carcinoma: comparative analysis with three DNA-based assays.

BACKGROUND: The aim of this study was to compare the detection of BRAF(V600E) by immunohistochemistry (IHC) using a mutation-specific antibody with molecular biology methods for evaluation of papillary thyroid carcinoma (PTC) patients. PATIENTS AND METHODS: This study concerned 198 consecutive conventional PTC patients, of which the majority were women (133/198; 67%), with a mean age of 56 years (range 19-79 years). BRAF mutation analysis was performed using DNA-based (direct sequencing, pyrosequencing, and SNaPshot) and IHC (VE1 antibody) methods. The sensitivity and specificity of IHC for BRAF(V600E) was compared with the molecular biology data. RESULTS: A BRAF mutational result was obtained in 194 cases. A BRAF(V600E) mutation was detected in 153/194 (79%) cases of PTC when using at least one molecular method, and in 151/194 (78%) cases with IHC. No false positive results were noted using IHC to detect the BRAF(V600E) mutation. Besides this mutation, other rare BRAF mutations (BRAF(V600K) and BRAF(K601E)), used as negative controls, were consistently negative with IHC. The sensitivity and specificity of IHC for the detection of this mutation were 98.7% and 100% respectively. The IHC test demonstrated excellent performance at a level equivalent to two DNA-based counterparts (pyrosequencing and SNaPshot). Failure to achieve a result was more frequent with the direct sequencing method than with the three other methods. CONCLUSION: IHC using the VE1 antibody is a specific and sensitive method for the detection of the BRAF(V600E) mutation in PTC. IHC may be an alternative to molecular biology approaches for the routine detection of this mutation in PTC patients.

Long-term quality of life and its predictive factors after oncologic surgery and microvascular reconstruction in patients with oral or oropharyngeal cancer.

The aims of this study were to evaluate long-term quality of life (QoL) and to determine its predictive factors after oncologic surgery and free flap reconstruction in patients with oral or oropharyngeal cancer. Patients treated at our institution between 2000 and 2009, who are alive and disease-free at least 1 year after therapy, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module. Eighty patients were included in our study. Global QoL score was 69.3 ± 22.7%. Global QoL and general symptoms were correlated with T stage, whereas head and neck symptoms were correlated with T stage and tumor involvement of the tongue base. Emotional and social functioning scales, and resumption of professional activity were significantly associated with global QoL. In conclusion, T stage, tumor involvement of the tongue base, professional status and emotional and social functions were the main determinants of QoL in our study.

In papillary thyroid carcinoma, TIMP-1 expression correlates with BRAF (V600E) mutation status and together with hypoxia-related proteins predicts aggressive behavior.

BRAF (V600E) causes upregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1), which promotes cell invasion in papillary thyroid carcinoma (PTC). Hypoxia-inducible factor-1α (HIF- α) is regulated by hypoxia and also by the BRAF-mediated signaling pathway in PTC. We assessed the association of expression of TIMP-1, HIF-1α, and hypoxia-inducible carbonic anhydrase IX (CAIX) and XII (CAXII) with clinical parameters in PTC. TPC-1/BRAF (WT) wild-type and BcPAP/BRAF (V600E) -mutated PTC cell lines were selected to study the effects of the BRAF (V600E) mutation and hypoxia on expression in vitro of TIMP-1, CAIX, and CAXII proteins by immunoblotting. Higher expression of all proteins was detected in BcPAP cells exposed to hypoxia. Tissue microarray immunohistochemistry analysis was performed to study protein expression in 114 BRAF-genotyped PTC samples. Expression data on tumor tissue were compared with clinicopathological variables. TIMP-1 expression had a sensitivity of 87 % and a specificity of 83 % in identifying a BRAF mutation (P < 0.001) and was associated with pT stage (P = 0.001), pN stage (P = 0.02), and multifocality (P = 0.03). HIF-1α expression correlated with pT stage (P = 0.05). CAIX expression was associated with pN stage (P = 0.02), and both CAIX (P = 0.004) and CAXII (P = 0.05) were strongly associated with vascular invasion. We conclude that TIMP-1 protein expression is a reliable surrogate marker for BRAF-mutated status in PTC. TIMP-1 and hypoxia-regulated proteins are promising as predictors of aggressiveness in PTC and warrant further investigation as new therapeutic targets for the treatment of highly aggressive forms of PTC.