Hydroalcoholic Extract of Rabbiteye Blueberry (Vaccinium ashei) Leaves Mitigates Unpredictable Chronic Mild Stress Model Inducing Depressive-Like Behavior in Rats.

Several studies reported that rabbiteye blueberry (Vaccinium ashei Reade) leaves present promising biological properties. To the best of our knowledge, no study investigated the possible application of their hydroalcoholic extract for treating mood disorders. Herein, we evaluated if the hydroalcoholic extract of rabbiteye blueberry (Vaccinium ashei Reade) leaves (HEV) promotes an antidepressant-like effect in rodents using chronic experimental approaches. The effect of repeated administration of HEV (50 mg/kg, p.o.) on the immobility time was assessed in the forced swimming test (FST) in an unpredictable chronic mild stress (UCMS) model. Repeated treatment with HEV reversed the depressive-like behavior induced by UCMS by reducing the immobility time. Besides, the exposure to HEV caused no changes in relative organ weights in rats submitted to UCMS. The results indicated that HEV administration presented antidepressant-like action devoid of toxic effects. Thus, it is possible to suggest its potential as a safe and accessible therapeutic tool in the management of depression and other related mood disorders.

Noise and landscape features influence habitat use of mammalian herbivores in a natural gas field.

Anthropogenic noise is a complex disturbance known to elicit a variety of responses in wild animals. Most studies examining the effects of noise on wildlife focus on vocal species, although theory suggests that the acoustic environment influences non-vocal species as well. Common mammalian prey species, like mule deer and hares and rabbits (members of the family Leporidae), rely on acoustic cues for information regarding predation, but the impacts of noise on their behaviour has received little attention. We paired acoustic recorders with camera traps to explore how average daily levels of anthropogenic noise from natural gas activity impacted occupancy and detection of mammalian herbivores in an energy field in the production phase of development. We consider the effects of noise in the context of several physical landscape variables associated with natural gas infrastructure that are known to influence habitat use patterns in mule deer. Our results suggest that mule deer detection probability was influenced by the interaction between physical landscape features and anthropogenic noise, with noise strongly reducing habitat use. In contrast, leporid habitat use was not related to noise but was influenced by landscape features. Notably, mule deer showed a stronger predicted negative response to roads with high noise exposure. This study highlights the complex interactions of anthropogenic disturbance and wildlife distribution and presents important evidence that the effects of anthropogenic noise should be considered in research focused on non-vocal specialist species and management plans for mule deer and other large ungulates.

El ruido de origen antropogénico es una perturbación compleja que provoca una variedad de respuestas en la fauna silvestre. La mayoría de los estudios que examina los efectos del ruido en fauna silvestre se enfoca en especies que se comunican con vocalizaciones, sin embargo, la teoría sugiere que el ambiente acústico es también un recurso clave para especies no-vocales. Especies de mamíferos comunes como el venado bura, liebres y conejos (miembros de la familia Leporidae), dependen de señales acústicas para detectar depredadores, pero los impactos del ruido en el comportamiento de estas especies han recibido poca atención de los investigadores. Usando grabadoras y cámaras trampa en conjunto, exploramos como los niveles diarios de ruido antropogénico generados por la extracción de gas natural impactaron la ocupación y detección de mamíferos herbívoros en un campo de extracción de energía en la fase de producción de desarrollo. Consideramos los efectos del ruido en el contexto de varias variables físicas del paisaje asociadas con la infraestructura del gas natural, que sabemos, influencian los patrones de uso de hábitat del venado bura. Nuestros resultados sugieren que la probabilidad de detección del venado bura fue influenciada por la interacción de las características físicas del paisaje y el ruido antropogénico, este último reduciendo de manera importante el uso de hábitat. En contraste, el uso de hábitat de lepóridos no se relacionó con ruido, pero fue influenciado por variables del paisaje. Notablemente, el venado bura mostro una predicción de respuesta fuerte a los caminos con niveles altos de ruido. Este estudio señala las complejas interacciones entre perturbaciones antropogénicas y la distribución de fauna silvestre. También presentamos evidencia importante que señala que los efectos del ruido antropogénico deben ser considerados en investigaciones enfocadas en especies especialistas no-vocales y planes de manejo para el venado bura y otros ungulados grandes.

Serum VEGF Predicts Clinical Improvement Induced by Cerebrolysin Plus Donepezil in Patients With Advanced Alzheimer's Disease.

Serum vascular endothelial growth factor (VEGF) increases with Alzheimer's disease (AD) severity and may prevent cognitive decline. However, information on the influence of AD drug therapy on circulating VEGF is limited. This study assessed changes in serum VEGF levels and its association with clinical and functional responses in mild to moderate AD patients who were treated with Cerebrolysin, donepezil, or the combined therapy in a randomized, controlled trial. Treatment with Cerebrolysin plus donepezil reduced elevated serum VEGF levels and improved functioning and cognition significantly compared with donepezil alone in patients with advanced AD, and treatment differences were more pronounced in patients with higher VEGF levels. Our results indicate that the combined therapy reversed the increase of serum VEGF in advanced AD, which was associated with cognitive and functional responses, particularly in patients with high baseline VEGF.

Advances in Interventional Endoscopic Ultrasound (EUS): A Technical Review.

Endoscopic ultrasound (EUS) has become the therapeutic intervention of choice for multiple diseases and continues to evolve rapidly. Its increasing use has allowed the development and adaptation of multiple, revolutionary devices and tools. Currently, there is paucity of randomized clinical trials evaluating multiple EUS-guided interventions and the vast majority of published data is heterogenous. However, the available literature on EUS-guided therapeutic interventions continues to expand and demonstrate its safety, efficacy and cost effectiveness in carefully selected patients when performed by expert endosonographers. The future of interventional EUS appears to be bright!

Revised Marshall Score: A New Approach to Stratifying the Severity of Acute Pancreatitis.

BACKGROUND: Modified Marshall Score is one of the severity scores for acute pancreatitis (AP) and is included in the Revised Atlanta Classification, but given its utilization of a set serum creatinine level (sCr), it may misclassify stable patients with chronic kidney disease (CKD) to a more severe class just due to their elevated sCr. AIMS: Our study aims to evaluate the role of CKD in AP and the possibility of utilizing acute kidney injury (AKI) into developing a new scoring system. METHODS: We retrospectively reviewed the electronic medical records of three hundred consecutive patients who were diagnosed with AP during hospitalization. Multiple demographic variables and clinical course indices were collected. Univariate logistic regression was then applied to predict mortality and ICU admission. Finally, receiver operating curve was utilized to compare original versus New Revised Marshall Score. RESULTS: Two hundred and eight-four (284) patients had a definitive diagnosis of AP. When comparing patients who had AKI on admission to those without AKI, the AKI group showed statistically significant higher mortality rate (5.6% vs. 1.1%, p = 0.04). Finally, we substituted the renal part of Marshall Score with our AKIN and we plotted the New "Revised" Marshall Score, which showed a higher AUROC compared to the original modified version (C-statistics 0.93 vs. 0.89, p < 0.05). CONCLUSION: We found that AKI predicts mortality and outperforms the use of a fixed sCr value alone. The use of our New Revised Marshall Score can accurately classify AP severity, avoiding misclassification of AP severity and providing better patient care.

Neurofibromatosis type I: mutation spectrum of NF1 in spanish patients.

Neurofibromatosis type I (NF1) is one of the most common genetic disorders in humans. NF1, a tumor predisposition syndrome, is caused by heterozygous pathogenic variants in the NF1 gene. Molecular genetic testing of NF1 is complex, especially because of the presence of a high number of partial pseudogenes, some of them with a high percentage of sequence identity. In this study, we have analyzed the largest cohort of NF1 Spanish patients (150 unrelated individuals suspected of having NF1 and 53 relatives, making a total of 203 individuals). Mutation analysis of the entire coding region was performed in all unrelated index patients. Additionally, the Multiplex Ligation-dependent Probe Amplification (MLPA) test of the NF1 gene and SPRED1 gene analysis (sequencing and MLPA test) was performed in some of the negative patients for NF1 point mutations. When fulfilling the National Institutes of Health (NIH) criterion for the clinical diagnosis of NF1, the detection rate was 79%. Among the 80 genetically confirmed NF1 probands, we detected 69 different pathogenic variants. Two mutations (3%) were gross deletions of the whole gene, the remaining 78 mutations (97%) were small changes spread among all NF1 exons. Among these 69 different mutations detected, 42 mutations were described elsewhere, and 27 mutations were novel mutations. When segregation was studied, 67% of mutations resulted de novo variants. No genetic mosaicism was detected on patients' parents.

Correction to: Endoscopic and surgical management of nonampullary duodenal neoplasms.

This article was updated to correct the author listing for Carlos Roberto Simons-Linares.

Endoscopic and surgical management of nonampullary duodenal neoplasms.

BACKGROUND: Sporadic nonampullary duodenal neoplasms (SNADN) can have malignant potential for which endoscopic and surgical resections are offered. We report combined gastroenterologic and surgical experience for treatment of SNADN, including endoscopic mucosal resection (EMR) and pancreas-preserving partial duodenectomy (PPPD). METHODS: We retrospectively reviewed 121 consecutive patients, who underwent 30 PPPDs and 91 EMRs for mucosal and submucosal SNADN. Decision to undergo EMR or surgical resection was based on expert endoscopist and surgeon discretion including multidisciplinary tumor board review. Main outcomes were recurrence rate of neoplasia and adverse events requiring hospital admission or prolonged care. EMRs were performed with submucosal lifting followed by snare resection. PPPD included total duodenectomy, supra-ampullary PPPD for neoplasms proximal to the ampulla, and infra-ampullary PPPD for lesions distal to the ampulla. Follow-up data were available for 65% of EMR and 73% of surgical patients. RESULTS: Surgically resected neoplasia was larger with more advanced neoplasia and submucosal lesions. En bloc resection was achieved in all surgical resections and in 53% of EMRs. Post-EMR, mucosal and submucosal neoplasia recurred in 32 and 0%, respectively, including five neoplasms (26%) after an initial negative esophagogastroduodenoscopy. All recurrences were treated endoscopically. Complications occurred in 14 endoscopically and eight surgically treated patients, none requiring surgical intervention. CONCLUSIONS: Post-EMR patients had higher recurrence of mucosal neoplasia, whereas submucosal neoplasms, mainly carcinoid, did not recur. Polyp size and positive resection margin were not associated with neoplasia recurrence. Patients with SNADN could benefit from a multidisciplinary approach to stratify the optimal treatment based on local expertise.

Bis-Pyrano Prenyl Isoflavone Improves Glucose Homeostasis by Inhibiting Dipeptidyl Peptidase-4 in Hyperglycemic Rats.

Isoflavones widely distributed in plants prevent diabetes. This study investigated the in vivo and in vitro effect of 3',4'-dihydroxy-6″,6″,6″',6″'-tetramethylbis(pyrano[2″,3″:5,6::2″',3″':7,8]isoflavone (bis-pyrano prenyl isoflavone) on glucose homeostasis in hyperglycemic rats. The ethyl acetate fraction from aerial parts of Polygala molluginifolia that contain isoflavones was assayed on glucose tolerance, on in vitro maltase activity and on protein glycation. The isoflavone bis-pyrano prenyl isolated from this fraction was investigated on glucose homeostasis. The in vivo action of the isoflavone exhibits an anti-hyperglycemic effect by improving glucose tolerance, augmenting the liver glycogen, inhibiting maltase activity, and stimulating glucagon-like peptide-1 (GLP-1) and insulin secretion. The in vitro isoflavone inhibits dipeptidyl peptidase-4 (DPP-4) activity since the glucose tolerance was improved in the presence of the isoflavone as much as sitagliptin, an inhibitor of DPP-4. However, the co-incubation with isoflavone and sitagliptin exhibited an additive anti-hyperglycemic action. The isoflavone increased the GLP-1 faster than the positive hyperglycemic group, which shows that the intestine is a potential target. Thus, to clarify the main site of action in which isoflavone improves glucose balance, the in vitro mechanism of action of this compound was tested in intestine using calcium influx as a trigger for the signal pathways for GLP-1 secretion. The isoflavone stimulates calcium influx in intestine and its mechanism involves voltage-dependent calcium channels, phospholipase C, protein kinase C, and stored calcium contributing for GLP-1 secretion. In conclusion, the isoflavone regulates glycaemia by acting mainly in a serum target, the DPP-4 inhibitor. Furthermore, the long-term effect of isoflavone prevents protein glycation. J. Cell. Biochem. 118: 92-103, 2017. © 2016 Wiley Periodicals, Inc.

Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases.

BACKGROUND: Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer's disease. METHODS: We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer's disease patients. RESULTS: Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy. CONCLUSION: Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer's disease cases with apolipoprotein E epsilon-4 allele.

Maternal serum omentin-1 profile is similar in humans and in the rat animal model.

Omentin-1 is an adipocytokine with anti-inflammatory activity that has been associated with different metabolic disorders. The aim of this study is to investigate the serum profiles of omentin-1 throughout human and rat pregnancy. Serum omentin-1 levels were determined by ELISA in a prospective cohort study of healthy pregnant women (n=40) during the three trimesters of pregnancy and in twenty healthy non-pregnant women during the follicular and luteal phase of the menstrual cycle. In addition, serum omentin-1 levels were measured in rats during different periods of pregnancy (gestational days 8, 12, 16, 19, and 21) and in an age-matched control (virgin) group of rats (n=12rats/group). Finally, immunohistochemistry was used to demonstrate the presence of omentin-1 protein in human and rat placenta. Omentin-1 immunoreactivity was detected in cytotrophoblasts, syncytiotrophoblasts, sparse Hofbauer cells, and endothelial cells of the stem villi of human placenta. Additionally, it was detected in the labyrinthine trophoblast and yolk sac layer of the rat placenta. Human and rat serum omentin-1 levels were significantly lower in the late gestational period when compared with the non-pregnant women and virgin rats (p<0.05). Serum omentin-1 changes were not significant throughout the gestation in both species (p>0.05). Human serum omentin-1 levels have an inverse relationship with triglyceride levels during pregnancy. Our findings have not determined the exact role of omentin-1 during pregnancy, concerning the metabolic control of triglycerides and other energy sources. Whether omentin-1 decrease implies a regulatory function is still not clear. Further studies are needed to address this issue and determine the role of omentin-1 in metabolic adaptations during normal human and rat pregnancy.

Exposure to endocrine disruptors promotes biofilm formation and contributes to increased virulence of Pseudomonas aeruginosa.

Anthropogenic activities contribute to the spread of chemicals considered as endocrine disruptors (ED) in freshwater ecosystems. While several studies have reported interactions of EDs with organisms in those ecosystems, very few have assessed the effect of these compounds on pathogenic bacteria. Here we have evaluated the impact of five EDs found in aquatic resources on the virulence of human pathogen P. aeruginosa. ED concentrations in French aquatic resources of bisphenol A (BPA), dibutyl phthalate (DBP), ethylparaben (EP), methylparaben (MP) and triclosan (TCS) at mean molar concentration were 1.13, 3.58, 0.53, 0.69, and 0.81 nM respectively. No impact on bacterial growth was observed at EDs highest tested concentration. Swimming motility of P. aeruginosa decreased to 28.4% when exposed to EP at 100 µM. Swarming motility increased, with MP at 1 nM, 10 and 100 µM (1.5-fold); conversely, a decrease of 78.5%, with DBP at 100 µM was observed. Furthermore, exposure to 1 nM BPA, DBP and EP increased biofilm formation. P. aeruginosa adhesion to lung cells was two-fold higher upon exposure to 1 nM EP. We demonstrate that ED exposure may simultaneously decrease mobility and increase cell adhesion and biofilm formation, which may promote colonisation and establishment of the pathogen.

Cord factors from atypical mycobacteria (Mycobacterium alvei, Mycobacterium brumae) stimulate the secretion of some pro-inflammatory cytokines of relevance in tuberculosis.

The ability to induce several cytokines relevant to tuberculosis (TNF-α, IL-1ß, IL-6, IL-12p40 and IL-23) by cord factor (trehalose dimycolate) from Mycobacterium alvei CR-21(T) and Mycobacterium brumae CR-270(T) was studied in the cell lines RAW 264.7 and THP-1, and compared to the ability of cord factor from Mycobacterium tuberculosis H37Rv, where this glycolipid appears to be implicated in the pathogenesis of tuberculosis. Details of the fine structure of these molecules were obtained by NMR and MS. The mycoloyl residues were identified as α and (ω-1)-methoxy in M. alvei CR-21(T) and α in M. brumae CR-270(T); in both cases they were di-unsaturated instead of cyclopropanated as found in M. tuberculosis. In RAW 264.7 cells, cord factors from M. alvei CR-21(T), M. brumae CR-270(T) and M. tuberculosis differed in their ability to stimulate IL-6, the higher levels corresponding to the cord factor from M. tuberculosis. In THP-1 cells, a similar overall profile of cytokines was found for M. alvei CR-21(T) and M. brumae CR-270(T), with high proportions of IL-1ß and TNF-α, and different from M. tuberculosis, where IL-6 and IL-12p40 prevailed. The data obtained indicate that cord factors from the atypical mycobacteria M. alvei CR-21(T) and M. brumae CR-270(T) stimulated the secretion of several pro-inflammatory cytokines, although there were some differences with those of M. tuberculosis H37Rv. This finding seems to be due to their particular mycoloyl substituents and could be of interest when considering the potential adjuvanticity of these molecules.

Ceratonia siliqua (carob) trees as natural habitat and source of infection by Cryptococcus gattii in the Mediterranean environment.

Recent Cryptococcus gattii infections in humans and animals, including several outbreaks in goats, were the basis of this environmental survey in six provinces of Spain. A total of 479 samples from 20 tree species were studied. Cryptococcus gattii was found for the first time in autochthonous Mediterranean trees in Spain. Fourteen isolates of this pathogen were obtained from seven trees of three different species: 12 from carob (Ceratonia siliqua), one from Mediterranean stone pine (Pinus halepensis) and another from eucalyptus (Eucalyptus camaldulensis). All C. gattii isolates were genotype AFLP4/VGI and mating type alpha, and were found to be genetically identical with C. gattii strains isolated from humans and animals in Spain. This supports the hypothesis that these trees may be a natural source for infection of humans and mammals in the Mediterranean area.

Modulation of Amyloid-ß and Tau in Alzheimer's Disease Plasma Neuronal-Derived Extracellular Vesicles by Cerebrolysin® and Donepezil.

BACKGROUND: Plasma neuronal-derived extracellular vesicles (NDEV) contain proteins of pathological, diagnostic, and therapeutic relevance. OBJECTIVE: We investigated the associations of six plasma NDEV markers with Alzheimer's disease (AD) severity, cognition and functioning, and changes in these biomarkers after Cerebrolysin®, donepezil, and a combination therapy in AD. METHODS: Plasma NDEV levels of Aß42, total tau, P-T181-tau, P-S393-tau, neurogranin, and REST were determined in: 1) 116 mild to advanced AD patients and in 20 control subjects; 2) 110 AD patients treated with Cerebrolysin®, donepezil, or combination therapy in a randomized clinical trial (RCT). Samples for NDEV determinations were obtained at baseline in the NDEV study and at baseline and study endpoint in the RCT. Cognition and functioning were assessed at the same time points. RESULTS: NDEV levels of Aß42, total tau, P-T181-tau, and P-S393-tau were higher and those of neurogranin and REST were lower in mild-to-moderate AD than in controls (p < 0.05 to p < 0.001). NDEV total tau, neurogranin, and REST increased with AD severity (p < 0.05 to p < 0.001). NDEV Aß42 and P-T181-tau correlated negatively with serum BDNF (p < 0.05), and total-tau levels were associated to plasma TNF-α (p < 0.01) and cognitive impairment (p < 0.05). Combination therapy reduced NDEV Aß42 with respect to monotherapies (p < 0.05); and NDEV total tau, P-T181-tau, and P-S396-tau were decreased in Cerebrolysin-treated patients compared to those on donepezil monotherapy (p < 0.05). CONCLUSION: The present results demonstrate the utility of NDEV determinations of pathologic and synaptic proteins as effective AD biomarkers, as markers of AD severity, and as potential tools for monitoring the effects of anti-AD drugs.

The Natural Course of Pancreatic Cysts in Inflammatory Bowel Disease: Results of a Long-term Follow-up.

OBJECTIVES: The natural course of pancreatic cysts in inflammatory bowel disease (IBD) is unknown. We aim to describe the natural course of pancreatic cysts in IBD and evaluate long-term outcomes. METHODS: A database of patients with abdominal imaging diagnosis of pancreatic cysts (2008-2019) was reviewed. Patients with IBD and pancreatic cysts (study group) and pancreatic cysts without IBD (controls) were selected. Outcomes were measured at 1, 3, 5, and 10 years. Several logistic regression models were used for analysis. RESULTS: Of the 1789 patients evaluated, 1690 had pancreatic cysts without IBD, and 78 had IBD and pancreatic cysts. Majority of cysts were intraductal papillary mucinous neoplasms. Patients with IBD and pancreatic cysts were more likely to be diagnosed with pancreatic cysts at a younger age (P < 0.001) and were more likely to undergo surgical intervention at a younger age (P < 0.001). CONCLUSIONS: This is the first study to evaluate the natural course of pancreatic cysts in IBD patients. Patients with IBD were more likely to have pancreatic cysts detected at a younger age. Despite the early presentation, there were no differences in long-term outcomes. Patients with IBD with pancreatic cysts should be managed similarly to those without IBD.

Use of Piptatherum miliaceum to enable the establishment success of Salvia rosmarinus in Technosols developed from pyritic tailings.

With this study we aimed to assess the effect of the prior development of Piptatherum miliaceum (Pm) in a Technosol on the establishment of Salvia rosmarinus (Sr) as a cash crop. An experimental pot was performed with two biochar (BCh) doses (BCh1 and BCh2) mixed with marble waste and pyritic tailings, with and without Pm. After 12 months of Pm growth, the pots with this species were divided into two sets: Sr alone and Sr + Pm. An agricultural soil (AGR) was used as an external control. The results showed that the growth of Sr led to similar shoot biomass to AGR. Sr + Pm reduced shoot biomass by 50%. Total soil organic and recalcitrant C, and total and recalcitrant N showed the highest values in vegetated pots, with no effect of the BCh rate. The decrease in the soil metals availability was related with increases in soil pH. BCh1Sr + Pm treatment showed a microbial community structure more similar to AGR, related to higher fungal and bacterial abundance, enzyme activities and soluble carbon. Thus, growing Sr + Pm seems a suitable strategy to improve soil properties, including microbial abundance, with low translocation of metals. Although the BCh rate did not affect plant growth or soil physicochemical properties, the lowest rate contributed to the growth of soil microorganisms better. The simultaneous growth of Sr + Pm reduced biomass production, and a source of available nutrients is also recommended. Further studies are needed to test this strategy in the field, and to ensure its suitability and a constant biomass production.

Pancreatitis After Pancreaticojejunostomy Procedure? A Tale Involving the Tail of the Pancreas.

Recurrent acute pancreatitis (RAP) involving the tail of the pancreas after pancreaticojejunosotomy (PJP) is rare, has very challenging management, and there is minimal literature. We describe a case of idiopathic RAP, complicated with chronic pancreatitis that failed medical and endoscopic management and required PJP. Unfortunately, RAP recurred after PJP, and we describe his clinical course and management.

Do Not Skip the Retroflexion: A Case of Disseminated Anorectal Mucosal Melanoma.

Less than 4% of melanomas are of mucosal origin, with primary anorectal mucosal melanomas comprising a small subset. Mucosal melanomas are often diagnosed at an advanced stage due to delay in patient presentation and obscured tumor origins leading to a more aggressive behavior and less favorable prognosis when compared with cutaneous melanomas. We present a case of metastatic anorectal mucosal melanoma with a negative colonoscopy 1 year earlier.