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.

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.

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 (AU)

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.

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 (AU)

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 (AU)

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.