Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing. PATIENTS AND METHODS: Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM. RESULTS: Among 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P < 0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P < 0.0001). CONCLUSIONS: Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

Correlation between proximal serrated polyp detection and clinically significant serrated polyps: inter-endoscopist variability.

INTRODUCTION AND AIMS: The adenoma detection rate (ADR) is the most important quality indicator for the prevention of colorectal cancer but serrated polyps are also precursor lesions of the disease. The aim of our study was to compare the detection rate of proximal serrated polyps (PSPs) and that of clinically significant serrated polyps (CSSPs) between endoscopists and analyze the relation of those parameters to the ADR. METHODS: An observational, prospective, cross-sectional study was conducted on all patients that underwent colonoscopy at the Policlínico Peruano Japonés within the time frame of July 2015 and August 2016. The ADR and PSP and CSSP detection rates between endoscopists were compared through multivariate logistic regression and the association between those parameters was calculated through the Pearson correlation coefficient. RESULTS: The study included 15 endoscopists and 1,378 colonoscopies. The PSP detection rate ranged from 1.8-17% between endoscopists and had an almost perfect correlation with the CSSP detection rate (p = 0.922), as well as strongly correlating with the ADR (p = 0.769). CONCLUSIONS: There was great variability in the PSP detection rate between endoscopists. It also had an almost perfect correlation with the CSSP detection rate and strongly correlated with the ADR. Those results suggest a high CSSP miss rate at endoscopy and a low PSP detection rate.

SEOM clinical guideline for management of adult medulloblastoma (2020).

Recent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Correlation between proximal serrated polyp detection and clinically significant serrated polyps: inter-endoscopist variability. / Correlación entre la detección de pólipos serratos proximales y pólipos serratos clínicamente significativos: variabilidad interendoscopista.

INTRODUCTION AND AIMS: The adenoma detection rate (ADR) is the most important quality indicator for the prevention of colorectal cancer but serrated polyps are also precursor lesions of the disease. The aim of our study was to compare the detection rate of proximal serrated polyps (PSPs) and that of clinically significant serrated polyps (CSSPs) between endoscopists and analyze the relation of those parameters to the ADR. METHODS: An observational, prospective, cross-sectional study was conducted on all patients that underwent colonoscopy at the Policlínico Peruano Japonés within the time frame of July 2015 and August 2016. The ADR and PSP and CSSP detection rates between endoscopists were compared through multivariate logistic regression and the association between those parameters was calculated through the Pearson correlation coefficient. RESULTS: The study included 15 endoscopists and 1,378 colonoscopies. The PSP detection rate ranged from 1.8-17% between endoscopists and had an almost perfect correlation with the CSSP detection rate (p = 0.922), as well as strongly correlating with the ADR (p = 0.769). CONCLUSIONS: There was great variability in the PSP detection rate between endoscopists. It also had an almost perfect correlation with the CSSP detection rate and strongly correlated with the ADR. Those results suggest a high CSSP miss rate at endoscopy and a low PSP detection rate.

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

BACKGROUND: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.

Fauna parasitária e relação parasito-hospedeiro de tambaquis criados na região do Baixo São Francisco, nordeste do Brasil / Parasitic fauna and parasite-host relationship of tambaqui reared in São Francisco river basin, Brazilian northeast

Este trabalho teve como objetivo avaliar a fauna parasitária de tambaquis na região do Baixo São Francisco-AL/SE-Brasil e correlacionar os índices de prevalência e intensidade média com fatores bióticos e abióticos. Foram coletados 252 espécimes para análise parasitológica de 10 pisciculturas. Os parasitos foram contabilizados, identificados, e determinaram-se os índices de prevalência e intensidade média, que foram correlacionados com fatores bióticos e abióticos. Dos peixes coletados, 65,5% estavam parasitados por pelo menos um táxon. Foram encontrados 10 táxons: Monogeneas, Ichthyophthirius multifiliis, tricodinídeos, Piscinoodinium pillulare, Ichthyobodo sp., Dolops carvalhoi, Lernaea cyprinacea, Procamallanus (Spirocamallanus) inopinatus, Henneguya sp. e Myxobolus sp. As maiores prevalências foram encontradas para Monogeneas (49,2%) e Myxobolus sp. (31,5%). Correlações negativas entre prevalência e fatores bióticos (peso e comprimento) foram observadas para Monogeneas (r2= -0,49; r2= -0,43), Myxobolus sp. (r²= -0,46; r²= -0,39) e Henneguya sp. (r²= -0,41; r²= -0,39). O fator abiótico temperatura apresentou correlação negativa com as prevalências de Lernaea cyprinacea (r= -0,39) e tricodinídeos (r= -0,33), enquanto a condutividade elétrica apresentou correlação positiva (r= 0,40) com a prevalência de tricodinídeos. Conclui-se que a fauna parasitária dos tambaquis cultivados na região do Baixo São Francisco é diversificada e com a carga parasitária dependente da qualidade de água e do estágio de desenvolvimento dos peixes.(AU)

This study investigated the parasitic fauna of tambaquis reared in lower Sao Francisco region-Al/SE-Brazil correlating parasitic indices to abiotic and biotic factors. A total of 252 specimens of tambaqui were collected in ten fish farms for parasitological analysis. The parasites were counted, identified and the parasitological indices were determined and correlated to biotic and abiotic factors. Of all collected fish, 65,5 % were parasitized by at least one taxon. Ten taxa were found: Monogeneans, Ichthyophthirius multifiliis, trichodinids Piscinoodinium pillulare, Ichthyobodo sp, Dolops carvalhoi, Lernaea cyprinacea, Procamallanus (Spirocamallanus) inopinatus, Henneguya sp. and Myxobolus sp. The higher prevalences were found to monogeneans (49.2%) and Myxobolus sp. (31.5%). Negative correlation of prevalence and biotic factor (weight and length) were observed to monogeneans (r 2 = -0.49, r 2 = -0.43), Myxobolus sp (r²= -0.46; r²= -0.39) and Henneguya sp (r²= -0.41; r²= -0.39). Abiotic factor of temperature presented a negative correlation to prevalence of Lernaea cyprinacea and trichodinids (r= -0.39 e r= -0.33, respectively) and the electric conductivity presented positive correlation to trichodinids (r= 0.40). It was concluded that parasitic fauna of tambaquis cultured in Lower São Francisco region is diversified and the parasitic load dependent on water parameters and fish growth.(AU)

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018).

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.

Molecular mechanisms involved in the protective actions of Selective Estrogen Receptor Modulators in brain cells.

Synthetic selective modulators of the estrogen receptors (SERMs) have shown to protect neurons and glial cells against toxic insults. Among the most relevant beneficial effects attributed to these compounds are the regulation of inflammation, attenuation of astrogliosis and microglial activation, prevention of excitotoxicity and as a consequence the reduction of neuronal cell death. Under pathological conditions, the mechanism of action of the SERMs involves the activation of estrogen receptors (ERs) and G protein-coupled receptor for estrogens (GRP30). These receptors trigger neuroprotective responses such as increasing the expression of antioxidants and the activation of kinase-mediated survival signaling pathways. Despite the advances in the knowledge of the pathways activated by the SERMs, their mechanism of action is still not entirely clear, and there are several controversies. In this review, we focused on the molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a response to treatment with raloxifene and tamoxifen.

First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study.

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.

Correction to: SEOM clinical guidelines for anaplastic gliomas (2017).

The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables. A multidisciplinary team is highly recommended in the management of these tumors.

Genotype-based selection of treatment of patients with advanced colorectal cancer (SETICC): a pharmacogenetic-based randomized phase II trial.

Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.

SEOM clinical guidelines for anaplastic gliomas (2017).

The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables. A multidisciplinary team is highly recommended in the management of these tumors.

Tumores neuroendocrinos de origen pulmonar: reporte de un caso / Neuroendocrine tumors of lung’s origin, a case report

Introduction or case story: Young female patient (24 years-old), without known morbid precedents. She comes for a ten-days period of symptoms characterized by fever of up to 38.5 °C and a dyspnoea grade III. Physical exam showed decreased vesicular murmur on the right pulmonary base with dullness and positive vocal vibrations. Exams: Thorax X-ray: Atelectasis condensation on the right pulmonary base. CT chest scan without contrast: Nodule located in an intermediate bronchus which generates atelectasis in the basal bronchi. Fibro-bronchoscopy (FOB): A tumour-like injury blocking 100% of the right intermediate bronchus’ duct. Biopsy: Pulmonary tissue with haemorrhagic areas, granular tissue with small cellular clusters of lobular disposal and glandular shape with eccentric central nuclei cells, with homogenous chromatin and without atypical mitosis. Immunohistochemistry: Intensely positive cells to synaptophysin and CD56. Diagnosis: Neuroendocrine Typical Carcinoid Tumor. Comments: The patient evolves without progression of dyspnoea, she is waiting for a surgical resolution of tumour at National Institute of Thorax.

Introducción o historia del caso: Mujer joven de 24 años de edad, sin antecedentes mórbidos, acudió por cuadro de 10 días de evolución, de fiebre de hasta 38,5 °C y disnea grado III. Al examen físico destacó a nivel pulmonar: murmullo pulmonar disminuido en base pulmonar derecha, matidez de la misma zona y vibraciones vocales positivas. Exámenes: Radiografía de Tórax: Condensación atelectásica en base pulmonar derecha. TAC de Tórax sin contraste: Imagen nodular a nivel de bronquio intermedio, que genera atelectasia en bronquios basales. Fibrobroncoscopía (FBC): Lesión tumoral que ocluye el 100% del lumen para bronquio intermedio derecho. Biopsia: Tejido pulmonar con áreas de hemorragia, tejido granulatorio y tumor con acúmulos celulares de disposición lobular y glanduliforme, con núcleos centrales excéntricos, cromatina homogénea, sin atipias. Inmunohistoquímica: Células intensamente positivas para sinaptofisina, y CD-56. Diagnóstico: Tumor Neuroendocrino Carcinoide típico Comentarios: Paciente evoluciona sin progresión de su disnea, esperando resolución quirúrgica del tumor en Instituto Nacional del Tórax.

Performance of different biofilters in a recirculating system for rainbow trout farming / Desempeño de diferentes biofiltros en un sistema de recirculación para cultivo de trucha arcoiris

ABSTRACT Objective. To evaluate the performance of different biofilters in a recirculating aquaculture system (RAS) for trout farming. Materials and methods. It was used a 1m3 plastic tank for fries farming; fabric bags to solids retention; a submersible pump; a constant water level and flow distribution box; six up flow biofilters in 3" PVC tube; sand of D10=0.45mm as carrier. The reactors were operated at local temperature and with hydraulic retention time (HRT) of 11 min, the biofilters were inoculated in the next way: R1-Control: RAS water; R2-Fish culture farm sludges; R3- Water from aerated lagoon of Antanas landfill (AL); R4-Aquarium sediments; R5- Aerated lagoon of AL sludges; R6-Sludges from sulfidogenic reactor of AL. The weight gain (WG) and the food conversion (FC) were evaluated, some physic-chemical parameters were monitored and the nitrogen and suspended solids removal efficiency were evaluated. Results. The WG of the cultured animals was 1.58 g/d and the FC was 1.41. There were no differences for ammonium and nitrite removal between the reactors; the average removal efficiencies were: ammonium 4.78%, nitrite 27.2%, nitrate 32.3%, suspended solids 37.5%; R4 and R5 reactors presented the best performance on nitrate removal, with average efficiencies of 47.4% and 42.8%. R3 presented the best SS removal with an average of 58.2%. Conclusions. The RAS water treatment system guaranteed appropriated liquid quality conditions for trout farming; the most efficient reactor for removal of the different forms of nitrogen was the inoculated with the aerated lagoon of AL sludges.

RESUMEN Objetivo. Evaluar el desempeño de diferentes biofiltros en un sistema de recirculación (SRA) para cultivo de trucha arcoiris. Materiales y métodos. Se utilizó: un tanque de 1m3 para cultivo de alevines, bolsas de lienzo para retención de sólidos, bomba sumergible, caja de nivel constante y distribución de flujo, seis biofiltros en tubo de PVC de 3", arena con D10=0.45mm como medio soporte. Los biofiltros se operaron a temperatura ambiente y con tiempo de retención hidráulica (TRH) de 11 min, se inocularon así: R1-Control: Aguas del SRA; R2-Lodos estación piscícola; R3-Agua Laguna aireada relleno sanitario Antanas (RSA); R4-Sedimentos acuarios; R5-Lodos laguna aireada RSA; R6-Lodos reactor sulfidogénico RSA. Se evaluó la ganancia de peso (GP) y la conversión alimenticia (CA), se monitorearon parámetros físico-químicos y se evaluó la eficiencia de remoción de nitrógeno y sólidos suspendidos. Resultados. La GP de los animales fue de 1.58 g/d y la CA de 1.41. No hubo diferencias para remoción de amonio ni nitritos entre reactores; las eficiencias medias de remoción fueron: amonio 4.78%, nitrito 27.2%, nitrato 32.3%, sólidos suspendidos 37.5%. Los reactores R4 y R5 presentaron mejor remoción de nitratos, con eficiencias medias de 47.4% y 42.8%. El R3 reportó la mejor remoción de SS con promedio del 58.2%. Conclusiones. El sistema de tratamiento del agua en el SRA garantizó condiciones de calidad del líquido, apropiadas para el cultivo de la trucha; el reactor más eficiente para la remoción de las formas de nitrógeno evaluadas fue el inoculado con lodos de la laguna aireada del RSA.

Recommendations in the management of epithelial appendiceal neoplasms and peritoneal dissemination from mucinous tumours (pseudomyxoma peritonei).

The epithelial appendiceal neoplasms are uncommon and are usually detected as an unexpected surgical finding. The general surgeon should be aware of the diversity of its clinical manifestations and biological behaviors along with the significance of the surgical treatment on the progression of the illness and the prognosis of the patients. The operative findings and, especially, tumor histology, determine the type of surgery. Intestinal histologic subtype behaves and should be treated similarly to the right colon neoplasms; while mucinous tumors, often discordant between histology and its aggressiveness, can be treated with a simple appendectomy or require complex oncological surgeries. Mucinous tumors are often associated with the presence of mucin or tumor implants in the abdominal cavity, being the clinical syndrome known as pseudomyxoma peritonei (PMP). PMP tends to present an indolent but deadly evolution and requires a multimodal approach as a single treatment with curative potential: complete cytoreductive surgery plus hyperthermic Intra-peritoneal chemotherapy (CCRS + HIPEC) now considered the standard of care in this pathology. The general surgeon should be aware of the governing principles of the treatment of appendiceal neoplasms with or without peritoneal dissemination, know the therapeutic frontiers in every situation (avoiding unnecessary or counterproductive surgeries) and sending early these patients to specialised centres in the radical management of malignant diseases of the peritoneum in the conditions and with the necessary information to facilitate a possible radical treatment.

GEINOFOTE: efficacy and safety of fotemustine in patients with high-grade recurrent gliomas and poor performance status.

PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.

Biliary tract cancers: SEOM clinical guidelines.

Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease.

Factors related to advanced colorectal neoplasm at the Policlínico Peruano Japonés.

BACKGROUND: Identifying persons at high risk for advanced colorectal neoplasia can aid in the prevention of colon cancer. Previous studies have shown that some patients can present with proximal advanced neoplasia with no distal findings. AIMS: To determine the factors related to advanced neoplasia and advanced proximal colorectal neoplasia in a Latin American population. MATERIAL AND METHODS: A prospective, cross-sectional, observational, analytic study was conducted. It included patients that underwent colonoscopy at the Policlínico Peruano Japonés within the time frame of January and July 2012. Advanced neoplasia was defined as the presence of lesions ≥ 10mm with a villous component, high-grade dysplasia, or carcinoma. The splenic flexure was the limit between the proximal and distal colon. RESULTS: A total of 846 patients were included in the study. Advanced neoplasia was detected in 108 patients (12.8%) and advanced proximal neoplasia in 55 patients (6.7%), 42 (76.4%) of whom had no neoplasia in the distal colon. Factors related to advanced neoplasia found in the multivariate analysis were age, at the intervals of 50-59 (p=0.019), 60-69 (p=0.016), and ≥ 70 years (0.002) and male sex (p=0.003). In the evaluation of advanced proximal neoplasia, the multivariate analysis identified the 60-69 year age interval (p=0.039) and advanced distal neoplasia (p=0.028) as factors related to advanced proximal disease. The ROC curve established the age cut-off point at 60 years for initially performing colonoscopy, rather than sigmoidoscopy. CONCLUSIONS: Age and sex are related to advanced neoplasia, whereas age and advanced distal neoplasia are related to advanced proximal neoplasia.

First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: A phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours.

BACKGROUND: Frail elderly patients with metastatic colorectal cancer (mCRC) are not candidates for chemotherapy. Monotherapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies may be an option for these patients with few systemic toxic effects. PATIENTS AND METHODS: Single-arm, multicentre, phase II trial including patients ⩾ 70y ears with wild-type (WT) KRAS (exon 2) mCRC, Eastern Cooperative Oncology Group (ECOG) status ⩽ 3, KPC (Köhne Prognostic Classification)--defined intermediate or high risk status, frailty and/or ineligibility for chemotherapy. Patients received panitumumab until progression or unacceptable toxicity. The primary end-point was progression free survival (PFS) rate at 6 months. RESULTS: The study included 33 patients (intention-to-treat (ITT) population). Median age: 81 years; sex: 66.7% male; high-risk KPC status: 45.4%. Median treatment duration was 14 weeks and 6-month PFS rate was 36.4% (95% confidence interval (CI): 20.0-52.8). The objective response rate: 9.1% (95% CI: 0-18.9) (all partial responses), and there were 18 stable diseases (54.5%). Median PFS was 4.3 months (95% CI: 2.8-6.4) and median overall survival (OS) was 7.1 months (95% CI: 5.0-12.3). There were no deaths or grade 4-5 adverse events (AEs) related to panitumumab and the most common grade 3-related AE was rash acneiform (15.2%). A significant association between clinical response and RAS status was observed (P=0.037). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS, N = 15), 6-month PFS rate was 53.3% (95% CI: 30.1-75.2) and median PFS and OS were 7.9 and 12.3 months, respectively. CONCLUSIONS: Single-agent panitumumab is active and well tolerated and may be a therapeutic option for high-risk frail elderly patients with WT RAS tumours considered not candidates for chemotherapy (clinicaltrials.gov identifier NCT01126112).