Recurrence of urothelial carcinoma. An unusual cause of upper gastrointestinal bleeding.

Gastrointestinal metastases of urothelial tumors are rare, implying an advanced stage of the disease and a poor prognosis. We report the case of a patient with a history of urothelial carcinoma in remission who presents with upper gastrointestinal bleeding secondary to gastric metastases due to tumor recurrence and we review recent literature on this topic.

Physiological demands and motion analysis of elite foil fencing.

The aim of this study was to determine the physiological demands and motion analysis of a simulated fencing competition. Eighteen fencers each completed 5 'poule' (5 touches) and 'direct elimination (DE)' (15 touches) fights. Expired gases were measured during 1 poule and DE fight. Heart rate (HR), ratings of perceived exertion (RPE) and movement data were recorded throughout all fights. Motion analysis was undertaken using the software LINCE PLUS. Differences between poule and DE fights were determined by either a paired t-test or a one-way repeated measures ANOVA. HR and RPE were significantly greater during DE compared to poule (170 ±10 vs 163 ±13 beats·min-1; P<0.05). A greater distance was covered during a DE fight compared to a poule fight (459.9 ± 117.7 m vs 162.6 ± 74.2 m; P<0.05). The average values of [Formula: see text] were 42.5 ±5.6 ml·kg-1·min-1 in men and 34.4 ±3.2 ml·kg-1·min-1 in women. Work-to-rest ratios reduced during the DE fights along with a lower average speed and increased max speed (11.7 ± 2.8 km∙h-1 vs 9.6 ± 1.6 km∙h-1; P<0.05). In conclusion, there is an increased physiological demand during a DE fight accompanied by a reduction in average speed and decreased work-to-rest ratio.

Non-tumoral metastatic lesions as a debut of primary biliary cholangitis and concomitant sarcoidosis.

Sarcoidosis is included within the multisystemic granulomatous diseases with autoimmune character. The case of a 51-year-old man with hemoptysis, cholestasis and bone lesions is presented. After ruling out infectious, inflammatory and neoplastic entities, a diagnosis of sarcoidosis and autoimmune hepatitis with primary biliary cholangitis was established.

Systematic review and meta-analysis regarding maternal apelin in pregnant women with and without preeclampsia.

Aims: To investigate maternal circulating apelin levels in pregnancies with and without preeclampsia.Design and Method: Systematic review and meta-analysis of observational studies reporting circulating apelin in women who develop preeclampsia. We searched databases for appropriate studies published through December 2021, without language restriction. The quality of studies was evaluated using the Newcastle-Ottawa-Scale. Data were pooled as mean difference (MDs) or standardized MDs (SMDs) and 95% confidence interval (95% CI). A random-effects model enabled reporting of differences between groups, minimizing the effects of uncertainty associated with inter-study variability on the effects of different endpoints.Results: We identified a total of 122 studies, and ten of them reported circulating apelin in women with and without preeclampsia. Maternal apelin did not show a difference in preeclamptic compared to normotensive women (SMD: -0.38, 95%CI -0.91 to 0.15), although there was high heterogeneity between the included studies (I2 = 95%). Participants with preeclampsia had higher body mass index, lower gestational age at delivery, and birth weight. Preeclamptic pregnant women with higher BMI showed significantly lower apelin levels in the subgroup analysis. There was no significant apelin difference in the preeclampsia severity sub-analysis.Conclusion: There was no significant difference in apelin levels in pregnant women with and without preeclampsia.

Endoscopic submucosal dissection: a country dissemination experience and outcomes.

OBJECTIVE: An increasing use of endoscopic submucosal dissection (ESD) has been reported in Western countries, although some differences in training schemes and outcomes have been described. We aimed to report the training model, implementation, and outcomes of ESD in Portugal. METHODS: All endoscopists trained at our center from our country (n = 9) were invited to a survey regarding: (a) training period; (b) ESD outcomes and (c) implementation of ESD in each respective center. RESULTS: All endoscopists completed the survey. Learning ESD was centered on human ESD assistance in a high-volume center during a median time of 6 months and complemented mainly by hands-on courses (89%). During the surveyed period, a total of 1229 ESD were performed, mostly in gastric locations (74%). Median complete R0 and curative resection rate were 92% (IQR, 81-96.8) and 87% (IQR, 74-93.3), respectively, and median perforation rate was 0.89% (IQR, 0.25-6.22). The main limitations encountered during the implementation of ESD were related to the lack of initial mentoring or insufficient expertise to progress to more difficult lesions. CONCLUSION: Learning ESD through participation in hands-on courses and visiting high-volume centers seems to be adequate to achieve a good competence at the initial stage of ESD, which in fact is in consonance with the European Society of Gastrointestinal Endoscopy recommendations. However, mentoring is essential for technical progression, and this represents the fundamental barrier during the adoption of ESD, which may be overcome by increasing hands-on training in animal or artificial simulators, but preferably with the implementation of a structured training program.

Gastric cancer screening: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Gastric cancer (GC) screening is recommended in high-risk populations, although screening methods and intervals vary. In intermediate-risk populations, screening through esophagogastroduodenoscopy (EGD) may be considered depending on local resources. The aim of this study was to compare GC screening methods regarding effect on mortality, diagnostic yield and adherence. METHODS: Systematic review and meta-analysis including studies evaluating population-based GC screening. Search was conducted in three online databases (MEDLINE, Scopus and clinicaltrials.gov), along with manual search. RESULTS: Forty-four studies were included. Studies in upper gastrointestinal series (UGIS) demonstrated that GC screening was associated with significantly lower GC mortality rates (OR 0.63, 95% CI 0.55 - 0.73). Benefits on mortality were also found in EGD and serum pepsinogen (PG) studies. EGD was associated with significantly higher GC (0.55%, 95% CI 0.39 - 0.75%) and early-GC (EGC) detection rates (0.48%, 95% CI 0.34 - 0.65%) when compared to UGIS (GC 0.19%, 95% CI 0.10 - 0.31%; EGC 0.08%, 95% CI 0.04 - 0.13%) and PG (GC 0.10%, 95% CI 0.05 - 0.16%; EGC 0.10%, 95% CI 0.04 - 0.19%). Non-invasive methods tended to higher adherence rates when compared to EGD. Regardless of the screening method, individualized recruitment performed better. DISCUSSION: Screening positively impacted GC mortality rates. EGD was associated with higher diagnostic yield, while UGIS and PG tended to higher adherence rates. Screening uptake was predominantly impacted by recruitment strategies independently of the adopted method.

Design and development of photoswitchable DFG-Out RET kinase inhibitors.

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase that is required for development of multiple human tissues, but which is also an important contributor to human cancers. RET activation through rearrangement or point mutations occurs in thyroid and lung cancers. Furthermore, activation of wild type RET is an increasingly recognized mechanism promoting tumor growth and dissemination of a much broader group of cancers. RET is therefore an attractive therapeutic target for small-molecule kinase inhibitors. Non-invasive control of RET signaling with light offers the promise of unveiling its complex spatiotemporal dynamics in vivo. In this work, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, enabling photonic control of RET activity. Based on the binding mode of DFG-out kinase inhibitors and using RET kinase as the test model, we developed a photoswitchable inhibitor with a quinoline "head" constituting the azoheteroarene. This azo compound was further modified by three different strategies to increase the difference in biological activity between the E-isomer and the light enriched Z-isomer. Stilbene-based derivatives were used as model compounds to guide in the selection of substituents that could eventually be introduced to the corresponding azo compounds. The most promising quinoline-based compound showed more than a 15-fold difference in bioactivity between the two isomers in a biochemical assay. However, the same compound showed a decreased Z/E (IC50) ratio in the cellular assay, tentatively assigned to stability issues. The corresponding stilbene compound gave a Z/E (IC50) ratio well above 100, consistent with that measured in the biochemical assay. Ultimately, a 7-azaindole based photoswitchable DFG-out kinase inhibitor was shown to display more than a 10-fold difference in bioactivity between the two isomers, in both a biochemical and a cell-based assay, as well as excellent stability even under reducing conditions.

Best additional management after non-curative endoscopic resection of esophageal squamous cell carcinoma: a systematic review and meta-analysis.

INTRODUCTION: Endoscopic resection (ER) is an accepted first-line treatment for superficial esophageal squamous cell carcinoma (ESCC), but when curative resection is not achieved, further treatment is not standardised. We aimed at evaluating outcomes of management strategies (esophagectomy, chemoradiotherapy/radiotherapy (CRT/RT) or follow-up (FUP)) after a non-curative ESCC ER. METHODS: A systematic review was performed evaluating outcomes of different management strategies after ESCC submitted to primary ER (T1a/T1b), without curative criteria (R1/Rx, T1a-m3/T1b, lymphovascular invasion (LVI) or poor differentiation). Primary outcomes included recurrence, overall survival (OS) and cancer-specific survival (CSS). Secondary outcomes consisted of treatment-related adverse events. RESULTS: Seventeen studies were included for qualitative analysis (16 observational and 1 randomized controlled trial) including 788 patients with ESCC submitted to ER, managed by additional CRT/RT (n = 530), surgery (n = 98) or FUP (n = 160). Eight studies suited quantitative analysis. Patients only followed up after ER experienced recurrence rates of 0-36.4% (OR 3.6 (95%CI 1.06-12.20) vs further treatments). When submitted to CRT/RT following non-curative ER, recurrence was observed in 0-27.2% (OR 8.00 (95%CI 1.74-36.80) whereas after surgery no recurrence was noticeable. Reported 5 y-OS after CRT/RT for non-curative ER ranged among 75-100% whereas, for those offered surgeries, 5 y-OS was 89.5%. OS ranged between 54.5% and 100% after FUP. CRT/RT and surgery-related adverse events ranged from 0% to 32% and 14% to 28.5%. CONCLUSIONS: Additional treatment should be provided in ESCC after non-curative ER. Adjuvant esophagectomy might be the preferred treatment to medically fit patients with high-risk features (namely LVI). Properly designed trials assessing the role of CRT/RT are needed to manage these patients.

Preeclampsia and gestational hypertension are associated to low maternal circulating kisspeptin levels: a systematic review and meta-analysis.

BACKGROUND: There are contradictory data concerning kisspeptin in gravids with preeclampsia and gestational hypertension (GH). OBJECTIVE: To conduct a meta-analysis of studies comparing maternal kisspeptin levels in gravids with and without preeclampsia or GH. MATERIAL AND METHODS: We searched PubMed, LILACS, and CNKI list of articles up to 20 August 2021, without language limitations, comparing circulating maternal kisspeptin levels, and maternal and neonatal outcomes in gravids with and without preeclampsia or GH. Meta-analyzed results are reported as standardized mean differences (SMD), and their 95% confidence interval (CI). RESULTS: Seven studies with a low-to-moderate risk of bias were eligible for meta-analysis. Gravids with preeclampsia or GH displayed significantly lower circulating kisspeptin levels (SMD, -0.68, 95% CI, -1.04 to -0.32), lower gestational ages at delivery (SMD, -2.22, 95% CI, -3.25 to -1.18), and birth weight (SMD, -2.16, 95% CI, -3.15 to -1.17), and significantly higher body mass indices (MD, 0.56, 95% CI, 0.24-0.88), systolic (SMD, 2.87, 95% CI, 2.22-3.53), and diastolic blood pressures (SMD, 2.57, 95% CI, 2.19-2.95). CONCLUSION: Gravids with preeclampsia or GH had lower kisspeptin levels as compared to normotensive controls.

Catastrophic antiphospholipid syndrome during pregnancy.

Catastrophic antiphospholipid syndrome (CAPS) is an uncommon and the most severe form of antiphospholipid syndrome (APS). A 33-week pregnant patient with Klippel-Trenaunay syndrome, past SARS-CoV-2 infection and type I fetal growth restriction with shortening of the fetal long bone was diagnosed in our center with a probable CAPS. Cesarean section was performed four days after the diagnosis due to the torpid evolution of the patient. Clinical improvement was noted a few days later and the mother and baby were discharged within a week. We review the current literature on CAPS during pregnancy and provide an updated view.

COVID-19 and endoscopic management of superficial gastrointestinal neoplastic lesions: a multinational cross-sectional survey.

INTRODUCTION: We aimed to report the impact of the pandemic lockdown period on the treatment and prognosis of superficial gastrointestinal neoplastic lesions. METHODS: A survey was completed by 11 centers from four continents regarding postponements during the early lockdown period of the pandemic, and the same period in 2019. RESULTS: In 2020, 55 % of the scheduled procedures were deferred, which was 11 times higher than in 2019; the main reasons were directly related to COVID-19. In countries that were highly affected, this proportion rose to 76 % vs. 26 % in those where there was less impact. Despite the absolute reduction, the relative distribution in 2019 vs. 2020 was similar, the only exception being duodenal lesions (affected by a 92 % reduction in mucosectomies). Although it is expected that the majority of postponements will not affect the stage (based on the results from biopsies and/or endoscopic appearance), 3 % of delayed procedures will probably require surgery. CONCLUSIONS: The lockdown period caused by the SARS-CoV-2 pandemic led to a substantial reduction in the number of endoscopic resections for neoplastic lesions. Nevertheless, based on clinical judgment, the planned median delay will not worsen the prognosis of the affected patients.

Image-enhanced endoscopy for gastric preneoplastic conditions and neoplastic lesions: a systematic review and meta-analysis.

BACKGROUND : Image-enhanced endoscopy (IEE) improves the accuracy of endoscopic diagnosis. We aimed to assess the value of IEE for gastric preneoplastic conditions and neoplastic lesions. METHODS : Medline and Embase were searched until December 2018. Studies allowing calculation of diagnostic measures were included. Risk of bias and applicability were assessed using QUADAS-2. Subgroup analysis was performed to explore heterogeneity. RESULTS : 44 studies met the inclusion criteria. For gastric intestinal metaplasia (GIM), narrow-band imaging (NBI) obtained a pooled sensitivity and specificity of 0.79 (95 %CI 0.72-0.85) and 0.91 (95 %CI 0.88-0.94) on per-patient basis; on per-biopsy basis, it was 0.84 (95 %CI 0.81-0.86) and 0.95 (95 %CI 0.94-0.96), respectively. Tubulovillous pattern was the most accurate marker to detect GIM and it was effectively assessed without high magnification. For dysplasia, NBI showed a pooled sensitivity and specificity of 0.87 (95 %CI 0.84-0.89) and 0.97 (95 %CI 0.97-0.98) on per-biopsy basis. The use of magnification improved the performance of NBI to characterize early gastric cancer (EGC), especially when the vessel plus surface (VS) classification was applied. Regarding other technologies, trimodal imaging also obtained a high accuracy for dysplasia (sensitivity 0.93 [95 %CI 0.85-0.98], specificity 0.98 [95 %CI 0.92-1.00]). For atrophic gastritis, no specific pattern was noted and none of the technologies reached good diagnostic yield. CONCLUSION : NBI is highly accurate for GIM and dysplasia. The presence of tubulovillous pattern and the VS classification seem to be useful to detect GIM and characterize EGC, respectively. These features should be used in current practice and to standardize endoscopic criteria for other technologies.

Seguimiento a largo plazo tras disección submucosa endoscópica de lesiones colorrectales en una cohorte española / No disponible

INTRODUCCIÓN: la disección submucosa endoscópica (DSE) en colon es una técnica en expansión en países occidentales. Existen pocos estudios con seguimiento a largo plazo. OBJETIVO: analizar supervivencia libre de enfermedad a largo plazo tras DSE y comparar las tasas de recidiva en función de diferentes factores. MATERIAL Y MÉTODOS: cohorte prospectiva de pacientes con DSE planeada entre septiembre de 2008 y diciembre de 2015. Cuando no fue posible técnicamente completar DSE se realizó disección híbrida en bloque o fragmentada. Se analizó la tasa de recurrencia a cinco años mediante curvas de Kaplan-Meier y se compararon en función de diferentes factores usando test de log-rank. RESULTADOS: se incluyó una cohorte inicial de 89 pacientes en los que se consiguió seguimiento en 69. De los 69 pacientes, en 31 (45 %) se realizó DSE; en once (16 %), DSE híbrida; y en 27 (39 %), DSE híbrida fragmentada. La mediana de seguimiento fue de 27 meses. La supervivencia libre de enfermedad a cinco años fue del 81 %. La media de endoscopias para eliminar la recurrencia fueron dos (rango 1-7) y ninguna requirió cirugía. La tasa de recidiva fue significativamente menor tras DSE "en bloque" respecto a fragmentada (15 % vs. 27 %, p = 0,036) y en resecciones R0 respecto a R1 (0 % vs. 26 %, p = 0,034). Las resecciones con márgenes laterales negativos en lesiones resecadas en bloque presentaron menor tasa de recidiva respecto a aquellas con márgenes afectos/desconocidos, que no alcanzaron la significación estadística (0 % vs. 28 %, p = 0,09). CONCLUSIONES: en nuestro estudio, la supervivencia libre de enfermedad a cinco años fue del 81 % y ningún paciente requirió cirugía durante el seguimiento. Las resecciones fragmentadas y R1 se asociaron de forma significativa con mayor tasa de recurrencia

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Disección submucosa endoscópica en lesiones gástricas epiteliales: resultados a largo plazo en una cohorte española / No disponible

INTRODUCCIÓN: la disección submucosa endoscópica sobre lesiones gástricas (DSE-G) es una técnica que permite la resección de tumores gástricos precoces en bloque, con una tasa de curación similar a la cirugía y una morbimortalidad menor. OBJETIVO: analizar la supervivencia total, la supervivencia libre de enfermedad y la tasa de recidiva en pacientes sometidos a DSE-G en una cohorte española a lo largo de su evolución clínica. MATERIAL Y MÉTODOS: estudio observacional prospectivo. Inclusión de pacientes sometidos a DSE-G de 2008 a 2015, con seguimiento entre seis y 60 meses. Se analizó la recurrencia a cinco años mediante curvas de Kaplan-Meier y los resultados fueron comparados entre diferentes factores (en bloque vs. resección fragmentada, resecciones curativas R0 vs. margen lateral afecto ML+) usando test log-rank. RESULTADOS: se analizaron 35 pacientes sometidos a DSE-G, con una mediana de seguimiento de 33,62 meses. Se identificaron cuatro recidivas en este periodo (11,4%), tres de ellas tratadas mediante nueva DSE-G. La presencia de ML+ en la pieza histológica se relacionó con mayor tasa de recidiva local durante el seguimiento (p = 0,06). Las resecciones fragmentadas presentaron un mayor riesgo de recidiva pero sin detectarse diferencias estadísticamente significativas (p = 0,49). No se registraron fallecimientos por neoplasia gástrica ni gastrectomía por persistencia de enfermedad en este periodo. La tasa de supervivencia global en nuestra serie fue de 94,3%. CONCLUSIONES: la DSE-G realizada en nuestro medio permite una tasa elevada de curación a largo plazo evitando la cirugía. Estos resultados se asemejan a las series europeas publicadas y aún se encuentran lejos de las tasas de curación y recidiva de las cohortes asiáticas. Los casos de recidiva local pueden ser controlados mediante endoscopia

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Long-term follow-up after endoscopic submucosal dissection of colorectal lesions in a Spanish cohort.

INTRODUCTION: ESD in the colon is an increasingly important technique in Western countries. There are few studies that include long term follow-up. AIM: to analyze the long term recurrence free survival rate after ESD and to compare recurrence rates according to different variables. METHODS: this was a prospective observational study of patients with a planned ESD from September 2008 to December 2015. When it was not possible to achieve an ESD, hybrid ESD was performed, either en bloc or piecemeal. Kaplan-Meier survival curves were used to assess the five year local recurrence free survival rate and the recurrence rate. The results were compared according to different factors. RESULTS: of the 89 patients scheduled for ESD who were initially enrolled in the study, 69 were finally included for follow-up. ESD was performed in 31 (45%) patients, KAR in eleven (16%) and pKAR in 27 (39%). The median follow-up was 27 months (range 6-60). The five year disease free survival rate was 81%. The average number of endoscopies needed to eliminate recurrence was two (range 2-7) and no patient required surgery for this reason. The recurrence rate was significantly higher in piecemeal resections vs en bloc resections (27% vs 15%, p = 0.036) and R1 resections vs R0 resections (26% vs 0%, p = 0.034). The presence of affected or unknown lateral margins in en bloc resections without other poor prognosis factors had higher recurrence rates but the difference was not statistically significant (28% vs 0%, p = 0.09). CONCLUSIONS: in our study, the five year disease free survival rate was 81% and no patient required surgery during follow-up. Piecemeal and R1 resections had significantly higher recurrence rates, as well as LM involvement, although this was not statistically significant.

Endoscopic submucosal dissection for gastric epithelial lesions: long-term results in a Spanish cohort.

INTRODUCTION: endoscopic submucosal dissection for gastric lesions (ESD-G) is a technique that allows en-bloc resection of early gastric tumors, with a cure rate similar to that of surgery but lower morbidity and mortality rates. OBJECTIVE: to assess total survival, disease-free survival and relapse rate during the course of disease in a Spanish cohort of patients undergoing ESD-G. MATERIAL AND METHODS: this was a prospective observational study of patients undergoing ESD-G from 2008 to 2015, with a follow-up ranging from six to 60 months. Recurrence at five years was analyzed using Kaplan-Meier curves and the results were compared according to several factors using the log-rank test. These included en-bloc versus piecemeal resection and R0 curative resection versus resection with affected lateral margins (LM+). RESULTS: a total of 35 patients undergoing ESD-G were assessed, with a median follow-up of 33.62 months. Four relapses were identified (11.4%) during this period, of which three were managed with repeat ESD-G. A histological specimen with LM+ was associated with a higher local relapse rate during follow-up (p = 0.06). Piecemeal resections had a higher relapse risk, although no statistically significant differences were identified (p = 0.49). No deaths from gastric cancer occurred and no gastrectomies due to persistent disease were performed during this period. The overall survival rate in our series was 94.3%. CONCLUSIONS: ESD-G in our setting provides high long-term cure rates, while avoiding surgery. These results are similar to those reported by the European series and remain far removed from the cure and relapse rates obtained in Asian cohorts. Local relapse cases may be monitored with endoscopy.