Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

High Levels of Heavy Metals detected in Feathers of an Avian Scavenger Warn of a High Pollution Risk in the Atacama Desert (Chile).

The Atacama Desert represents the highest levels of mining exploitation in Chile, which inexorably results in high levels of pollution. Raptors, and particularly scavengers, have shown their usefulness to evaluate exposure to environmental contaminants in polluted scenarios. In this study, we used primary feathers from a local avian scavenger, turkey vulture Cathartes aura, to evaluate the exposure to cadmium (Cd), lead (Pb), copper (Cu) and zinc (Zn) in two locations from the southern Atacama Desert (coastal and inland) and a third location from the bordering semiarid region, in northern Chile. All metals were detected in all analyzed samples (n = 54). Mean concentrations in Coastal Atacama were 0.68 ± 0.84 ppm for Cd; 1.97 ± 2.01 ppm for Pb; 59.11 ± 80.69 ppm for Cu; and 107.96 ± 51.00 ppm for Zn, while mean concentrations in Inland Atacama were 0.55 ± 0.42 ppm for Cd; 3.37 ± 2.61 ppm for Pb; 91.66 ± 77.74 ppm for Cu; and 214.03 ± 99.08 ppm for Zn. Mean concentrations in Coastal Coquimbo were 0.63 ± 0.69 ppm for Cd; 1.57 ± 0.92 ppm for Pb; 18.09 ± 6.12 ppm for Cu; and 149.37 ± 105.56 ppm for Zn. These differences could be explained by differences on abundance of mining settlements among areas. According to the literature, these values are very high for all metals, exceeding in some cases those values referred as responsible of health disorders in birds. We strongly recommend further research looking at potential adverse effects caused by heavy metal pollution on the health of human and wildlife populations in the southern Atacama Desert.

Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer.

Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results: A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions: Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation. ClinicalTrials.gov: NCT01091168.

Per- and polyfluoroalkyl substances in plasma and feathers of nestling birds of prey from northern Norway.

Plasma samples from nestlings of two top predators, White-tailed eagle (Haliaeetus albicilla) and Northern goshawk (Accipiter gentilis) from northern Norway were analysed for a wide range of per- and polyfluoroalkyl substances (PFASs). Body feathers from the White-tailed eagles were also analysed and significant associations between specific PFASs in blood plasma and body feathers were found (0.36

Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors.

The fibroblast growth factor receptor (FGFR) cascade plays crucial roles in tumor cell proliferation, angiogenesis, migration and survival. Accumulating evidence suggests that in some tumor types, FGFRs are bona fide oncogenes to which cancer cells are addicted. Because FGFR inhibition can reduce proliferation and induce cell death in a variety of in vitro and in vivo tumor models harboring FGFR aberrations, a growing number of research groups have selected FGFRs as targets for anticancer drug development. Multikinase FGFR/vascular endothelial growth factor receptor (VEGFR) inhibitors have shown promising activity in breast cancer patients with FGFR1 and/or FGF3 amplification. Early clinical trials with selective FGFR inhibitors, which may overcome the toxicity constraints raised by multitarget kinase inhibition, are recruiting patients with known FGFR(1-4) status based on genomic screens. Preliminary signs of antitumor activity have been demonstrated in some tumor types, including squamous cell lung carcinomas. Rational combination of targeted therapies is expected to further increase the efficacy of selective FGFR inhibitors. Herein, we discuss unsolved questions in the clinical development of these agents and suggest guidelines for management of hyperphosphatemia, a class-specific mechanism-based toxicity. In addition, we propose standardized definitions for FGFR1 and FGFR2 gene amplification based on in situ hybridization methods. Extended access to next-generation sequencing platforms will facilitate the identification of diseases in which somatic FGFR(1-4) mutations, amplifications and fusions are potentially driving cancer cell viability, further strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors.

[Adverse effects and complications of continuous intestinal infusion of levodopa-carbidopa in a cohort of patients with Parkinson's disease in a tertiary hospital]. / Efectos adversos y complicaciones de la infusión intestinal continua de levodopa-carbidopa en una cohorte de pacientes con enfermedad de Parkinson de un hospital terciario.

INTRODUCTION: Continuous intestinal infusion of levodopa/carbidopa is a second-line treatment indicated in advanced stages of Parkinson's disease (PD). For its implantation, a percutaneous endoscopic gastrostomy must be performed. OBJECTIVES: The main objective has been to describe the frequency and characteristics of the side effects associated with this treatment. As a secondary objective, we have analyzed the epidemiological and clinical characteristics of the PD patients who have received this treatment in our hospital. PATIENTS AND METHODS: Descriptive, single-center, retrospective study for a consecutive sample of PD patients treated with Continuous intestinal infusion of Levodopa/Carbidopa from the beginning of 2006 to the end of August 2021. RESULTS: 81 treatment planifications have been analyzed. Treatment success (duration greater than 12 months) was achieved in 78.1% (n = 50) of the patients in whom this follow-up period was available. The median duration of treatment was 35 months. 58.6% of the patients presented some type of complication. A total of 43 minor complications and 16 serious adverse events were reported. CONCLUSION: The constitution of an experienced multidisciplinary team is essential to guarantee the adequate management and follow-up of these patients.

TITLE: Efectos adversos y complicaciones de la infusión intestinal continua de levodopa-carbidopa en una cohorte de pacientes con enfermedad de Parkinson de un hospital terciario.Introducción. La infusión intestinal continua de levodopa/carbidopa (IICLC) es un tratamiento de segunda línea indicado en fases avanzadas de la enfermedad de Parkinson (EP). Para su implantación se debe realizar una gastrostomía endoscópica percutánea. Objetivos. El objetivo principal ha sido describir la frecuencia y las características de los efectos secundarios asociados a este tratamiento. Como objetivo secundario se han analizado las características epidemiológicas y clínicas de pacientes afectos de EP que han recibido o reciben tratamiento con IICLC. Pacientes y métodos. Estudio descriptivo, unicéntrico y retrospectivo para una muestra consecutiva de pacientes con EP tratados con IICLC desde principios de 2006 hasta finales de agosto de 2021. Resultados. Se han analizado 81 planificaciones. El éxito del tratamiento (duración mayor de 12 meses) se alcanzó en el 78,1% (n = 50) de los pacientes en los que se disponía de ese período de seguimiento. La duración media del tratamiento fue de 35 meses. El 58,6% de los pacientes presentó algún tipo de complicación. Se notificaron 43 complicaciones leves y 16 complicaciones graves. Conclusión. La constitución de un equipo multidisciplinar experimentado es fundamental para garantizar un manejo y seguimiento adecuado de estos pacientes.

Status of PI3K inhibition and biomarker development in cancer therapeutics.

The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival. The 'phosphate and tensin homologue deleted from chromosome 10' (PTEN) tumor suppressor gene plays a critical role as a negative regulator of this pathway. An array of genetic mutations and amplifications has been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to some classic cytotoxics and targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex machinations and interactions. This knowledge has enabled the evolution of rationally designed drugs targeting elements of this pathway. It is important that the development of suitable biomarkers continues in parallel to optimize use of these agents. A new generation of PI3K inhibitors is now entering early clinical trials, with much anticipation that they will add to the growing armamentarium of targeted cancer therapeutics.

Use of fully covered self-expanding metal stents for the management of benign biliary conditions.

BACKGROUND AND AIM: biliary self-expanding metal stents (SEMS) have the advantage of being inserted undeployed with very small sizes and provide, when fully opened, large diameters for biliary drainage. However, their use in benign conditions has been very limited, mainly because of difficulty in their extraction. We present our initial experience with a fully covered SEMS (Wallflex) for the management of benign problems of the bile duct. PATIENTS AND METHODS: in a prospective study, stents of 8 mm in diameter and 4, 6 or 8 cm long were inserted by means of ERCP. These SEMS were chosen when according to medical judgement it was thought that diameters greater than 10 French (3.3 mm) were needed for proper biliary drainage. Stents were extracted also endoscopically, several months later when deemed clinically appropriate. RESULTS: twenty biliary SEMS were inserted. Reasons for insertion were: large intrahepatic biliary fistula after hydatid cyst surgery (1), perforation of the papillary area following endoscopic sphincterotomy (2), coaxial insertion to achieve patency in obstructed uncovered stents inserted in benign conditions (3), benign strictures (7), multiple and large common bile duct stones that could not be extracted because of tapering and stricturing of the distal common bile duct (7). In all cases, successful biliary drainage was achieved and there were no complications from insertion. Stents were easily extracted after a mean time of 132 days (36-270) in place. Complete resolution of biliary problems was obtained in 14 patients (70%). CONCLUSIONS: in our initial experience, the fully covered Wallflex biliary stent was removed without any complication after being in place in the common bile duct for a mean time of over four months. Therefore, it could be used in the management of benign biliary conditions.

[Cellulitis after a cat bite]. / Celulitis tras mordedura de gato.

Animal bite wounds are common. Domestic companion animals inflict the majority of these wounds. The most important percentage of contagions are due to cat bites, and often by Pasteurella species. We present two cases of Pasteurella multocida infection after a cat bite.Thus, in this article we review the most relevant clinical features related with this aetiological agent and some aspects about antimicrobial susceptibility.

Long-term follow-up of patients with small-bowel angiodysplasia on capsule endoscopy. Determinants of a higher clinical impact and rebleeding rate.

BACKGROUND: the clinical impact of small-bowel angiodysplasia has not been defined. We present a prospective study to determine the features of individuals with a higher risk of rebleeding or a worse clinical outcome. PATIENTS AND METHODS: thirty patients with angiodysplasia found on CE were included and followed for 12 months. Angiodysplasia were classified by their size as small ( 10 mm). We also studied angiodysplasia lesion numbers in each patient. Rebleeding was defined as a hemoglobin drop of more than 2 g/dl in the absence of melena or hematochezia in the case of occult GI bleeding, or with any or both manifestations. RESULTS: a therapeutic procedure was carried out in 13 patients (43.4%). Individuals with large angiodysplasia had higher transfusion requirements, a higher proportion of therapeutic procedure performed after CE, lower hemoglobin concentration, and a lower rebleeding rate. Patients with ten or more angiodysplasia lesions had also higher transfusion requirements and lower hemoglobin levels, but we found no differences in the number of therapeutic procedures or rebleeding rate between both groups. On follow up rebleeding was detected in 5 patients (16.7%), all of them with small angiodysplasias. Rebleeding was more frequent in patients who did not receive further interventions (23.53 vs. 7.69%; p = 0.037). CONCLUSIONS: angiodysplasia size >or= 10 mm determines a worse clinical impact and more possibilities of receiving a therapeutic procedure. Our findings support that patients with large lesions would benefit from therapeutic interventions with a reduction in rebleeding rate.

[Palliative management of malignant gastric outlet obstruction with endoscopically inserted self-expanding metal stents].

AIM AND BACKGROUND: the insertion of self-expanding metal stents to palliate malignant gastric outlet obstruction is a minimally invasive procedure that is being increasingly used. We discuss experience with this technique in a level-II hospital in the Spanish National Health System. PATIENTS AND METHODS: a retrospective five-year study (2003-2007) was conducted in 23 patients who underwent 27 procedures aimed at resolving malignant gastric outlet obstruction (mean, 0.45 procedures per month) using endoscopically inserted noncovered stents (Wallstent and Wallflex). RESULTS: insertion was technically feasible in all 27 (100%) attempts, with satisfactory clinical results in 25 cases (92.5%). Endoscopy alone was used 10 times (37%), and both endoscopy and fluoroscopy on 17 (63%) occasions. After stent insertion, one patient was intervened for treatment, and a patient with an unsuccessful prosthesis received a palliative surgical bypass. Four stents became obstructed by tumoral ingrowth, and patency was reestablished by inserting a new stent. Obstructive jaundice caused by stents covering the papilla of Vater occurred in three cases. There were no other complications or mortality due to the procedure. Mean survival was 104 days (range 28-400, SD +/- 94). CONCLUSIONS: in our experience endoscopic insertion of self-expanding metal stents appears to be a safe and efficient palliative method for malignant gastric outlet obstruction, and can be performed successfully in a center with our characteristics.

Targeting FGFR pathway in breast cancer.

Developments in breast cancer biology over the last years have permitted deconstructing the molecular profile of the most relevant breast cancer subtypes. This has led to an increase in therapeutic options, including more effective personalized therapy for breast cancer and substantial improvements in patient outcomes. Although currently there are only a few targeted therapies approved for metastatic breast cancer, the discovery of druggable kinase gene alterations has radically changed cancer treatment by providing novel and successfully actionable drug targets. Fibroblast growth factors and their receptors (FGFRs) participate in different physiologic processes and also play an essential role in cancer cell proliferation, survival, differentiation, migration, and apoptosis. This article summarizes the main molecular alterations of FGFRs, as well as the available preclinical and clinical data with FGFR inhibitors in breast cancer, and discusses new opportunities for the clinical development of these agents in patients with breast cancer.

Outcomes of bile duct drainage by means of ERCP in geriatric patients / Resultados del drenaje de la vía biliar por CPRE en pacientes con edad geriátrica.

BACKGROUND AND OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) is usually the procedure of choice for relieving bile duct obstruction. a large number of patients undergoing this intervention are geriatric population (aged 75 years of age and older). Our aim was to assess the efficacy of ERCP in this group of patients as compared to younger ones. PATIENTS AND METHODS: A retrospective study. All patients in whom a therapeutic biliary endoscopy had been performed over a four-year period of time (2002-2005) were included. RESULTS: 178 geriatric patients and 159 younger ones underwent ERCP. No differences were found in successful biliary drainage (97.7 vs. 98.7%), complication number (11.8 vs. 14.4%), or mortality rate (1.1 vs. 0.6%). On the other hand, more common bile duct stones were found in geriatric patients (57.3 vs. 39.6%, p = 0.004), and also more self-expanding metal stents were employed to drain malignant obstructive jaundice (47 vs. 8%, p = 0.0035). In the youngest group, more ERCPs were repeated in the same patients (4 vs. 10%, p = 0.001). CONCLUSIONS: The geriatric population showed similar success and morbidity and mortality rates when compared to younger patients in draining their bile duct by means of ERCP. Common bile duct stones were more frequently found in geriatric patients. No patients needing an ERCP should be excluded only because of their age.

[Pancreatobiliary maljunction. Not only an Eastern disease]. / Unión biliopancreática anómala. Una enfermedad no exclusiva de pacientes orientales.

Pancreatobiliary maljunction, an extramural junction of the pancreatic and biliary ducts in the duodenum, apparently beyond the scope of intramural sphincter function, is thought to be a preferential disease of Eastern people. However, this diagnosis is increasingly being made in other populations. We present a 41-year-old woman who presented with intermittent epigastric pain and mild raise in amylase levels. MRCP did not offer a definitive diagnosis, perhaps because of lack of experience in this disease. Finally, ERCP showed a pancreatobiliary maljunction, type acute angle, but with a complex connection between the choledocus and the pancreatic duct. Fusiform dilation of the common bile duct and of the left main hepatic duct were also present. The patient was referred for extrahepatic biliary resection and a diversion procedure. But also because of lack of experience in this disease, a wait-and-see approach was undertaken. In conclusion, pancreatobiliary maljunction will be increasingly diagnosed in western communities and more diagnostic and therapeutic experience will be needed.

Estrus variation in anticonflict-like effects of the mGlu5 receptor antagonist MTEP, microinjected into lateral septal nuclei of female Wistar rats.

Anticonflict-like effects of the mGlu5 receptor antagonist MTEP (systemic administrations: 1.50, 3.0 or 6.0 mg/kg; i.p.; intra-lateral septal nuclei or intra-medial septal region infusions: 2.5 microg/microl, 5.0 microg/microl or 10.0 microg/microl) were assessed in Wistar rats during late proestrus or metestrus-diestrus. Results showed that control rats displayed an increased number of immediately punished reinforcers during late proestrus (P < 0.05), when compared to metestrus-diestrus. During late proestrus, systemic administrations (3.0 mg/kg, P < 0.05; 6.0 mg/kg P < 0.05) or intra-lateral septal nuclei infusions (5.0 microg/microl, P < 0.05; 10.0 microg/microl, P < 0.05) of MTEP increased the number of immediately punished reinforcers received. During metestrus-diestrus only the highest doses of MTEP (systemic administration: 6.0 mg/kg P < 0.05; intra-lateral septal nuclei infusions: 10.0 microg/microl, P < 0.05) increased the number of immediately punished reinforcers obtained. MTEP infusions into the medial septum produced neither of these anticonflict effects. In conclusion, data showed an estrus variation in those anticonflict-like effects of the mGlu5 receptor antagonist MTEP, systemically administered or microinjected into lateral septal nuclei of female Wistar rats.

Real time PCR for the diagnosis of benzimidazole resistance in trichostrongylids of sheep.

This report describes a new molecular method for the diagnosis of benzimidazole susceptibility or resistance in three main species of trichostrongylids of sheep (Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus vitrinus). This assay is based on the use of real time polymerase chain reaction (PCR) to detect mutations of residue 200 on isotype 1 of beta-tubulin. The technique allows calculation of the proportion of each allelic variant as it combines kinetic (real time quantitative) PCR with allele-specific amplification and requires no post-PCR processing. The level of resistance in the population is determined by the proportion of the beta-tubulin codon 200 TAC allele. Hence, it was observed that the proportion of the resistant allele in susceptible strains ranged between 24% and 32.3%; in resistant strains this value increased to between 71.3% and 86.3%. Furthermore, there was a good correlation between real time PCR, faecal egg count reduction test, egg hatch assay and conventional allele-specific PCR, in both resistant and susceptible strains. A sensitive, rapid, highly reproducible and inexpensive technique for detecting resistance to benzimidazoles in a worm population has been developed.

Isolation rearing induced fear-like behavior without affecting learning abilities of Wistar rats.

1. Isolation-reared rats display fear-like behavior and depressive-like behavior in several behavioral tasks, suggesting that isolation rearing may model certain aspects of human psychopathologies. 2. After weaning (20 days old), male and female Wistar rats were isolation-reared during 20, 50 or 70 days. After that, they were tested in the elevated plus maze test, and in the open field test. Another group of isolation-reared rats (70 days of isolation) were tested in an auto-shaping task. 3. Isolation-reared rats displayed high levels of fear-like behavior in the elevated plus-maze test, and hyperlocomotion in the open field test. But, isolation-reared rats learned an auto-shaping task. 4. In conclusion, isolation rearing induced fear-like behavior, without affect learning abilities of rats.