Medical versus surgical treatment of first trimester spontaneous abortion: A cost-minimization analysis

[EN]Background: Traditionally the gold-standard technique for the treatment of spontaneous abortion has been uterine evacuation by aspiration curettage. However, many studies have proposed medical treatment with misoprostol as an alternative to the conventional surgical treatment. The aim of this study was to apply cost minimization methods to compare the cost and effectiveness of the use of vaginal misoprostol as a medical treatment for first trimester spontaneous abortion with those of evacuation curettage as a surgical treatment. Methodology/principal findings: We present a longitudinal, prospective and quasi-experimental research study including a total of 547 patients diagnosed with first-trimester spontaneous abortion, in the period from January 2013 to December 2015. Patients were offered medical treatment with 800 mg vaginal misoprostol or evacuation curettage. Patients treated with misoprostol were followed-up at 7 days and a transvaginal ultrasound was performed to confirm the success of the treatment. If it failed, a second dose of 800 mg of vaginal misoprostol was prescribed and a new control ultrasound was performed. In case of failure of medical treatment after the second dose of misoprostol, evacuation curettage was indicated. The effectiveness of each of the treatment options was calculated using a decision tree. The cost minimization study was carried out by weighting each cost according to the effectiveness of each branch of the treatment. Of the 547 patients who participated in the study, 348 (64%) chose medical treatment and 199 (36%) chose surgical treatment. The overall effectiveness of medical treatment was 81% (283/348) and surgical treatment of 100%. The estimated final cost for medical treatment was € 461.92 compared to € 2038.72 for surgical treatment, which represents an estimated average saving per patient of € 1576.8. Conclusions/significance: Medical treatment with misoprostol is a cheaper alternative to surgery: in the Spanish Public Healthcare System, it is five times more inexpensive than curettage. Given its success rates higher than 80%, mild side effects, controllable with additional medication and the high degree of overall satisfaction, it should be prioritized over the evacuation curettage in patients who meet the treatment criteria

How to improve the precision of Bethesda System diagnostic categories I and III

Fine-needle aspiration (FNA) has a primary role in the diagnosis of thyroid nodules. FNA allows us to differentiate benign lesions from malignant ones in most of the cases. However, management of Bethesda System diagnostic categories I (Nondiagnostic or Unsatisfactory) and III (Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance) are a clinical challenge./nThe aim of this work is to expose the options we have to improve the diagnosis of those categories using a multidisciplinary approach, an active follow-up, repeating FNA, applying immunohistochemical and/or molecular technics or even perform a core needle biopsy./nSome or all of these choices are especially useful to identify category III, but active follow-up or additional FNA are preferred to detect category I.Introducción y objetivo: La punción aspiración con aguja fina es el método de elección para el diagnóstico del nódulo tiroideo, permitiendo discriminar entre lesiones malignas y benignas en un alto porcentaje de pacientes. Sin embargo, las categorías diagnósticas I (No diagnóstico o insatisfactorio) y III (Atipia o Lesión folicular de Significado Incierto) del Sistema Bethesda suponen un reto en el manejo de los nódulos tiroideos. El objetivo del presente trabajo es exponer las opciones de que se disponen en el momento actual para intentar incrementar la rentabilidad de estos diagnósticos. Síntesis: En primer lugar, el abordaje multidisciplinar de los casos, la posibilidad de seguimiento, la repetición de la punción aspiración, la complementación del diagnóstico incorporando técnicas inmunohistoquímicas o moleculares, y finalmente la posibilidad de realizar una biopsiacilindro. Conclusiones: Estas alternativas son especialmente útiles en la categoría diagnóstica III, mientras que se prefiere la opción de seguimiento o repetición de PAAF en la categoría diagnóstica I

Giant Isolated Omphalocele: Role of Prenatal Diagnosis in Prognostic Asessment and Perinatal Management

Article ID 4578912[EN]Omphalocele is a congenital malformation of the abdominal wall consisting of a protrusion of the abdominal contents at the base of the umbilical cord. It has a high association with genetic and structural defects; however, if the latter is ruled out, its prognosis improves significantly. Prenatal diagnosis has a key role in this condition as omphalocele can be diagnosed by ultrasound in the first trimester scan, enabling a coordinated approach strategy to achieve the best perinatal results. We present a case report of a pregnant patient with a fetus having a giant omphalocele in which prenatal diagnosis played a decisive role, allowing the coordination of a multidisciplinary team, which was crucial in the immediate care of the newborn

Spatio-temporal tumor heterogeneity in metastatic CRC tumors: a mutational-based approach

[EN] It is well known that activating mutations in the KRAS and NRAS genes are associated with poor response to anti-EGFR therapies in patients with metastatic colorectal cancer (mCRC). Approximately half of the patients with wild-type (WT) KRAS colorectal carcinoma do not respond to these therapies. This could be because the treatment decision is determined by the mutational profile of the primary tumor, regardless of the presence of small tumor subclones harboring RAS mutations in lymph nodes or liver metastases. We analyzed the mutational profile of the KRAS, NRAS, BRAF and PI3KCA genes using low-density microarray technology in samples of 26 paired primary tumors, 16 lymph nodes and 34 liver metastases from 26 untreated mCRC patients (n=76 samples). The most frequent mutations found in primary tumors were KRAS (15%) and PI3KCA (15%), followed by NRAS (8%) and BRAF (4%). The distribution of the mutations in the 16 lymph node metastases analyzed was as follows: 4 (25%) in KRAS gene, 3 (19%) in NRAS gene and 1 mutation each in PI3KCA and BRAF genes (6%). As expected, the most prevalent mutation in liver metastasis was in the KRAS gene (35%), followed by PI3KCA (9%) and BRAF (6%). Of the 26 cases studied, 15 (58%) displayed an overall concordance in the mutation status detected in the lymph node metastases and liver metastases compared with primary tumor, suggesting no clonal evolution. In contrast, the mutation profiles differed in the primary tumor and lymph node/metastases samples of the remaining 11 patients (48%), suggesting a spatial and temporal clonal evolution. We confirm the presence of different mutational profiles among primary tumors, lymph node metastases and liver metastases. Our results suggest the need to perform mutational analysis in all available tumor samples of patients before deciding to commence anti-EGFR treatment

Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile

[EN]Circulating myeloma tumor cells (CTCs) as defined by the presence of peripheral blood (PB) clonal plasma cells (PCs) are a powerful prognostic marker in multiple myeloma (MM). However, the biological features of CTCs and their pathophysiological role in MM remains unexplored. Here, we investigate the phenotypic, cytogenetic, and functional characteristics as well as the circadian distribution of CTCs vs paired bone marrow (BM) clonal PCs from MM patients. Our results show that CTCs typically represent a unique subpopulation of all BM clonal PCs, characterized by downregulation (P < .05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). Fluorescence in situ hybridization analysis of fluorescence-activated cell sorter-sorted CTCs also unraveled different cytogenetic profiles vs paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when cocultured with BM stromal cells. Most interestingly, CTCs showed a circadian distribution which fluctuates in a similar pattern to that of CD34(+) cells, and opposite to stromal cell-derived factor 1 plasma levels and corresponding surface expression of CXC chemokine receptor 4 on clonal PCs, suggesting that in MM, CTCs may egress to PB to colonize/metastasize other sites in the BM during the patients' resting period

Ductus venosus agenesis as a marker of Pallister-Killian Syndrome

[EN]The ductus venosus (DV) is a shunt that allows the direct flow of well-oxygenated blood from the umbilical vein (UV) to the coronary and cerebral circulation through the foramen ovale. Its agenesis has been associated with chromosomal abnormalities and rare genetic syndromes, structural defects, intrauterine growth restriction (IUGR) and even antepartum fetal demise. Pallister-Killian Syndrome (PKS) is a rare sporadic disorder with specific tissue mosaic distribution of an extra 12p isochromosome (i(12p)). Its main clinical features are moderate to severe intellectual disability/neuromotor delay, skin pigmentation abnormalities, typical facial appearance, variable association with multiple congenital malformations and epilepsy. Though prenatal findings (including congenital diaphragmatic hernia, ventriculomegaly, congenital heart disease, polyhydramnios, and rhizomelic shortening) have been described in literature, prenatal diagnosis is difficult as there are no associated identification signs no distinctive or pathognomonic signs, and some of these malformations are hard to identify prenatally. The tissue mosaicism linked to this syndrome and the decrease of the abnormal clone carrier of the i(p12) after successive trypsinizations of cultured cells makes the diagnosis even more challenging. We present the case of a 27.5 weeks pregnant woman with a fetal ductus venosus agenesis (DVA) as the main guide marker. To our knowledge this is the first case published in literature reporting a DVA as a guide sign to diagnose a complex condition as Pallister-Killian syndrome. We also underscore the key role of new genetic techniques as microarrays to avoid misdiagnosis when only a subtle sonographic sign is present in complex conditions like this

Cesarean Hysterectomy in Abnormally Invasive Placenta: The Role of Prenatal Diagnosis

[EN]An abnormally invasive placenta (AIP) is a placenta that cannot be removed spontaneously or manually without causing severe bleeding. It is a dangerous condition associated with a high rate of maternal and perinatal morbidity and mortality due to the high rate of massive bleeding and visceral injuries. The standardized ultrasound diagnostic criteria have helped improve its early diagnosis, which is essential to plan coordinated actions to reduce associated morbimortality. We present a case report in which ultrasound diagnosis played a decisive role, enabling the coordination of a multidisciplinary team and improving the immediate care of both mother and newborn. Cesarean hysterectomy was performed with minimal blood loss and a good postsurgical recovery

COVID-19 qPCR testing in women admitted for delivery in Spain: Is universal testing worthy?: A commentary

[EN]The current coronavirus disease 2019 (Covid-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expanding globally becoming a so serious public health emergency that drastic measures across all continents, including nationwide lockdowns and border closures have been necessary to slow down the spreading of the disease. Pregnant women and their fetuses represent a high-risk population during infectious disease outbreaks and they are a challenge in terms of health care. Spain has been one of the most affected countries by the pandemic, with more than 243,000 positive cases and 27,000 deaths at the end of May. Castilla y León has been the third with the highest number of cases (19,104 infections and 1928 deaths on June 11th) among the 17 autonomous communities of Spain. Of the nine provinces that make up the Community of Castilla y León, Salamanca is the second both in number of infections (4280) and deaths (369, 19% of the whole Community). Salamanca University Hospital is one of the largest hospitals in the Community, with 2000 deliveries per year on average. From the beginning of the pandemic, testing with nasopharyngeal swabs and a quantitative polymerase-chain-reaction (qPCR) was performed in the Emergency Department on patients with Covid-19 disease symptoms and an outpatient program was implemented to trace positive patient’s contacts. As evidence on the existence of a large number of asymptomatic positive patients who could act as carriers was reported, the Obstetrics Department asked the qPCR test to be performed on all patients admitted both for delivery and to the obstetrics ward, to guarantee admission in a safe environment and to reduce the chance of transmission to other patients and to the healthcare staff. From 23/03, the qPCR test was carried out to detect SARS-CoV-2 in all women admitted for delivery. Since then there have been 366 deliveries up to 11/06. Of these, 25 patients (15%) have tested positive for the virus. Twelve of them were detected by qPCR on admission for delivery being all of them asymptomatic. It should be noted that two of these patients were referred from a private centre where serological screening with IgM-positive antibodies was carried out. On admission, both women tested negative for qPCR; however, considering the chance of being either Covid-19 early stage or qPCR false negative, they were treated as if they were positive [6]. qPCR test was repeated a week later becoming positive in one of them. The reasons for admission in these patients were all obstetric: six were admitted in labour, two presented premature rupture of membranes at term (PROM), two had preterm premature rupture of membranes (PPROM), one postterm pregnancy was admitted for induction and one term pregnancy presented severe pre-eclampsia. Another nine patients were detected through the outpatient contact tracing program. Six of them were asymptomatic whilst three had mild symptoms. One of the patients in this group who was positive at 31 weeks gestation and whose qPCR was negative at 33 weeks was admitted with an intrauterine fetal death and required an emergent caesarean section due to severe pre-eclampsia and disseminated intravascular coagulation. Four patients were tested by the hospital Emergency Department being all symptomatic: two of them had mild symptoms and were discharged under home isolation and contact tracing recommendations. The other two presented severe pneumonia being admitted to the Internal Medicine Ward. One of them developed a threatened preterm labor resistant to tocolysis, which ended in preterm delivery at 32 weeks gestation. The other patient suffered a severe worsening and required admission to Intensive Care Unit for a week. In our experience, 72% of the positive patients were asymptomatic (n = 18) and 20% presented mild symptoms that allowed outpatient control, without hospital admission (n = 5). Only 8% (n = 2) required admission for severe symptoms, mainly pneumonia. These data are important, as without a prior screening test we could be facing a positive patient unaware, thus increasing the risk of transmission and therefore the spread of infection. From the beginning of the crisis, admission protocols in the Obstetric Department were adapted to avoid the separation of the positive mother from her child and to guarantee, on the one hand, the isolation from the rest of the women in the ward, preventing the spread of infection to the negative patients, and on the other hand, the necessary intimacy and comfort for both mother and new-born. The implementation of qPCR testing in a universal basis has been a key factor on this point. None of the new-borns developed Covid-19 symptoms or required admission for this reason. Spain has also been one of the countries with the highest number of infected healthcare staff to date and where the shortage of protective equipment has been particularly noticeable during the most serious moments of the crisis. In our department, almost 20% of the medical staff has been infected during the pandemic (5/26). Although it is not possible to specify, it is very likely that most of these infections had occurred during the time prior to the declaration of the state of alert and the routine performance of screening tests, with patients being attended without adequate protective measures. This is particularly important not only because of the loss of health care capacity for the population as the effective number of available health care workers is reduced, but also because, if these infected workers are themselves asymptomatic, they can act as carriers of the disease and spread it further. For all the above reasons, universal Covid-19 screening in pregnant women prior to admission for delivery is beneficial not only for the women themselves, who will get more appropriate care, but also to reduce the risk of exposure of the healthcare staff, to trace the Covid-19 status in her contacts and relatives and to implement measures to slow down the spread of the pandemic

Prognostic implications of EGFR protein expression in sporadic colorectal tumors: Correlation with copy number status, mRNA levels and miRNA regulation

[EN]Sporadic colorectal cancer (sCRC) is the third most frequent cancer worldwide and the second most common cause of cancer-related deaths (mainly due metastatic dissemination). We investigated the immunohistochemical expression of frequently altered proteins in primary tumors from 51 patients (25 liver metastatic and 26 non-metastatic cases) with a median 103 months follow-up (103 months). We evaluated EGFR copy number (using SNP arrays and FISH) and its expression and regulation (by mRNA and miRNA arrays). We found differences between metastatic and non-metastatic sCRCs for MLH1 (p = 0.05), PMS2 (p = 0.02), CEA (p < 0.001) and EGFR (p < 0.001) expression. EGFR expression was associated with lymph node metastases (p = 0.001), liver metastases at diagnosis (p < 0.001), and advanced stage (p < 0.001). There were associations between EGFR expression-, EGFR gene copy number- and EGFR mRNA levels. We found potential interactions of two miRNAs targeting EGFR expression, (miR-134 and miR-4328, in non-metastatic and metastatic tumors, respectively). EGFR expression was associated with a worse outcome (p = 0.005). Multivariate analysis of prognostic factors for overall survival identified that, the expression of EGFR expression (p = 0.047) and pTNM stage (p < 0.001) predicted an adverse outcome. EGFR expression could be regulated by amplification or polysomies (in metastatic tumors), or miRNAs (miRNA-134, in non-metastatic tumors). EGFR expression in sCRC appears to be related to metastases and poor outcome.This work has been partially supported by grants from the Gerencia Regional de Salud de Castilla y León, Valladolid, Spain (GRS2051/A/19), CIBERONC from the ISCIII (CB16/12/00400) and the Fundación Memoria de Don Samuel Solórzano Barruso, Salamanca, Spai