Effects of a Primary Care Antimicrobial Stewardship Program on Meticillin-Resistant Staphylococcus aureus Strains across a Region of Catalunya (Spain) over 5 Years.

Primary care antimicrobial stewardship program (ASP) interventions can reduce the over-prescription of unnecessary antibiotics, but the impact on the reduction in bacterial resistance is less known, and there is a lack of available data. We implemented a prolonged educational counseling ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, which was compared to a pre-intervention period, a significant reduction in antibiotic prescriptions occurred, particularly those associated with greater harmful effects and resistance selection. There was also a decrease in methicillin-resistant Staphylococcus aureus (MRSA) strains and in their co-resistance to other antibiotics, particularly those with an ecological impact.

Prognostic parameters on baseline and interim [ 18 F]FDG-PET/computed tomography in diffuse large B-cell lymphoma patients.

OBJECTIVE: 2-[ 18 F]fluoro-2-deoxy- d -glucose PET/computed tomography ([ 18 F]FDG-PET/CT) is a widely used imaging method in the management of diffuse large B-cell lymphomas (DLBCL). Our aim was to investigate the prognostic performance of different PET biomarkers in a multicenter setting. METHODS: We investigated baseline volumetric values [metabolic tumor volume (MTV) and total lesion glycolysis (TLG), also normalized for body weight] segmented with three different methods [>SUV4 (glob4); 41% isocontour (41pc), and a gradient-based lesion growing algorithm (grad)] and interim parameters [Deauville score, maximal standardized uptake value (ΔSUVmax), modified qPET, and ratio PET (rPET)] alongside clinical parameters (stage, revised International Prognostic Index), using 24-month progression-free survival as the clinical endpoint. Receiver operating characteristics analyses were performed to define optimal cutoff points for the continuous PET parameters. RESULTS: A total of 107 diffuse large B-cell lymphoma patients were included (54 women; mean age: 53.7 years). MTV and TLG calculations showed good correlation among glob4, 41pc, and grad methods; however, optimal cutoff points were markedly different.Significantly different PFS was observed between low- and high-risk groups according to baseline MTV, body weight-adjusted (bwa) MTV, TLG, bwaTLG, as well as interim parameters Deauville score, ΔSUVmax, mqPET, and rPET. Univariate Cox regression analyses showed hazard ratios (HRs) lowest for bwaMTVglob4 (HR = 2.3) and highest for rPET (HR = 9.09). In a multivariate Cox-regression model, rPET was shown to be an independent predictor of PFS ( P = 0.041; HR = 9.15). Combined analysis showed that ΔSUVmax positive patients with high MTV formed a group with distinctly poor PFS (35.3%). CONCLUSION: Baseline MTV and TLG values and optimal cutoff points achieved with different segmentation methods varied markedly and showed a limited prognostic impact. Interim PET/CT parameters provided more accurate prognostic information with semiquantitative 'Deauville-like' parameters performing best in the present study.

Impact of a Primary Care Antimicrobial Stewardship Program on Bacterial Resistance Control and Ecological Imprint in Urinary Tract Infections.

Antimicrobial stewardship programs (ASPs) are a central component in reducing the overprescription of unnecessary antibiotics, with multiple studies showing benefits in the reduction of bacterial resistance. Less commonly, ASPs have been performed in outpatient settings, but there is a lack of available data in these settings. We implemented an ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, compared to the pre-intervention period, a significant reduction in antibiotic prescription occurred, with a reduction in resistance in E. coli urinary isolates. ASP activities also were found to be cost-effective, with a reduction in medication prescription.

Combined Visual and Semiquantitative Evaluation Improves Outcome Prediction by Early Midtreatment 18F-FDG PET in Diffuse Large B-Cell Lymphoma.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immunochemotherapy after 2 cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying 2 different methods of interpretation: the Deauville visual 5-point scale (5-PS) and a change in SUV (ΔSUV) by semiquantitative evaluation. Methods: In total, 145 patients with newly diagnosed DLBCL underwent pretreatment PET and PET-2 assessment. PET-2 was classified according to both 5-PS and percentage ΔSUV. Receiver-operating-characteristic analysis was performed to compare the accuracy of the 2 methods for predicting progression-free survival. Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET-) groups and compared. Results: Both with 5-PS and with ΔSUV-based evaluations, significant differences were found between the progression-free survival of iPET- and iPET+ patient groups (P < 0.001). Visually, the best negative predictive value (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if the Deauville score was 4-5 (89% and 59%, respectively). Using the 66% ΔSUV cutoff reported previously, NPV and PPV were 80% and 76%, respectively. ΔSUV at the 48.9% cutoff, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). The 5-PS and a semiquantitative ΔSUV of less than 48.9% for each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100%, respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL patients, iPET had good prognostic value interpreted either visually or semiquantitatively. We determined that the most effective ΔSUV cutoff was 48.9% and that when combined with 5-PS assessment, a positive PET-2 result was highly predictive of treatment failure.

The role of PET-CT in patients with incidental gallbladder cancer.

INTRODUCTION: After a cholecystectomy, incidental gallbladder cancer (IGC) requires accurate imaging studies to determine the actual extent of the disease to properly tailor subsequent treatment. The aim of this study was to evaluate the utility of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) to provide optimal pre-treatment staging in patients with IGC. MATERIAL AND METHODS: Between January 2006 and August 2008, all patients with IGC and at least muscular layer invasion were studied with (18)FDG PET-CT. The examination was considered positive when the standardized uptake values (SUV) were >/=2.5. In all instances patients were offered to undergo definitive exploration and possible radical resection. RESULTS: The series included 32 patients, 26 women and 6 men, with a median age of 57 years (range 30-81 years). The examination was performed at a median time of 6 weeks after cholecystectomy (range 2-52 weeks). (18)FDG PET-CT was negative in 13 patients and positive in 19 patients: 9 with localized potentially resectable disease (PRD) and in 10 with disseminated disease. Of the 13 patients with negative PET-CT, 9 refused surgery and 4 underwent formal exploration: 3 patients were resected with no disease identified in the final pathology report (FPR) and 1 was not resected as a result of peritoneal carcinomatosis. Of the 9 with PRD, 4 patients refused reoperation and 5 underwent exploration: 3 were resected with residual disease noted in the FPR and 2 did not undergo resection because of dissemination. Two patients with disseminated disease were reoperated and in both instances disseminated disease was confirmed. The median survival for the entire group was 20.3 months (range 1.6-32.9 months). The median survival for those patients with negative PET-CT was 13.5 months (range 5.6-32.9 months), 6.2 months (range 1.6-18.7 months) for localized potentially resectable disease and 4.9 months (range 2-14.1 months) for disseminated disease (P < 0.003). CONCLUSIONS: For patients presenting with stage T1b or greater IGC, the use of (18)FDG PET-CT will help reduce the number of patients undergoing non-therapeutic re-exploration and may help to determine the likely prognosis. (18)FDG PET-CT might be a useful tool for the selection of patients for potentially curative treatment.

Prospective international cohort study demonstrates inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma.

UNLABELLED: The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). METHODS: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. RESULTS: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. CONCLUSION: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.

Combined PET and biopsy evidence of marrow involvement improves prognostic prediction in diffuse large B-cell lymphoma.

UNLABELLED: Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. METHODS: The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. RESULTS: Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (n = 231) were 81% (95% confidence interval [CI], 76%-86%) for event-free survival (EFS) and 88% (83%-91%) for overall survival (OS); cases identified only on PET (n = 61), 81% (69%-89%) for EFS and 88% (77%-94%) for OS; cases indentified only on biopsy (n = 10), 80% (41%-95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (n = 25), 45% (25%-64%) for EFS and 55% (32%-73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/biopsy-positive cases were 2.67 (95% CI, 1.48-4.79) for EFS and 3.94 (1.93-8.06) for OS. CONCLUSION: This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow (18)F-FDG uptake identified on the staging PET scan. Abnormal (18)F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.

Thyroid metastases from gallbladder cancer.

BACKGROUND: Gallbladder cancer is an aggressive malignancy and radical resection is the only curative therapy available. Metastatic disease in the thyroid is rarely seen; however, different studies have confirmed that the most common primary tumor source is the kidney. CASE REPORT: Thyroid metastases from tumors originating in the gastrointestinal tract have been reported. We report a patient with gallbladder cancer (T2N1M0) treated with radical resection and postoperative chemoradiation who developed thyroid metastases.

[Detection of neuroendocrine tumors by positron emission tomography-computed tomography with 68Ga-DOTATATE: report of one case]. / Una nueva modalidad diagnóstica para la detección de tumores neuroendocrinos con 68Ga-DOTATATE PET/CT: caso clínico.

We report a 74-year-old male with liver metastases from a neuroendocrine tumor (NET) of unknown origin. Conventional imaging studies with ultrasound, computed tomography colonoscopy and Positron emission tomography-computed tomography (PET/CT) with 18Fluor odeoxyglucose did not identify the site of origin of the primary tumor. The patient was submitted for a PET/CT scan with a new radiopharmaceuticai, the somatostatin analogue 68Ga-DOTATATE. This new technique demonstrated increased focal uptake at the ileocecal valve. This lesion and other two liver metastases were surgically removed. The histopathology and immunohistochemistry analysis confirmed the diagnosis of NET (carcinoid). This case illustrates the advantages of the PET/CT scan with 68Ga-DOTATATE.

[Fibrolamellar liver carcinoma: report of two cases and review of the literature]. / Carcinoma hepatocelular variedad fibrolamelar metastásico en menores de 20 años: Reporte de 2 casos tratados con intención curativa y revisión de la literatura.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare histologic variant of hepatocellular carcinoma that appears most commonly in teenagers and young adults. The diagnosis is often made incidentally and surgical resection is the only curative treatment. Here we report two cases of incidental FLC involving a 19 year-old male, initially diagnosed with screening abdominal ultrasound, and a 14 year-old female that presented with abdominal pain. Diagnostic workup consisted of abdominal PET/CT and MR1 Imaging studies and tissue diagnosis was confirmed with percutaneous liver biopsy. Both patients were treated with radical liver resection/tumor excision. However, tumor recurrence was observed in both during short-term follow-up. The male patient was treated successfully with surgical treatment however the female patient succumbed top regression of disease.

Tratamiento de tumores neuroendocrinos (TNE) con péptidos análogos de la somatostatina marcados con radionucleidos / Treatment of neuroendocrine tumors (NET) with radiolabelled somatostatin analogues

Propósito. Los TNE avanzados tienen escasa respuesta a radioterapia o quimioterapia, el tratamiento sistémico con análogos de la SST radiactivos es una herramienta promisoria en su tratamiento. Presentamos nuestra experiencia, pionera en Latinoamérica, utilizando análogos de SST marcados con 90Y ó 177Lu. Material. Evaluamos 40 pacientes (50.3 años, rango 12-74) con TNE confirmados histológicamente y sobre-expresión de receptores de SST demostrada mediante imágenes. SPECT (111In-DOTATOC) ó PET/CT (68Ga-DOTATATE). Se evaluó respuesta clínica, laboratorio, imágenes con 111In-DOTATATE, post-terapia con 90Y ó 177Lu, 68Ga-DOTATATE PET/CT o TAC. Resultados. Observamos progresión de enfermedad en 10 (25.0 por ciento), remisión parcial en 25 (62.5 por ciento), enfermedad estable en 3 (7.5 por ciento) y remisión completa en 2 (5.0 por ciento). Hubo escasa toxicidad sin deterioro renal significativo. Observamos reducción tumoral y mejoría de calidad de vida en la mayoría de los pacientes. Conclusión. La terapia con radiopéptidos es un procedimento seguro y efectivo en el tratamiento de TNE avanzados.

Purpose. Advanced NETs have little response to radiotherapy or chemotherapy, systemic treatment with radioactive SST analogous is a promissory tool in its treatment. We present our pioneering experience in Latin America using analogous of SST labeled either with 90Y or 177Lu. Materials. We evaluated 40 patients (50.3 years, range 12-74) with histological proved NET and SST receptors over-expression demonstrated by SPECT or PET/CT images with 111In-DOTATOC or 68Ga-DOTATATE. We evaluated clinical response, laboratory test, images with 111In-DOTATATE, 90Y, 177Lu, and 68Ga-DOTATATE PET/CT or CT. Results. We observed progression of disease in 10 (7,5 percent), partial remission in 25 (62,5 percent), stable disease in 3 (7,5 percent) and complete remission in 2 (5,0 percent). There was little toxicity without significant renal deterioration. We observed tumor mass reduction and improvement of quality of life in most of the patients. Conclusion. The therapy with radiopeptides is a safe and effective procedure in the treatment of advanced NET.

[Myocardial pyrophosphate uptake in cardiac amyloidosis: report of case]. / Captación miocárdica de pirofosfato en amiloidosis cardíaca. Caso clínico.

We report a previously healthy 73 years old woman, who was hospitalised with increasing dyspnea and signs of congestive heart failure. Echocardiography showed a normal left ventricular cavity with increased echogenicity of its walls and severe pulmonary hypertension. A lung ventilation/perfusion scintigraphy concluded that there was a low probability for pulmonary embolism. Coronary angiography was normal. A restrictive cardiomyopathy due to amyloid deposits was suspected. Myocardial pyrophosphate scintigraphy showed intense pyrophosphate uptake in the left ventricle wall. An abdominal fat tissue biopsy was positive for amyloid deposits.

Carcinoma hepatocelular variedad fibrolamelar metastásico en menores de 20 años: Reporte de 2 casos tratados con intención curativa y revisión de la literatura / Fibrolamellar liver carcinoma: Report of two cases

Fibrolamellar hepatocellular carcinoma (FLC) is a rare histologic variant of hepatocellular carcinoma that appears most commonly in teenagers and young adults. The diagnosis is often made incidentally and surgical resection is the only curative treatment. Here we report two cases of incidental FLC involving a 19 year-old male, initially diagnosed with screening abdominal ultrasound, and a 14 year-old female that presented with abdominal pain. Diagnostic workup consisted of abdominal PET/CT and MRI Imaging studies and tissue diagnosis was confirmed with percutaneous liver biopsy. Both patients were treated with radical liver resection/tumor excision. However, tumor recurrence was observed in both during short-term follow-up. The male patient was treated successfully with surgical treatment however the female patient succumbed top regression of disease.

Una nueva modalidad diagnóstica para la detección de tumores neuroendocrinos con 68Ga-DOTATATE PET/CT: Caso clínico / Detection of neuroendocrine tumors by positron emission tomography-computed tomography with 68Ga-DOTATATE: Report of one case

We report a 74-year-old maie with liver metastases from a neuroendocrine tumor (NET) of unknown origin. Conventionai imaging studies with ultrasound, computed tomography coionoscopy and Positron emission tomography-computed tomography (PET/CT) with 18Flúor odeoxyglucose did not identify the site of orígin of the primary tumor. The patient was submitted for a PET/CT sean with a new radiopharmaceuticai, the somatostatin anaiogue 68Ga-DOTATATE. This new technique demostrated increased focal uptake at the ileocecal valve. This lesión and other two liver metastases were surgically removed. The histopathology and immunohistochemistry analysis confirmed the diagnosis of NET (carcinoid). This case illustrates the advantages of the PET/CT sean with 68Ga-DOTATATE.

Gallium-68 (68Ga); the revival of an old positron emission tomography (PET) agent: the leading experience in Chile

In January 2008, we set up a 68Ge/ 68Ga generator able to produce enough quantities of 68Ga to label the same polypeptides, somatostatin analogos, used to treat patients suffering from neuroendocrine tumors. As far as we know, this is the first time that such a device is installed in Latin-America for specific PET/CT imaging different from 18F. During the last three months we have studied 30 patients for staging, re-staging and treatment control of neuroendocrine tumors using PET/CT images with 68Ga-DOTATATE. In all cases the image quality was excellent, providing clinically useful information in most of them. 68Ga is a very promising positron emitter radionuclide, cyclotron-independent, to label peptides and other molecules that open a wide window for Molecular Imaging.

En Enero de 2008 instalamos un generador de 68Ge/ 68Ga capaz de producir cantidades suficientes de 68Ga para marcar los mismos péptidos, análogos de la somatostatina, utilizados para el tratamiento de pacientes con tumores neuroendocrinos. De acuerdo con nuestro conocimiento, esta es la primera vez que se utilizada este aparato en Latinoamérica para obtener imágenes PET/CT específicas con un agente diferente al 18F. Durante los últimos tres meses hemos estudiado 30 pacientes con tumores neuroendocrinos con 68Ga-DOTATATE para etapificación, re-etapificación y control de tratamiento mediante imágenes PET/CT. En todos los casos la calidad de la imagen fue excelente proporcionando información clínicamente útil en la mayoría de ellos. 68Ga es un promisorio radionucleido emisor de positrones, independiente de un ciclotrón, para marcar péptidos y otras moléculas abriendo una amplia ventana para las Imágenes Moleculares.