Mitotic counts in one high power field in breast core biopsies is equivalent to counts in 10 high power fields.

Mitotic rate is an important prognostic predictor in invasive breast carcinoma. Current guidelines recommend counting mitoses from 10 contiguous high power fields (HPFs) in the core biopsy. We propose a method to score mitotic activity in 1 HPF at the most mitotically active area of the tumour edge, or the interface between invasive tumour and benign breast tissue. We propose a score of 1, 2, or 3, corresponding to ≤1, 2, or ≥3 mitoses in 1 HPF, respectively. A total of 141 breast core biopsies with corresponding surgical excisions were blindly examined. We counted the number of mitotic figures in 1 HPF and in 10 contiguous HPFs in the core biopsy and compared with the mitotic count from 10 contiguous HPFs in the excision which is considered the gold standard. Concordance rates and interobserver agreement rates were calculated. The concordance rate was 82.3%, 78.7% and 82.3% between 1 HPF versus 10 HPFs in the core biopsy, 1 HPF in the core biopsy versus 10 HPFs in the excision and 10 HPFs in the core biopsy vs 10 HPFs in the excision, respectively. In the core biopsy, all three investigators agreed in 73.8% and 83.7% of the cases using the 1 HPF method and the 10 HPFs method, respectively; in the excision specimen, agreement was reached in 82.3% of the cases. The 1 HPF method showed similar concordance rate and interobserver agreement compared to the conventional method in the prediction of the mitotic score in the excision in all score groups. When stratified by mitotic score, the 1 HPF method predicted superior correlation with excision in the score 1 group than the 10 HPFs method, but not in the score 2 or 3 groups. From these findings we conclude that the proposed 1 HPF method can be used in clinical practice to grade invasive breast carcinomas in core biopsies, with the possibility of being utilised in small biopsies with less than 10 HPFs of invasive carcinoma.

Ectasia coronaria y miocardiopatía hipertrófica: una entidad infrecuente / Coronary artery ectasia and hypertrophic cardiomyopathy: case report

Resumen Se presenta el caso de un paciente de 54 años que consulta por angina de esfuerzo de 2 años de evolución en quien se identifica una dilatación ectásica del árbol coronario con lesiones ateroscleróticas críticas y miocardiopatía hipertrófica septal obstructiva. Una revisión bibliográfica revela que es una asociación infrecuente de la cual solo existen reportes de casos aislados.

Abstract We present the case of a 54-year-old patient who presented with a history of 2 years with angina. Invasive studies revealed critical coronary artery stenosis coexisting with obstructive hypertrophic miopathy. This is a rare association with only isolated case reports.

Left ventricular assist device (LVAD) program in Chile: first successful experience in South America.

BACKGROUND: The need to have a variety of tools to deal with end-stage heart failure (ES-HF), along with the limited heart transplantation availability encouraged us to create a pilot Left ventricular assist device (LVAD) program in a public health care system hospital in Chile. METHODS: A retrospective analysis of the first nine patients of an ongoing LVAD program initiated on August 2013 was performed, completing an average of 30 months of follow-up. The most important events regarding to morbidity and mortality are described. RESULTS: Nine patients with ES-HF underwent LVAD implantation surgery; one of them died 23 days after surgery and another died after 11 months. One patient successfully underwent heart transplantation after 16 months of HeartWare ventricular assist device (HVAD) support; the other six patients remain in the program and have an average follow-up of 846 days at the time of this study (range, 23-1,481 days). The survival rate at 6, 12 and 18 months follow-up was 89%, 78% and 78% respectively. CONCLUSIONS: This new pioneering LVAD program in Chile has been successful and now constitutes a vital adjunct to all who work in heart transplantation and ES-HF programs. It offers an effective therapeutic alternative when there is a severe donor shortage, in cases of atypical blood types, emergencies, exceptional cases with contraindication for heart transplantation or when there is important donor-receiver size mismatch.

The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma.

Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/ß signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/ß protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.

National Accreditation Program for Breast Centers Demonstrates Improved Compliance with Post-Mastectomy Radiation Therapy Quality Measure.

BACKGROUND: The National Accreditation Program for Breast Centers (NAPBC) was established in 2008 by the American College of Surgeons as a quality-improvement program for patients with breast disease. An NAPBC quality measure states post-mastectomy patients with ≥4 positive lymph nodes should receive lymph node radiation therapy (PMRT). Our objective was to examine how NAPBC accreditation has affected compliance with this quality measure. STUDY DESIGN: Women who underwent mastectomy at either an NAPBC-accredited center or a Commission on Cancer-only accredited hospital were identified (2006 to 2013) in the National Cancer Data Base. The NAPBC centers accredited from 2009 to 2011 were included in the analysis. Patients were nested within centers using a mixed effects model to identify PMRT rates at each center before and after accreditation, adjusting for patient and tumor characteristics. RESULTS: Of 34,752 patients from 477 NAPBC-accredited centers and 958 Commission on Cancer-only accredited hospitals who underwent mastectomy with ≥4 positive lymph nodes, 21,638 patients received PMRT during the study period (62.3%). The NAPBC centers yielded a significantly higher rate of PMRT than Commission on Cancer hospitals (66.0% vs 59.2%; p < 0.001). For each year of accreditation (2009 to 2011), centers had significantly higher rates of radiation in the accreditation year compared with the year before accreditation (p < 0.001). Within those centers, the rate of radiation increased post-accreditation in each accreditation year (2009: 62.1% to 71.9%; 2010: 65.5% to 73.2%; 2011: 67.5% to 70.4%). CONCLUSIONS: The NAPBC accreditation is associated with higher PMRT rates and better adherence to the PMRT quality measure. Future studies with more centers and longer follow-up are needed to determine whether this trend continues.

[Left ventricular assistant devices for end-stage heart failure: report of two cases]. / Asistencia ventricular intracorpórea en falla cardiaca terminal

In the last 2 decades, there have been significant advances in medical treatment of heart failure. However, there is a group of patients who are refractory to the available medical therapy and progress inevitably to a state of end-stage heart failure, whose only therapeutic alternative is cardiac transplantation. But this is an option limited by the scarce availability of donors. Therefore many patients die waiting for an organ. Recently, extra or intracorporeal left ventricular devices have emerged as a viable alternative for patients with end-stage heart failure waiting for a heart transplant. These devices discharge the left ventricle, increasing cardiac output and improving systemic perfusion. This year, in our hospital we began a left ventricular device implantation program for the most severely ill patients on the waiting list for cardiac transplantation. We report two males aged 30 and 53 years, in whom a left ventricular device was successfully implanted, using a minimally invasive surgical technique developed at the University of Hannover in Germany.

Asistencia ventricular intracorpórea en falla cardiaca terminal / Left ventricular assistant devices for end-stage heart failure: report of two cases

In the last 2 decades, there have been significant advances in medical treatment of heart failure. However, there is a group of patients who are refractory to the available medical therapy and progress inevitably to a state of end-stage heart failure, whose only therapeutic alternative is cardiac transplantation. But this is an option limited by the scarce availability of donors. Therefore many patients die waiting for an organ. Recently, extra or intracorporeal left ventricular devices have emerged as a viable alternative for patients with end-stage heart failure waiting for a heart transplant. These devices discharge the left ventricle, increasing cardiac output and improving systemic perfusion. This year, in our hospital we began a left ventricular device implantation program for the most severely ill patients on the waiting list for cardiac transplantation. We report two males aged 30 and 53 years, in whom a left ventricular device was successfully implanted, using a minimally invasive surgical technique developed at the University of Hannover in Germany.

Tumor intracardíaco como presentación de leiomiomatosis intravascular / Intracardiac tumor as presentation of intravascular leiomyomatosis

Presentamos un caso de leiomiomatosis intravascular que se extiende a cavidades cardiacas derechas, siendo tratado mediante cirugía en un tiempo.

We present a case of an intravenous leiomyomatosis extending into the right cardiac chambers, which was treated by one stage surgery.

Near-complete pathological response with preoperative chemotherapy in a patient with metaplastic breast carcinoma.

Metaplastic breast carcinoma (MBC) is a rare form of breast cancer comprising less than 1% of all invasive breast carcinomas. There are no clinical studies available for the management of this rare disease and MBC is associated with a poor prognosis. We present a case of a 50-year-old female patient with MBC who showed a favorable response with preoperative chemotherapy. The patient presented with a palpable left breast mass, and diagnostic breast imaging showed a 4.4 cm mass in the left breast, which was biopsied. Pathological review led to a diagnosis of MBC. Staging workup for distant metastasis was negative. She received four cycles of dose-dense AC (doxorubicin and cyclophosphamide), followed by 10 weekly doses of carboplatin (area under the curve=2) and paclitaxel (80 mg/m). The patient underwent partial mastectomy and sentinel lymph node sampling, and pathological review indicated a near-complete pathological response, with few scattered malignant cells at the tumor bed. A current review of the literature on MBC is summarized in this report.

Shock cardiogénico refractario: rescate con ECMO, asistencia ventricular y trasplante / Cardiogenic shock: rescue with ECMO, ventricular assist and heart transplantation

Presentamos un caso de infarto agudo al miocardio complicado con shock cardiogénico y arritmias ventriculares refractarias. El paciente requirió oxigenación por membrana extracorpórea (ECMO) antes de su traslado a un hospital con asistencia ventricular izquierda (LVAD) y programa de trasplante de corazón. El paciente tuvo una buena recuperación después de 16 días de soporte con LVAD seguido de trasplante cardiaco, lo que muestra los beneficios de la terapia multimodal en casos complejos de shock cardiogénico refractario.

A case of acute myocardial infarction complicated with cardiogenic shock and refractory ventricular arrhythmias is described. The patient required extracorporeal membrane oxygenation (ECMO) prior to transfer to a hospital with a left ventricular assist device (LVAD) and heart transplantation program. He made a good recovery after 16 days of LVAD support followed by heart transplantation, showing the benefits of multimodal therapy incomplex cases of refractory cardiogenic shock Palabras clave: Infarto agudo del miocardio, shock cardiogénico,asistencia biventricular, ECMO.

The Value of Combined Large Format Histopathology Technique to Assess the Surgically Removed Breast Tissue following Neoadjuvant Chemotherapy: A Single Institution Study of 40 Cases.

Historically, neoadjuvant chemotherapy has been used to treat patients with advanced breast disease in an attempt to convert them into candidates for breast conservation surgery. The ultimate goal of histopathologic examination of the specimens removed after neoadjuvant chemotherapy is the identification of either residual disease or positive identification of the tumor bed. We report a series of 40 patients treated with neoadjuvant chemotherapy and evaluation of the surgical specimens by a combination of standard histopathology and the use of large format histopathology techniques.

Fixation time does not affect expression of HER2/neu: a pilot study.

It is said that HER2/neu expression by immunohistochemical analysis varies with the time of fixation. The purpose of this pilot study was to determine the impact of the length of fixation in 10% buffered formalin on the expression of HER2/neu by immunohistochemical analysis. We studied tissue samples from 10 invasive breast cancer cases after fixation for 3, 48, 72, 96, and 120 hours. The tissue was processed immediately after fixation, resembling routine practice. The 50 resulting blocks were then batch stained with PATHWAY HER2/neu clone 4B5 rabbit monoclonal antibody using the Ventana Ultraview DAB detection kit in a Ventana BenchMark XT processor (Ventana, Tucson, AZ). The stained slides were reviewed and scored. We found no significant difference in the intensity of the stain or the percentage of cells stained regardless of the time in fixation. Fixation times between 3 and 120 hours in 10% buffered formalin do not appear to have an impact on the expression of HER2/neu by immunohistochemical analysis.

Reproducibility in the diagnosis of needle core biopsies of non-palpable breast lesions: an international study using virtual slides published on the world-wide web.

AIMS: To conduct an internet-based study using virtual slides (VS) of sterotactic core biopsy specimens of non-palpable breast lesions in order to evaluate interobserver reproducibility between pathologists. METHODS AND RESULTS: A total of 18 breast lesions, determined to be histologically complex by two pathologists, were selected. Digitized VSs were then created using QuickTime Virtual Reality technology (Apple, Cupertino, CA, USA) and posted on the world-wide web. In all, 10 pathologists completed the evaluations of 18 VSs using the five diagnostic categories (B1-B5) from the European guidelines for quality assurance in breast cancer screening and diagnosis. Their results were compared with those of every other participating pathologist, and were then individually compared with the results of a highly experienced breast pathologist (referee). Of the 18 cases, 10 (56%) were classified by the referee as borderline (B3 and B4). Comparisons with reference values showed a less than satisfactory level of reproducibility (median kappa(w) = 0.60). As regards interobserver reproducibility, results showed that, in general, the level of agreement was not satisfactory (median kappa(w) = 0.53). CONCLUSIONS: Overall, the findings are comparable to those quality control studies using circulating slides when analysis is done on borderline cases.

Fixation time does not affect the expression of estrogen receptor.

The purpose of this pilot study was to determine the impact of the length of fixation in 10% buffered formalin on the expression of estrogen receptor by immunohistochemical analysis. We studied tissue samples from 10 invasive breast cancer cases after fixation for 1, 3, 6, and 9 to 10 hours. The tissue was processed immediately after fixation, resembling routine practice. Then the 40 blocks were incubated with antiestrogen receptors SP1, 6F11, and 1D5. The stained slides were reviewed and scored. We found no significant difference in the intensity of the stain or the percentage of cells stained regardless of the time in fixation or the antibody used. Fixation times between 1 and 9 hours in 10% formalin do not seem to have an impact on the expression of estrogen receptor by immunohistochemical analysis, at least in these high-expressing tumors.

Guideline implementation for breast healthcare in low- and middle-income countries: diagnosis resource allocation.

A key determinant of breast cancer outcome in any population is the degree to which newly detected cancers can be diagnosed correctly so that therapy can be selected properly and provided in a timely fashion. A multidisciplinary panel of experts reviewed diagnosis guideline tables and discussed core implementation issues and process indicators based on the resource stratification guidelines. Issues were then summarized in the context of 1) clinical assessment, 2) diagnostic breast imaging, 3) tissue sampling, 4) surgical pathology, 5) laboratory tests and metastatic imaging, and 6) the healthcare system. Patient history provides important information for the clinical assessment of breast and comorbid disease that may influence therapy choices. Focused clinical breast examination and complete physical examination provide guidance on the extent of disease, the presence of metastatic disease, and the ability to tolerate aggressive therapeutic regimens. Breast imaging improves preoperative diagnostic assessment and also permits image-guided needle sampling. Diagnostic mammography was not considered mandatory in low- and middle-income countries when resources are lacking. Needle biopsy is preferred to surgical excision for the initial diagnosis of suspicious breast lesions, unless resources are unavailable. Mastectomy should never be used as a method of tissue diagnosis. The availability of predictive tumor markers, especially estrogen receptor testing, is critical when endocrine therapies are available; quality assessment of immunohistochemistry testing is important to avoid false-negative results. Incremental allocation of resources can help address economic disparities and help ensure equity in access to timely diagnosis.

Breast pathology guideline implementation in low- and middle-income countries.

The quality of breast healthcare delivery and the ultimate clinical outcome for patients with breast cancer are directly related to the quality of breast pathology practices within the healthcare system. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary from October 1 to 4, 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for the early detection, diagnosis, and treatment in low-income and middle-income countries (LMCs). From this group, a subgroup of experts met to address the specific needs and concerns related to breast pathology program implementation in LMCs. Specific recommendations were made by the group and process indicators identified in the areas of personnel and training, cytology and histopathology interpretation, accuracy of pathology interpretation, pathology reporting, tumor staging, causes of diagnostic errors, use of immunohistochemical markers, and special requirements to facilitate breast conservation therapy. The group agreed that the financial burden of establishing and maintaining breast pathology services is counterbalanced by the cost savings from decreased adverse effects and excessive use of treatment resources that result from incorrect or incomplete pathologic diagnosis. Proper training in breast pathology for pathologists and laboratory technicians is critical and provides the underpinnings of programmatic success for any country at any level of economic wealth.

Re-establishing a surgical pathology service in Kumasi, Ghana: case report and discussion of barriers and key elements of a successful collaboration between low- and high-resource countries.

At Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana, a breakdown of technical equipment and lack of pathologists resulted in closure of the surgical pathology laboratory in 2004. At an international meeting in January 2005, 1 USA and 1 Norwegian pathologist were asked if their departments could help with the pathology problem at KATH. This article describes the proposals, the barriers encountered, and the key elements of the final successful collaboration between a low-resource and a high-resource country. The proposal to the USA hospital focused on receiving specimens for diagnosis. A detailed proposal was not developed, as several key operational barriers were identified early on, including legal issues, technical capacity issues, and staff capacity issues. The proposal to the University Hospital of North Norway (UNN) resulted in development of a 5-year plan to reestablish surgical pathology at KATH. Two KATH technicians came to UNN and trained in the histopathology laboratory for 3 months. On their return, they started producing slides at KATH. Since April 2006, weekly shipments of hematoxylin and eosin (H & E) stained slides have been sent to UNN by courier service. When needed, paraffin blocks are sent on request. In March 2006, 2 young Ghanaian physicians were received as trainees at the UNN to do full resident work and training with the aim of being approved as specialists in pathology in Ghana by 2010. Full surgical pathology service and training of new pathologists on site are expected to be reestablished at KATH by 2010.