Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Langmuir films study on lipid-containing artificial tears.

Lipid-containing artificial tears are a type of artificial tears that use lipid components in order to restore the lipid layer of the tear film. One of these components is lecithin which can be applied in spray solutions containing lecithin liposomes. In this work the behavior of three of these commercial tears based on lecithin, Innoxa, Opticalm and Optrex, are studied using the Langmuir technique. The obtained isotherms are presented, discussed and compared. This technique seems useful in order to see the film behavior of the lipid components of these tears and determine some important parameters such as fluidity and extension at the air-water interface, and allows us to discern differences between these commercial tears. Innoxa and Optrex tears are more similar to each other than to Opticalm tears. Opticalm presents more fluidity, probably due to the presence of more insaturations in the fatty acid chains of the phospholipids of the lecithin used in fabrication.

AFM in mode Peak Force applied to the study of un-worn contact lenses.

Contact lenses (CLs) are of common use and the biocompatibility, topography and mechanical properties of the used materials are of major importance. The objective of this contribution is to apply the AFM in mode Peak Force to obtain surface topography and mechanical characteristics of un-worn CLs of different materials. One material of hydrogel, two of siloxane-hydrogel and one of rigid gas-permeable were used in the study. The results obtained with different materials have been compared, at a nanoscopic level, and the conclusions are diverse. There is no significant influence of the two environments used to measure the characteristics of the CLs, either water or saline solution. The pHEMA hydrogel CL (Polymacon of Soflens) shows the highest values of roughness, adhesion and elastic modulus. The siloxane-hydrogel CL named Asmofilcon A of PremiO presents the lowest values of mean roughness (Ra), root-mean-square roughness (RMS or Rq), adhesion (Adh) and elastic modulus (Ym), meanwhile the siloxane-hydrogel CL named Lotrafilcon B of Air Optix presents the lowest value of skewness (Rsk) and the rigid gas-permeable CL, named RXD, presents the lowest values of kurtosis (Rku) and maximum roughness (Rmax).

Predictive factors of successful sperm retrieval in azoospermia.

INTRODUCTION: Testicular sperm extraction with intracytoplasmic sperm injection is the standard treatment for azoospermia. The objective of this study is to identify predictive factors of successful sperm retrieval. MATERIALS AND METHODS: Between June 2003 and May 2011, we tried testicular sperm extraction (TESE) in 74 azoospermic patients in the Reproductive Medicine Unit of Son Espases Hospital (Palma de Mallorca). Serum follicle stimulating hormone (FSH) and inhibin B levels, testicular histology, genetic study, presence or not of cryptozoospermia and testicular volume were examined. RESULTS: Spermatozoa were successfully recovered in 47.2% of the total patients, in 36% of non-obstructive azoospermic patients and in 100% of obstructive azoospermic patients. Low inhibin B and high FSH were correlated to sperm retrieval failure. The cutoff points were determined using ROC curves that were 67 pg/mL for inhibin B and 12.2 mUI/mL for FSH. Spermatozoa were not successfully retrieved in any patient with Y microdeletions in AZFa,b regions. Spermatozoa were successfully retrieved in 100% of the patients with CFTR mutations. The highest sperm retrieval rate was for hypospermatogenesis, followed by maturation arrest and Sertoli-cell-only. Spermatozoa were successfully retrieved in all cryptozoospermic patients. Although using a non-significant test, there seems to be a correlation between higher testicular volume and a higher probability of successful sperm retrieval. CONCLUSIONS: Except for Y microdeletions in AZFa,b regions, there is no predictive factor of testicular sperm retrieval to rule out a patient for TESE. Lower inhibin B is more related to sperm retrieval failure than higher FSH. Sperm retrieval is possible for all cases of CFTR mutations but in any case of microdeletion Y in AZFa,b. The lack of germ cells is correlated with a high probability of sperm retrieval failure. The presence of cryptozoospermia is correlated with a high probability of sperm retrieval success. We do not find a statistically significant relation between testicular volume and successful sperm retrieval.

Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE / Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group

Objetivos: El diagnóstico fotodinámico (DFD) con hexaminolevulinato se ha empezado a utilizar recientemente para mejorar la detección del cáncer vesical no músculo invasivo. Nuestro objetivo principal fue comparar el rendimiento diagnóstico de DFD frente a endoscopia con luz blanca convencional (LB) en nuestro medio. Material y métodos: Se realizó cistoscopia fluorescente con hexaminolevulinato en el momento de la RTU a 305 pacientes de 7 hospitales españoles. Todas las lesiones detectadas con LB y DFD fueron enumeradas y registradas en una base de datos online. Se analizó histopatológicamente cada lesión por separado. En 148 pacientes se tomaron además biopsias múltiples aleatorias (BMA). Resultados: Se biopsiaron un total de 1.659 lesiones: 522 identificadas con DFD y LB, 237 sólo con DFD, 19 sólo con LB y 881 BMA. De 600 neoplasias diagnosticadas DFD detectó 563, LB 441 y BMA 29 (20 CIS). La tasa media de sobredetección de DFD sobre LB fue del 31,9% globalmente, pero en el caso del CIS fue del 209%. La sensibilidad de DFD fue 93,8% y la de LB 78,2%. La especificidad de DFD fue 81,5% y la de LB 90,5%. En el 23% de los pacientes se detectó al menos una lesión neoplásica más con DFD que con LB. Conclusión: La RTU con hexaminolevulinato mejora el rendimiento diagnóstico y la calidad de la resección del cáncer vesical superficial, especialmente del CIS. La mayor sensibilidad de DFD es a costa de una menor especificidad. En nuestro estudio BMA rescató algunos falsos negativos de DFD para detectar CIS (AU)

Objectives: Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. Material and methods: Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. Results: A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. Conclusions: Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD (AU)

[Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group]. / Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE.

OBJECTIVES: Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. MATERIAL AND METHODS: Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. RESULTS: A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. CONCLUSIONS: Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD.

Characterization of Langmuir and Langmuir-Blodgett films of a thiomacrocyclic ionophore by surface pressure and AFM.

The new synthesized thiomacrocyclic ionophore 4-phenyl-4-sulfide-11-(1-oxodecyl)-1,7-dithia-11-aza-4-phosphacyclotetradecane has proven to form Langmuir and Langmuir-Blodgett (LB) films. This ionophore shows a large affinity for copper(II) ions. Thus, the influence of the subphase composition on the surface pressure-area isotherms has been studied. The LB films have been observed by AFM and the effect of the subphase composition and the deposition surface pressure on the LB films is discussed. AFM image morphology has been correlated to the ionophore molecular structure. Surface pressure-area isotherms and AFM images show that the presence of copper(II) ions has an important role in the film structure.

Adsorption of recombinant human bone morphogenetic protein rhBMP-2m onto hydroxyapatite.

Recombinant human mature bone morphogenetic protein 2 (rhBMP-2m) has been expressed to study its adsorption onto precipitated hydroxyapatite (HA). The influence on the adsorption process of different parameters such as pH and concentrations of calcium, phosphate or NaCl has been investigated. Although the adsorption proceeds rapidly at the initial stages, the maximum adsorbed amount is reached after four hours. The process is notably influenced by adding calcium or phosphate to the system but, while calcium ions increase the adsorption of rhBMP-2m onto HA, phosphate ions inhibit it. The influence of pH and NaCl concentration are notable but less important than those of calcium and phosphate. The adsorption data fit well to a Langmuir adsorption isotherm. The values of the isotherm parameters have been calculated and discussed, and an adsorption mechanism has been proposed.

Selective dissection of levels II-III with intraoperative control of the upper and middle jugular nodes: a therapeutic option for the N0 neck.

BACKGROUND: Selective neck dissections are accepted elective treatment in N0 patients. We present the results of a dissection of levels II to III and intraoperative pathologic control of a sample of subdigastric and supraomohyoid nodes in a group of patients with laryngeal carcinoma. When intraoperative analysis was positive, dissection of levels IV and V was completed. METHODS: Between 1991 and 1997, 145 neck dissections with intraoperative control were carried out in 79 patients with laryngeal carcinomas. Postoperative radiotherapy was used in 49 patients. RESULTS: There were occult metastases in 29 neck dissections (20%). In 22 cases (15%), tumor was found in the nodes sent to intraoperative pathologic study, and dissection of levels IV and V was completed. In 7 additional cases tumor was found in the postoperative study. The sensitivity of the use of frozen sections in the detection of occult metastases was 76%. In no case were positive nodes found at level V. There was no regional relapse in any of the 145 selective neck dissections. CONCLUSIONS: The lateral selective neck dissection is an effective method in the elective treatment of the neck of N0 laryngeal carcinoma patients. Dissection of level IV can be spared when intraoperative biopsy specimens of a sample of the subdigastric and supraomohyoid nodes are negative. According to our results, at present we do not consider it necessary to dissect level V in selective neck dissections in patients with laryngeal carcinoma.

Endoscopic laser surgery in the treatment of radiation failure of early laryngeal carcinoma.

BACKGROUND: This study was undertaken to analyze the local control rates and survival of patients undergoing endoscopic laser surgery for squamous cell carcinoma of the larynx as a salvage procedure for recurrent tumors after radiotherapy. METHODS: Twenty-four patients underwent endoscopic laser surgery for radiation failure at our hospital from 1988 to 1995. All patients were men, between 45 and 88 years old. The localization of the recurrence was in the supraglottis in 3 cases and in the glottis in 21 cases. The postirradiation recurrences were staged rT1 in 18 patients and rT2 in 6 patients. RESULTS: Local recurrence after laser surgery developed in six patients (25%) who had a total laryngectomy. Voice preservation was thus achieved in 75% of patients. No patient died because of the laryngeal cancer, and the observed 5-year survival rate was 76%. CONCLUSIONS: These results indicate that in selected cases, endoscopic laser surgery may be used successfully for treating radiation failure of early laryngeal carcinomas.

[Bourneville's tuberous sclerosis associated with double uterus and vagina (didelphic uterus)]. / Esclerosis tuberosa de Bourneville asociada a duplicidad uterovaginal (útero didelfo).

INTRODUCTION: We describe a case that fulfill the diagnostic criteria for the tuberous sclerosis (Bourneville disease), and presents a double uterus and double vagina (didelphic uterus). We have not found any reference ti this association in the literature (MEDLINE search from July 1986 to December 1996). CLINICAL CASE: A 38-year-old woman with mental retardation and seizures who has been with carbamazepine since age 14. In 1979 a double vagina was diagnosed and a resection of a vaginal thin wall was performed. Laparoscopy showed a double uterus and multiple granulations of mesothelial proliferation in the Douglas sac. She has a remarkable behavior disorder with conjugal and familiar problems as well as a chronic renal insufficiency. The examination show a patient with a mental retardation, cutaneous hypopigmentation, facial adenomas sebaceums of Pringle, and ataxia, the rest of exploration was normal. The cranial CT show multiples calcified subependymal nodules. An abdominopelvic CT revealed several lesions in the liver parenchymal, and the pancreas head, compatible with hamartomas or lipomas, big kidneys with bilateral cysts and angiomyolipomas, and didelphic uterus. The cytogenetic study showed a normal karyotype (46,XX) and the molecular cytogenetic study (Fluorescence in situ hybridization, FISH) of chromosomes 2, 3, 4, 9, 11, 12 and 16 showed no chromosomal reangement. CONCLUSIONS: Eventhough both Bourneville disease and didelphic uterus have individually been associated with chromosomal abnormalities, our cytogenetic studies show no chromosomal reangement or abnormality despite the coexistence of both disease in our patient. In the bibliographic search that we have performed we have not found any report of a case like the one we describe here.

Montgomery salivary bypass tube in the reconstruction of the hypopharynx. Cost-benefit study.

This study analyzes the postoperative complications and the functional results in 61 patients who underwent total laryngectomy with partial or total (circumferential) pharyngectomy reconstructed with a pectoralis major myocutaneous flap, in relation to the use of the Montgomery Salivary Bypass Tube (MSBPT). There were no significant differences regarding frequency of postoperative cervical complications in relation to the use of the MSBPT. The median hospital stay for patients without the MSBPT (36 days) was significantly higher than that for patients with the MSBPT (25 days). Although the MSBPT did not modify the rate of complications at the cervical level, it did reduce their severity. A financial study showed the cost-effectiveness of using the MSBPT. Systematic use of the MSBPT is recommended after total laryngectomy with partial or total pharyngectomy reconstructed with a pectoralis major myocutaneous flap.

Second neoplasm in patients with head and neck cancer.

BACKGROUND: The improvement in locoregional control of head and neck carcinomas over the last decades does not appear to modify the final survival of these patients, mainly due to the appearance of distant metastases and second neoplasms. We ran a study to evaluate the incidence of second neoplasms and their characteristics in patients with head and neck carcinoma treated in our hospital. METHODS: A retrospective study was undertaken to analyze the appearance of second neoplasm, its characteristics, and repercussion on the survival in 1845 patients with carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx diagnosed and treated in our department between 1984 and 1995. RESULTS: A group of 302 patients (16%) developed a second neoplasm. The incidence of second neoplasms was 4% per year and was constant during the follow-up period. Second neoplasms were mainly carcinomas located in head and neck (40%), lungs (31%), or esophagus (9%). Twenty percent of second neoplasms were tumors located outside the aerodigestive tract. The appearance of a second neoplasm significantly worsened the survival. CONCLUSIONS: Four percent per year of patients with carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx develop a second neoplasm, most frequently a carcinoma of the aerodigestive tract. This leads to a significant worsening of survival.

[Differential features of transglottic carcinoma]. / Características diferenciales de los carcinomas transglóticos.

A study was made of the differential features of transglottic laryngeal carcinomas. We made a retrospective study of patients with laryngeal carcinoma diagnosed in our center from 1985 to 1996. In this period, 1212 laryngeal carcinomas were diagnosed, of which 99 (8%) were considered transglottic. In relation to factors such as sex, toxic habits, level of histological differentiation or affected nodes, patients with transglottic carcinomas had characteristics that were intermediate between patients with glottic and supraglottic carcinomas. An analysis was made of the treatments and the results obtained in patients treated with radical intention and a minimum follow-up of 3 years. The treatment most frequently used in patients with transglottic carcinoma was surgery (total laryngectomy) and complementary radiotherapy. The 5-year actuarial adjusted survival rate jor patients with transglottic carcinoma was 78%, which was intermediate between the survival rates of patients with glottic (90%) or supraglottic (69%) carcinoma.

[Congenital dyserythropoietic anemia morphologically type I with a positive HEMPAS phenomenon]. / Anemia diseritropoyética congénita morfológicamente de tipo I con fenómeno de HEMPAS positivo.

A patient with clinical and morphological anaemia of type I is described. Surprisingly, the Ham's test yield positive with 2 of 20 compatible serum. Only other such case is recorded in the literature. We revised the literature and comment the unclassified cases reported.

Influence of age on laryngeal carcinoma.

The constant increase in human life expectancy has led to a higher proportion of oncologic patients of advanced age. The clinical characteristics of 272 patients with laryngeal carcinoma diagnosed when they were 70 or older are compared with those of a group of younger patients with the same kind of tumor. The advanced age group showed a higher proportion of women, less tobacco and alcohol use, a predominance of glottic location, and a higher previous morbidity. The T category was similar in both groups, but the advanced age group had a higher proportion of N0 tumors. The planning of treatment was similar in the two groups of patients, except for less use of both chemotherapy and partial larynx surgery in the advanced age group. Results in terms of local and regional control, distant metastasis, and 5-year adjusted survival were similar in both groups of patients. The results suggest that advanced age is not a determining factor when considering radical treatment in a patient with laryngeal carcinoma.

Laryngeal carcinoma in patients without a history of tobacco and alcohol use.

BACKGROUND: The medical literature on laryngeal carcinomas in patients without a history of tobacco and alcohol use is sparse. METHODS: A retrospective review of 933 laryngeal carcinomas treated in our center between January 1984 and December 1993 was made. Characteristics and results of patients with history of tobacco and alcohol use were compared with those who used neither. RESULTS: Of all patients with laryngeal carcinomas, 31 (3.3%) had no history of tobacco and alcohol use. In this group of patients, distribution between sexes was similar, and the mean age of patients was 70 years, compared with 63 years in the group with a history of tobacco and alcohol use. The survival rate was better in the former group. CONCLUSIONS: Patients without a history of tobacco and alcohol use who developed laryngeal cancer showed different characteristics compared with smokers or drinkers; they were an average of 10 years older, they showed no male predominance, and their lesions were mainly located in the glottis, which permitted early diagnosis and a higher survival rate.

[Results of salvage treatment of carcinoma of the larynx recurring after radiotherapy]. / Resultados del tratamiento de repesca en carcinomas de laringe recidivados tras radioterapia.

An analysis is made of salvage treatments and their results after unsuccessful radiotherapy in 113 carcinomas of the larynx. A group of 27 patients (24%) was excluded from salvage treatment. In the remaining 86 patients (76%), radical surgical salvage treatment was tried: total laryngectomy (74 cases) or partial surgery (12 cases). Four of the 12 patients treated with partial surgery suffered a second local relapse, which was rescued by new surgery. Treatment was successful in 72% of the laryngectomized patients and in all those treated with partial surgery. Survival correlated with local (T) and regional (N) extension of the initial tumor, its location, and simultaneous regional relapse. In contrast, survival did not correlate with the time interval between end of radiotherapy and relapse, or with local tumoral extension in the resection piece in surgically treated cases (rpT).

[Complications of total laryngectomy in relation to the previous radiotherapy]. / Complicaciones de la laringectomía total en función del uso previo de radioterapia.

Different factors, particularly prior radiotherapy, are associated with the occurrence of postoperative complications after total laryngectomy. We compared the postoperative complications of 50 patients who underwent total laryngectomy without prior radiotherapy and those of 50 patients who underwent total laryngectomy for tumor recurrence or persistence after radiotherapy. Twenty-four percent of the patients without previous irradiation suffered cervical complications compared with 26% of the patients with previous irradiation. The most frequent cervical complication was pharyngo-cutaneous fistula, which occurred in 12% of the non-irradiated patients and in 18% of the irradiated patients. There were no significant differences in the frequency of complications or in the occurrence of fistulas in relation to prior radiotherapy. In the group of irradiated patients, the proportion of major fistulas was greater. The occurrence of cervical complications, particularly pharyngo-cutaneous fistulas, significantly prolonged the hospital stay.

Blood transfusions in laryngeal cancer: effect on prognosis.

METHODS: To evaluate the influence of homologous perioperative transfusion on oncologic control and survival in patients with larynx and hypopharynx carcinomas, we conducted a retrospective study of 269 patients with larynx and hypopharynx carcinoma treated by major surgical procedures. A total of 20 variables were analyzed for each patient. RESULTS: Perioperative transfusion was required in 86 (32%) patients, with packed red blood cells being used in all cases. Recurrence at a local, regional, or distant level was 31% for nontransfused and 35% for transfused patients. The 5-year adjusted survival was 68% for patients without transfusion and 63% for patients with transfusion. Neither the univariate nor the multivariate analysis showed that perioperative transfusion or the number of units of packed red blood cells used had any prognostic capacity. CONCLUSIONS: Homologous perioperative transfusion did not imply a significant risk regarding global control or survival in our larynx or hypopharynx cancer patients.