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(1) Background: Intravesical mitomycin-C (MMC) combined with hyperthermia is increasingly used in non-muscle invasive bladder cancer (NMIBC), especially in the context of a relative BCG shortage. We aim to determine real-world data on the long-term treatment outcomes of adjunct hyperthermic intravesical chemotherapy (HIVEC) with MMC and a COMBAT® bladder recirculation system (BRS), (2) Methods: A prospective observational trial was performed on patients with NMIBC treated with HIVEC using BRS in nine academic institutions in Spain between 2012–2020 (HIVEC-E). Treatment effectiveness (recurrence, progression and overall mortality) was evaluated in patients treated with HIVEC MMC 40mg in the adjuvant setting, with baseline data and a clinical follow-up, that comprise the Full Analysis Set (FAS). Safety, according to the number and severity of adverse effects (AEs), was evaluated in the safety (SAF) population, composed by patients with at least one adjunct HIVEC MMC instillation, (3) Results: The FAS population (n = 502) received a median number of 8.78 ± 3.28 (range 1–20) HIVEC MMC instillations. The median follow-up duration was 24.5 ± 16.5 (range 1–81) months. Its distribution, based on EAU risk stratification, was 297 (59.2%) for intermediate and 205 (40.8%) for high-risk. The figures for five-year recurrence-free and progression-free survival were 50.37% (53.3% for intermediate and 47.14% for high-risk) and 89.83% (94.02% for intermediate and 84.23% for high-risk), respectively. A multivariate analysis identified recurrent tumors (HR 1.83), the duration of adjuvant HIVEC therapy &lt, 4 months (HR 1.72) and that high-risk group (HR 1.47) were at an increased risk of recurrence. Independent factors of progression were high-risk (HR 3.89), recurrent tumors (HR 3.32) and the induction of HIVEC therapy without maintenance (HR 2.37). The overall survival was determined by patient age at diagnosis (HR 3.36) and the treatment duration (HR 1.82). The SAF population (n = 592) revealed 406 (68.58%) patients without AEs and 186 (31.42%) with at least one AE: 170 (28.72%) of grade 1–2 and 16 (2.7%) of grade 3–4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), skin rash (4.9%), spasms (3.7%) and hematuria (3.6%), (4) Conclusions: HIVEC using BRS is efficacious and well tolerated. A longer treatment duration, its use in naïve patients and the intermediate-risk disease are independent determinants of success. Furthermore, a monthly maintenance of adjunct MMC HIVEC diminishes the progression rate of NMIBC.

Resumen Introduccion El Blastocystis hominis (B. hominis) es un protozoo comunmente encontrado en el tracto gastrointestinal. Existen dudas sobre su significado clinico. El metronidazol (MTZ) es el tratamiento aconsejado de primera linea. Material y metodos Se realizo una revision retrospectiva entre 2011 y 2012. Se seleccionaron de forma aleatoria 151 de 383 muestras positivas para B. hominis . Los criterios de inclusion fueron: clinica sugestiva, indicacion de tratamiento y realizacion de control microbiologico. Se realizo una revision sistematica de los estudios que evaluan el efecto de MTZ sobre la infestacion por B. hominis . Resultados Cuarenta y seis pacientes cumplian criterios de inclusion (el 64% eran mujeres; edad, 44,2 ± 2 anos). Se utilizo MTZ en 39 pacientes, de los cuales 31 obtuvieron respuesta clinica (79,5%) pero solo 15 respuesta microbiologica (48,4%). No se aprecio una relacion dosis-efecto. Veinte pacientes sin respuesta microbiologica inicial recibieron una segunda tanda de tratamiento (MTZ, cotrimoxazol, paramomicina, otros), con una respuesta microbiologica del 70%. De forma global, se consiguio la curacion de B. hominis en un 72% (IC95%: 57-83%). De 54 tratamientos asociados a respuesta clinica, se produjo respuesta microbiologica en 31 (57%); mientras que de los 12 que se siguieron de ausencia de respuesta clinica solo se observo la curacion microbiologica en 2 (17%) (p = 0,022). La tasa de erradicacion en la revision sistematica oscilo entre 0 y 100%. Conclusiones Parece existir relacion entre la respuesta clinica y microbiologica al tratamiento de B. hominis . En nuestro entorno geografico la respuesta microbiologica al tratamiento con MTZ es insuficiente. La revision sistematica muestra que la respuesta a MTZ es muy variable.

// Clara Esteban-Jurado 1 , David Gimenez-Zaragoza 2 , Jenifer Munoz 1 , Sebastia Franch-Exposito 1 , Miriam Alvarez-Barona 3 , Teresa Ocana 1 , Miriam Cuatrecasas 4 , Sabela Carballal 1 , Maria Lopez-Ceron 1 , Maria Marti-Solano 5 , Marcos Diaz-Gay 1 , Tom van Wezel 6 , Antoni Castells 1 , Luis Bujanda 7 , Judith Balmana 8 , Victoria Gonzalo 9 , Gemma Llort 10 , Clara Ruiz-Ponte 3 , Joaquin Cubiella 11 , Francesc Balaguer 1 , Rosa Aligue 2 , Sergi Castellvi-Bel 1 1 Gastroenterology Department, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Catalonia, Spain 2 Biomedical Sciences Department, School of Medicine, University de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain 3 Galician Public Foundation of Genomic Medicine (FPGMX), Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Genomics Medicine Group, Hospital Clinico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain 4 Department of Pathology, Hospital Clinic, Biobanc Clinic-IDIBAPS, Barcelona, Catalonia, Spain 5 Department of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, Germany 6 Leiden University Medical Center (LUMC), Leiden, Netherlands 7 Gastroenterology Department, Hospital Donostia–Instituto Biodonostia, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Basque Country University (UPV/EHU), San Sebastian, Spain 8 High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d’Hebron and Vall d’Hebron Institute of Oncology, Barcelona, Spain 9 Gastroenterology Department, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain 10 Clinical Oncology Department, Corporacio Parc Tauli, Sabadell, Barcelona, Spain 11 Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Instituto de Investigacion Biomedica Ourense, Pontevedra y Vigo, Ourense, Spain Correspondence to: Sergi Castellvi-Bel, email: sbel@clinic.cat Keywords: colorectal neoplasm, colorectal adenoma, genetic predisposition to disease, POLE, POLD1 Received: January 04, 2017 Accepted: February 18, 2017 Published: March 01, 2017 ABSTRACT Germline mutations in POLE and POLD1 have been shown to cause predisposition to colorectal multiple polyposis and a wide range of neoplasms, early-onset colorectal cancer being the most prevalent. In order to find additional mutations affecting the proofreading activity of these polymerases, we sequenced its exonuclease domain in 155 patients with multiple polyps or an early-onset colorectal cancer phenotype without alterations in the known hereditary colorectal cancer genes. Interestingly, none of the previously reported mutations in POLE and POLD1 were found. On the other hand, among the genetic variants detected, only two of them stood out as putative pathogenic in the POLE gene, c.1359 + 46del71 and c.1420G > A (p.Val474Ile). The first variant, detected in two families, was not proven to alter correct RNA splicing. Contrarily, c.1420G > A (p.Val474Ile) was detected in one early-onset colorectal cancer patient and located right next to the exonuclease domain. The pathogenicity of this change was suggested by its rarity and bioinformatics predictions, and it was further indicated by functional assays in Schizosaccharomyces pombe . This is the first study to functionally analyze a POLE genetic variant outside the exonuclease domain and widens the spectrum of genetic changes in this DNA polymerase that could lead to colorectal cancer predisposition.

Background Serrated polyposis syndrome (SPS) has been associated with an increased risk of colorectal cancer (CRC). Accordingly, intensive surveillance with annual colonoscopy is advised. The aim of this multicenter study was to describe the risk of advanced lesions in SPS patients undergoing surveillance, and to identify risk factors that could guide the prevention strategy. Methods From March 2013 to April 2015, 296 patients who fulfilled criteria I and/or III for SPS were retrospectively recruited at 18 centers. We selected patients in whom successful clearing colonoscopy had been performed and who underwent subsequent endoscopic surveillance. Advanced neoplasia was defined as CRC, advanced adenoma, or advanced serrated lesion that were ≥ 10 mm and/or with dysplasia. Cumulative incidence of advanced neoplasia was calculated and independent predictors of advanced neoplasia development were identified. Results In 152 SPS patients a total of 315 surveillance colonoscopies were performed (median 2, range 1 – 7). The 3-year cumulative incidence of CRC and advanced neoplasia were 3.1 % (95 % confidence interval [CI] 0 – 6.9) and 42.0 % (95 %CI 32.4 – 51.7), respectively. Fulfilling both I + III criteria and the presence of advanced serrated lesions at baseline colonoscopy were independent predictors of advanced neoplasia development (odds ratio [OR] 1.85, 95 %CI 1.03 – 3.33, P = 0.04 and OR 2.62, 95 %CI 1.18 – 5.81, P = 0.02, respectively). During follow-up, nine patients (5.9 %) were referred for surgery for invasive CRC (n = 4, 2.6 %) or because of polyp burden (n = 5, 3.3 %). After total colectomy, 17.9 % patients developed advanced neoplasia in the retained rectum. Conclusions Patients with SPS have a substantial risk of developing advanced neoplasia under endoscopic surveillance, whereas CRC incidence is low. Personalized endoscopic surveillance based on polyp burden and advanced serrated histology could help to optimize prevention in patients with SPS.

Objective Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. Design From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. Results In 296 patients with SPS with a median follow-up time of 45 months (IQR 26–79.7), a median of 26 (IQR 18.2–40.7) serrated polyps and 3 (IQR 1–6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). Conclusions Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.

The development of genotyping technologies has allowed for wider screening for inherited causes of variable outcomes following drug administration. We have performed a genome-wide association study (GWAS) on 221 colorectal cancer (CRC) patients that had been treated with 5-fluorouracil (5-FU), either alone or in combination with oxaliplatin (FOLFOX). A validation set of 791 patients was also studied. Seven SNPs (rs16857540, rs2465403, rs10876844, rs10784749, rs17626122, rs7325568 and rs4243761) showed evidence of association (pooled P-values 0.020, 9.426E-03, 0.010, 0.017, 0.042, 2.302E-04, 2.803E-03) with adverse drug reactions (ADRs). This is the first study to explore the genetic basis of inter-individual variation in toxicity responses to the administration of 5-FU or FOLFOX in CRC patients on a genome-wide scale. © 2013 Macmillan Publishers Limited. All rights reserved 1470-269X/13.

Introduction Blastocystis hominis (B. hominis) is a protozoan commonly found in the gastrointestinal tract. There are doubts about its clinical significance. Metronidazole (MTZ) is the recommended first-line treatment. Materials and methods A retrospective review was carried out between 2011 and 2012. A total of 151 samples were randomly selected from 383 samples positive for B. hominis . Inclusion criteria were: suggestive symptoms, treatment indication and microbiological follow-up. A systematic review was performed of all studies that evaluated the effect of MTZ on B. hominis infection. Results Forty-six patients met the inclusion criteria (64% women; age, 44.2 ± 2 years). MTZ was used in 39 patients, 31 of whom obtained a clinical response (79.5%) but only 15 a microbiological response (48.4%). No dose-effect relationship was observed. Twenty patients with no initial microbiological response received a second round of treatment (MTZ, cotrimoxazole, paramomycin, others), with a microbiological response in 70%. Overall, B. hominis was cured in 72% (95% CI: 57–83%). Of 54 treatments associated with a clinical response, a microbiological response occurred in 31 (57%), while in the remaining 12 with no clinical response, microbiological cure was observed in only 2 (17%) ( P = .022). The eradication rate in the systematic review varied between 0% and 100%. Conclusions There seems to be a relationship between the clinical and microbiological response to B. hominis treatment. The microbiological response to MTZ treatment is insufficient in our geographical setting. The systematic review shows that the response to MTZ is very variable.