Efficacy of erlotinib in patients with relapsed gliobastoma multiforme who expressed EGFRVIII and PTEN determined by immunohistochemistry.

Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new phase II trial enrolled 40 patients and was design to be stopped in case of fewer than two responses in the first 13 patients. Patient eligibility included histopathology criteria, radiological progression, more than 18 years old, Karnofsky performed status, KPS > 50, and adequate bone marrow and organ function. There was no limit to the number of prior treatments for relapses. No enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were response and progression-free survival at 6 months (PFS6). Thirteen patients (6 men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53 years, median KPS was 80, and median prior treatments for relapses were 2. There was one partial response and three stable diseases (one at 18 months). PFS at 6 months was 20 %. Dose reduction for toxicity was not needed in any patient. Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7 months (95 % IC 1.41-4.7). As conclusion, monotherapy with erlotinib in GBM relapses patients with high protein expression for PTEN (+++), EGFR (+++), and EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.

A hybrid approach: a safe option for surgical treatment of early-stage cervical cancer.

OBJECTIVE: The aim of the study was to describe the surgical treatment of early-stage cervical cancer (CC) via minimally invasive surgery (MIS) and a sequential hybrid approach combining MIS and mini-Pfannenstiel. Evaluate sentinel lymph node (SLN) detection using a hybrid tracer (ICG-99m Tc nanocolloid). PATIENTS AND METHODS: Prospective, observational, descriptive, single-center study conducted at Son Espases University Hospital between January 2019 and September 2021. Patients with early-stage CC (FIGO 2018 IA1 with ILV-IIA1) who underwent surgical treatment with a follow-up of at least one year were included. RESULTS: Thirty early-stage CC patients were included, of whom four (13.3%) were upstaged due to positive SLNs. In these cases, laparotomy was avoided, and paraaortic lymphadenectomy was performed via MIS approach. Twenty-six patients had a radical hysterectomy: 15 underwent a hybrid approach, 10 laparoscopy, and one laparotomy. Patients undergoing laparoscopic surgery had a smaller estimated tumor size than those undergoing the hybrid approach. The overall SLN detection rate was 96.1%, with 88.5% of cases occurring bilaterally. Five out of 26 patients (19.2%) presented SLN macrometastases, and five (19.2%) had atypical drainage. Surgery refined staging in 33.3% (10/30) of cases. No recurrences were reported after an average follow-up of 32 months. CONCLUSIONS: MIS for SLN avoids laparotomy leading to rapid recovery and early adjuvant treatment initiation in nodal metastasis. In our study, tumor size is an important clinical implication in the surgical approach to be used. The hybrid tracer provided a high detection rate and combined the advantages of the two tracers. The hybrid approach has a quick recovery and optimal results.

Proliferative activity in C-cell hyperplasia and medullary thyroid carcinoma. Evaluation by PCNA immunohistochemistry and AgNORs staining.

C cell hyperplasia (CCH) is a preneoplastic lesion that precedes the development of medullary thyroid carcinoma (MTC) in familial cases. It has been hypothesized that CCH progressively acquires the neoplastic phenotype after presenting some genetic changes that involve oncogenes and tumor suppressor genes. The proliferative activity of nodular C cell hyperplasia (NCCH) and early MTC has been assessed by PCNA (Proliferating Cell Nuclear Antigen) immunohistochemistry and nucleolar organizer regions silver staining (AgNOR) in surgical specimens of seven patients with familial MTC. The ratios of PCNA-positive nuclei in NCCH (mean 1.2, range 0.2-4) were lower than in MTC (mean 2, range 1-7%). The AgNOR scores for NCCH (mean 1.53, range 1.10-1.90) were also lower than for MTC (mean 2.10, range 1.90-2.64). The results suggest that C cells progressively acquire a higher proliferative activity in agreement with the severity of the morphologic changes in the process of hyperplasia-neoplasia that leads to widely invasive MTC.

[Importance of 5569G/A polymorphism in intron 4 of HFE gene in the diagnosis of hereditary hemochromatosis]. / Importancia del polimorfismo 5569G/A del intrón 4 del gen HFE en el diagnóstico de la hemocromatosis hereditaria.

BACKGROUND: The presence of the 5569A polymorphism may lead to misdiagnosis of patients susceptible of hereditary hemochromatosis (HH). For that reason, samples containing the Cys282Tyr mutation were revised and the frequency of this polymorphism in our environment was assessed. PATIENTS AND METHOD: Twenty samples were retested and 56 controls were included. The study was performed by PCR-RFLP. RESULTS: The diagnosis was confirmed in 8 cases susceptible of error. However, an amplification deficiency of normal alleles was detected in 2 heterozygous (17%). The allelic frequency of the 5569A polymorphism in the control population was 14.3%. CONCLUSIONS: Although misdiagnosis was not committed, we recommend changing to any primer that does not include the 5569G/A polymorphism in the study of HH.

[The quality control of a photoprotector bag against ultraviolet light]. / Control de calidad de una bolsa fotoprotectora de luz ultravioleta.

The action of light on parenteral nutritional solutions may affect the stability of many of their ingredients. The aim of this study is to perform quality controls on a commercial photoprotective bag by quantifying the degradation of riboflavin in isotonic saline solution during forty-eight hours. Thirty solutions were prepared using 5 mg of riboflavin in 500 ml of saline solution. These were divided into three batches; one not protected from the light, one in a black bag and the third in a commercial bag. Samples were taken at 0 and 48 hours, and were analyzed by spectrophotometry. Solutions were prepared using 1.75 mg of riboflavin in 500 ml of saline solution. The same method was followed, and the samples were analyzed by fluorometry. The results were analyzed using the Student t test. The black bag was seen to be superior to the other two as a protector against ultraviolet light. There were no significant differences between the commercial bag and the non-protective bag.

[An evaluation of the effect of light on a commercial solution of amino acids for parenteral nutrition]. / Valoración del efecto de la luz sobre una solución comercial de aminoácidos para nutrición parenteral.

There are few studies on the stability of amino acids in solutions prior to mixing for parenteral nutrition, and even few studies which evaluate the contribution of light to their deterioration. The present study was carried out with the aim of becoming familiar with this parameter of stability in the working conditions of our Pharmacy Service. Two batches of Aminoplasmal L-10 were taken, one of which was subjected to direct low intensity sunlight and the other was maintained in the dark, as a control batch, for between 3-6 months. At the end of this time, complete aminograms were performed by ionic interchange chromatography. The measurements of concentrations of each amino acid were obtained for each batch. A Student T test was used to show that there were no significant differences between them after both 3 and 6 months. It was therefore concluded that the amino acid solution we had tested was maintained stable under the light exposure conditions of our Service after 6 months.

[Microbial growth in parenteral nutrition. II. Effects of osmolality]. / Estudio del crecimiento microbiano en nutrición parenteral. II. Influencia de la osmolaridad.

Study on the behaviour of five microorganisms in different formulations of Parenteral Nutrition (PN) different from each other with regard to osmolarity. The organisms investigated were Staphylococcus aureus (ATCC (12600), Bacillus subtilis (ATCC 6051), Pseudomonas aeruginosa (ATCC 9027), Enterobacter cloacae (ATCC 13047) y Candida albicans (LSH 3156 D). It was observed no direct relation between microbial growth and osmolarity in PN. C. albicans showed the best growth in all the formulations tested, followed by E. Cloacae. The number of the other microorganisms is reduced, and in general, except B. subtilis grow or are reduced in a lesser extension when the glucose solutions added are at 30 or 40%.

[Visa at a tertiary hospital]. / El visado en un hospital de tercer nivel.

OBJECTIVE: To analyze the visa application process and his activity at a tertiary hosipital. MATERIAL AND METHODS: Descriptive study of the drug s visa activity during the period April 2011-April 2012. We designed a database and defined categories on the study variables: patients and recipes. For patients admitted to the Visa Unit, issues detected were recorded based on a previously established classification. RESULTS: 6738 patients were included. They involved the visa of 8,465 recipes. The visa was applied to 170 drugs and nutrition products different, being the majority Tacrolimus. During this period, we detected a total of 420 incidents being the most frequent «No clinical document¼ (46.67%) and the «Formal completion errors¼ (28.57%). CONCLUSIONS: This work has allowed a more detailed analysis of the activity, the types of incidents and the identification of areas for improvement.

Objetivo: Analizar el procedimiento de visado y su actividad en un hospital de tercer nivel. Material y métodos: Estudio descriptivo del procedimiento de visado durante el período abril 2011-abril 2012. Se diseñó una base de datos y se definieron categorías relativas a las variables de estudio: pacientes y recetas. Para los pacientes atendidos en la Unidad de Visado se registraron las incidencias detectadas en base a una clasificación previamente establecida. Resultados: Se incluyeron 6.738 pacientes (8.465 recetas visadas). Se visaron 170 medicamentos y productos de nutrición diferentes, siendo el mayoritario Tacrolimus. Se detectaron un total de 420 incidencias, siendo las más frecuentes la «Ausencia de documento clínico¼ (46,67 %) y los «Errores formales de cumplimentación¼ (28,57%). Conclusiones: El presente trabajo ha permitido un conocimiento más pormenorizado de la actividad, los tipos de incidencias y la identificación de áreas de mejora.

Cationic surfactants derived from lysine: effects of their structure and charge type on antimicrobial and hemolytic activities.

Three different sets of cationic surfactants from lysine have been synthesized. The first group consists of three monocatenary surfactants with one lysine as the cationic polar head with one cationic charge. The second consists of three monocatenary surfactants with two amino acids as cationic polar head with two positive charges. Finally, four gemini surfactants were synthesized in which the spacer chain and the number and type of cationic charges have been regulated. The micellization process, antimicrobial activity, and hemolytic activity were evaluated. The critical micelle concentration was dependent only on the hydrophobic character of the molecules. Nevertheless, the antimicrobial and hemolytic activities were related to the structure of the compounds as well as the type of cationic charges. The most active surfactants against the bacteria were those with a cationic charge on the trimethylated amino group, whereas all of these surfactants showed low hemolytic character.

El visado en un hospital de tercer nivel / Visa at a tertiary hospital

Objetivo: Analizar el procedimiento de visado y su actividad en un hospital de tercer nivel. Material y métodos: Estudio descriptivo del procedimiento de visado durante el período abril 2011-abril 2012. Se diseñó una base de datos y se definieron categorías relativas a las variables de estudio: pacientes y recetas. Para los pacientes atendidos en la Unidad de Visado se registraron las incidencias detectadas en base a una clasificación previamente establecida. Resultados: Se incluyeron 6.738 pacientes (8.465 recetas visadas). Se visaron 170 medicamentos y productos de nutrición diferentes, siendo el mayoritario Tacrolimus. Se detectaron un total de 420 incidencias, siendo las más frecuentes la "Ausencia de documento clínico" (46,67 %) y los "Errores formales de cumplimentación" (28,57%).Conclusiones: El presente trabajo ha permitido un conocimiento más pormenorizado de la actividad, los tipos de incidencias y la identificación de áreas de mejora (AU)

Objective: To analyze the visa application process and his activity at a tertiary hosipital. Material and methods: Descriptive study of the drug s visa activity during the period April 2011-April 2012. We designed a database and defined categories on the study variables: patients and recipes. For patients admitted to the Visa Unit, issues detected were recorded based on a previously established classification. Results: 6738 patients were included. They involved the visa of 8,465 recipes. The visa was applied to 170 drugs and nutrition products different, being the majority Tacrolimus. During this period, we detected a total of 420 incidents being the most frequent "No clinical document" (46.67%) and the "Formal completion errors" (28.57%).Conclusions: This work has allowed a more detailed analysis of the activity, the types of incidents and the identification of areas for improvement (AU)

Multiple idiopathic mucosal neuromas: a minor form of multiple endocrine neoplasia type 2B or a new entity?

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant process characterized by medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas. A point mutation at codon 918 of the RET protooncogene has been observed in approximately 90% of patients and families with MEN 2B. Mucosal neuromas are the most consistent and distinctive feature (100% of patients) of MEN 2B and are considered pathognomonic. We describe a 35-year-old woman with mucosal neuromas of the lower lip and tongue that appeared in early childhood. Examination did not reveal other abnormalities. After a follow-up of more than 22 years with periodic clinical, biochemical, and radiologic studies, no evidence of MEN 2B has been detected. Analysis of the RET protooncogene exons 10, 11, and 16 did not demonstrate point mutation in the MEN 2B region (M918T).

Expression of the ret proto-oncogene in phaeochromocytoma. An in situ hybridization and northern blot study.

The expression and distribution of ret proto-oncogene mRNA were investigated in five phaeochromocytomas of both familial and sporadic types by in situ hybridization (ISH) using digoxigenin-labelled cRNA probes and Northern blot (NB) analysis with random priming labelled cDNA probes. The probes corresponded to the tyrosine kinase domain of the gene. An excellent correlation was found between the ISH and NB results. By both techniques, the expression of the ret proto-oncogene was detected in three of the five cases, two of four familial tumours, and the only sporadic tumour that was studied. The results confirm that ret is frequently expressed in phaeochromocytomas and suggest that it might be an important event in their development and/or progression.

Sex-steroid hormone receptors in human medullary thyroid carcinoma.

Three complementary techniques were used to detect sex-steroid hormone receptors in tumor tissues from seven patients with medullary thyroid carcinoma: steroid binding analysis, enzyme immune assay, and immunohistochemistry. The presence of estrogen receptors was detected by steroid binding analysis in one of seven patients, although in very low concentrations (3.17 to 5.06 fmol/mg protein). These results were confirmed by enzyme immune assay (6.35 to 9.32 fmol/mg protein). Progesterone receptors were found in five of seven patients by steroid binding analysis (11.1 to 47.9 fmol/mg protein), and progesterone receptor results were confirmed by enzyme immune assay (8.1 to 34.1 fmol/mg protein). By immunohistochemistry, progesterone receptors were focally detected in all cases, whereas all tumors were negative for estrogen receptors. In summary, our results confirm the presence of sex-steroid hormone receptors, particularly progesterone receptors in medullary thyroid carcinoma. The presence of progesterone receptors in medullary thyroid carcinoma apparently does not require the continuous presence of estrogen receptors.

Analysis of RET protooncogene point mutations distinguishes heritable from nonheritable medullary thyroid carcinomas.

BACKGROUND: The distinction of sporadic from inherited medullary thyroid carcinomas (MTCs) is of clinical importance because of the differences in prognosis, and the need for family screening for genetic counseling required in the latter. Germline mutations in the RET protooncogene are associated with multiple endocrine neoplasia (MEN) type 2A, familial medullary thyroid carcinoma (FMTC), and MEN type 2B. Somatic point mutations in the same gene have been identified in a subset of sporadically occurring medullary thyroid carcinomas. METHODS: A nonisotopic polymerase chain reaction-(PCR) based single strand conformation polymorphism (SSCP) analysis and heteroduplex gel electrophoresis method was used to screen DNA extracted from 32 formaldehyde fixed and paraffin embedded MTC specimens and normal tissue or blood of the same patient for point mutations in RET exons 10, 11, and 16. Point mutations were identified by nonisotopic cycle sequencing of PCR-products using an automated DNA-sequencer. Results were compared with the disease phenotype, clinical findings, and follow-up. RESULTS: Six different missense germline mutations were identified at cysteine residues 618, 630, and 634 of the cysteine-rich extracellular RET domain encoded by exons 10 and 11 in all patients with FMTC and MEN 2A. The frequency of mutations at codon 634 was higher in patients with MEN 2A than with FMTC and a 634 Cys-->Arg mutation was associated with parathyroid disease in three patients. A germline Met-->Thr point mutation at codon 918 of the RET tyrosine kinase domain was identified in all three patients with MEN 2B. Two patients with clinically sporadic MTCs and negative family history exhibited a RET germline mutation at codon 634, indicating the presence of an nonpredicted inherited MTC. Furthermore, one patient had a 618 Cys-->Ser mutation in the tumor and nontumorous thyroid DNA but not in blood DNA, indicating a mosaic mutation affecting thyroid tissue but not blood cells. Tumor specific (somatic) Met-->Thr point mutations at codon 918 were identified in 5 of 13 sporadic MTCs. The remaining eight sporadic MTCs lacked mutations in all three RET exons tested. CONCLUSIONS: This study demonstrates that (1) the molecular methods are not only suitable to identify asymptomatic individuals at risk for MEN 2A, FMTC, and MEN 2B but also to distinguish heritable from nonheritable MTCs using archival tissue specimens, and (2) that more MTCs than clinically expected are heritable, indicating the need for genetic analysis of all patients with MTC.

Traquelectomía radical laparoscópica / Laparoscopic radical thachelectomy

En este capítulo se revisa la utilidad, indicaciones y abordaje quirúrgico de este nuevo método de tratamiento del cáncer inicial de cuello uterino

The usefulness indications and surgical approach of this new meted of treatment in early cervical cancer are reviewed in this chapter