Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer

PurposeSome patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications.MethodsRAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies).ResultsTwenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test).ConclusionThirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.

Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer.

PURPOSE: Some patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications. METHODS: RAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies). RESULTS: Twenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test). CONCLUSION: Thirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.

Comparative study of blood lead levels in Uruguayan children (1994-2004).

Lead does not fulfill any physiological function in the human body. It is generally accepted that the blood lead level (BLL) is the best exposure index, as there is an excellent correlation between the actual exposure of the individual and the concentration of lead in blood. In Uruguay, lead contamination becomes a matter of public concern in 2001, giving rise to a sensitization in the population, which in many cases brought about a change in hygienic and dietary habits of the children. In 2004, after the leaded gasoline phasing out process in Uruguay was completed, we studied non-exposed children to correlate BLL with variables such as age, sex, area of residence, and available environmental lead data and compared these results with those from our similar screening studies 10years ago. The main result of this comparison is that BLL from children in our country had a significant decrease between 1994 and 2004.

[Morphology of severe mycoses. Role of the pathologist in the diagnosis]. / Expresión morfológica de las infecciones fúngicas graves. Participación del patólogo en el diagnóstico.

Mycoses are diseases caused by fungi. To be regarded as pathogenic, a fungus has to be able to complete a number of steps in order to initiate infection. Although culture remains the gold standard to diagnose the causative agent, presumptive identification of these fungi in histologic slides is of great value because invasion is only demonstrated in tissue sections. When culture is not available, histopathologic examination may be the sole source of information about the nature of the infection. To make a diagnosis, the pathologist needs to be familiar with the morphologic appearance of the different types of fungi, and has also to be aware of the limitations in their identification. The purpose of this work is to review the current problems on this subject, specially referring to the most frequent severe mycoses of our environment.

[Value of the expression of p21RAS, P53, Bcl-2 oncoproteins and Ki-67(MIB-1) antigen of cellular proliferation in the diagnosis and prognosis of thyroi]. / Aplicación de las oncoproteínas p21RAS, p53, Bcl-2 y del factor de proliferación celular Ki-67(MIB-1) en el diagnóstico y pronóstico de tumores tiroid.

INTRODUCTION: The thyroid gland is a good organ for the study of genetic alterations in tumoural development and progress. The study of oncogenes and antigens of cellular proliferation is of interest. MATERIAL AND METHODS: 36 cases of thyroid adenomas, 58 papillary carcinomas, 32 follicular carcinomas, 2 anaplastic carcinomas and 12 medullary carcinomas were selected. Clinical and histological prognostic factors were studied and an immunohistochemical study with Ki-67 (MIB-1), p53, Bcl-2 and p21 RAS antibodies was performed. RESULTS: The proliferative rate Ki-67 (MIB-1) showed statistical differences in adenomas and follicular carcinomas. The p53 protein did not appear in adenomas, but was shown in those carcinomas with bigger histological dedifferentiation. A relationship was also established with greater age, larger size and progression of the tumour. The Bcl-2 protein was high in the normal thyroid, in the adenomas and in the carcinomas, decreasing in correlation with histological dedifferentiation, and totally disappearing in the anaplastic carcinomas. In medullary carcinomas its disappearance was correlated with mortality. The intense expression of the p21 RAS protein in papillary carcinomas is statistically correlated with advanced clinical studies. CONCLUSIONS: The differences in the proliferative rate between adenomas and follicular carcinomas can be of help in differential diagnosis. The p53 manifestation and the loss of the Bcl-2 expression are correlated with the histological redifferentiation process. An intense manifestation of p21 RAS in papillary carcinoma is correlated with tumoural progression.

[The impact of technology in Pathological Anatomy and the contribution of this speciality to technological development]. / Impacto de la Tecnología en la Anatomía Patológica y aportación de esta especialidad al desarrollo tecnológico.

It is obvious that technology has contributed throughout history to the development of the different sciences. In this article, we define the concept of Pathology as a medical speciality, and we explain its influence in a hospital, considering very different fields such as education, research, quality control, hospital information, and patient care. This speciality has undergone a considerable evolution, to which technological innovation has undoubtedly contributed. As a basic discipline, it is of great importance in pre and post-graduate training, in the medical education at the hospital or outside it, and in the fields previously mentioned. Its relation with other disciplines such us Chemistry, (fixation and dyeing), Physics (mechanical devices), Mathematics (algorithms, morphometry, statistics...) and Telecommunications (telepathology, image analysis...) is examined and their contribution to Pathology is evaluated. We are also aware of contributions made by Pathology to technological innovation in the evaluation of different diagnostic methods or in the recent therapeutic technologies based on Radiotherapy, Hyperthermia, laser, prothesis, etc.; where histological examination provides accurate information about the therapeutic capacity or side-effects, or the rejection reactions caused, aiding the research to obtain adequate results.

[Isolated laryngeal involvement as the first manifestation of Wegener's disease. A case report]. / Afectación laríngea aislada como primera manifestación de la enfermedad de Wegener. A propósito de un caso.

A 74-year-old woman with a 4-month history of hoarseness had a granulomatous lesion of the vocal cords by laryngoscopy and a normal physical examination. Wegener's granulomatosis was confirmed by biopsy. Early treatment with trimethoprim-sulfamethoxazole prevented the evolution toward a more severe systemic form of the disease. The patient remains asymptomatic a year and a half after treatment.

Klippel-Trenaunay syndrome: a very infrequent cause of microcalcifications in mammography.

We report a case of Klippel-Trenaunay syndrome which was suggested by microcalcifications detected on routine mammograms. Based on mammographic findings subcutaneous localization was suspected and a skin with subcutaneous cellular tissue biopsy was performed, confirming the microcalcifications at this level. The anatomopathologic report consisted of increase in vascularization in the subcutaneous adipose tissue due to capillary and small-venule proliferation, with intramural calcium deposits.

Nonpalpable, well-defined, probably benign breast nodule: management by fine-needle aspiration biopsy and long-interval follow-up mammography.

The management of nonpalpable, well-defined breast nodules by short-interval, 6-month follow-up mammography is widely accepted. We have, however, been managing these type of lesions with fine-needle aspiration biopsy (FNAB), guided by sonography or stereotaxic approach, in order to reduce the number of follow-up mammograms. We recommended surgical biopsy only in cases with malignant or suspicious cytology. Patients with benign cytology or inadequate sample were included in a 12-month-interval mammography surveillance program. In the series we present, two carcinomas were diagnosed among 145 lesions (1.38 %). Both had shown malignancy in FNAB. Another two cases, suspicious of malignancy in FNAB, finally resulted benign in histology. The remaining 141 nodules, monitored for at least 2 years, or surgically removed at the patient's request, have not shown signs of malignancy, regardless of a diagnosis of either benign or inadequate sample in FNAB. Sensitivity and negative predictive value of FNAB have therefore been 100 % in this series. No notable differences were observed between stereotaxic and sonographic guidance, except the percentage of inadequate samples (20.3 % by sonography; 25.9 % by stereotaxic sampling). We conclude that stereotaxic or sonographic FNAB is a very accurate diagnostic method in lesions of this type, allowing long-interval surveillance of the nodules with nonsuspicious cytological results.