Objective: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions: Endotracheal Intubation Adverse Events. Main variables of interests: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30â¯minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65â¯mmHg recoded at least once or SBPâ¯<â¯90â¯mmHg for 30â¯minutes, a new requirement or increase of vasopressors, fluid bolus >15â¯mL/kg to maintain the target blood pressure; cardiac arrest. Results: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. Clinical Trial registration: www.clinicaltrials.gov identifier: NCT04909476.
Objetivo: Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ââen unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito: Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes: Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones: Eventos adversos de la intubación endotraqueal. Principales variables de interés: El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65â¯mmHg registrada al menos una vez o PASâ¯<â¯90â¯mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15â¯mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados: Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión: En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes. Registro de ensayos clínicos: www.clinicaltrials.gov identificador: NCT04909476.
Objective Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions Endotracheal Intubation Adverse Events. Main variables of interests The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent (AU)
Objetivo Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones Eventos adversos de la intubación endotraqueal. Principales variables de interés El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes (AU)
Humans , Male , Female , Middle Aged , Aged , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Pandemics , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Intubation, Intratracheal/adverse effects , Prospective Studies , Risk Factors
OBJECTIVE: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. SETTING: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. PATIENTS: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. INTERVENTIONS: Endotracheal Intubation Adverse Events. MAIN VARIABLES OF INTERESTS: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30â¯minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65â¯mmHg recoded at least once or SBPâ¯<â¯90â¯mmHg for 30â¯minutes, a new requirement or increase of vasopressors, fluid bolus >15â¯mL/kg to maintain the target blood pressure; cardiac arrest. RESULTS: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. CONCLUSION: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT04909476.
COVID-19 , Heart Arrest , Respiratory Distress Syndrome , Respiratory Insufficiency , Adult , Humans , SARS-CoV-2 , Critical Illness , Hypoxia
This article reports a new technique to restore iliac bone integrity with a customized titanium device designed by CAD/CAM, in patients undergoing deep circumflex iliac artery (DCIA) composite flap harvest. Eight consecutive patients who underwent the repair of major head and neck defects with DCIA flaps were enrolled retrospectively. Computed tomography scans of the pelvis were obtained preoperatively. Starting from DICOM data, each personalized device was designed using modelling software and was finally made by additive manufacturing using a laser sintering machine. After surgery, the patients were followed up at 3-month intervals to evaluate the incidence of complications and the long-term outcome at the donor site. A subcutaneous seroma developed in one patient and an inguinal skin burn occurred in another. At a median follow-up of 12 months, the patients did not report pain, or any gait or sensory disturbance at the donor site. There was no occurrence of bulging, herniation, or instability or inflammation near the device for the entire follow-up duration. All patients were satisfied with the aesthetic result. In conclusion, reconstruction of the iliac bone with a customized device is safe and well tolerated. We recommend use of this device in patients deemed at high risk of herniation. Further studies are needed to confirm the stability of the device in the long term.
Plastic Surgery Procedures , Esthetics, Dental , Humans , Iliac Artery , Ilium/diagnostic imaging , Ilium/surgery , Retrospective Studies
OBJECTIVES: To evaluate the diagnostic utility of individual cytological criteria and their best combination to differentiate benign from malignant perianal gland proliferative lesions in dogs. MATERIALS AND METHODS: Retrospective study of cytological samples of canine perianal gland proliferative lesions that had subsequent histopathological confirmation. RESULTS: Seventy-seven perianal gland nodules from 56 dogs were included. Histologically, lesions were diagnosed as hyperplasia (n=2), adenoma (n=53), epithelioma (n=6) and carcinoma (n=16). Of the 28 cytological criteria assessed, 13 showed promise for distinguishing benign from malignant lesions. A diagnostic algorithm with an 87% accuracy (sensitivity, 90.9%; specificity, 85.4%) was developed from these data. CLINICAL SIGNIFICANCE: Cytological evaluation can provide useful information for presurgical differentiation between benign and malignant hepatoid gland proliferative lesions. The proposed algorithm must be validated and tested for reproducibility in further, preferably larger, series of cases.
Anal Gland Neoplasms , Carcinoma/veterinary , Dog Diseases/diagnosis , Animals , Dogs , Perianal Glands , Reproducibility of Results , Retrospective Studies
Mast cell tumours (MCTs) are often diagnosed by cytology based on the identification of purple intracytoplasmic granules with methanolic Romanowsky stains, including May-Grünwald-Giemsa (MGG). In clinical practice, aqueous rapid stains (RS) are commonly used, but mast cell granules may not stain properly. Aim of this prospective study was to investigate the frequency of MCT hypogranularity with RS and its potential implications in tumour identification, cytological grading assessment and recognition of nodal metastatic disease. Cytological preparations of canine primary MCTs and metastatic lymph nodes with subsequent histopathological confirmation were included. For each case, good-quality smears were stained with both MGG and RS and comparatively assessed. Eleven of 60 (18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically high-grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be made. Accuracy in cytological grading assessment (85%) did not differ between RS and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS and 3 independent observers failed to identify nodal MCT metastases in 7% to 18% of RS-stained smears. This study confirms that, in limited cases, RS can be ineffective in staining MCT granules, particularly in high-grade tumours, thus making diagnosis more dependent on experience and quality of preparations. In dubious cases, methanolic stains should be applied. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be more challenging.
Coloring Agents/therapeutic use , Dog Diseases/diagnosis , Eosine Yellowish-(YS)/therapeutic use , Mastocytosis/veterinary , Methylene Blue/therapeutic use , Animals , Biopsy, Fine-Needle/veterinary , Dog Diseases/pathology , Dogs , Mast Cells/pathology , Mastocytosis/diagnosis , Mastocytosis/pathology , Mastocytosis, Cutaneous/diagnosis , Mastocytosis, Cutaneous/pathology , Mastocytosis, Cutaneous/veterinary , Mastocytosis, Systemic/diagnosis , Mastocytosis, Systemic/pathology , Mastocytosis, Systemic/veterinary , Prognosis , Prospective Studies
Feline large granular lymphocyte (LGL) lymphoma is an uncommon subtype of lymphoma characterized by a grave prognosis and scarce response to chemotherapy. There are limited reports on clinico-pathological and prognostic factors. One-hundred and 9 cats with newly diagnosed LGL lymphoma that underwent initial staging (including hematology, serum biochemistry, thoracic radiographs and abdominal ultrasound), and followed-up were retrospectively evaluated. LGL lymphoma was localized within the gastrointestinal tract with or without extra-intestinal involvement in 91.7% of the cases, and at extra-gastrointestinal sites in 8.3%. Symptoms were frequent. Anemia (31.2%) and neutrophilia (26.6%) were commonly observed, and 14 (12.8%) cats had neoplastic circulating cells. Frequent biochemistry abnormalities included elevated ALT (39.4%) and hypoalbuminemia (28.4%). Twenty (54.1%) of 37 cats had elevated serum LDH. Treatment varied among cats, and included surgery (11%), chemotherapy (23%), corticosteroids (38.5%) and no treatment (27.5%). Median time to progression (MTTP) was 5 days, and median survival time (MST) 21 days. MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response. A small subset of cats (7.3%) survived more than 6 months, suggesting that a more favorable clinical course can be found among LGL lymphoma patients.
Cat Diseases/pathology , Lymphoma/veterinary , Animals , Cat Diseases/diagnosis , Cat Diseases/mortality , Cats , Female , Lymphoma/diagnosis , Lymphoma/mortality , Lymphoma/pathology , Male , Prognosis , Retrospective Studies , Survival Analysis
BACKGROUND: This study describes the feasibility of Contrast Enhanced Ultrasonography (CEUS) in the diagnostic work-up of non-cardiac thoracic disorders of small animals. The second aim is to assess the usefulness of CEUS as a direct guide for sample procedures. RESULTS: Forty animals, 28 dogs and 12 cats, were included in the study. Thoracic disorders included 23 pulmonary lesions [primary carcinoma (14), lymphoma (1), sarcoma (1), histiocytic sarcoma (1), abscess (1) and pneumonia (5)] and 17 mediastinal lesions [lymphoma (8), thymoma (3), mesothelioma (1), melanoma (1), carcinomatous lymphadenopathy (1), mixsosarcoma (1), lipoma (1), and abscess (1)]. The majority of neoplastic pulmonary lesions showed an inhomogeneous distribution of contrast medium, whereas inflammatory lesions had a homogenous distribution with typical pulmonary vessels ramification. The majority of mediastinal malignant lesions showed an inhomogeneous distribution pattern. The lung and mediastinal abscesses had peripheral enhancement of the wall with an avascular center. All cytological and biopsy samples obtained after CEUS were diagnostic. Quantitative analysis, performed in 19/23 pulmonary lesions, showed a statistically significant difference (P < 0.0001) between the arrival time of the malignant (7.27 s - range 4.46-13.52 s) and benign (4.52 s - range 2.87-6.06 s) pulmonary lesions. CONCLUSIONS: CEUS may be a useful tool for the evaluation of non-cardiac thoracic lesions. The contrast medium allows for the precise definition of lesion edges, the presence of necrotic areas, and the distribution of pulmonary vessels. Based on our preliminary results, the use of ultrasonographic contrast medium can be recommended for improving the diagnostic usefulness of cytology and biopsy sampling, because CEUS may help to define necrotic areas from viable tissue.
Cat Diseases/diagnostic imaging , Dog Diseases/diagnostic imaging , Lung Diseases/veterinary , Mediastinal Diseases/veterinary , Ultrasonography/veterinary , Animals , Cats , Contrast Media , Dogs , Feasibility Studies , Female , Lung Diseases/diagnostic imaging , Male , Mediastinal Diseases/diagnostic imaging , Prospective Studies
BACKGROUND: Osteosarcoma (OSA) should be differentiated from other less frequent primary bone neoplasms, metastatic disease, and tumor-like lesions, as treatment and prognosis can vary accordingly. Hence, a preoperative histologic diagnosis is generally preferred. This requires collection of multiple biopsies under general anesthesia, with possible complications, including pathological fractures. Fine-needle aspiration cytology would allow an earlier diagnosis with a significant reduction of discomfort and morbidity. HYPOTHESIS/OBJECTIVES: The aim of this study was to compare the accuracy of cytological and histologic biopsies in the diagnosis of canine osteodestructive lesions. ANIMALS: Sixty-eight dogs with bone lesions. METHODS: Retrospective study. Accuracy was assessed by comparing the former diagnosis with the final histologic diagnosis on surgical or post-mortem samples or, in the case of non-neoplastic lesions, with follow-up information. RESULTS: The study included 50 primary malignant bone tumors (40 OSAs, 5 chondrosarcomas, 2 fibrosarcomas, and 3 poorly differentiated sarcomas), 6 carcinoma metastases, and 12 non-neoplastic lesions. Accuracy was 83% for cytology (sensitivity, 83.3%; specificity, 80%) and 82.1% for histology (sensitivity, 72.2%; specificity, 100%). Tumor type was correctly identified cytologically and histologically in 50 and 55.5% of cases, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The accuracy of cytology was similar to histology, even in the determination of tumor type. In no case was a benign lesion diagnosed as malignant on cytology. This is the most important error to prevent, as treatment for malignant bone tumors includes aggressive surgery. Being a reliable diagnostic method, cytology should be further considered to aid decisions in the preoperative setting of canine bone lesions.
Bone Diseases/veterinary , Dog Diseases/diagnosis , Animals , Biopsy, Fine-Needle/veterinary , Bone Diseases/diagnosis , Bone Diseases/pathology , Bone Neoplasms/diagnosis , Bone Neoplasms/pathology , Bone Neoplasms/veterinary , Bone and Bones/pathology , Chondrosarcoma/diagnosis , Chondrosarcoma/pathology , Chondrosarcoma/veterinary , Diagnosis, Differential , Dog Diseases/pathology , Dogs , Female , Fibrosarcoma/diagnosis , Fibrosarcoma/pathology , Fibrosarcoma/veterinary , Male , Osteosarcoma/diagnosis , Osteosarcoma/pathology , Osteosarcoma/veterinary , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity
This study investigated Kit receptor dysregulations (cytoplasmic immunohistochemical expression and/or c-KIT mutations) in cats affected with splenic mast cell tumours. Twenty-two cats were included. Median survival time was 780 days (range: 1-1219). An exclusive splenic involvement was significantly (P = 0.042) associated with longer survival (807 versus 120 days). Eighteen tumours (85.7%) showed Kit cytoplasmic expression (Kit pattern 2, 3). Mutation analysis was successful in 20 cases. Fourteen missense mutations were detected in 13 out of 20 tumours (65%). Eleven (78.6%) were located in exon 8, and three (21.6%) in exon 9. No mutations were detected in exons 11 and 17. Seven mutations corresponded to the same internal tandem duplication in exon 8 (c.1245_1256dup). Although the association between Kit cytoplasmic expression and mutations was significant, immunohistochemistry cannot be considered a surrogate marker for mutation analysis. No correlation was observed between c-Kit mutations and tumour differentiation, mitotic activity or survival.
Cat Diseases/metabolism , Mastocytosis/veterinary , Proto-Oncogene Proteins c-kit/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Splenic Neoplasms/veterinary , Animals , Cat Diseases/enzymology , Cat Diseases/genetics , Cats , Female , Male , Mastocytosis/enzymology , Mastocytosis/genetics , Mastocytosis/metabolism , Mutation/genetics , Proto-Oncogene Proteins c-kit/genetics , Receptor Protein-Tyrosine Kinases/genetics , Splenic Neoplasms/enzymology , Splenic Neoplasms/genetics , Splenic Neoplasms/metabolism
T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects children and less commonly adults. Female genital tract and particularly uterus involvement in acute ALL is rare. This report presents the CT features of a 64-year-old woman with uterine relapse of T-cell ALL, occurring 11 months after the diagnosis, as a second, unique relapse of disease. The patient was asymptomatic when a CT examination showed a homogenous thickness of the uterine wall in comparison with the previous CT examination. Histology from biopsy specimens, obtained through hysteroscopy, confirmed T-cell ALL localisation (TdT+, CD10+, CD3c+ and CD2+). The uterus could be a site of relapse in patients suffering from ALL. Even though an MRI examination could better demonstrate the disease in cases of suspected female genital tract involvement by ALL, the comparison of differences between a present and a previous CT examination is sufficient to suspect the diagnosis.
Leukemic Infiltration/diagnostic imaging , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnostic imaging , Tomography, X-Ray Computed , Uterus/diagnostic imaging , Antigens, Differentiation, T-Lymphocyte/analysis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Breast Neoplasms/drug therapy , DNA Nucleotidylexotransferase/analysis , Female , Humans , Hysteroscopy , Immunophenotyping , Middle Aged , Neoplasms, Second Primary , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , T-Lymphocytes/chemistry , T-Lymphocytes/pathology
OBJECTIVES: This study aimed to evaluate the agreement between microscopic and molecular testing for differentiating feline intestinal bowel disease and small cell alimentary lymphoma in duodenal endoscopic biopsies. METHODS: Four different diagnostic methods (cytology, histology, immunohistochemistry and clonality) were sequentially applied to 77 cases of feline chronic enteropathies. The agreement between the different diagnostic methods was calculated and survival data were obtained to assess the most reliable method for predicting outcome. RESULTS: Seventy-seven cases were included in the study. On multivariate survival analysis, only the clonality-based diagnosis of lymphoma was significantly associated with poor survival, with a risk of enteropathy-related death 2·8 times higher. By comparing the other tests with clonality, specificity was high (87 to 97%), whereas sensitivity was 36·8% for cytology, 39·5% for histology, 63·2% for immunohistochemistry, resulting in an overall accuracy of 62·3, 68·8 and 80·5%, respectively. CLINICAL SIGNIFICANCE: Clonality analysis can consistently increase the possibility of correctly and early diagnosing small cell lymphoma on endoscopic biopsies. Histological suspicion of alimentary lymphoma, even if not confirmed by clonality, should never be ignored, as it may represent a debutant form of lymphoma or it may later progress to lymphoma.
Cat Diseases/diagnosis , Inflammatory Bowel Diseases/veterinary , Intestinal Neoplasms/veterinary , Lymphoma/veterinary , Animals , Cat Diseases/pathology , Cats , Diagnosis, Differential , Duodenoscopy/veterinary , Duodenum/pathology , Female , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/pathology , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/pathology , Lymphoma/diagnosis , Lymphoma/pathology , Male , Sensitivity and Specificity , Specimen Handling
OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of various medications (bisphosphonates, anti-resorptive, and anti-angiogenic drugs). ONJ pathogenesis is still unclear although some risk factors have been recognized. Of these, rheumatoid arthritis (RA) has been hypothesized as a potential risk factor for developing ONJ. This observational study will describe a multicenter case series of patients affected with RA and ONJ, and it will attempt to evaluate the association between features of ONJ and pharmacological, systemic, and site variables. METHODS: Demographic, pharmacological, and clinical data from 18 RA patients with ONJ were collected and registered from three Italian centers (i.e., Palermo, Verona, and Padua) from 2004 to 2013. RESULTS: Sixteen (88.9%) patients were in therapy for RA: 9 of 18 (50.0%) with systemic steroids, 3 of 18 (16.7%) with methotrexate, and 4 of 18 (22.2%) with both medications. Two patients were not receiving treatment for RA. All patients took NBPs for secondary osteoporosis (average NBP duration of 69 months, range: 20-130): Fifteen (83.3%) patients were treated with single NBPs, while three (16.7%) with different molecules; one patient was also treated with denosumab. Mandible was affected more frequently (66.7%) than maxilla (33.3%); one patient presented multiple ONJ events. CONCLUSIONS: This is the first multicenter case series in the international literature regarding our topic. Focusing on our data, it could be hypothesized that patients with RA may be more susceptible to ONJ than the majority of osteometabolic patients. In our opinion, it could be important to monitor also denosumab or other biological drug side effects.
Arthritis, Rheumatoid/drug therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Aged , Female , Humans , Male , Middle Aged
Sebaceous gland tumours represent the third most common skin tumours in dogs, but diagnostic criteria for tumours with basal differentiation (i.e. sebaceous epithelioma) are poorly defined and there is lack of correlation with biological behaviour. The aim of this study was to identify the main histological criteria associated with malignancy in 30 canine sebaceous gland tumours with a predominant reserve cell population. For each case, tumour proliferative activity was assessed by determining mitotic index and the Ki67/MIB-1 index. Additional histological features included endophytic or exophytic growth, proportion of reserve/intermediate/mature cells, connection to the epidermis, nuclear characteristics, peripheral invasion, neoplastic emboli and necrosis. Mitotic and Ki67 indexes were variable, but correlated (R = 0.66; P < 0.001), and both were significantly higher in infiltrative tumours (P = 0.018 and P < 0.001, respectively). No significant difference in histological features was observed between tumours comprised of more or less than 90% reserve cells, nor among tumours showing proliferative activity in sebocytes. This study suggests that high proliferative activity and peripheral invasion should be considered the most significant parameters for the differentiation between benign and malignant sebaceous gland tumours. Furthermore, the incidence of circumanal gland and testicular tumours in these dogs was significantly higher compared with an age-matched control population, suggesting a potential androgen-related pathway for the tumourigenesis of canine sebaceous gland neoplasms.
Dog Diseases/pathology , Sebaceous Gland Neoplasms/veterinary , Animals , Cell Proliferation , Dogs , Female , Immunohistochemistry , Male , Mitotic Index , Sebaceous Gland Neoplasms/pathology
Mast cell tumor (MCT) is a common canine cutaneous neoplasm with variable biological behavior. A 2-tier histologic grading system was recently proposed by Kiupel et al to reduce interobserver variation and eliminate prognostic uncertainty of the Patnaik system. This study compared the ability of these 2 grading systems to predict survival in a cohort of dogs with MCTs. However, surgical margins were unknown, and the risk of developing new/metastatic MCTs was not studied. Histologic grade was assessed according to both systems for 137 surgically resected cutaneous MCTs. The relationship between grade and survival was evaluated. According to the Patnaik system, 18 MCTs (13.1%) were classified as grade I, 83 (60.6%) as grade II, and 36 (26.3%) as grade III. Grade III was associated with a poorer prognosis (P < .001), but no significant difference between grades I and II was detected. Grading according to the Patnaik system was based on consensus grading among 3 pathologists, and interobserver variability was not considered. All grade I MCTs were low grade in the Kiupel system, and all grade III were high grade. Among grade II, 71 (85.6%) were low grade, and 12 (14.4%) were high grade, with a 1-year survival probability of 94% and 46%, respectively (P < .001). The 2-tier system had a high prognostic value and was able to correctly predict the negative outcomes of some grade II MCTs. Data also confirm that histologic grading cannot predict biological behavior of each MCT and should be supplemented with molecular methods for more accurate prognostication.
Dog Diseases/pathology , Mastocytosis, Cutaneous/veterinary , Skin Neoplasms/veterinary , Animals , Dogs , Kaplan-Meier Estimate , Mast Cells/pathology , Mastocytosis, Cutaneous/pathology , Neoplasm Grading/veterinary , Observer Variation , Prognosis , Retrospective Studies , Skin Neoplasms/pathology
The aim of this retrospective study was to describe clinical features, treatment and outcome of 21 dogs with metastatic cancer of unknown primary (MCUP), a biopsy-proven malignancy being diagnosed at a metastatic stage, in which the anatomical origin of the primary tumour cannot be detected. All dogs underwent total-body computed tomography. Signalment, type and duration of clinical signs, metastasis site, pathology results, treatment and outcome were recorded. Carcinoma was the most common diagnosis (57.1%), followed by sarcoma, melanoma and mast cell tumour. The median number of disease sites per dog was 2, with bones, lymph nodes, lungs and spleen being the most frequent metastatic locations. The median survival for all dogs was 30 days. Overall, a primary site was not identified in 20 (95.2%) dogs. MCUP encompasses a variety of different pathologic entities and harbours a poor prognosis.
Carcinoma/veterinary , Dog Diseases/pathology , Mastocytoma/veterinary , Melanoma/veterinary , Neoplasms, Unknown Primary/veterinary , Sarcoma/veterinary , Animals , Bone Neoplasms/secondary , Bone Neoplasms/veterinary , Carcinoma/secondary , Dog Diseases/mortality , Dogs , Female , Lung Neoplasms/secondary , Lung Neoplasms/veterinary , Lymphoma/veterinary , Male , Mastocytoma/secondary , Melanoma/secondary , Retrospective Studies , Sarcoma/secondary , Splenic Neoplasms/secondary , Splenic Neoplasms/veterinary
This study reports the main clinicopathological features of primary lung cancer (PLC) in 37 dogs, with special regard to the pathogenetic and prognostic role of epidermal growth factor receptor (EGFR) overexpression. For each case the following characteristics were evaluated: tumour-node-metastasis (TNM) stage, tumour histotype, histological grade, mitotic activity and immunohistochemical expression of EGFR. In samples with available normal lung tissue, the amount of background anthracosis was also measured by image analysis. In 27 tumours (73%) a variable number of cells (20-100%) stained positively for EGFR. The proportion of EGFR-positive tumours was significantly higher in cases with background anthracosis, and the amount of anthracosis was correlated with the percentage of positive tumour cells. Additionally, a trend towards shortened survival for the high EGFR group was observed. These findings suggest an involvement of EGFR signalling pathway in canine PLC, a negative prognostic significance of protein overexpression and its potential implication in air pollution carcinogenesis.
Dog Diseases/metabolism , ErbB Receptors/metabolism , Gene Expression Regulation, Neoplastic/physiology , Lung Neoplasms/veterinary , Air Pollution/adverse effects , Animals , Anthracosis/genetics , Anthracosis/metabolism , Anthracosis/veterinary , Dog Diseases/genetics , Dog Diseases/pathology , Dogs , ErbB Receptors/genetics , Female , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Risk Factors
Feline cutaneous mast cell tumors (FeCMCTs) are characterized by variable biological behavior. Development of multiple nodules and potential visceral involvement, along with inconsistency of conventional prognostic aids, justify uncertainty in differentiating benign from malignant forms. c-Kit proto-oncogene activating mutations have been reported in feline mast cell tumors (MCTs), but their prognostic relevance was not investigated. This study was performed on FeCMCTs with variable clinical outcome to assess whether Kit cytoplasmic immunohistochemical labeling can be regarded as indicative of c-Kit mutations and to evaluate the relationship between Kit dysregulation and survival. Twenty-four cats diagnosed with a primary cutaneous MCT were enrolled. Kit immunohistochemical pattern and c-Kit (exons 8, 9, 11) mutational status were assessed in 34 tumor samples. Risk factors affecting survival were a number of mitoses greater than 5 per 10 HPFs (P = .017) and cytoplasmic Kit labeling (P = .045). Increased mitotic activity was associated with Kit cytoplasmic expression (P = .01). c-Kit encoding mutations were present in 19 (56%) tumors (exon 8, 19%; exon 9, 71%; exon 11, 10%), however, they were not significantly related to protein expression and they had no influence on prognosis. Additionally, in 6 of 9 (67%) cats, multiple nodules from the same cat had different mutational statuses. Mutations in the fifth immunoglobulin-like domain of Kit occur frequently in FeCMCT, but they are variably associated with aberrant protein expression and do not appear to be strictly correlated with biological behavior. These findings need to be confirmed in larger series, and exploration of further genomic regions of c-Kit is warranted.
Cat Diseases/enzymology , Cat Diseases/metabolism , Gene Expression Regulation, Enzymologic/physiology , Gene Expression Regulation, Neoplastic/physiology , Mastocytosis, Cutaneous/veterinary , Proto-Oncogene Proteins c-kit/metabolism , Animals , Cats , DNA Mutational Analysis/veterinary , Histological Techniques/veterinary , Immunohistochemistry/veterinary , Italy , Mastocytosis, Cutaneous/enzymology , Mastocytosis, Cutaneous/metabolism , ROC Curve
Canine nodular dermatofibrosis is a rare skin disease associated with renal cystadenoma or cystadenocarcinoma and uncommonly with uterine leiomyoma. It is generally seen in German shepherd dogs, but has been also reported in other breeds, and a relationship has been suggested with mutation of the gene encoding folliculin (FLCN), which is located on chromosome 5. A 10-year-old female golden retriever was presented because of numerous firm cutaneous nodules up to 4 cm in diameter over the entire body surface. Cytological and histopathological examinations confirmed generalized cutaneous nodular dermatofibrosis, but ultrasonography of both kidneys ruled out renal neoplasia. Ovariohysterectomy was performed because of prolonged oestrus periods. Microscopical examination of the excised tissues confirmed the absence of uterine neoplasia, but identified rete adenoma of the right ovary. Abdominal ultrasound performed repeatedly over a 5-year follow-up period did not identify any alteration in the renal parenchyma. Molecular studies excluded the presence of any mutation in the FLCN gene.
Dog Diseases/diagnosis , Dog Diseases/pathology , Skin Diseases/veterinary , Animals , Dog Diseases/genetics , Dogs , Estrone/genetics , Female , Kidney Neoplasms/pathology , Mutation/genetics , Skin Diseases/diagnosis , Skin Diseases/pathology
Feline head and neck squamous cell carcinoma (SCC) is a loco-regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials.
Carcinoma, Squamous Cell/veterinary , Cat Diseases/therapy , Head and Neck Neoplasms/veterinary , Radiotherapy/veterinary , Animals , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Cats , Female , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Male , Pilot Projects , Treatment Outcome
