Clinical and pathological analysis of epidural inflammation in intervertebral disk extrusion in dogs

BACKGROUND Little is known about the pathologic changes in the epidural space after intervertebral disk (IVD) extrusion in the dog. OBJECTIVES To analyze the pathology of the epidural inflammatory response, and to search for correlations between this process and clinical findings. METHODS Clinical data from 105 chondrodystrophic (CD) and nonchondrodystrophic (NCD) dogs with IVD extrusion were recorded. Epidural material from these dogs was examined histopathologically and immunohistochemically. Using statistical analysis, we searched for correlations between severity of epidural inflammation and various clinical and pathologic variables. RESULTS Most dogs exhibited an epidural inflammatory response, ranging from acute invasion of neutrophils to formation of chronic granulation tissue. The mononuclear inflammatory infiltrates consisted mostly of monocytes and macrophages and only few T and B cells. Surprisingly, chronic inflammatory patterns also were found in animals with an acute clinical history. Severity of the epidural inflammation correlated with degree of the epidural hemorrhage and nucleus pulposus calcification (P = .003 and .040), but not with age, chondrodystrophic phenotype, neurologic grade, back pain, pretreatment, or duration. The degree of inflammation was statistically (P = .021) inversely correlated with the ability to regain ambulation. CONCLUSION AND CLINICAL IMPORTANCE Epidural inflammation occurs in the majority of dogs with IVD extrusion and may develop long before the onset of clinical signs. Presence of calcified IVD material and hemorrhage in the epidural space may be the triggers of this lesion rather than an adaptive immune response to the nucleus pulposus as suggested in previous studies. Because epidural inflammation may affect outcome, further research is warranted.

Immunolocalization and pathological alterations following Strongyloides venezuelensis infection in the lungs and the intestine of MHC class I or II deficient mice

The present study, investigated the mechanisms involved in the immune responses of Major Histocompatibility Complex class I or class II knockout mice, following Strongyloides venezuelensis infection. Wild-type C57BL/6 (WT), MHC II(-/-) and MHC I(-/-) mice were individually inoculated with 3000 larvae (U) of S. venezuelensis and sacrificed on days 1, 3, 5, 8, 13 and 21 post-infection (p.i.). Samples of blood, lungs and small intestines were collected. The tissue samples were stained with hematoxylineosin for the pathological analysis. The presence of the parasite was demonstrated by immunoperoxidase analysis. MHC II(-/-) mice presented a significantly higher number of adult worms recovered from the small intestine on day 5 p.i. and presented elevated numbers of eggs in the feces. The infection by S. venezuelensis was completely eliminated 13 days after infection in WT as well as in MHC I(-/-) mice. In MHC II(-/-) mice, eggs and adult worms were still found on day 21 p.i., however, there was a significant reduction in their numbers. In the lung, the parasite was observed in MHC I(-/-) on day 1 p.i. and in MHC II(-/-) mice on days 1 and 5 p.i. In the small intestine of WT mice, a larger number of parasites were observed on day 8 p.i. and their absence was observed after day 13 p.i. Through immunohistochemistry analysis, the parasite was detected in the duodenum of WT on days 5 and 8 p.i., and in knockout mice on days 5, 8 and 13 p.i.; as well as in posterior portions of the small intestine in MHC I(-/-) and MHC II(-/-) on day 13 p.i., a finding which was not observed in WT mice. We concluded that immunohistochemistry analysis contributed to a more adequate understanding of the parasite localization in immunodeficient hosts and that the findings aid in the interpretation of immunopathogenesis in Strongyloides infection. (C) 2008 Elsevier B.V. All rights reserved.

Occult Axillary Lymph Node Metastases in Breast Cancer Do Matter: Results of 10-Year Survival Analysis

Axillary lymph node status is one of the most powerful prognostic factors for patients with breast cancer and is often critical in stratifying patients into adjuvant treatment regimens. In 203 apparently node-negative cases of breast cancer, a combination of immunohistochemical staining and step-sectioning identified occult metastases in 25% of cases. Ten-year follow-up information is available for these patients. Histologic features of the primary tumor and immunohistochemical staining for estrogen receptor, progesterone receptor, Her-2, and p53 were also evaluated. With multivariate analysis, both occult metastases and higher histologic grade of the primary tumor were independent predictors of disease-free survival. Histologic grade was the only significant independent predictor of overall survival. Estrogen receptor, progesterone receptor, Her-2, and p53 status did not predict the presence of metastases or survival when all tumor types were considered together. Metastases >0.5 mm significantly predicted a poorer disease-free survival when invasive ductal carcinomas were considered alone. Histologic grade was significantly associated with disease-free survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients. The presence of occult metastases approached significance for overall survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients.

Predicting necrosis in residual mass analysis after retroperitoneal lymph node dissection: a retrospective study

Background: Recent studies have demonstrated that pathological analysis of retroperitoneal residual masses of patients with testicular germ cell tumors revealed findings of necrotic debris or fibrosis in up to 50% of patients. We aimed at pursuing a clinical and pathological review of patients undergoing post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in order to identify variables that may help predict necrosis in the retroperitoneum. Methods: We performed a retrospective analysis of all patients who underwent PC-RPLND at the University Hospital of the University of Sao Paulo and Cancer Institute of Sao Paulo between January 2005 and September 2011. Clinical and pathological data were obtained and consisted basically of: measures of retroperitoneal masses, histology of the orchiectomy specimen, serum tumor marker and retroperitoneal nodal size before and after chemotherapy. Results: We gathered a total of 32 patients with a mean age of 29.7; pathological analysis in our series demonstrated that 15 (47%) had necrosis in residual retroperitoneal masses, 15 had teratoma (47%) and 2 (6.4%) had viable germ cell tumors (GCT). The mean size of the retroperitoneal mass was 4.94 cm in our sample, without a difference between the groups (P = 0.176). From all studied variables, relative changes in retroperitoneal lymph node size (P = 0.04), the absence of teratoma in the orchiectomy specimen (P = 0.03) and the presence of choriocarcinoma in the testicular analysis after orchiectomy (P = 0.03) were statistically significant predictors of the presence of necrosis. A reduction level of 35% was therefore suggested to be the best cutoff for predicting the absence of tumor in the retroperitoneum with a sensitivity of 73.3% and specificity of 82.4%. Conclusions: Even though retroperitoneal lymph node dissection remains the gold standard for patients with residual masses, those without teratoma in the primary tumor and a shrinkage of 35% or more in retroperitoneal mass have a considerably smaller chance of having viable GCT or teratoma in the retroperitoneum and a surveillance program could be considered.

Microlithiasis of the gallbladder: role of endoscopic ultrasonography in patients with idiopathic acute pancreatitis

OBJECTIVES: Causes may be found in most cases of acute pancreatitis, however no etiology is found by clinical, biological and imaging investigations in 30% of these cases. Our objective was to evaluate results from endoscopic ultrasonography (EUS) for diagnosis of gallbladder microlithiasis in patients with unexplained (idiopathic) acute pancreatitis. METHODS: Thirty-six consecutive non-alcoholic patients with diagnoses of acute pancreatitis were studied over a five-year period. None of them showed signs of gallstones on transabdominal ultrasound or tomography. We performed EUS within one week of diagnosing acute pancreatitis. Diagnosis of gallbladder microlithiasis on EUS was based upon findings of hyperechoic signals of 0.5-3.0 mm, with or without acoustic shadowing. All patients (36 cases) underwent cholecystectomy, in accordance with indication from the attending physician or based upon EUS diagnosis. RESULTS: Twenty-seven patients (75%) had microlithiasis confirmed by histology and nine did not (25%). EUS findings were positive in twenty-five. Two patients had acute cholecystitis diagnosed at EUS that was confirmed by surgical and histological findings. In two patients, EUS showed cholesterolosis and pathological analysis disclosed stones not detected by EUS. EUS diagnosed microlithiasis in four cases not confirmed by surgical treatment. In our study, sensitivity, specificity and positive and negative predictive values to identify gallbladder microlithiasis (with 95% confidence interval) were 92.6% (74.2-98.7%), 55.6% (22.7-84.7%), 86.2% (67.4-95.5%) and 71.4% (30.3-94.9%), respectively. Overall EUS accuracy was 83.2%. CONCLUSIONS: EUS is a very reliable procedure to diagnose gallbladder microlithiasis and should be used for the management of patients with unexplained acute pancreatitis. This procedure should be part of advanced endoscopic evaluation.

Development of chronic cardiomyopathy in canine Chagas disease correlates with high IFN-gamma, TNF-alpha, and low IL-10 production during the acute infection phase

When infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-gamma and TNF-alpha production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi. Pathological analysis showed severe splenomegaly, lymphadenopathy and myocarditis in all infected dogs during the acute phase of the disease, with cardiomegaly, inflammation and fibrosis observed in 83% of the animals infected by T. cruzi during the chronic phase. The data indicate that infected animals producing IL-10 in the heart during the chronic phase and showing high IL-10 production in the culture supernatant and serum during the acute phase had lower cardiac alterations (myocarditis, fibrosis and cardiomegaly) than those with high IFN-gamma and TNF-alpha levels. These animals produced low IL-10 levels in the culture supernatant and serum during the acute phase and did not produce IL-10 in the heart during the chronic phase of the disease. Our findings showed that Beagle dogs are a good model for studying the immunopathogenic mechanism of Chagas disease, since they reproduce the clinical and immunological findings described in chagasic patients. The data suggest that the development of the chronic cardiac form of the disease is related to a strong Th1 response during the acute phase of the disease, while the development of the indeterminate form results from a blend of Th1 and Th2 responses soon after infection, suggesting that the acute phase immune response is important for the genesis of chronic cardiac lesions. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.

Appendiceal Mucocele – Unexpected Diagnosis in a Gynecology Department

Appendiceal mucocele is a rare entity, occuring in < 1% among appendicectomies, with a female predominance 4/1 (F/M) and a mean age of more than 50 years. The preoperative diagnosis is difficult; in most cases, it´s an intraoperative finding. In such work, we describe the two clinical cases occurring in last 10 years in our Department. Case 1 - 56 years old, posmenopausal, referred to our Department (02/2004) because an asymptomatic right adnexal septated cystic image, 53x48mm, with hipovascularized septa and a vascularised capsule with low flow resistance (IR 0,57). CA 125 elevated (71,3 U/mL).Exploratory laparotomy: an ovary increased, with a gelatanious consistency and an appendicular enlargement. Extemporaneous examination: a pseudomixoma peritonei, associated with a mucinous appendicular and an ovary tumor. It was performed a radical surgery. The histo-pathological analysis showed a mucinous cystadenoma of the appendix with peritoneal mucinous dissemination involving the ovary. Expectant attitude since the surgery, without clinical and imaging signs of recurrence. Case 2- 62 years old posmenopausal and asymptomatic woman, with a large adnexal mass detected on routine pelvic ultrasound: heterogeneous, 94x84mm without vascularisation signs in its interior. CEA was elevated (41,47U/ml). Exploratory laparotomy (02/2010): enlarged appendix and macroscopically normal pelvic organs. An appendicectomy was performed. The histo-pathological analysis showed a 10cm mucinous cystadenoma of the appendix and signs of localized (visceral peritoneal surface) pseudomyxoma peritonei. Currently she’s clinically well, in an expectant attitude. Despite mucoceles of the appendix are rare, they should be considered in women presenting with abnormal quadrant masses.

Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis.

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean±sd 1.6±1.1 versus 5.3±4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.

Adénome pléomorphe simulant une dacryoadénite [Pleomorphic adenoma mimicking dacryoadenitis].

A 56-year-old female patient displayed an increased volume of her left lacrimal gland with pain and inflammation. On CT scan, a hyperdense lacrimal mass was found in the left lacrimal fossa. Observation was the first course, for no steroid therapy could be applied because of evolving digestive ulcers. After 9 months of observation, the gland was surgically removed en bloc through a wide anterolateral approach. Pathological analysis of the gland showed a pleomorphic adenoma. This case illustrates the advantage of a wide surgical approach in treating lacrimal gland tumors, in order to avoid or limit the risk of recurrence.

Computed tomography-guided percutaneous biopsy of pancreatic masses using pneumodissection

Objective To describe the technique of computed tomography-guided percutaneous biopsy of pancreatic tumors with pneumodissection. Materials and Methods In the period from June 2011 to May 2012, seven computed tomography-guided percutaneous biopsies of pancreatic tumors utilizing pneumodissection were performed in the authors' institution. All the procedures were performed with an automatic biopsy gun and coaxial system with Tru-core needles. The biopsy specimens were histologically assessed. Results In all the cases the pancreatic mass could not be directly approached by computed tomography without passing through major organs and structures. The injection of air allowed the displacement of adjacent structures and creation of a safe coaxial needle pathway toward the lesion. Biopsy was successfully performed in all the cases, yielding appropriate specimens for pathological analysis. Conclusion Pneumodissection is a safe, inexpensive and technically easy approach to perform percutaneous biopsy in selected cases where direct access to the pancreatic tumor is not feasible.

Oral fibrosarcoma in jararaca (Bothrops pubescens): anatomopathological and immunohistochemical aspects

Abstract A 4-year-old female captive-bred snake of the genus Bothrops showed swelling on the left side of the oral cavity, suggesting the development of neoplasia. The mass was removed surgically and sent for pathological examination. Two months later a new increase in volume in the same site was observed, suggesting recurrence. The lesion was completely removed and sent for pathological analysis. Histologically, the two-samples consisted of a mass with highly-cell density composed of spindle-shaped anaplastic cells arranged in interwoven bundles, distributed throughout the tissue extension and, occasionally, polygonal cells arranged in irregular fascicles. The Masson trichrome staining showed modest amount of collagen supporting the neoplastic cells. PAS-positive content was not observed in the cytoplasm of neoplastic cells. Histological and histochemical findings indicated that it was a spindle cell neoplasm, but the classification was not possible. Immunohistochemistry was requested and performed using the streptavidin-biotin-peroxidase method. The markers used were anti-vimentin, anti-PCNA, anti-EMA, anti-melan A and anti-melanosome, anti-desmin, anti-actin, anti-CD68 and anti- S100protein. The neoplastic cells were immunoreactive for vimentin and PCNA and negative for the other antibodies. The morphology characterization, histochemical and immunohistochemical analysis of neoplastic cells allowed the definitive diagnosis of oral fibrosarcoma.

Metformin reduces the stimulatory effect of obesity on in vivo Walker-256 tumor development and increases the area of tumor necrosis

Aims: The objective of this study was to analyze the influence of obesity and insulin resistance on tumor development and, in turn, the effect of insulin sensitizing agents. Main methods: Male offspring of Wistar rats received monosodium glutamate (400 mg/kg) (obese) or saline (control) from the second to sixth day after birth. Sixteen-week-old control and obese rats received 5 x 10(5) Walker-256 tumor cells, subcutaneously injected into the right flank. Some of the obese and control rats received concomitant treatment with metformin (300 mg/kg) by gavage. At the 18th week, obesity was characterized. The percentage of rats that developed tumors, the tumor relative weight and the percentage of cachexia incidence were analyzed. The tumor tissue was evaluated histologically by means of hematoxylin and eosin staining. Key findings: Metformin did not correct the insulin resistance in obese rats. The tumor development was significantly higher in the obese group, whereas metformin treatment reduced it. After pathological analysis, we observed that the tumor tissues were similar in all groups except for adipocytes, which were found in greater quantity in the obese and metformin-treated obese groups. The area of tumor necrosis was higher in the group treated with metformin when compared with the untreated one. Significance: Metformin reduced Walker-256 tumor development but not cachexia in obese rats. The reduction occurred independently of the correction of insulin resistance. Metformin increased the area of necrosis in tumor tissues, which may have contributed to the reduced tumor development. (C) 2011 Elsevier Inc. All rights reserved.

Avaliação das atividades anti-toxoplásmica, antioxidante e antiinflamatória dos monoterpenos timol (lippia sidoides) e estragol (croton zenhtneri)

Toxoplasmosis, a benign disease in normal healthy individuals, can have serious effects in pregnant women and immunocompromised patients. It is a parasitic disease caused by Toxoplasma gondii (Tg), an obligatory intracellular protozoan. The prophylactic and therapeutic arsenal against this parasite is very restricted. Thus, there is an ongoing search for novel drugs and therapeutic strategies. A promising alternative is a rational approach using medicinal plants. This study aimed to standardize methodologies for assessing the toxicological, antiproliferative, antioxidant, antiinflammatory and anti-Toxoplasma effects of Estragole and Thymol compounds isolated from species of plants (Lippia sidoides and Croton zenhtneri) commonly used in the Cariri region of Ceara State, Brazil. First we evaluated in vivo toxicity and conducted a pathological analysis of mice livers. In vivo antiinflammatory activity was assessed using air pouch and paw edema methods. Cytotoxicity assays were performed and antiproliferative, antioxidant and nitric oxide production analyzed. Anti-Toxoplasma activity was evaluated in a congenital experimental model with varying stages of maternal infection using the ME-49 strain and a non- congenital model by using ME-49 and RH strains. The results suggest low to moderate toxicity for both compounds. Thymol was more toxic in vivo and in vitro, having greater pathological repercussion than Estragole. The compounds were inactive for antiproliferative activity. Thymol showed better antioxidant activity, while Estragole stimulated nitric oxide production in macrophages. Both showed significant antiinflammatory activity. In non-congenital Tg infection, both compounds were active only against the ME49 strain. In congenital infection, Estragole (oral route) improved the newborn weight of infected mothers compared with untreated controls. Subcutaneous administration of the two compounds increased the weight of offspring born to infected mothers compared with untreated controls. We concluded that Estragole and Thymol exhibit important biological and anti-Toxoplasma activities. Further studies are needed to elucidate the mechanism of action of these compounds and other possible activities not investigated in the present study

Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki--67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki--67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki--67 and local recurrence in STSs. The use of Ki--67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression.

Prevalência de Helicobacter pylori e vírus Epstein-barr em crianças e adolescentes

Introdução: Infecções por Helicobacterpylori(HP) e vírusEpstein-Barr (VEB) são comuns no mundo todo, embora o HP seja o maior fator em doenças gastroduodenais, seu percentual de associação com VEB é incerto. Tanto o VEB quanto o HP são classificados como carcinógenos classe 1 pela Organização Mundial de Saúde, e uma substancial fração de indivíduos se tornam co-infectados na adultice. Esses dois patógenos podem potencializar sinergicamente para causar gastrite crônica perpetua. O objetivo deste trabalho foi verificar a prevalência de HP e do vírus Epstein-Barr em crianças e adolescentes. Material e Método: Estudo descritivo, do tipo transversal. Foram analisadas amostras de mucosa gástrica de 64 crianças e adolescentes através do Teste da Urease para diagnóstico do HP, da técnica de PCR para detecção da cepa cagA de H. pylori, da técnica de hibridização in situ para detecção do EBV e da análise patológica para determinação de características histopatológicas. Resultados: A prevalência de HP nas crianças e adolescentes em estudo foi de 53,1% enquanto a prevalência de VEB foi 3,1%. Entre os pacientes infectados por HP, a maioria (94,3%) apresentava gastrite a endoscopia digestiva alta, sendo gastrite enantemática a mais comumente encontrada. Na análise histopatológica, também a maioria (97,1%) dos pacientes apresentava algum grau de gastrite, com 80% classificados com gastrite crônica moderada. Cepas cagA positivas foram encontradas em 64,7% dos infectados com HP e entre estes todos tinham gastrite, com predomínio de gastrite crônica moderada (54%), no entanto não se observou correlação com significância estatística entre esses achados. Em adição, também não houve significância estatística para a associação entre infecção por HP e por VEB na população estudada, a baixa prevalência de VEB nesta análise sugere que esse vírus não é um agente etiológico das lesões da mucosa gástrica. No nosso conhecimento, este é o primeiro estudo que relaciona estes dois agentes infecciosos na mucosa gástrica de crianças e adolescentes do norte do Brasil. Conclusão: A maioria dos achados deste estudo se assemelha aos relatos da literatura, contudo evidenciou-se a necessidade de estudos com maior casuística, envolvendo a população pediátrica imunocompetente afim de melhor esclarecer se há ou não correlação entre a infecção por HP e VEB em nossa região.