David Oddo

Vertical transmission of Trypanosoma cruzi in the Province of Choapa, IV Region, Chile: Preliminary Report (2005-2008)

Congenital Chagas disease acquired special importance in Chile after the certification of the control of Triatoma infestans and transmission by blood donors affected with Trypanosoma cruzi. In order to establish adequate protocols for intervention and control in infected mother-neonate pairs in endemic zones of Chagas disease, we present partial results (2005-2008) of a pilot project which is being carried out in the Province of Choapa, IV Region, Chile, whose objectives are: determine the current prevalence of the disease in pregnant women, estimate the incidence of vertical transmission of T. cruzi to newborns, determine the lineages of the parasite present in mothers who do and do not transmit the disease, determine the prevalence of Chagas disease in maternal grandmothers of neonates and study placental histopathology. Preliminary results indicated that in this study period, 3.7% of the women who gave birth in the Province have Chagas disease and 2.5% of their newborns were infected. The most frequent T. cruzi genotypes found in mothers studied during pregnancy were TCI and TCIId, either alone or in mixed infections. A high percentage (74.3%) of the grandmothers studied was infected with the parasite. In 29 placentas from mothers with Chagas disease we observed edema, necrosis, fibrinoid deposits and slight lymphoplasmocyte infiltration. In three placentas we found erythroblastosis and in one of them amastigote forms of T. cruzi; this was one of the cases of congenital infection. The evaluation of the diagnostic and control protocols generated will allow us to determine if it has been possible to modify the natural history of vertical transmission of T. cruzi in Chile.

Congenital infection by Trypanosoma cruzi in an endemic area of Chile: a multidisciplinary study

BACKGROUND This study investigated the prevalence of Chagas disease (ChD) in pregnant women in Choapa Province (IV Region, Chile) and the vertical transmission of Trypanosoma cruzi. METHOD ELISA and IFI IgG for ChD was performed for the pregnant women. PCR for T. cruzi was done for all chagasic mothers and their newborns. The congenital infection was confirmed by serial positive PCR and/or ELISA or IFI IgG after age of nine months. The placentas of mothers, with and without ChD, were submitted for histopathology and immunohistochemical study. RESULTS From 4831 deliveries in 2005-2009 with a serological coverage of 88.6%, it was established that 147 cases (3.4%) had ChD. More than 80% of the pregnancies had a physiological evolution and 90% of the newborn were term. Congenital transmission was demonstrated in six children (4.7%) of the 127 newborn studied by serial PCR (at birth and/or between 3-18 months) and/or ELISA or IIF IgG after age nine months. Most of congenital cases were asymptomatic (67%). The histopathology shows edema, necrosis, fibrinoid deposit in the placentas of 28 of 29 chagasic mothers. In three cases the immnunochemistry demonstrated a decrease in actin expression in trophoblast cells. In one congenital case amastigote nests was observed. CONCLUSIONS These results indicate that T. cruzi infection in pregnant women and vertical transmission in Chile are still prevalent. For this reason it is important to propose control measures in endemic areas of the country.

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

BACKGROUND AND AIM Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). MATERIALS AND METHODS We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. RESULTS 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). CONCLUSIONS In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

Evaluación del valor pronóstico de la relación neutrófilos/linfocitos en cáncer de mama de subtipos agresivos

Background: The white blood cell count is one of the most sensitive markers associated with inflammation. The neutrophil/lymphocyte count ratio may be an independent factor for breast cancer mortality. Aim: To assess the predictive value of the neutrophil/lymphocyte ratio for mortality in breast cancer. Material and methods: Review of the database of a cancer center of a University hospital. Patients with infiltrating breast cancer treated between 1997 and 2012 were selected. The pathology type and lymph node involvement were obtained from the pathology report. The expression of estrogen, progesterone and Human Epidermal Growth Factor Receptor 2 (HER2) was determined by immunohistochemistry or in situ fluorescent hybridization (FISH). The absolute peripheral neutrophil and lymphocyte counts were obtained from a complete blood count obtained at least three months before treatment. Patients were followed for a median of 61 months (range 1-171). Results: From 323 eligible patients, after excluding those in stage IV and those without an available complete blood count, 131 patients were analyzed (81 with negative receptors and 117 HER2 enriched). The neutrophil/lymphocyte ratio was similar in both type of tumors (2.1 and 1.91 respectively). Twenty two patients died during follow up. Surviving patients with HER2 enriched tumors had a lower neutrophil/lymphocyte ratio than those who died (1.79 and 3.21 respectively, p < 0.01). In a multivariate analysis, including age, tumor stage and lymph node involvement as confounding factors, the neutrophil/lymphocyte ratio was still significantly associated with a risk of death with a hazard ratio of 2.56. Conclusions: A high neutrophil/lymphocyte ratio in the complete blood count can be a predictor of death in breast cancer.

Rinosporidiosis conjuntival diagnosticada mediante estudio histopatológico

Escolar de 11 anos, de sexo femenino, proveniente de la Region del Bio-Bio, sin antecedentes de viajes, consulto por ojo rojo, blefaritis y epifora sanguinolenta; al examen oftalmologico revelo una pseudomembrana. La sospecha clinica fue de una conjuntivitis folicular. Se realizo la remocion quirurgica de la lesion y en el estudio histopatologico se observaron lesiones caracteristicas de rinosporidiosis, correspondiente a quistes de 50-150 μm con pared quitinosa y numerosas endosporas. La rinosporidiosis es una infeccion causada por Rhinosporidium seeberi, que afecta con mayor frecuencia la cavidad nasal, pero puede tambien afectar el ojo, aparato urogenital y la via aerea, entre otros. Es considerado endemico en paises de Asia y Africa, pero dado el aumento de viajes a estas regiones es importante reconocer este agente como causal de polipos en la zona nasal y ocular.

Can Histological Grade and Mitotic Index Replace Ki67 to Determine Luminal Breast Cancer Subtypes

Introduction: Breast cancer can be classified into subtypes based on immunohistochemical markers, with Ki67 expression levels being used to divide luminal BC tumors in luminal A and B subtypes; however, Ki67 is not routinely determined due to a lack of standardization. Objective: To evaluate histological grade and Eliminate: the mitotic index to determine if they can be used as an alternative method to Ki67 staining for luminal subtype definition. Methods: We evaluated estrogen receptor positive breast cancer tissue samples. Pathological analysis included determination of Ki67. A low level of Ki67 was defined as <14% positive cells. Results: We evaluated 151 breast cancer samples; 24 (15,9%) were classified as I; 74 as HG II (49%), and 53 (35,1%) as HG III. The median value for Ki67 was 13% (range: <1% - 82%) and for MI was 2 (0-12). Histological grade I tumors exhibited Ki67 values significantly lower than HG II and III tumors (Anova, Tamhane test p=0,001). A higher Ki67 value was related to a higher MI (Rho Sperman p=0,336; R2= 0,0273). ROC curve analysis determined that a MI ≥ 3 had a sensibility of 61.9% and specificity of 66.7% in predicting a high Ki67 value (≥14%) (area under the curve: 0,691; p =0,0001). A HG I tumor or HG II-III with MI ≤2, had a high probability of corresponding to a LA tumor (76,3%), as defined using Ki67 expression, while the probability of a LB subtype was higher with HG II-III and a MI ≥3 (57.4%). Global discrimination was 68.1%. Conclusions: For the LA subtype, our predictive model showed a good correlation of HG and MI with the classification based on Ki67<14%. In the LB subtype, the model showed a weak correlation; therefore Ki67 determination seems to be needed for this group of patients.

Nephrotic syndrome due to minimal change disease secondary to spider bite: clinico-pathological case of a non-described complication of latrodectism

Abstract The patient was an 18-year-old man who developed nephrotic syndrome after a ‘wheat spider’ bite (Latrodectus mactans). Due to this atypical manifestation of latrodectism, a renal biopsy was performed showing minimal change disease. The nephrotic syndrome subsided after 1 week without specific treatment. This self-limited evolution suggests that the mechanism of podocyte damage was temporary and potentially mediated by a secondary mechanism of hypersensitivity or direct effect of the α-latrotoxin. The patient did not show signs of relapse in subsequent checkup. This is the first reported case of nephrotic syndrome due to a minimal change lesion secondary to latrodectism.

Clinico-Pathologic Subtypes of Breast Cancer Primary Tumors Are Related to Prognosis after Recurrence

Background: Pathological factors, based mainly on immunohistochemistry (IHC) and histological differentiation, are mostly used to differentiate breast cancer (BC) subtypes. Our present aim was to describe the characteristics and survival of a relapsing BC patient cohort based on clinico-pathologic subtypes determined for the primary tumors. Methods: We used a clinico- pathological definition of BC subtypes based on histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR), and epidermal growth factor receptor type 2 (HER2) expression assessed by IHC. We determined variables associated with loco-regional recurrence (LRR), second primaries (SP), systemic recurrence (SR) and post-recurrence survival (PRS). Results: Out of 1,702 patients, 240 (14%) had an event defined as recurrence. Those with recurrent disease were significantly younger than those without, and were initially diagnosed at more advanced stages, with larger tumors, greater lymph nodal involvement and higher HG. With a median follow up of 61 months (1-250), 4.6% of patients without recurrence and 56.6% of patients with an event defined as recurrence had died. The median PRS for the LRR group was 77 months; 75 months for those who developed a SP and 22 months for patients with an SR (p <0.0001). In SR cases, the median PRS was shorter for ER- tumors than for ER+ tumors (15 vs. 26 months, respectively; p = 0.0019, HR 0.44; CI: 0.25-0.44). Conclusions: Subtype, defined through classic histopathologic parameters determined for primary tumors, was found to eb related to type of recurrence and also to prognosis after relapse.