RESUMEN
BACKGROUND: Patients with primary cutaneous melanoma are at increased risk for subsequent new primary melanomas. Indoor tanning is a recognized risk factor for melanoma. This study was aimed at determining the association between indoor tanning and the occurrence of multiple primary melanoma. METHODS: This was a retrospective case-control study of cases with multiple primary melanoma and sex-matched controls with single primary melanoma retrieved at a 1:2 ratio from the Biological Sample and Nevus Bank of the Melanoma Center of the University of Pittsburgh Cancer Institute. Logistic regression models were used to examine the association between multiple primary melanoma and risk factors. RESULTS: In total, 330 patients (39.1% men) with a median age of 51 years were enrolled. Compared with patients who had a single primary melanoma, patients with multiple melanomas were younger at the diagnosis of their first primary melanoma and were more likely to be discovered at stage 0 or I and to have had indoor tanning exposure, a family history of melanoma, atypical moles, dysplastic nevi, and a Breslow thickness less than 1 mm. Compared with patients' first melanomas, subsequent melanomas were more likely to be thinner or in situ. The estimated probability of the locus for the second primary being the same as that for the first primary melanoma was 34%. In a multivariate analysis after adjustments for age, a family history of melanoma, the presence of atypical and dysplastic nevi, and recreational sun exposure, indoor tanning remained significantly associated with the occurrence of multiple primary melanoma (odds ratio, 2.75; 95% confidence interval, 1.07-7.08; P = .0356). CONCLUSIONS: Indoor tanning is associated with an increased risk of second primary melanoma. Subsequent melanomas are more likely to be thin or in situ and to occur in different anatomic locations.
Asunto(s)
Melanoma/epidemiología , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Inducidas por Radiación/epidemiología , Nevo Pigmentado/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Melanoma/etiología , Melanoma/patología , Persona de Mediana Edad , Neoplasias Primarias Múltiples/etiología , Neoplasias Primarias Múltiples/patología , Neoplasias Inducidas por Radiación/patología , Nevo Pigmentado/etiología , Nevo Pigmentado/patología , Factores de Riesgo , Piel/patología , Piel/efectos de la radiación , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Baño de Sol , Curtiembre , Melanoma Cutáneo MalignoRESUMEN
LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted. BACKGROUND: The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance. METHODS: In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab. RESULTS: Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3-7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5-14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib. CONCLUSION: The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.
Asunto(s)
Neoplasias Colorrectales , Factor A de Crecimiento Endotelial Vascular , Anilidas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Humanos , Panitumumab/farmacología , Panitumumab/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras) , PiridinasRESUMEN
BACKGROUND: Despite institutional perioperative bundles and national infection prevention guidelines, surgical site infection (SSI) after a major abdominal operation remains a significant source of morbidity. Negative pressure therapy (NPT) has revolutionized care for open wounds but the role of closed incision NPT (ciNPT) remains unclear. STUDY DESIGN: We conducted a multi-institutional randomized controlled trial evaluating SSI after major elective colorectal or hepatopancreatobiliary surgery (Clinical Trial Registration: NCT01905397). Patients were randomized to receive conventional wound care vs ciNPT (Prevena Incision Management System, 3M Health Care, San Antonio, TX). The primary endpoint was postoperative incisional SSI. SSI incidence was evaluated at inpatient days 4 or 5 and again at postoperative day 30. With 144 patients studied, the estimated power was 85% for detecting a difference in SSIs between 17% and 5% (conventional vs ciNPT; 1-sided α = 0.1). Secondary endpoints included SSI type, length of stay, 30-day readmission, and mortality. T-tests were used to compare continuous variables between treatments; similarly, chi-square tests were used to compare categorical variables. A p value of <0.05 was considered significant, except in the primary comparison of incisional and organ SSIs. RESULTS: During the 2013 to 2021 time period, 164 patients were randomized, and of those, 138 were evaluable (ciNPT n = 63; conventional n = 75). Incisional SSIs occurred in 9 (14%) patients in the ciNPT group and 13 (17%) patients in the conventional group (p = 0.31). Organ or space SSIs occurred in 7 (11%) patients in the ciNPT group and 10 (13%) in the conventional therapy group (p = 0.35). CONCLUSIONS: In this multi-institutional, randomized controlled trial of patients undergoing colorectal or hepatopancreatobiliary surgery, incidence of incisional SSIs between ciNPT and conventional wound therapy was not statistically significant. Future trials should focus on patient populations undergoing specific procedures types that have the highest risk for SSI.
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Neoplasias Colorrectales , Procedimientos Quirúrgicos del Sistema Digestivo , Terapia de Presión Negativa para Heridas , Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Resultado del Tratamiento , Herida Quirúrgica/complicaciones , Terapia de Presión Negativa para Heridas/métodosRESUMEN
OBJECTIVE: To determine the incidence of and potential risk factors for postoperative regurgitation and vomiting (PORV), postoperative nausea and vomiting (PONV), and aspiration pneumonia in geriatric dogs using premedication with maropitant and famotidine, intraoperative fentanyl, and postoperative fentanyl as part of an anesthetic protocol. ANIMALS: 105 client-owned geriatric dogs that underwent general anesthesia for a major surgical procedure between January 2019 and March 2020. PROCEDURES: Medical records were reviewed to collect data on signalment, historical gastrointestinal signs, American Society of Anesthesiologists (ASA) score, indication for surgery, duration of anesthesia and surgery, patient position during surgery, mode of ventilation, and perioperative administration of maropitant, famotidine, anticholinergics, opioids, colloidal support, NSAID, corticosteroids, and appetite stimulants. The incidence of postoperative regurgitation, vomiting, nausea, and aspiration pneumonia was calculated, and variables were each analyzed for their association with these outcomes. RESULTS: 2 of 105 (1.9%) dogs regurgitated, 1 of 105 (1.0%) dogs developed aspiration pneumonia, 4 of 105 (3.8%) dogs exhibited nausea, and no dogs vomited. Identified possible risk factors included older age (≥ 13 years old) for postoperative regurgitation, regurgitation for postoperative aspiration pneumonia, and high ASA score (≥ 4) for both regurgitation and aspiration pneumonia. CONCLUSIONS AND CLINICAL RELEVANCE: The use of an antiemetic protocol including maropitant, famotidine, and fentanyl in geriatric dogs resulted in very low incidences of PORV, PONV, and aspiration pneumonia. Future prospective studies are warranted to further evaluate and mitigate postoperative risks.
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Anestesia , Antieméticos , Enfermedades de los Perros , Neumonía por Aspiración , Náusea y Vómito Posoperatorios , Anestesia/efectos adversos , Anestesia/veterinaria , Animales , Antieméticos/uso terapéutico , Enfermedades de los Perros/cirugía , Perros , Famotidina/uso terapéutico , Fentanilo/uso terapéutico , Incidencia , Neumonía por Aspiración/etiología , Neumonía por Aspiración/prevención & control , Neumonía por Aspiración/veterinaria , Náusea y Vómito Posoperatorios/complicaciones , Náusea y Vómito Posoperatorios/prevención & control , Náusea y Vómito Posoperatorios/veterinaria , Quinuclidinas/uso terapéuticoRESUMEN
Progressive disease is common following anal sacculectomy for apocrine gland anal sac adenocarcinoma (AGASACA); additional therapy may prolong survival. Adherence to medical recommendations influences therapeutic success in humans. The purpose of this study was to assess the adherence to follow-up recommendations in dogs with AGASACA. Medical records of patients that underwent anal sacculectomy for AGASACA, with or without iliosacral lymphadenectomy, between July 2015 and July 2018, were reviewed at eight referral institutions to assess post-operative recommendations and owner adherence to recommendations. One hundred and seventy-four dogs were included, of which 162 underwent unilateral anal sacculectomy, 12 underwent bilateral anal sacculectomy and 39 underwent concurrent iliosacral lymphadenectomy. Seventy-six owners (44%) received recommendations for staging at the time of discharge, histopathology results or at the first follow-up visit. One hundred and forty owners (80%) received recommendations for treatment following the initial surgery. Fifty of seventy-six (66%) owners pursued at least one staging recommendation and 69 of 140 (49%) owners pursued some kind of adjuvant treatment recommendation. Overall, 16 of 76 (21%) were adherent to staging recommendations with 20 adherent for the first year following surgery (26%). Forty-seven of 140 (34%) were adherent to treatment recommendations with 54 (39%) adherent for the first year. Owners that were adherent to restaging recommendations at 1 year following surgery were significantly more likely to pursue treatment for progressive disease (P = .014). Further work is required to assess owner motivation and evaluate strategies to improve adherence, given the potential impact on patient treatment.