LIFT procedure: postoperative outcomes, risk factors for fistula recurrence and continence impairment.

Ligation of the intersphincteric fistula tract has been recently employed as definitive treatment of anal fistulas. However, it carries a potential risk of continence impairment, fistula recurrence, and repeated operations. This study aimed to assess postoperative outcomes related to this procedure and evaluate the potential influence of preoperative and intraoperative features. Patients who underwent LIFT procedure between June 2012 and September 2021 were retrospectively analyzed. Patients were divided according to whether they developed fistula recurrence and on the history of a surgery prior to the LIFT. Preoperative features, postoperative outcomes, and risk factors adverse outcomes were analyzed. Forty-eight patients were included, of which 25 received primary LIFT, being the high transsphincteric fistula pattern the most frequent (62.5%). The median follow-up was 13.3 months, with a recurrence rate of 20.8%, of which the majority presented an intersphincteric fistula pattern (50%); and continence impairment rate of 16.7%. A higher prevalence of diabetes (p = 0.026) and a trend towards a higher prevalence of patients with a history of high transsphincteric fistula (0.052) were observed in the group with fistula recurrence. The history of diabetes and the operation time with a cut-off value ≥ 69 min showed a trend as a risk factors for developing fistula recurrence (0.06) and postoperative continence impairment (0.07), respectively. The LIFT procedure seems to be safe in terms of morbidity, with a reasonable incidence of recurrences, showing better results when it is primarily performed. Preoperative characteristics should be considered as they may impact outcomes.

Adult intussusception: still a challenging diagnosis for the surgeon.

INTRODUCTION AND AIM: Intussusception is rare in adults and can occur in the small bowel and colon. Its atypical presentation makes the diagnosis difficult. The aim of the present study was to evaluate the causes, clinical characteristics, and treatment outcomes of adult intussusception and to determine whether there was an association between etiology and clinical presentation. MATERIALS AND METHODS: A retrospective study was carried out on patients above 18 years of age that were treated for intussusception at a tertiary care hospital, between 2000 and 2020. The findings were summarized utilizing descriptive and inferential statistics. RESULTS: Twenty-eight cases were identified. Median patient age was 46 years (18-80) and median symptom duration was 18 days. Abdominal pain was the most frequent symptom (96.42%). The intussusceptions registered were enteroenteric (14), ileocecal (4), ileocolonic (4), colocolonic (5), and colorrectal (1). Intussusception etiology was benign in 15 cases, 9 were associated with malignancy, and 4 were idiopathic. Surgery was performed on 11 patients with enteroenteric intussusception and on all the cases of ileocecal, ileocolonic, colocolonic, and colorectal intussusception. There were 2 events of perioperative mortality (8%) and 8 of postoperative morbidity (32%). No significant differences were found regarding symptom duration or length of hospital stay, when the etiologic groups were compared. CONCLUSIONS: Intussusception is rare in adults. Diagnosis is a challenge because of the nonspecific signs and symptoms. Surgical resection should be considered in the definitive treatment and management should be individualized according to the patient's comorbidities, clinical presentation, and risk of malignancy.

Current status of precision medicine in pediatric oncology in Spain: a consensus report by the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.

Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆.

BACKGROUND: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). PATIENTS AND METHODS: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. RESULTS: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan-Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. CONCLUSIONS: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755).

Conversion from laparoscopic to open cholecystectomy: Risk factor analysis based on clinical, laboratory, and ultrasound parameters.

INTRODUCTION AND AIMS: The standard of care for gallbladder disease is laparoscopic cholecystectomy. Difficult dissection of the hepatocytic triangle and bleeding can result in conversion to open cholecystectomy, which is associated with increased morbidity. Identifying risk factors for conversion in the context of acute cholecystitis will allow patient care to be individualized and improve outcomes. MATERIALS AND METHODS: A retrospective case-control study included all patients diagnosed with acute cholecystitis, according to the 2018 Tokyo Guidelines, admitted to a tertiary care academic center, from January 1991 to January 2012. Using logistic regression, we analyzed variables to identify risk factors for conversion. Variables that were found to be significant predictors of conversion in the univariate analysis were included in a multivariate model. We then performed an exploratory analysis to identify the risk factor summation pathway with the highest sensitivity for conversion. RESULTS: The study included 321 patients with acute cholecystitis. Their mean age was 49 years (±16.8 SD), 65% were females, and 35% were males. Thirty-nine cases (12.14%) were converted to open surgery. In the univariate analysis, older age, male sex, gallbladder wall thickness, and pericholecystic fluid were associated with a higher risk for conversion. In the multivariate analysis all of the variables, except pericholecystic fluid, were associated with conversion. Our risk factor summation model had a sensitivity of 84%. CONCLUSIONS: Preoperative clinical data can be utilized to identify patients with a higher risk of conversion to open cholecystectomy. Being aware of such risk factors can help improve perioperative planning and preparedness in challenging cases.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

Multidisciplinary consensus on optimising the detection of NTRK gene alterations in tumours.

The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionised the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children; and they are either rare tumours with common NTRK fusions that may be diagnostic, or more prevalent tumours with rare NTRK fusions. To assess currently available evidence on this matter, three key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathological Anatomy (SEAP), and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical, and therapeutic aspects of NTRK-fusion tumours. This document also discusses the challenges related to the routine detection of these genetic alterations in a mostly public Health Care System.

Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I-II trials for paediatric cancer during the first month of state of alarm in Spain. METHODS: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. RESULTS: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity, or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate). CONCLUSIONS: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.

Conversion from laparoscopic to open cholecystectomy: Risk factor analysis based on clinical, laboratory, and ultrasound parameters. / Conversión de colecistectomía laparoscópica a abierta: análisis de factores de riesgo con base en parámetros clínicos, de laboratorio y de ultrasonido.

INTRODUCTION AND AIMS: The standard of care for gallbladder disease is laparoscopic cholecystectomy. Difficult dissection of the hepatocytic triangle and bleeding can result in conversion to open cholecystectomy, which is associated with increased morbidity. Identifying risk factors for conversion in the context of acute cholecystitis will allow patient care to be individualized and improve outcomes. MATERIALS AND METHODS: A retrospective case-control study included all patients diagnosed with acute cholecystitis, according to the 2018 Tokyo Guidelines, admitted to a tertiary care academic center, from January 1991 to January 2012. Using logistic regression, we analyzed variables to identify risk factors for conversion. Variables that were found to be significant predictors of conversion in the univariate analysis were included in a multivariate model. We then performed an exploratory analysis to identify the risk factor summation pathway with the highest sensitivity for conversion. RESULTS: The study included 321 patients with acute cholecystitis. Their mean age was 49 years (±16.8 SD), 65% were females, and 35% were males. Thirty-nine cases (12.14%) were converted to open surgery. In the univariate analysis, older age, male sex, gallbladder wall thickness, and pericholecystic fluid were associated with a higher risk for conversion. In the multivariate analysis all of the variables, except pericholecystic fluid, were associated with conversion. Our risk factor summation model had a sensitivity of 84%. CONCLUSIONS: Preoperative clinical data can be utilized to identify patients with a higher risk of conversion to open cholecystectomy. Being aware of such risk factors can help improve perioperative planning and preparedness in challenging cases.

Laparoscopic Roux-en-Y gastric bypass in the treatment of obesity: evidence based update through randomized clinical trials and meta-analyses.

Bariatric surgery was introduced in 1953, but during the last 20 years its popularity has increased after the development of significant Romaevidenced based breakthroughs in the field. Currently, approximately 150 long-term randomized clinical trials and 40 meta-analyses support and give credibility to the surgical approaches for the treatment of obesity and its related metabolic disturbances. Bariatric surgery has demonstrated improved outcomes compared to medical treatment, conduct therapy, and endoscopic procedures. Roux-en-Y gastrojejunostomy (RYGB) and Sleeve gastrectomy (SG) are the surgical procedures most frequently performed, due to their satisfactory results and security profile. There is sufficient evidence in medical literature to perform these procedures when indicated; however, there are still several controversies regarding technical aspects that need to be further explored.

Contrast-enhanced swallow study sensitivity for detecting esophagojejunostomy leakage. / Sensibilidad del trago de contraste hidrosoluble para la detección de fugas de anastomosis esofagoyeyunal.

INTRODUCTION AND AIM: Sixty percent of the patients with gastric carcinomas are candidates for surgical resection through total gastrectomy and esophagojejunostomy, the latter of which is associated with leaks in up to 12.3% of cases. There is no standardized procedure for diagnosing anastomotic leaks. The aim of the present study was to establish the diagnostic sensitivity of the contrast-enhanced swallow study for detecting esophagojejunostomy leakage after total gastrectomy. MATERIALS AND METHODS: A retrospective analysis was conducted on patients that underwent total gastrectomy due to gastric adenocarcinoma, within the time frame of 2002 and 2017. Demographic, clinical, and laboratory factors were identified, emphasizing the clinical and radiologic detection of anastomotic leaks. Descriptive statistics were carried out and the sensitivity of the contrast-enhanced swallow study for diagnosing leakage was calculated. RESULTS: Fifty-eight patients were included in the study. Their mean age was 61.5 years. A total of 55.2% of the patients were men and 44.8% were women. Gastric adenocarcinoma was the indication for gastrectomy in 100% of the cases. Anastomotic leak presented in 31.01% of the patients. Diagnostic sensitivity of the contrast-enhanced swallow study for detecting leaks was 66%. CONCLUSIONS: According to our analysis, the contrast-enhanced swallow study had limited diagnostic efficiency for detecting anastomotic leaks, with a sensitivity of 66%. We suggest maintaining high diagnostic suspicion in patients with studies that are initially negative and basing decisions on a more extensive approach.

ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain.

INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.

Improving the quality of care in the molecular era for children and adolescents with medulloblastoma.

PURPOSE: Elevated mortality and morbidity rates persist in pediatric patients with medulloblastoma. We present a clinical audit of a real-world cohort of patients in search for pragmatic measures to improve their management and outcome. METHODS/PATIENTS: All pediatric patients with medulloblastoma treated between 2003 and 2016 at a Spanish reference center were reviewed. In the absence of internationally accepted quality indicators (QIs) for pediatric CNS tumors, diagnostic, therapeutic, survival, and time QIs were defined and assessed. RESULTS: Fifty-eight patients were included, 24% were younger children (< 3 years), 36% high risk (anaplastic, metastasis, or surgical residue > 1.5 cm2), and 40% standard risk. Five-year OS was 59.2% (95% CI 47-75); 5-year PFS 36.4% (95% CI 25-53). Five main areas of quality assurance were identified: diagnosis, global strategy, frontline treatment modalities, outcomes, and long-term and end-of-life care. A set of 34 QIs was developed and applied. Lack of central pathology review, delay in the incorporation of novel molecular markers, and absence of a neurocognitive and quality-of-life evaluation program were some of the audit findings. CONCLUSIONS: This real-world research study resulted in the development of a pragmatic set of QIs, aimed to improve clinical audits and quality of care given to children and adolescents with medulloblastoma. We hope that our findings will serve as a reference to further develop a quality assurance system with specific QIs for pediatric CNS tumors in the future and that this will ultimately improve the survival and quality of life of these patients.

Plant structure predicts leaf litter capture in the tropical montane bromeliad Tillandsia turneri / A estrutura da planta determina a folhagem interceptada pela bromelia Tillandsiaturneri

Abstract Leaves intercepted by bromeliads become an important energy and matter resource for invertebrate communities, bacteria, fungi, and the plant itself. The relationship between bromeliad structure, defined as its size and complexity, and accumulated leaf litter was studied in 55 bromeliads of Tillandsia turneri through multiple regression and the Akaike information criterion. Leaf litter accumulation in bromeliads was best explained by size and complexity variables such as plant cover, sheath length, and leaf number. In conclusion, plant structure determines the amount of litter that enters bromeliads, and changes in its structure could affect important processes within ecosystem functioning or species richness.

Resumo As folhagens interceptadas pelas bromélias é um importante recurso para a comunidade de invertebrados, bactérias, fungos e para a própria planta. Estudou-se a relação entre a estrutura de 55 bromélias de Tillandsia tumeri, definida como o tamanho, a complexidade da planta, a folhagem acumulada por meio de regressão múltipla e o critério de informação de Akaike. Encontrou-se que as variáveis de tamanho, cobertura, comprimento da bainha e a variável de complexidade do número de folhas explicam a acumulação de folhas nas bromélias. Em conclusão, a estrutura do planta determina a quantidade de folhas armazenada na bromélia e os câmbios da estrutura da bromélia poderiam afetar importantes processos de funcionamento do ecossistema ou a riqueza de espécies.

Plant structure predicts leaf litter capture in the tropical montane bromeliad Tillandsia turneri.

Leaves intercepted by bromeliads become an important energy and matter resource for invertebrate communities, bacteria, fungi, and the plant itself. The relationship between bromeliad structure, defined as its size and complexity, and accumulated leaf litter was studied in 55 bromeliads of Tillandsia turneri through multiple regression and the Akaike information criterion. Leaf litter accumulation in bromeliads was best explained by size and complexity variables such as plant cover, sheath length, and leaf number. In conclusion, plant structure determines the amount of litter that enters bromeliads, and changes in its structure could affect important processes within ecosystem functioning or species richness.

A master dynamic flow diagram for the shear thickening transition in micellar solutions.

The shear thickening behavior of dilute micellar solutions of hexadecyltrimethylammonium-type surfactants with different counterions (tosylate, 3- and 4-fluorobenzoate, vinylbenzoate and salicylate) and of n-alkyltetradecylammonium bromide (CnTAB), with n = 14, 16 and 18, is examined here. These solutions undergo a shear thickening transition due to the formation of shear-induced structures (SISs) in the shear range studied. Here we report a relationship between the shear thickening intensity and the differences in the hydrophobicity of counterions according to the Hofmeister-like anion series, which leads to a master flow diagram. This master flow diagram is produced by plotting a normalized shear thickening intensity (Iη - 1)/(Imax - 1) versus CD/CD,max, where Iη is the shear-thickening intensity, defined as the largest viscosity obtained in the shear-thickening transition (STT) at a given surfactant concentration CD divided by the Newtonian viscosity η0, and Imax is the largest intensity value obtained in the STT at a surfactant concentration CD,max. The master flow diagram is built using several cetyltrimethylammonium-type surfactants with different counterions, according to a Hofmeister-like series, and by n-alkyltetradecylammonium bromide surfactants with different alkyl chain lengths.

Landscape of early clinical trials for childhood and adolescence cancer in Spain.

PURPOSE: Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. METHODS: All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. RESULTS: 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. CONCLUSIONS: Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

Effects of electrolyte concentration and counterion valence on the microstructural flow regimes in dilute cetyltrimethylammonium tosylate micellar solutions.

The shear thickening behavior and the transition to shear thinning are examined in dilute cetyltrimethylammonium tosylate (CTAT) micellar solutions as a function of surfactant concentration and ionic strength using electrolytes with different counterion valence. Newtonian behavior at low shear rates, followed by shear thickening and shear thinning at higher shear rates, are observed at low and intermediate surfactant and electrolyte concentrations. Shear thickening diminishes with increasing surfactant concentration and ionic strength. At higher surfactant or electrolyte concentration, only a Newtonian region followed by shear thinning is detected. A generalized flow diagram indicates two controlling regimes: one in which electrostatic screening dominates and induces micellar growth, and another, at higher electrolyte and surfactant concentrations, where chemical equilibrium among electrolyte and surfactant counterions controls the rheological behavior by modifying micellar breaking and reforming. Analysis of the shear thickening behavior reveals that not only a critical shear rate is required for shear thickening, but also a critical deformation, which appears to be unique for all systems examined, within experimental error. Moreover, a superposition of the critical shear rate for shear thickening with surfactant and electrolyte concentration is reported.