Public Perceptions of Neurotechnologies Used to Target Mood, Memory, and Motor Symptoms.

Background: Advances in the development of neurotechnologies have the potential to revolutionize treatment of brain-based conditions. However, a critical concern revolves around the willingness of the public to embrace these technologies, especially considering the tumultuous histories of certain neurosurgical interventions. Therefore, examining public attitudes is paramount to uncovering potential barriers to adoption ensuring ethically sound innovation. Methods: In the present study, we investigate public attitudes towards the use of four neurotechnologies (within-subjects conditions): deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), pills, and MRI-guided focused ultrasound (MRgFUS) as potential treatments to a person experiencing either mood, memory, or motor symptoms (between-subjects conditions). US-based participants (N=1052; stratified to be nationally representative based on sex, race, age) were asked about their perceptions of risk, benefit, invasiveness, acceptability, perceived change to the person, and personal interest in using these neurotechnologies for symptom alleviation. Results: Descriptive results indicate variability between technologies that the U.S. public is willing to consider if experiencing severe mood, memory, or motor symptoms. The main effect of neurotechnology revealed DBS was viewed as the most invasive and risky treatment and was perceived to lead to the greatest change to who someone is as a person. DBS was also viewed as least likely to be personally used and least acceptable for use by others. When examining the main effects of symptomatology, we found that all forms of neuromodulation were perceived as significantly more beneficial, acceptable, and likely to be used by participants for motor symptoms, followed by memory symptoms, and lastly mood symptoms. Neuromodulation (averaging across neurotechnologies) was perceived as significantly riskier, more invasive, and leading to a greater change to person for mood versus motor symptoms; however, memory and motor symptoms were perceived similarly with respect to risk, invasiveness, and change to person. Conclusion: These results suggest that the public views neuromodulatory approaches that require surgery (i.e., DBS and MRgFUS) as riskier, more invasive, and less acceptable than those that do not. Further, findings suggest individuals may be more reluctant to alter or treat psychological symptoms with neuromodulation compared to physical symptoms.

Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens.

Cyclic nucleotide binding domains (CNB) confer allosteric regulation by cAMP or cGMP to many signaling proteins, including PKA and PKG. PKA of phylogenetically distant Trypanosoma is the first exception as it is cyclic nucleotide-independent and responsive to nucleoside analogues (Bachmaier et al., 2019). Here, we show that natural nucleosides inosine, guanosine and adenosine are nanomolar affinity CNB ligands and activators of PKA orthologs of the important tropical pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania. The sequence and structural determinants of binding affinity, -specificity and kinase activation of PKAR were established by structure-activity relationship (SAR) analysis, co-crystal structures and mutagenesis. Substitution of two to three amino acids in the binding sites is sufficient for conversion of CNB domains from nucleoside to cyclic nucleotide specificity. In addition, a trypanosomatid-specific C-terminal helix (αD) is required for high affinity binding to CNB-B. The αD helix functions as a lid of the binding site that shields ligands from solvent. Selectivity of guanosine for CNB-B and of adenosine for CNB-A results in synergistic kinase activation at low nanomolar concentration. PKA pulldown from rapid lysis establishes guanosine as the predominant ligand in vivo in T. brucei bloodstream forms, whereas guanosine and adenosine seem to synergize in the procyclic developmental stage in the insect vector. We discuss the versatile use of CNB domains in evolution and recruitment of PKA for novel nucleoside-mediated signaling.

High Persistence of Novel Polyfluoroalkyl Betaines in Aerobic Soils.

Some contemporary aqueous film-forming foams (AFFFs) contain n:3 and n:1:2 fluorotelomer betaines (FTBs), which are often detected at sites impacted by AFFFs. As new chemical replacements, little is known about their environmental fate. For the first time, we investigated the biotransformation potential of 5:3 and 5:1:2 FTBs and a commercial AFFF that mainly contains n:3 and n:1:2 FTBs (n = 5, 7, 9, 11, and 13). Although some polyfluoroalkyl compounds are precursors to perfluoroalkyl acids, 5:3 and 5:1:2 FTBs exhibited high persistence, with no significant changes even after 120 days of incubation. While the degradation of 5:3 FTB into suspected products such as fluorotelomer acids or perfluoroalkyl carboxylic acids (PFCAs) could not be conclusively confirmed, we did identify a potential biotransformation product, 5:3 fluorotelomer methylamine. Similarly, 5:1:2 FTB did not break down or produce short-chain hydrogen-substituted polyfluoroalkyl acids (n:2 H-FTCA), hydrogen-substituted PFCA (2H-PFCA), or any other products. Incubating the AFFF in four soils with differing properties and microbial communities resulted in 0.023-0.25 mol % PFCAs by day 120. Most of the products are believed to be derived from n:2 fluorotelomers, minor components of the AFFF. Therefore, the findings of the study cannot be fully explained by the current understanding of structure-biodegradability relationships.

Suspect screening of pharmaceuticals, illicit drugs, pesticides, and other emerging contaminants in Argentinean Piaractus mesopotamicus, a fish species used for local consumption and export.

The widespread distribution of contaminants of emerging concern (CECs) is a major concern due to their potential effects on human health and the environment. The insufficient sewage treatment plant infrastructures is a global problem most accentuated in less developed countries and results in the discharge of CECs to water bodies. Pacu (Piaractus mesopotamicus) is a ray-finned freshwater fish species native to the Paraná basin. It is also the most produced aquaculture fish species in Argentina since 2012. Though uninvestigated to date, the occurrence of CECs in pacu may be of high relevance due to production volumes and relevance to human exposure through fish consumption. In this study, we applied a high-resolution mass spectrometry screening method to qualitatively analyze over 100 CECs in pacu. Four extraction/cleanup methods were tested on pooled pacu fillet, including solid-phase extraction and QuEChERS. The method that produced the highest number of detections was selected for further analysis of pacu purchased in supermarkets and fish markets in Argentina between 2017 and 2020. Residues of pesticides, antibiotics, pharmaceuticals, personal care products, plasticizers, sweeteners, drug metabolites, stimulants, and illegal drugs were detected in the samples. A total of 38 CECs were detected, ranging between 24 and 35 CECs per individual sample. 100% of the samples had positive detections of caffeine, 1,7-dimethylxanthine, xanthine, benzoylecgonine, methylparaben, ethylparaben, bis(2-ethylhexyl) phthalate (DEHP), metolachlor, carbendazim, salicylic acid, 2,4-D, saccharin, cyclamate, and dodecanedioic acid. Mappings generated with correspondence analysis were used to explore similarities/dissimilarities among the detected compounds. To our knowledge this is the first report of saccharin, cyclamate, 2,4 - D, carbendazim, metolachlor, ethylparaben, propylparben, bisphenol A, DEHP, and benzotriazole in fish from Argentina, and the first report on the presence of lisinopril, metropolol acid and dodecanedioic acid in fish worldwide.

Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET.

Pulsed electron-electron double resonance spectroscopy (PELDOR/DEER) and single-molecule Förster resonance energy transfer spectroscopy (smFRET) are frequently used to determine conformational changes, structural heterogeneity, and inter probe distances in biological macromolecules. They provide qualitative information that facilitates mechanistic understanding of biochemical processes and quantitative data for structural modelling. To provide a comprehensive comparison of the accuracy of PELDOR/DEER and smFRET, we use a library of double cysteine variants of four proteins that undergo large-scale conformational changes upon ligand binding. With either method, we use established standard experimental protocols and data analysis routines to determine inter-probe distances in the presence and absence of ligands. The results are compared to distance predictions from structural models. Despite an overall satisfying and similar distance accuracy, some inconsistencies are identified, which we attribute to the use of cryoprotectants for PELDOR/DEER and label-protein interactions for smFRET. This large-scale cross-validation of PELDOR/DEER and smFRET highlights the strengths, weaknesses, and synergies of these two important and complementary tools in integrative structural biology.

Fast screening of saxitoxin, neosaxitoxin, and decarbamoyl analogues in fresh and brackish surface waters by on-line enrichment coupled to HILIC-HRMS.

The proliferation of harmful cyanobacterial algal blooms is of concern due to the associated release of toxins affecting ecosystems and human health. The paralytic shellfish poison saxitoxin (STX) is a small polar alkaloid that can occur in inland and marine aquatic environments. Here, we optimized a fast and sensitive analytical method for the determination of STX, neosaxitoxin (NeoSTX), and their decarbamoyl analogues in surface waters. The method involves a simple filtration, addition of isotope-labelled internal standard (ILIS), and analysis by on-line solid-phase extraction coupled to hydrophilic interaction liquid chromatography high-resolution mass spectrometry (on-line SPE-HILIC-HRMS). Except glass fiber filters, other tested materials (e.g., nylon, nitrocellulose) provided suitable filtration performance. Time-dependent adsorptive losses occurred during the LC-MS batch sequence if glass autosampler vials were used, while no such effect was observed for polypropylene autosampler vials. Matrix effects were evaluated for 4 different quantification scenarios, including external vs. internal curves and neat reagent water vs. matrix-matched curves. Matrix-matched calibration with ILIS correction (NeoSTX-15N7) provided the best performance overall. The analytical method was validated in freshwater lake water and estuarine brackish water (30‰ salinity), with suitable determination coefficients (R2 > 0.9975), matrix spike accuracy (90-107%), and intraday/interday precision (RSD of 0.61-16%). Method limits of detection (LOD in lake water: 0.72-3.9 ng/L) are also improved over most of the recent literature. The method was applied to a set of 302 surface water samples collected in Canada, France, and the United Kingdom, and positive detections were reported for STX (max: 98 ng/L), decarbamoyl-STX (max: 15 ng/L), and NeoSTX (max: 87 ng/L).

A framework for the analysis of polar anticancer drugs in wastewater: On-line extraction coupled to HILIC or reverse phase LC-MS/MS.

With the consumption of chemotherapy agents, residues of anticancer drugs may be increasingly found in hospital and municipal wastewaters. Quantification of these highly polar micropollutants remains challenging due to poor chromatographic retention on typical reversed phases. This study investigated different solid-phase extraction (SPE) materials for automated on-line preconcentration of complex matrices (hospital and municipal wastewaters) and various chromatographic column options. A hyper crosslinked hydroxylated polystyrene-divinylbenzene copolymer SPE sorbent coupled on-line with hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) yielded suitable limits of detection (LOD: 1-2 ng L-1) for 5-fluorouracil (5-FU) and 2',2'-difluorodeoxyuridine (dFdU). Optimization of chromatographic conditions led to a single LC-MS/MS method for the analysis of other cytostatic drugs including cytarabine (CYT), gemcitabine (GEM), methotrexate (MTX), ifosfamide (IFO), cyclophosphamide (CYC) and capecitabine (CAP). The filter membrane for sample pre-treatment, HPLC mobile phase additives, and on-line SPE loading parameters were also investigated. The methods were validated in wastewater matrix with suitable determination coefficients (R2 range: 0.9982-0.9999), LODs (0.5-5 ng L-1), accuracy (78-111%), intraday precision (2.6-12%), and interday precision (2.1-13%). The occurrence of cytostatic drugs was examined in field-collected water samples from hospital effluents and municipal wastewater treatment plants (WWTP) in Canada. CAP (3.7-64 ng L-1), dFdU (6.1-300 ng L-1), and MTX (1.8-68 ng L-1) were frequently detected across both matrix types, while IFO was detected in hospital wastewater (23-140 ng L-1) but not in municipal WWTPs.

Improved extraction of multiclass cyanotoxins from soil and sensitive quantification with on-line purification liquid chromatography tandem mass spectrometry.

Cyanotoxins are associated with harmful cyanobacterial blooms, but also exist in biological soil crusts and soils irrigated with cyanobacteria-contaminated water. To achieve an accurate analysis of cyanotoxins in soil, effective extraction, purification and determination methods are imperative. The most challenging aspect is extracting cyanotoxins from soil, due to their tendency to bind strongly to the soil matrix. We used a methanol-ammonium acetate solution to efficiently extract 17 cyanotoxins (microcystins, cylindrospermopsin, anatoxins, anabaenopeptins and cyanopeptolin) from soil. The extract was purified by on-line solid-phase extraction coupled with ultra-high-performance liquid chromatography tandem mass spectrometry. The optimized procedure involved two ultrasonication cycles of 15 min with 4 mL of methanol + 200 mM ammonium acetate, which recovered 60% to >90% of the added cyanotoxins from five soils with diverse organic matter, pH and texture. The method improved extraction by up to 10 times compared to a methanol/water solution. Linearity, accuracy and precision were validated on matrix-mixed soil with surrogate microcystin and cylindrospermopsin internal standards. Limits of detection were 0.001-0.3 ng g-1, depending on the cyanotoxins. The method was used to analyze cyanotoxins in 25 field-collected soils from Quebec, Canada. Out of the 25 soil samples, 11 soils had at least one cyanotoxin, and up to 8 different cyanotoxins were detected in one soil. The sum of all microcystins congeners was from 0.02 to 31 ng microcystins g-1 soil. We also detected anabaenopeptin, the first reported occurrence of this cyanotoxin in soil.

Widespread occurrence and spatial distribution of glyphosate, atrazine, and neonicotinoids pesticides in the St. Lawrence and tributary rivers.

The occurrence and spatial distribution of selected pesticides were investigated along a 200-km reach of the St. Lawrence River (SLR) and tributaries in Quebec, Canada. Surface water samples (n = 68) were collected in the summer 2017 and analyzed for glyphosate, atrazine (ATZ), 8 systemic insecticides (acetamiprid, clothianidin, dinotefuran, fipronil, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam) and some metabolites. Overall, 99% of the surface water samples were positive to at least one of the targeted pesticides. The most recurrent compounds were glyphosate (detection frequency: 84%), ATZ (82%), thiamethoxam (59%), desethylatrazine (DEA: 47%), and clothianidin (46%). Glyphosate displayed variable levels (4-3,000 ng L-1), with higher concentrations in south tributaries (e.g., Nicolet and Yamaska). In positive samples, the sum of ATZ and DEA varied between 5 and 860 ng L-1, and the sum of 6 priority neonicotinoids between 1.5 and 115 ng L-1. From Repentigny to the Sorel Islands, the spatial distribution of pesticides within the St. Lawrence River was governed by the different upstream sources (i.e., Great Lakes vs. Ottawa River) due to the limited mixing of the different water masses. Cross-sectional patterns revealed higher concentrations of glyphosate and neonicotinoids in the north portions of transects, while the middle and south portions showed higher levels of atrazine. In Lake St. Pierre and further downstream, cross-sections revealed higher levels of the targeted pesticides near the southern portions of the SLR. This may be due to the higher contributions from south shore tributaries impacted by major agricultural areas, compared to north shore tributaries with forest land and less cropland use. Surface water samples were compliant with guidelines for the protection of aquatic life (chronic effects) for glyphosate and atrazine. However, 31% of the samples were found to surpass the guideline value of 8.3 ng L-1 for the sum of six priority neonicotinoids.

Transformation of novel polyfluoroalkyl substances (PFASs) as co-contaminants during biopile remediation of petroleum hydrocarbons.

Aqueous film forming foams (AFFFs) containing perfluoroalkyl and polyfluoroalkyl substances (PFASs) are commonly deployed to extinguish hydrocarbon fuel fires, resulting in petroleum hydrocarbons coexisting with PFASs in contaminated soil. Nutrient-amended and aerated biopiles used for petroleum hydrocarbon bioremediation could cause unintended transformation of polyfluorinated substances into perfluoroalkyl carboxylates (PFCAs). The study sought to examine environmental behaviors of PFASs in engineered treatment facilities by monitoring AFFF-derived PFASs under three nutrient conditions. The influence of nutrient levels on degradation kinetics and efficiency was found to vary between the two chemical classes and among individual PFASs. A high number of compounds including the zwitterionic polyfluoroalkyl betaines that have aged in the field for two years were continuously biotransforming in lab reactors, demonstrating their slow kinetics and environmental persistence. The low yield to PFCAs implies that the processes such as the formation of bound residues or irreversible sorption might play a major role in reducing detectable levels of zwitterionic PFASs. The high persistence of betaines was further confirmed by the behaviors of a freshly spiked sulfonamide betaine. The study demonstrated complex chemical dynamics in AFFF-impacted soils and the challenges for predicting the fate of PFASs in soil biopiling facilities.

Degradation and defluorination of 6:2 fluorotelomer sulfonamidoalkyl betaine and 6:2 fluorotelomer sulfonate by Gordonia sp. strain NB4-1Y under sulfur-limiting conditions.

6:2 fluorotelomer sulfonamidoalkyl betaine (6:2 FTAB) is a major component of aqueous film-forming foams (AFFFs) used for firefighting and is frequently detected, along with one of its suspected transformation products, 6:2 fluorotelomer sulfonate (6:2 FTSA), in terrestrial and aquatic ecosystems impacted by AFFF usage. Biochemical processes underlying bacterial biodegradation of these compounds remain poorly understood due to a lack of pure culture studies. Here, we characterized the water-soluble and volatile breakdown products of 6:2 FTSA and 6:2 FTAB produced using Gordonia sp. strain NB4-1Y cultures over seven days under sulfur-limited conditions. After 168 h, 99.9% of 60 µM 6:2 FTSA was degraded into ten major breakdown products, with a mol% recovery of 88.2, while 70.4% of 60 µM 6:2 FTAB was degraded into ten major breakdown products, with a mol% recovery of 84.7. NB4-1Y uses two pathways for 6:2 FTSA metabolism, with 55 mol% of breakdown products assigned to a major pathway and <1.0 mol% assigned to a minor pathway. This work indicates that rapid transformation of 6:2 FTSA and 6:2 FTAB can be achieved under controlled conditions and improves the bacterial metabolism of these compounds.

Xanthogranulomatous Prostatitis, a Rare Prostatic Entity.

There are several benign prostatic pathologies that can clinically mimic a prostate adenocarcinoma. Xanthogranulomatous prostatitis is a benign inflammatory condition of the prostate and a rare entity. A 47-year old male, with 3 years of lower urinary tract symptoms, with a palpable hypogastric tumor, digital rectal examination: solid prostate, of approximately 60 g. Initial PSA was 0.90 ng/mL. He underwent surgical excision of the lower abdominal nodule and prostatectomy. Histopathology showed xanthogranulomatous prostatitis, without malignancy. Xanthogranulomatous prostatitis is an extremely rare entity that can simulate prostate adenocarcinoma, therefore having a correct histopathological diagnosis is essential.

MYRIAD AFTER MYRIAD: THE PROPRIETARY DATA DILEMMA.

Myriad Genetics' long-time monopoly on BRCA gene testing was significantly narrowed by the Supreme Court's decision in AMP v. Myriad Genetics, Inc., and will be further narrowed in the next few years as many of its still-valid patents expire. But these developments have not caused the company to acquiesce in competition. Instead, it has launched a litigation offensive against a number of actual and potential competitors, suing them for infringement of numerous unexpired patents that survived the Supreme Court case. A parallel strategy may have even greater long-term significance, however. In announcing expanded operations in Europe, Myriad has emphasized that it will rely less on patents and more on its huge proprietary database of genetic mutations and associated health outcomes-a strategy that could be used in the United States as well. Myriad has built that database over its many years as a patent-based monopolist in the BRCA testing field, and has not shared it with the medical community for more than a decade. Consequently, Myriad has a unique ability to interpret the health significance of patients' genetic mutations, particularly in the case of rare "variants of unknown significance." This article reviews the current state of Myriad's patent portfolio, describes its ongoing litigation offensive, and then analyzes its proprietary database strategy. The article argues that Myriad's strategy, while legally feasible, undercuts important values and objectives in medical research and health policy. The article identifies several ways in which the research and health care communities might fight back, but acknowledges that it will be a difficult uphill fight.

Active vs. reactive threat responding is associated with differential c-Fos expression in specific regions of amygdala and prefrontal cortex.

Active avoidance (AA) is an important paradigm for studying mechanisms of aversive instrumental learning, pathological anxiety, and active coping. Unfortunately, AA neurocircuits are poorly understood, partly because behavior is highly variable and reflects a competition between Pavlovian reactions and instrumental actions. Here we exploited the behavioral differences between good and poor avoiders to elucidate the AA neurocircuit. Rats received Sidman AA training and expression of the activity-dependent immediate-early gene c-fos was measured after a shock-free AA test. Six brain regions with known or putative roles in AA were evaluated: amygdala, periaqueductal gray, nucleus accumbens, dorsal striatum, prefrontal cortex (PFC), and hippocampus. Good avoiders showed little Pavlovian freezing and high AA rates at test, the opposite of poor avoiders. Although c-Fos activation was observed throughout the brain, differential activation was found only in subregions of amygdala and PFC. Interestingly, c-Fos correlated with avoidance and freezing in only five of 20 distinct areas evaluated: lateral amygdala, central amygdala, medial amygdala, basal amygdala, and infralimbic PFC. Thus, activity in specific amygdala-PFC circuits likely mediates the competition between instrumental actions and Pavlovian reactions after AA training. Individual differences in AA behavior, long considered a nuisance by researchers, may be the key to elucidating the AA neurocircuit and understanding pathological response profiles.

[Value of (99m)Tc tetrofosmin scan in well-differentiated thyroid cancer].

BACKGROUND: Patients with cold thyroid nodules without ultrasound malignant suspicion and with benign/undetermined cytology may be subjected to follow-up surveillance. 99mTc-tetrofosmin scan (99mTc-TS) may identify patients where this observation can be performed with more certainty. Absence of uptake never occurs in carcinoma patients. Our objective was to determine the 99mTc-TS negative predictive value (NPV) in patients with cold thyroid nodules. METHODS: An evaluation with 99mTc-TS was conducted prior to surgery in patients with thyroid gland tumor who were candidates for surgery. All patients underwent thyroidectomy according to histology; NPV and test sensitivity were evaluated when compared with the histopathological result. Then, 296-370 MBq (8-10 mCi) of 99mTc-tetrofosmin was administered, and scan images were evaluated after 120 min. Scan result was reported as a) with increased metabolic activity (IMA) or b) without increased metabolic activity (WIMA). RESULTS: Included in the study were 86 consecutive patients. In 60 patients the scan showed IMA, 20/60 (33%) with carcinoma, 67% with benign nodule. In 26 (30.2%) the scan was WIMA. In this group, 3/26 (11.5%) had carcinoma and (88.4%) had a benign neoplasia. Sensitivity = 91.43 (95% CI = 80.73-100), specificity = 45.10 (95% CI = 30.46-59.73), positive predictive value = 53.33 (95% CI = 39.8-66.79) and NPV = 88.46 (95% CI 74.26-100). Negative probability ratio = 0.19. CONCLUSIONS: IMA-99mTc-TS is less specific in thyroid cancer; nevertheless, in WIMA patients the possibility of carcinoma is 13%. Most patients (70%) showed IMA, 33% with carcinoma. WIMA-NPV = 30%. 99mTc-TS may be useful in the therapeutic decision of patients with thyroid nodule with concerns about surgery. Its usefulness lies in the NPV.

Valor de la gammagrafía con Tc-99m-tetrofosmín en el diagnóstico del cáncer bien diferenciado de tiroides / Value of (99m)Tc tetrofosmin scan in well-differentiated thyroid cancer

Introducción: Los pacientes con nódulos tiroideos hipocaptantes sin sospecha ultrasonográfica y con citología benigna o indeterminada pueden ser vigilados. El gammagrama con Tc- 99m-tetrofosmín (Tc-99m-TS) identifica pacientes en los que la vigilancia es más segura. La ausencia de captación nunca ocurre en pacientes con carcinoma. El objetivo de este estudio fue conocer el valor predictivo negativo del Tc-99m-TS en pacientes con nódulo tiroideo. Material y métodos: Evaluación preoperatoria con Tc-99m-TS de pacientes con nódulo tiroideo candidatos a cirugía. Tiroidectomía de acuerdo con el diagnóstico en todos. Evaluación de valor predictivo negativo y sensibilidad al comparar con el resultado histopatológico. Se administraron 296-370 MBq (8-10 mCi) de Tc-99m-TS; evaluación de imágenes a los 120 minutos. Resultado reportado con actividad metabólica aumentada (AMA) o sin actividad metabólica aumentada (SAMA). Resultados: Se incluyeron 86 pacientes consecutivos. Sesenta (69.7 %) tuvieron AMA, 20/60 con carcinoma (33 %), en 67 % el diagnóstico fue de nódulo benigno. En 26 (30.2 %) SAMA, 11.5 % tuvo carcinoma y 88.4 % neoplasia benigna. Sensibilidad de 91.43 % (IC 95 % = 80.73-100 %), especificidad de 45.10 % (IC 95 % = 30.46-59.73), valor predictivo positivo de 53.33 % (IC 95 % = 39.8-66.79), valor predictivo negativo de 88.46 % (IC 95 % = 74.26-100). Razón de verosimilitud negativa = 0.19. Conclusiones: Tc-99m-TS con AMA es poco específico en cáncer tiroideo; en pacientes SAMA 13 % tiene carcinoma. La mayoría de los pacientes (70 %) mostró AMA, 33 % con carcinoma. Valor predictivo negativo en grupo SAMA = 88 %. Tc-99m-TS podría ser útil en la decisión terapéutica de pacientes con nódulo tiroideo en los que existe duda de cirugía; su utilidad radica en el valor predictivo negativo.

BACKGROUND: Patients with cold thyroid nodules without ultrasound malignant suspicion and with benign/undetermined cytology may be subjected to follow-up surveillance. 99mTc-tetrofosmin scan (99mTc-TS) may identify patients where this observation can be performed with more certainty. Absence of uptake never occurs in carcinoma patients. Our objective was to determine the 99mTc-TS negative predictive value (NPV) in patients with cold thyroid nodules. METHODS: An evaluation with 99mTc-TS was conducted prior to surgery in patients with thyroid gland tumor who were candidates for surgery. All patients underwent thyroidectomy according to histology; NPV and test sensitivity were evaluated when compared with the histopathological result. Then, 296-370 MBq (8-10 mCi) of 99mTc-tetrofosmin was administered, and scan images were evaluated after 120 min. Scan result was reported as a) with increased metabolic activity (IMA) or b) without increased metabolic activity (WIMA). RESULTS: Included in the study were 86 consecutive patients. In 60 patients the scan showed IMA, 20/60 (33%) with carcinoma, 67% with benign nodule. In 26 (30.2%) the scan was WIMA. In this group, 3/26 (11.5%) had carcinoma and (88.4%) had a benign neoplasia. Sensitivity = 91.43 (95% CI = 80.73-100), specificity = 45.10 (95% CI = 30.46-59.73), positive predictive value = 53.33 (95% CI = 39.8-66.79) and NPV = 88.46 (95% CI 74.26-100). Negative probability ratio = 0.19. CONCLUSIONS: IMA-99mTc-TS is less specific in thyroid cancer; nevertheless, in WIMA patients the possibility of carcinoma is 13%. Most patients (70%) showed IMA, 33% with carcinoma. WIMA-NPV = 30%. 99mTc-TS may be useful in the therapeutic decision of patients with thyroid nodule with concerns about surgery. Its usefulness lies in the NPV.

[Partial pharyngolaryngectomies for treatment of pharyngolaryngeal cancer]. / Faringo-laringectomías parciales para el tratamiento del cáncer faringolaríngeo.

BACKGROUND: We undertook this study to evaluate the results obtained with conservation therapy of the larynx in patients with laryngopharyngeal epidermoid carcinoma. METHODS: Patients with stages I and II epidermoid cancer of the larynx and pharynx were included. All patients were evaluated endoscopically, functionally, and with cervical tomography. Results of the procedures were evaluated on the basis of oncological control and laryngeal function (voice, swallowing and ventilation). RESULTS: There were 41 male patients with a median age of 55 years. In 32 patients, surgery was the initial treatment and in nine patients as rescue treatment after radiotherapy. In 58.5% the location was glottic, in 22% supraglottic, in 12% glotto-supraglottic and in 7% vallecular and hypopharynx. Subtotal laryngectomy was performed with cricohyoidepiglottopexy in 18 patients, frontolateral in 11, supraglottic in 5, subglottic-epiglottectomy in 3, hemipharyngolaryngectomy in 3, and in one hemiglottectomy. The time until decannulation and removal of nasogastric catheter depended on the type of surgery. One patient (2%) had to be subjected to a rescue laryngectomy due to constant aspiration. This patient demonstrated residual tumor in the sample. Nine patients had some type of complication, the most frequent being wound infection (7.3%). One patient died postoperatively due to sepsis (2.4%), and another patient died due to systemic causes 4 months after the intervention. Median follow-up time is 25 months and no patient has presented tumor recurrence. CONCLUSIONS: Voice conservation surgery is an alternative to mutilation of the larynx in patients with locally advanced neoplasms of the larynx with a high risk of recurrence if treated with radiotherapy.

Faringo-laringectomías parciales para el tratamiento del cáncer faringolaríngeo / Partial pharyngolaryngectomies for treatment of pharyngolaryngeal cancer

BACKGROUND: We undertook this study to evaluate the results obtained with conservation therapy of the larynx in patients with laryngopharyngeal epidermoid carcinoma. METHODS: Patients with stages I and II epidermoid cancer of the larynx and pharynx were included. All patients were evaluated endoscopically, functionally, and with cervical tomography. Results of the procedures were evaluated on the basis of oncological control and laryngeal function (voice, swallowing and ventilation). RESULTS: There were 41 male patients with a median age of 55 years. In 32 patients, surgery was the initial treatment and in nine patients as rescue treatment after radiotherapy. In 58.5% the location was glottic, in 22% supraglottic, in 12% glotto-supraglottic and in 7% vallecular and hypopharynx. Subtotal laryngectomy was performed with cricohyoidepiglottopexy in 18 patients, frontolateral in 11, supraglottic in 5, subglottic-epiglottectomy in 3, hemipharyngolaryngectomy in 3, and in one hemiglottectomy. The time until decannulation and removal of nasogastric catheter depended on the type of surgery. One patient (2%) had to be subjected to a rescue laryngectomy due to constant aspiration. This patient demonstrated residual tumor in the sample. Nine patients had some type of complication, the most frequent being wound infection (7.3%). One patient died postoperatively due to sepsis (2.4%), and another patient died due to systemic causes 4 months after the intervention. Median follow-up time is 25 months and no patient has presented tumor recurrence. CONCLUSIONS: Voice conservation surgery is an alternative to mutilation of the larynx in patients with locally advanced neoplasms of the larynx with a high risk of recurrence if treated with radiotherapy.

[Human papillomavirus: association with head and neck cancer]. / Virus del papiloma humano asociado a cáncer de cabeza y cuello.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. In 2005, 400,000 cases of HNSCC were diagnosed worldwide. The most frequently affected site is the oral cavity. Alcohol/tobacco consumption is the most important risk factor for this neoplasia; nevertheless, since 1983 it has been suggested that human papilloma viruses (HPV) have a role in HNSCC, mainly in the oropharynx (level 1 evidence). We undertook this study to determine HPV prevalence and types in patients with HNSCC. METHODS: Presence of HPV was determined by polymerase chain reaction and staged by in situ hybridization. We analyzed stage, tumor site of origin, sexual practices, and alcohol/tobacco consumption. Fisher's exact test and Student's t-test were used for statistical analysis. We performed a multiple regression analysis for adjustment of variables. RESULTS: There were 118 patients were HPV positive and oropharyngeal and laryngeal cancer patients were the most frequently affected (55% and 50%, respectively). HPV-16 was most frequently isolated (70%). Laryngeal cancer patients suffered the highest ratio of HPV-16 infection (68.7%). Factors associated with HPV (univariate analysis) were age >50 years, tobacco/alcohol consumption and male gender. In multivariate analysis, none of the variables showed importance (p >0.5); HPV infection was more frequent in patients with history of alcohol/tobacco consumption (p = 0.6). CONCLUSIONS: There was HPV presence in 42% of HNSCC patients, HPV-16 in 70%, with the oropharynx and larynx being the most affected sites. No variables are associated with the virus presence. HPV is a co-factor in HNSCC etiology.

The number of sentinel nodes identified as prognostic factor in oral epidermoid cancer.

In patients with oral cavity epidermoid cancer without palpable nodes, the standard cervical treatment is supraomohyoid dissection; nevertheless, lymphatic mapping with sentinel node (SN) biopsy has been useful and allows the identification of a group of patients where neck dissection may be prevented. The objective of this study was to examine which factors diagnose the possibility of metastasis in SN. A non-randomized prospective study was performed during a two year period and included patients with T1-2, N0 oral cavity cancer >4 mm thick, SN was identified by blue dye and Rhenium colloid. All patients underwent pre-operatory lymphogammagraphy and elective-selective neck dissection. Age, gender, tumor site, T, tumor thickness and number of sentinel nodes found were evaluated. In 48 patients, at least one sentinel node was found, 2 per patient on average. 10.4% showed drainage outside the supraomohyoid region, 13/48 had nodular metastasis, 4 with negative SN(8.3%). T, location, thickness and number of SN are related to non-SN metastasis. Identification of 3SN or more was related to the possibility of SN metastasis p=0 (RR 10.1, I. C. 95% 1.1 91.2). The combined technique (dye-colloid) offers a high index of success in the identification of SN in patients with oral cavity cancer, while lymphogammagraphy identifies patients with anatomically unexpected drainage. Patients with T1 less than 2cm, not located on the tongue with thickness <5 mm and more than 2 SN were less likely to have metastasis in non-sentinel nodes. The identification of at least 3 sentinel nodes decreases the possibility of identifying patients with hidden metastasis (p=0.04).