Association between rainfall and Escherichia coli in live bivalve molluscs harvested in Sardinia, Italy.

Rainfall is generally accepted as one of the most important factors associated with an increased level of E. coli in bivalve molluscs. Performing microbiological risk assessment is relevant to official control authorities to determine the sanitary status of harvesting areas and, therefore, develop monitoring strategies and identify management practices that could be used to improve the quality and safety of the final product. The present study aimed to investigate the impact of rainfall on the content of E. coli in bivalve molluscs farmed in Sardinia (Italy). Enumeration of E. coli was performed according to the Most Probable Number (MPN) method (ISO 16649-3) on 1,920 bivalve samples collected from 7 regional counties between 2018 and 2020. Bivalve molluscs samples included 955 mussels (Mytilus galloprovincialis), 500 oysters (Crassostrea gigas), 325 clams (Ruditapes decussatus), 94 warty venus (Venus verrucosa), and 46 lagoon cockles (Cerastoderma glaucum). Rainfall data were obtained by the Department of Meteorology of the ARPA Sardegna. For each sampling site, GPS coordinates were used to identify gauge stations within catchment areas. Cumulative rain (mm) was recorded 1, 3, 5, 7, and 15 days before sampling, among which the 7-day cumulative rain was the strongest predictor of E. coli counts. Several thresholds of 7-day cumulative rain (from <10 mm up to >300 mm) before sampling were used to estimate the chances of a non-compliant sample (E. coli levels above the limit for sanitary class A; 230 MPN/100 g). The 7-day cumulative rain was positively associated with the chances of non-compliance. When the 7-day cumulative rain before sampling was >300 mm, 80.5 % of the samples were non-compliant, and the odds of a non-compliant sample were 23.6 times higher, as compared to samples harvested when the 7-day cumulative rainfall was <10 mm. Precipitation data could be a useful tool for interpreting anomalous results from official control authorities and reduce the costs that originate from closure of production areas.

The Current and Evolving Role of Immunotherapy in Metastatic Colorectal Cancer.

Immunotherapy can be considered a therapeutic revolution in oncology, with great impact on many tumor types, such as melanoma and non-small cell lung cancer. However, in metastatic colorectal cancer, the benefits in terms of prolonged tumor control and high response rate are limited to the rare subgroup of tumors with high mutation burden - mostly tumors that harbor microsatellite instability (MSI) or a deficient mismatch repair system (dMMR), or tumor microsatellite stability and damaging mutations in the exonuclease domains of POLE or POLD. The KEYNOTE-028 uncontrolled phase II trial demonstrated an impressive antitumor activity of pembrolizumab in patients with treatmentrefractory Lynch-associated tumors, including colorectal cancer. Nivolumab with or without ipilimumab confirmed the efficacy of immune checkpoint inhibitors in patients with previously treated dMMR / MSI metastatic colorectal cancer. The recent KEYNOTE-177 phase III trial demonstrated that pembrolizumab significantly reduced the relative risk of disease progression or death and improved progression-free survival in patients with treatment-naive dMMR / MSI metastatic colorectal cancer in comparison with first-line chemotherapy with or without biologics. Unfortunately, current pharmacological strategies with immunotherapy have not been successful for most patients with microsatellite stable metastatic colorectal cancer. In this review, we critically appraise the applicability of immune checkpoint inhibitors in dMMR/MSI metastatic colorectal cancer. We also discuss the recent negative trials of immunotherapy combinations in microsatellite stabl.

Combined rapid urease test and histology for the diagnosis of helicobacter pylori infection

Significance@#Accurate detection of Helicobacter pylori (HP) is essential for the diagnosis of HP infection. The use of antibiotics and proton pump inhibitors (PPI) may result in false-negative rapid urease test (RUT) results. We aimed to determine the sensitivity and specificity of RUT compared with histology and assess the detection rate of combined RUT and histology for HP infection. @*Methodology@#Retrospective data collection was performed on 192 patients who were tested for both RUT and histology at the time of upper endoscopy from 2017 to 2018. At least two gastric biopsies (1 from corpus, 1 from antrum) were taken each for RUT and histology. The endoscopy was performed by a single gastroenterologist and a single pathologist was responsible for interpreting the histology with hematoxylin and eosin (H&E) and Giemsa stain. The gold standard test for the diagnosis of HP infection was histology. Demographic profile, RUT and histology results were reviewed. Tests for diagnostic accuracy were computed using SPSSv23. @*Results@#192 patients were tested for RUT and histology. 52(27.1%) were males and 140(72.9%) were females with a mean age of 54±17 years. Epigastric pain was the most common indication (42.7%). 24(12.5%) patients tested positive for HP infection. Among these; 16(8.3%) tested positive for both RUT and histology(true-positive), while 8(4.2%) tested negative for RUT but had positive histology(false-negative). 6 out of 8(75%) patients with false negative results had PPI use. The sensitivity and specificity of RUT for the diagnosis of HP infection were 66.7 and 98.2%, respectively. While the positive and negative likelihood ratio were 37.3 and 0.34, respectively with a diagnostic odds ratio of 110. @*Conclusion@#The HP detection rate of RUT combined with histology increased by 33% compared with RUT alone. RUT is a highly specific test for diagnosing HP infection. Given its modest sensitivity, histology plays an important role in the diagnosis of HP infection, especially in patients taking PPIs. We recommend doing histology when RUT is negative to increase the HP detection rate.

Outcomes of Patients With Metastatic Anal Cancer According to HIV Infection: A Multicenter Study by the Latin American Gastrointestinal Oncology Group (SLAGO).

BACKGROUND: HIV-positive patients are underrepresented in clinical trials of metastatic squamous cell carcinoma of the anal canal (mSCCA). We aimed to compare the clinical outcomes of mSCCA patients according to HIV infection. METHODS: This was a retrospective multicenter cohort study of consecutive patients with mSCCA. All HIV-positive patients received antiretroviral therapy. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and response rate (RR). RESULTS: From January 2005 to December 2019, 113 patients were included: 20 (17.6%) had HIV infection. HIV-positive patients were younger at diagnosis and more frequently male, and 20% (n = 8) received exclusively best supportive care in comparison with 8.6% of HIV-negative patients (P = .13). Both groups were similar in terms of Eastern Cooperative Oncology Group (ECOG) performance status, pattern of metastatic disease, and type of first-line chemotherapy. Five (25%) HIV-positive and 36 (38.7%) HIV-negative patients received second-line therapies (P = .24). RR and median PFS in first-line were similar between the groups: 35% and 30.1% (P = .78) and 4.9 and 5.3 months (P = .85) for patients with and without HIV infection, respectively. At a median follow-up of 26 months, median OS was 11.3 months (95% confidence interval [CI] 10.1 to 26.4) for HIV-infected patients versus 14.6 months (95% CI 11.1 to 18.1) for HIV-negative patients (P = .92). In the univariate analysis for OS, only ECOG performance status was significant. CONCLUSION: HIV-positive mSCCA patients under antiretroviral therapy have oncological outcomes similar to those of HIV-negative patients. These patients should be included in trials of mSCCA.

Disease-Free Survival and Time to Complete Response After Definitive Chemoradiotherapy for Squamous-Cell Carcinoma of the Anus According to HIV Infection.

BACKGROUND: The standard treatment for localized squamous-cell carcinoma of the anal canal is definitive chemoradiotherapy. A meta-analysis of published studies conducted by our group showed significantly lower rates of disease-free survival (DFS) and overall survival at 3 years among HIV-positive patients. We aimed to compare detailed treatment outcomes between the groups of HIV-positive and -negative patients. PATIENTS AND METHODS: We performed a retrospective multicenter study of a comparative cohort of consecutive patients with histologic diagnosis of localized squamous-cell carcinoma of the anal canal who received definitive chemoradiotherapy. Patients' characteristics and outcomes were compared according to HIV status. The primary end points were time to complete response (CR) and DFS time. RESULTS: From June 2001 to September 2018, a total of 185 patients were included; 43 (30.2%) were HIV positive and 142 (69.8%) were HIV negative. The overall CR rates were 67.4% and 91.5% for HIV-positive and -negative patients, respectively (P < .001). The median follow-up was 47.8 months and the median time to experience CR was 7.8 months (95% confidence interval [CI], 5.7-10.5) for HIV-positive versus 4.89 months (95% CI, 4.54-5.25) for HIV-negative (P < .001) patients. The median DFS times were 79.7 months (95% CI, 56.8-102.6) and 127.9 months (95% CI, 112.6-143.2) for HIV-positive and -negative patients, respectively (P = .02). There was a trend toward greater grade 3/4 toxicity in the HIV-positive group. CONCLUSION: HIV-positive patients take longer to experience CR and present worse DFS. These findings have clinical implications because waiting longer to define CR among these patients may prevent unnecessary anorectal amputations.

Increase in Utilization of Nipple-Sparing Mastectomy for Breast Cancer: Indications, Complications, and Oncologic Outcomes.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting the oncologic safety of NSM has led to its widespread use and broadened indications. In this study, we examine the indications, complications, and long-term outcomes of therapeutic NSM. METHODS: From 2003 to 2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year, while complications were compared by procedure year using generalized mixed-effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined. RESULTS: Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45 years (range 24-75) and median follow-up among survivors was 39.4 months. Three hundred and fifty-seven (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs. 77%; p < 0.001). There was no difference in family history, genetic mutations, smoking status, neoadjuvant chemotherapy, prior radiation, nodal involvement, or tumor subtype. Twenty-one (4.5%) nipple excisions were performed, of which 14 were performed for cancer at the nipple margin. Forty-four breasts (9.4%) had complications that required re-operation. Fifteen patients had locoregional recurrence or distant metastasis. CONCLUSIONS: NSM use for invasive carcinoma has doubled at our institution since 2011, while postoperative complications and recurrence rates remain low. Our experience supports the selective use of NSM in the malignant setting with careful patient selection.

Association between obesity and mortality in adult patients receiving invasive mechanical ventilation: A systematic review and meta-analysis. / Asociación entre obesidad y mortalidad en pacientes adultos que reciben ventilación mecánica invasiva: una revisión sistemática y metaanálisis.

OBJECTIVE: To evaluate if there is an association between obesity and mortality in the Intensive Care Unit (ICU) in adult patients receiving invasive mechanical ventilation. DESIGN: Systematic review with meta-analysis. SCOPE: ICU. DATA SOURCE: A search was made in MEDLINE, Cochrane Library, CINAHL and Global Health databases without language restriction, until February 21, 2017. SELECTION OF STUDIES: Studies that reported mortality in the ICU in obese versus non-obese patients who received IMV were included. MAIN VARIABLES: Mortality in the ICU. RESULTS: 2163 articles were found, of which 14 studies were included. No statistically significant differences were found between obese and non-obese patients with respect to the variable mortality in the ICU (OR: 0.94, 95% CI: 0.81-1.10, P=.45). CONCLUSION: No relationship was found between the subgroup of obese adult patients receiving IMV and the mortality variable in the ICU.

Seroepidemiology of Chikungunya Virus Among Febrile Patients in Eight Health Facilities in Central and Northern Mozambique, 2015-2016.

BACKGROUND: The burden and spread of chikungunya virus (CHIKV) are rapidly increasing worldwide, but the epidemiology in Mozambique is barely known. The aim of this study was to determine the seroepidemiology of CHIKV in central and northern Mozambique. METHODS: A cross-sectional study was conducted between March 2015 and May 2016 in eight health facilities situated in central and northern Mozambique to recruit 392 patients with undifferentiated febrile illness from outpatient clinics. Serum samples from each participant were screened using commercially available enzyme-linked immunosorbent assay for detection of anti-CHIK IgM and IgG antibodies. A subset of study samples (n = 37) was further tested by the plaque reduction neutralization assay (PRNT). RESULTS: The median age of participants was 23 years (IQR: 7-34), and 45.7% were female. The frequency of participants with seropositivity for IgM and IgG anti-CHIKV antibodies was 1.5% (6/392) and 28.6% (112/392), respectively. Patients with seropositivity for IgM anti-CHIKV were significantly younger. Frequency of patients with seropositivity for IgG anti-CHIKV increased with age. Frequency of patients with seropositivity for IgM anti-CHIKV was higher in Tete province, but most patients with seropositivity for IgG anti-CHIKV infection were from Cabo Delgado and Sofala provinces. CONCLUSIONS: Our data demonstrate serological evidence of CHIKV in central and northern Mozambique, expanding the limited evidence of the virus in the country. We recommend that CHIKV should be considered in the differential diagnosis of febrile illness throughout the country.

Aflibercept en retinopatía diabética / Aflibercept in diabetic retinopathy

CONTEXTO CLÍNICO: La retinopatía diabética (RD) es una de las principales causas de pérdida de visión principalmente entre pacientes entre 25 y 74 años.1 El 10% de los pacientes con diabetes tienen una limitación visual severa y 2% de ellos llega a la ceguera. La prevalencia de la RD aumenta con el tiempo de duración de la diabetes. Se calcula que en Argentina hay 2.600.000 personas diabéticas, de las cuales 700.000 tienen algún grado de retinopatía y 135.000 presentan RD proliferativa o edema macular (EM). La ceguera por RD es prevenible en un 80% de los casos con una detección y tratamiento temprano asociado a un manejo general. 3 Se han desarrollado y evaluado muchas intervenciones preventivas y terapéuticas con el objetivo de minimizar la morbilidad asociada a la RD. Preventivamente se sugiere un control estricto de la glucemia de forma precoz, mientras que para el tratamiento la cirugía láser de fotocoagulación es la principal recomendación.1 Se considera un cambio clínicamente significativo en el tratamiento de la RD, a la mejora de 2 escalones en la Escala de Gravedad de Retinopatía Diabético (DRSS, su sigla del inglés Diabetic Retinopathy Severity Scale) y una media de diferencia de 4 letras en agudeza visual. Adicionalmente, existen alternativas farmacológicas para el tratamiento del edema macular diabético (EMD) incluyen las drogas antiangiogénicas(Anti-VEGF) intravítreas y los corticoesteroides intravítreos. Los agentes Anti-VGEF (inhibidores del factor de crecimiento vascular endotelial) (bevacizumab, ranibizumab y aflibercept) han demostrado ser eficaces en el tratamiento de los pacientes con edema macular diabético. Se postula al aflibercept como una droga superior a los otros Anti-VGEF y a los corticoides en cuanto a la mejoría de la agudeza visual sin aumento importante de los efectos adversos. TECNOLOGÍA: El aflibercept es una proteína de fusión recombinante humana de los dominios de los receptores de VEGF humano 1 y 2 y la región Fc de las IgG humana de unión de todas las isoformas de VEGF A. Es um bloqueante potente y específico de VEGF subtipo A y del factor de crecimiento placentario relacionado (PIGF, su sigla del inglés Placental Growth Factor), factores angiogénicos. El tratamiento anti-VEGF previene el crecimiento inapropiado de vasos nuevos en la retina y disminuir la permeabilidad vascular reduciendo el edema macular. Las drogas Anti-VGEF bloquean a las citosinas, como el factor de crecimiento vascular endotelial (VEGF), los cuales son los responsables de la angiogénesis y del aumento de la permeabilidade vascular, presentes en la RD y en el EMD, siendo estos los principales responsables de la disminución en la agudeza visual. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de aflibercept para retinopatía diabética. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cuatro ECAs, cuatro RS, dos series de casos, cuatro GPC, una evaluación económica, dos evaluaciones de tecnología sanitaria e ocho informes de políticas de cobertura aflibercept en retinopatia diabética. CONCLUSIONES: Existe evidencia de alta calidad para considerar que el aflibercept en pacientes con retinopatia diabética con compromiso severo de la agudeza visual y con un espesor central de la retina mayor a 400 micrones produce mejoras en la agudeza visual de forma clínica y estadísticamente significativas en comparación a otras drogas inhibidoras del crecimiento vascular (Anti-VGEF) durante el primer año de seguimiento,si bien dicha diferencia disminuye durante el segundo año de seguimiento. Existe evidencia de moderada calidad que no establece diferencias entre el aflibercept y los otros anti-VGEF en el desarrollo de efectos adversos sistémicos. Asimismo, evidencia de alta calidad permite considerar que el aflibercept, en la misma patología, produce mejoras considerables en la agudeza visual de forma clínica y estadísticamente significativas en comparación a la terapia de fotocoagulación con láser durante el primer año de seguimiento, al igual que otras drogas Anti-VGEF, aunque dicha diferencia disminuye en el seguimiento a dos años. Sin embargo, de acuerdo a evidencia de moderada calidad en relación a la terapia prolongada con aflibercept en pacientes con edema macular diabético existe incertidumbre en cuanto a la incidencia algunos eventos adversos sistémicos serios, y sobre la mortalidad por todas las causas en comparación a la terapia láser. Informes de Evaluaciones de Tecnología Sanitaria realizados en Canadá y Reino Unido consideran que la terapia con aflibercept podría ser costo-ahorrativa en comparación a la terapia con ranibizumab em pacientes con edema macular diabético (EMD). En cuanto al perfil de seguridad, las mismas informan que no hubo mayores problemas asociados con aflibercept y que basándose en la práctica clínica y los resultados de los ensayos, el mismo es bien tolerado. Las evaluaciones económicas analizadas en países de altos ingresos no consideran al aflibercept uma droga costo-efectiva. No existen evaluaciones económicas que estudien el impacto de esta droga em Argentina. Existe consenso en las guías de práctica clínica consultadas para recomendar al aflibercept como una alternativa terapéutica en pacientes con retinopatía diabética. Las políticas de cobertura consultadas provenientes de financiadores públicos y privados de Europa y Estados Unidos brindan cobertura. En cuanto a América Latina, los financiadores públicos consultados, no brindan cobertura.

Axillary Dissection and Nodal Irradiation Can Be Avoided for Most Node-positive Z0011-eligible Breast Cancers: A Prospective Validation Study of 793 Patients.

OBJECTIVE: To determine rates of axillary dissection (ALND) and nodal recurrence in patients eligible for ACOSOG Z0011. BACKGROUND: Z0011 demonstrated that patients with cT1-2N0 breast cancers and 1 to 2 involved sentinel lymph nodes (SLNs) having breast-conserving therapy had no difference in locoregional recurrence or survival after SLN biopsy alone or ALND. The generalizability of the results and importance of nodal radiotherapy (RT) is unclear. METHODS: Patients eligible for Z0011 had SLN biopsy alone. Prospectively defined indications for ALND were metastases in ≥3 SLNs or gross extracapsular extension. Axillary imaging was not routine. SLN and ALND groups and radiation fields were compared with chi-square and t tests. Cumulative incidence of recurrences was estimated with competing risk analysis. RESULTS: From August 2010 to December 2016, 793 patients met Z0011 eligibility criteria and had SLN metastases. Among them, 130 (16%) had ALND; ALND did not vary based on age, estrogen receptor, progesterone receptor, or HER2 status. Five-year event-free survival after SLN alone was 93% with no isolated axillary recurrences. Cumulative 5-year rates of breast + nodal and nodal + distant recurrence were each 0.7%. In 484 SLN-only patients with known RT fields (103 prone, 280 supine tangent, 101 breast + nodes) and follow-up ≥12 months, the 5-year cumulative nodal recurrence rate was 1% and did not differ significantly by RT fields. CONCLUSIONS: We confirm that even without preoperative axillary imaging or routine use of nodal RT, ALND can be avoided in a large majority of Z0011-eligible patients with excellent regional control. This approach has the potential to spare substantial numbers of women the morbidity of ALND.

Ventilación mecánica invasiva como tratamiento de la insuficiencia respiratoria aguda en pacientes infectados por el virus de la inmunodeficiencia humana / Invasive mechanical ventilation as a treatment of Severe respiratory insufficiency in patients infected by the immunodeficiency virus human

Objetivo: Conocer la prevalencia y las características epidemiológicas de los pacientes infectados por el virus de la inmunodeficiencia humana que requirieron ventilación mecánica invasiva más de 12 horas para tratar la insuficiencia respiratoria aguda en la Unidad de Cuidados Intensivos de un Hospital General de Agudos. Asimismo, se realizó un análisis comparativo entre los pacientes con el virus de la inmunodeficiencia humana y aquellos sin el virus. Materiales y Métodos: Estudio descriptivo, prospectivo y longitudinal llevado a cabo entre el 1 de agosto de 2012 y el 31 de julio de 2014. Se incluyeron adultos con ventilación mecánica invasiva por más de 12 horas debido a insuficiencia respiratoria aguda. Se realizó un análisis multivariado de regresión logística para identificar la asociación entre muerte en la Unidad de Cuidados Intensivos y virus de la inmunodeficiencia humana. Resultados: Ingresaron 344 pacientes en la Unidad, el 46,80% requirió ventilación mecánica invasiva por insuficiencia respiratoria aguda, con una prevalencia del virus de la inmunodeficiencia humana del 12,42%. Los pacientes infectados tenían una media de la edad de 39.42 ± 11.58 vs. 49.37 ± 20.54. En un análisis multivariado, se observó que los pacientes infectados corrían un mayor de riesgo de morir en la Unidad de Cuidados Intensivos que los no infectados (OR: 5,125; IC95% 1,725-15,226; p = 0,003). Conclusión: Los pacientes con el virus de la inmunodeficiencia humana que recibieron ventilación mecánica invasiva más de 12 horas para tratar la insuficiencia respiratoria aguda tuvieron un riesgo cinco veces más alto de morir en la Unidad de Cuidados Intensivos que los no infectados. (AU)

Objective: To know the prevalence and epidemiological characteristics of patients infected with human immunodeficiency virus requiring invasive mechanical ventilation for more than 12 hours as a treatment for acute respiratory failure at the Intensive Care Unit of a General Acute Care Hospital in Buenos Aires City. A comparative analysis was also performed between subjects with human immunodeficiency virus and those not infected. Materials and Methods: Descriptive, prospective and longitudinal study conducted between August 1st, 2012 and July 31st, 2014. Adults with invasive mechanical ventilation for more than 12 hours due to acute respiratory failure were included. A multivariate logistic regression analysis was performed to identify the association between mortality in the Intensive Care Unit and human immunodeficiency virus. Results: A total of 344 patients were admitted to the Intensive Care Unit, 46.80% of them required invasive mechanical ventilation for acute respiratory failure, with a prevalence of human immunodeficiency virus of 12.42%. The average age of infected patients was 39.42 ± 11.58 vs. 49.37 ± 20.54. In a multivariate analysis it was observed that patients with human immunodeficiency virus had more risk of death in the Intensive Care Unit than those not infected (OR: 5.12%, CI95% 1.72-15.22; P=0.003). Conclusion: The risk of death of subjects with human immunodeficiency virus who received invasive mechanical ventilation for more than 12 hours as a treatment for acute respiratory failure was five-fold higher than that of those uninfected patients.(AU)

Conservative mastectomies for breast cancer and risk-reducing surgery: the Memorial Sloan Kettering Cancer Center experience.

Demand for conservative mastectomies continues to increase as more patients choose to undergo breast reconstruction, often with simultaneous contralateral prophylactic mastectomy (CPM). In addition, the increasing use of risk-reducing surgery in high-risk groups has contributed to the increased use of these techniques. We have reviewed the indications and outcomes of a large group of patients undergoing nipple-sparing mastectomy (NSM) at this institution. In total, 728 nipple-sparing mastectomies (NSMs) were performed in 413 patients between 2000 and 2013, for treatment of breast cancer (n=269) or risk reduction (n=459). Of 728 NSMs performed, 177 (24.3%) were in patients known to have a BRCA1 or BRCA2 germline mutation, or a genetic variant of uncertain significance. There was an incidental finding of ductal carcinoma in situ (DCIS) or invasive carcinoma in 22 (4.8%) and 8 (1.7%) of 459 prophylactic NSMs, respectively. In addition, unexpected invasive carcinoma was found in 17 of 98 therapeutic NSMs (17.3%) performed for DCIS. At median follow-up of 49 months, there were no known cases of local recurrence and only one case of regional recurrence. Immediate breast reconstruction was performed in 409 patients, most of whom underwent tissue expander/implant based procedures (n=401). Although 273 breasts (37.5%) had some evidence of skin desquamation at follow-up, most resolved spontaneously with 47 breasts (6.5%) requiring debridement. Other complications included hematoma in seven breasts (1%) and wound infection in 31 breasts (4.3%). Expander/implant removal was required in 20 cases (2.8%). The nipple-areola complex (NAC) was subsequently excised in 10 of 728 breasts (1.4%) due to oncologic concerns following assessment of retroareolar tissue. NSM was successful in most patients with an acceptable complication rate and in few patients subsequently undergoing removal of the NAC. Patients requiring mastectomy for breast cancer or risk reduction may now benefit from conservative mastectomy techniques such as NSM, resulting in improved cosmesis and, possibly, a reduced psychological impact.

Risk-reducing mastectomy.

Mastectomy rates have significantly increased over the last decades, likely due to the rising trend of risk-reducing mastectomies (RRM) in the treatment and prevention of breast cancer. Growing evidence suggests that aggressive risk-reducing surgical strategies are only justified in high-risk breast cancer situations. Notably, in this selected cohort of women, prophylactic mastectomies offer evident benefit for local and contralateral disease control, and may also provide a survival benefit. Nevertheless, the extent of the increasing frequency of this operation is not explained by the broadening of the medical indications alone. Here we analyze the current evidence regarding RRM, its clinical practice, and possible explanations for the rising phenomenon of aggressive surgical locoregional control strategies.

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer.

BACKGROUND: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. OBJECTIVE: To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. METHODS: Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center (São Paulo-Brazil). CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). RESULTS: KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P = 0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. CONCLUSION: Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.

Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR.

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in Apc(Min/+) mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD2. To assess, we produced Apc(Min/+) mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced Apc(Min/+) mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30-40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in Apc(Min/+) mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. Apc(Min/+) mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD2 signals acting through PTGDR in suppression of intestinal tumors.

Molecular and epidemiological data on Anisakis spp. (Nematoda: Anisakidae) in commercial fish caught off northern Sardinia (western Mediterranean Sea).

Anisakiasis is a fish-borne zoonosis caused by third stage larvae of the nematode Anisakis sp. present in fish or cephalopods. This is the first contribution to the molecular identification and epidemiology of Anisakis spp. in commercial fish from the Gulf of Asinara (Sardinia, western Mediterranean Sea). Between April 2006 to November 2011, 777 specimens of 10 fish species (Engraulis encrasicolus, Merluccius merluccius, Micromesistius poutassou, Phycis blennoides, Sardina pilchardus, Sardinella aurita, Scomber colias, Sphyraena viridensis, Trachurus mediterraneus, Trachurus trachurus) were examined for Anisakis sp. larvae. A total of 1286 larvae were found in 218 fish. The great majority of larvae were located in the body cavity, and only a small part (60, 4.7%) in the muscle. All the Type I larvae (1272) were identified as Anisakis pegreffii and all the Type II (14) as Anisakis physeteris, confirming that A. pegreffii is the dominant species and the most important agent of human anisakiasis in the western Mediterranean Sea.

Axillary dissection can be avoided in the majority of clinically node-negative patients undergoing breast-conserving therapy.

BACKGROUND: The extent to which ACOSOG Z0011 findings are applicable to patients undergoing breast-conserving therapy (BCT) is uncertain. We prospectively assessed how often axillary dissection (ALND) was avoided in an unselected, consecutive patient cohort meeting Z0011 eligibility criteria and whether subgroups requiring ALND could be identified preoperatively. METHODS: Patients with cT1,2cN0 breast cancer undergoing BCT were managed without ALND for metastases in <3 sentinel nodes (SNs) and no gross extracapsular extension (ECE). Patients with and without indications for ALND were compared using Fisher's exact and Wilcoxon rank sum tests. RESULTS: From August 2010 to November 2012, 2,157 invasive cancer patients had BCT. A total of 380 had histologic nodal metastasis; 93 did not meet Z0011 criteria. Of 287 with ≥1 H&E-positive SN (209 macrometastases), 242 (84 %) had indications for SN only. ALND was indicated in 45 for ≥3 positive SNs (n = 29) or ECE (n = 16). The median number of SNs removed in the SN group was 3 versus 5 in the ALND group (p < 0.0001). Age, hormone receptor and HER2 status, and grade did not differ between groups; tumors were larger in the ALND group (p < 0.0001). Of ALND patients, 72 % had additional positive nodes (median = 1; range 1-19). No axillary recurrences have occurred (median follow-up, 13 months). CONCLUSIONS: ALND was avoided in 84 % of a consecutive series of patients having BCT, suggesting that most patients meeting ACOSOG Z0011 eligibility have a low axillary tumor burden. Age, ER, and HER2 status were not predictive of ALND, and the criteria used for ALND (≥3 SNs, ECE) reliably identified patients at high risk for residual axillary disease.

An extensive investigation into the prevalence and the genetic and serological diversity of toxigenic Vibrio parahaemolyticus in Italian marine coastal waters.

The relationship between Vibrio parahaemolyticus strains isolated from the aquatic environment and those isolated from cases of infection in humans is poorly understood due to the low prevalence of tdh- and/or trh-positive strains in the environment. To address this concern, it would be useful to analyse the genetic relationships among environmental and food strains and with reference to clinical isolates, also applying molecular typing methods. The aim of this study was to evaluate the prevalence of toxigenic V.parahaemolyticus in Italian coastal waters and seafood, to examine intra-species variability and to identify, using serotyping and pulsed-field gel electrophoresis (PFGE), relationships among strains from different sources, geographical origin and period of isolation. Of the 192 V.parahaemolyticus strains isolated in different Italian areas and examined in this study, 25 (13.0%) proved to carry the trh gene while none of the strains proved positive to the search by PCR for tdh and Group-Specific-toxRS genes. The prevalence of toxigenic strains in the Tyrrhenian Sea was significantly lower than that calculated for the Ligurian coasts. Regarding the sources of isolation, the higher prevalence of trh-positive V.parahaemolyticus was revealed in fish, followed by clams, plankton, oysters, mussels and lastly seawater. Within the toxigenic strains, 16 serotypes and 20 distinct PFGE patterns were identified. Two clusters, which included a total of 8 V.parahaemolyticus strains, were specifically associated with the North Adriatic Sea area and were stable over time. Our results demonstrate that trh-positive V.parahaemolyticus strains circulated in Italy in the period 2002-2009 with a prevalence higher than that reported from other European and extra-European countries, confirming that toxigenic V.parahaemolyticus is an emerging public health concern in Italy, regardless of its pandemic potential.

Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: Nipple-sparing mastectomy (NSM) has been gathering increased recognition as an alternative to more traditional mastectomy approaches. Initially, questions concerning its oncologic safety limited the use of NSM. Nevertheless, mounting evidence supporting the practice of NSM for both prophylactic and oncologic purposes is leading to its more widespread use and broadened indications. METHODS: Using a prospectively maintained database, we reviewed our experience of 353 NSM procedures performed in 200 patients over the past 10 years. RESULTS: The indications for surgery were: 196 prophylactic risk-reduction (55.5%), 74 ductal carcinoma in situ (DCIS) (20.8%), 82 invasive cancer (23.2%), and 1 phyllodes tumor (0.5%). The nipple areolar complex (NAC) was entirely preserved in 341 mastectomies (96.7%). There were 11 patients (3.1%) who were found to have cancer at the nipple margin, warranting further excision. A total of 69 breasts (19.5%) had some degree of skin desquamation or necrosis, but only 12 (3.3%) required operative debridement, of which 3 breasts (1%) necessitated removal of a breast implant. Also, 6 patients (2%) were treated for infection. Of the 196 prophylactic NSMs, 11 specimens (5.6%) were found to harbor occult cancer (8 DCIS and 3 invasive cancers). One patient who underwent NSM for invasive ductal carcinoma in 2006 developed metastatic disease to her brain. No other recurrences are attributable to the 353 NSMs. CONCLUSIONS: The trends demonstrate the increasing acceptance of NSM as a prophylactic procedure as well as for therapeutic purposes. Although NSM is not standard, our experience supports the selective use of NSM in both prophylactic and malignant settings.