Background: Cholangiocarcinoma (CCA) is a primary hepatic tumor, frequently found in patients with liver cirrhosis and biliary tract diseases. Its varieties include isolated CCA or “combined hepatocellular-cholangiocarcinoma” (cHCC-CCA). The latter is uncommon, with poorly defined diagnostic criteria and natural history. Aim: To characterize patients with cirrhosis with a pathological diagnosis of CCA and cHCC-CCA. Material and Methods: Forty-nine liver biopsies with a pathological diagnosis of CCA were reviewed. The clinical records of patients were reviewed to fetch demographic variables, etiology of cirrhosis and clinical presentation. Results: Eight of the 49 patients had cirrhosis (16% of CCA biopsies reviewed). Their median age was 64 (27-71) years and five were females. Four patients had CCA, three patients cHCC-CCA and one had a bifocal tumor. Patients in the CCA group were more commonly symptomatic. Alpha-fetoprotein and CA 19-9 levels were elevated in one of eight and four of six patients, respectively. Within 12 months from diagnosis, five of eight patients died. Conclusions: In most of these cases, the diagnosis of cHCC-CCA and CCA was made in the liver explant study without previous imaging diagnosis. This reinforces the usefulness of the histological study, in specific cases, prior to liver transplantation and emphasizes the importance of systematic explant exploration in these cases.

Abstract Non-invasive techniques are useful to quantify the degree of liver fibrosis. Hepatic elastography by ARFI (Acoustic Radiation Force Impulse) has been less studied in our setting. Objective: To describe patients with chronic liver disease (CLD) studied by ARFI, evaluating concordance, advantages or limitations compared with non-invasive biochemical scores (APRI and FIB-4) to graduate liver fibrosis. Patients and methods: Retrospective and descriptive study of patients undergoing ARFI between 2013-2019 with a clinical and laboratory history obtained from an electronic medical record. Descriptive statistics and association by c2 were used, with a significance value of p < 0.05. Results: ARFI was performed 815 times in 731 patients; 488 subjects met inclusion criteria. ARFI was compared between more frequent pathologies. There was a higher frequency of advanced fibrosis (F3 - F4) in Alcoholic Liver Disease (ALD) (42%) and Hepatitis C virus (HCV) (29%) (p < 0.001) and absence or minimal fibrosis (F0-F1) in Non-Alcoholic Fatty Liver Disease (NAFLD) (89%), Hepatitis B Virus (HBV) (77%) and Autoimmune Liver Disease (73%) (p < 0.001). Splenomegaly was associated with F3 - F4 (p < 0.001). Greater liver echogenicity was observed in NAFLD (93%), ALD (84%) and HCV (74%) (p < 0.001). The ARFI, FIB-4 and APRI score tended to increase according to the degree of fibrosis, being concordant in F3-4. When comparing F0-F1 by ARFI with FIB-4 and APRI, there was dispersion of the values in the serological scores. Conclusion: FIB-4, APRI and ARFI can be helpful in estimating F3-F4, however, they could underestimate or overestimate severity in F0-F1. ARFI would add relevant morphological aspects in CLD.

Resumen Las técnicas no invasivas son útiles para cuantificar el grado fibrosis hepática. La elastografía hepática por ARFI (acoustic radiation force impulse) ha sido poco estudiada en nuestro medio. Objetivo: Describir pacientes con enfermedad hepática crónica (EHC) estudiados por ARFI, evaluando concordancia, ventajas o limitaciones comparada con scores bioquímicos no invasivos (APRI [índice de relación de AST/recuento de plaquetas] y FIB-4 [índice que incluye edad, niveles de AST, ALT y recuento plaquetario]) para graduar fibrosis hepática. Pacientes y métodos: Estudio retrospectivo y descriptivo de pacientes sometidos a ARFI entre 2013 y 2019 con antecedentes clínicos y datos de laboratorio obtenidos de ficha clínica electrónica. Se usó estadística descriptiva y asociación por χ2, con valor de significación de p < 0,05. Resultados: Se realizó ARFI en 815 ocasiones en 731 pacientes; 488 sujetos cumplían criterios de inclusión. La ARFI se comparó entre patologías más frecuentes. Hubo mayor frecuencia de fibrosis avanzada (F3-F4) en enfermedad hepática alcohólica (EHA) (42%) y virus de la hepatitis C (VHC) (29%) (p < 0,001) y ausencia o mínima fibrosis (F0-F1) en enfermedad hepática grasa no alcohólica (EHGNA) (89%), virus de la hepatitis B (VHB) (77%) y enfermedad hepática autoinmune (73%) (p < 0,001). La esplenomegalia se asoció a F3-F4 (p < 0,001). Mayor ecogenicidad hepática se observó en EHGNA (93%), EHA (84%) y VHC (74%) (p < 0,001). La puntuación de ARFI, FIB-4 y APRI tendió a aumentar según grado de fibrosis, siendo concordante en F3-4. Al comparar F0-F1 por ARFI con FIB-4 y APRI, existió dispersión de los valores en los scores serológicos. Conclusión: FIB-4, APRI y ARFI pueden constituir una ayuda en la estimación de F3-F4, sin embargo, podrían subestimar o sobreestimar la severidad en F0-F1. La ARFI agregaría aspectos morfológicos relevantes en EHC.

RESUMO Objetivo: Descrever as características basais de pacientes ambulatoriais com RT-PCR positivo para SARS-CoV-2 e definir se os sintomas de alerta para gravidade (febre, dispneia e dor torácica de início recente) podem prever piora clínica durante o período de isolamento. Métodos: Trata-se de um estudo epidemiológico, observacional e descritivo. Entre março e setembro de 2020, foram incluídos todos os pacientes ambulatoriais com teste positivo para SARS-CoV-2 em um centro médico terciário localizado em Santiago do Chile. Variáveis demográficas, comorbidades, sintomas de alerta para gravidade e outros sintomas foram compilados usando pesquisas de seguimento em intervalos específicos. Também foram calculados o risco de piora clínica (hospitalização) e as razões de risco (RR) ajustadas. Resultados: Foi incluído um total de 7.108 pacientes. A mediana de idade foi de 38 anos (variação: 0-101), e 52% eram homens. No início do estudo, 77% dos pacientes relataram sintomas característicos de infecção por SARS-CoV-2. Os sintomas recentes mais prevalentes foram cefaleia (53%), mialgia (47%) e febre (33%). De acordo com as pesquisas de seguimento, a incidência de sintomas diminuiu durante o período de isolamento; no entanto, 28% dos pacientes ainda apresentavam sintomas no dia 14. O risco de hospitalização para pacientes com febre e dispneia de início recente durante o período de seguimento foi RR = 7,43 (IC95%: 3,85-14,3; p < 0,01) e RR = 5,27 (IC95%: 1,52-18,30; p < 0,01 para ambos), respectivamente. A dor torácica de início recente não mostrou associação com a piora clínica. Conclusões: Nesta amostra de pacientes ambulatoriais com um diagnóstico recente de infecção por SARS-CoV-2, um monitoramento dos sintomas baseado em pesquisa foi útil para identificar aqueles com risco de piora clínica. Febre e dispneia de início recente durante o período de isolamento foram consideradas sintomas de alerta associados ao agravamento clínico e justificam avaliação médica imediata.

ABSTRACT Objective: To describe baseline characteristics of outpatients with a positive RT-PCR for SARS-CoV-2 and to define whether “red flags” (new-onset fever, dyspnea, and chest pain) can predict clinical worsening during the isolation period. Methods: This was an epidemiological, observational, descriptive study. Between March and September of 2020, all outpatients who tested positive for SARS-CoV-2 at a tertiary medical center located in Santiago de Chile were included. Demographic variables, comorbidities, red flags, and other symptoms were compiled using follow-up surveys at specific time points. The risk of clinical worsening (hospitalization) and adjusted hazard ratios (HRs) were calculated. Results: A total of 7,108 patients were included. The median age was 38 years (range, 0-101), and 52% were men. At baseline, 77% of the patients reported having characteristic symptoms of SARS-CoV-2 infection. The most prevalent onset symptoms were headache (53%), myalgia (47%), and fever (33%). According to the follow-up surveys, the incidence of symptoms decreased during the isolation period; however, 28% of the patients still presented with symptoms on day 14. The risk of hospitalization for patients with new-onset fever and dyspnea during the follow-up period was HR = 7.43 (95% CI, 3.85-14.3, p<0.01) and HR = 5.27 (95% CI, 1.52-18.30; p < 0.01 for both), respectively. New-onset chest pain showed no association with clinical worsening. Conclusions: In this sample of outpatients with a recent diagnosis of SARS-CoV-2 infection, a survey-based monitoring of symptoms was useful to identify those at risk of clinical worsening. New-onset fever and dyspnea during the isolation period were considered as red flags associated with clinical worsening and warrants prompt medical evaluation.

Environmental factors may influence the development of Inflammatory Bowel Disease and modify its natural history. The objective of this review is to evaluate current evidence about environmental factors associated with the disease. A better knowledge about the pathogenesis of the disease can lead to better treatment strategies and suggestions to prevent the disease.

Background: Primary non-response and secondary loss of response (LOR) are significant problems of biological therapy for inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) in IBD patients receiving these drugs can improve outcomes. Aim: To measure serum infliximab levels and anti-infliximab antibodies (ATI) in patients with IBD post-induction phase and during maintenance therapy assessing the clinical course of IBD. Patients and Methods: Prospective study of IBD patients receiving infliximab between July 2016-May 2017. Group-A included patients who received induction therapy while Group-B included patients who were in maintenance therapy. TDM was performed in serum samples collected at weeks-14 and 30 in Group-A and before the infliximab maintenance dose in Group-B. Clinical scores, fecal calprotectin and endoscopic score were also evaluated. Results: Of 14 patients in Group-A, 57% achieved endoscopic response. Median serum infliximab concentrations at week-14 and 30 were 2.65 AU/mL (0.23-32.58) and 2.3 AU/mL (0.3-16.8), respectively. Patients with mucosal healing had non-significantly higher median infliximab concentrations at week- 14, as compared to week 30 (median 3.2 vs 2.2 AU/ml, respectively, p 0.6). ATI >10 ug/mL were found in one and seven patients at week-14 and 30, respectively. At 52 weeks of follow-up, four patients (31%) had LOR. Group-B included 36 patients, 33% had LOR. Median serum concentrations of infliximab were 1.4 AU/mL (0.27-7.03). No significant differences in serum infliximab concentration were observed between patients in remission and those with inflammatory activity. Seventeen patients had ATI >10 ug/mL. Conclusions: Clinical algorithms using TDM might help to optimize the pharmacological therapy of IBD.

Background: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested. Aim: To describe the efficacy and safety of FMT for the treatment of recurrent CDI. Patients and Methods: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction. Results: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary. Conclusions: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.

Primary colorectal lymphoma is a rare form of presentation of gastrointestinal tract lymphomas. Inflammatory bowel disease and its treatment are risk factors for its development. We report a 47-year-old male patient with Ulcerative Colitis of two years of evolution, treated initially with azathioprine and later on with infliximab. Due to a relapse in symptoms after the second dose of infliximab, a new coloncoscopy was performed showing a rectal ulcerative lesion, corresponding to a large cell Non-Hodgkin's Lymphoma. The patient was successfully treated with RCHOP chemotherapy (Rituximab cyclophosphamide doxorubicin vincristine prednisone). He is currently in disease remission.

There are no evidence-based guidelines about prophylaxis against Pneumocystis jiroveci pneumonia in inflammatory bowel disease. We report a case of P. jiroveci pneumonia in patient with Crohn's disease receiving infliximab and methotrexate. This case emphasizes the importance of considering the possibility of this infection in inflammatory bowel disease patients treated on biological therapy.

Background: Different strains of invasive Escherichia coli (E. coli), isolated from intestinal mucosa of patients, are related to the pathogenesis of inflammatory bowel diseases (IBD). Aim: To evaluate an association between intracellular E. coli and IBD; its clinical characteristics and use of steroids. Material and Methods: Sixty one patients with Crohn's disease and 83 with ulcerative colitis were studied. To determine the intracellular E. coli content, colonoscopy biopsies of these patients and 29 control subjects were processed using the gentamicin protection assay. Differences in the bacterial content between patient groups were evaluated using Mann-Whitney test, while the association between presence of E. coli with endoscopic activity, location/extension and use of corticosteroid as anti-inflammatory treatment were evaluated with Fisher's exact test or Chi-square test. Results: E. coli strains were detected in 36.1, 39.3 and 10.3% of patients with ulcerative colitis, Crohn's disease and controls, respectively. The number of bacteria per biopsy in Crohn's disease and ulcerative colitis was significantly higher than in controls (p < 0.01 between patients and controls). In ulcerative colitis, significant associations were found between the presence of bacteria and disease location and use of corticosteroids. In Crohn's disease, no association was found. Conclusions: IBD are associated with the presence of intracellular E. coli strains in the intestinal mucosa, suggesting an alteration in the microbiota or loss of integrity of the epithelial barrier. The association of intracellular E. coli with clinical features and the use of corticosteroids in ulcerative colitis suggests that different factors could promote colonization or proliferation of these bacteria.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohn’s Disease (CD). However, a significant number of these patients do not respond at all or cease to respond to antibodies against TNF. In this clinical situation, the options include intensification of anti-TNF therapy by either increasing the dose or by shortening the administration interval, the use of a second anti-TNF or medications with a different mechanism of action. Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against α4β1 and α4β7 integrins, is safe and effective in inducing and maintaining remission in active CD patient’s refractory to anti-TNF. In spite of this, Natalizumab use has been limited because of an increased risk of progressive multifocal leukoencephalophaty which results from reactivation of the John Cunningham (JC) virus. However, the presence of antibodies against JC virus in serum can be used to reduce the risk for this complication. We report three patients with Crohn’s disease refractory to treatment with infliximab, who responded successfully to the use of Natalizumab.

Background: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. Aim: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways. Material and Methods: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. Results: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases. Conclusions: This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.

The relationship between Microscopic Colitis and Inflammatory Bowel Disease is unclear. However, when both are diagnosed they seem to be part of a broader spectrum of the same disease, more than just a coincidence. We report a 55 years old woman with Ulcerative Colitis limited to the rectum with complete clinical and endoscopic response to standard treatment and adequate surveillance for 13 years, who abandoned treatment and control. After eight years, she consulted for mild-to-moderate non-bloody diarrhea lasting several months. Colonoscopy and basic laboratory did not show any alterations. Nevertheless, random biopsies had a characteristically pattern compatible with Lymphocytic Colitis. After the first week of treatment with budesonide the patient was asymptomatic and still in clinical remission, with negative fecal calprotectin at 6 months’ follow-up.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with medical and psychological complications. Addressing psychosocial aspects of treatment, such as quality of care and disability remains a challenge. The quality of care for IBD patients is not optimal at the present time and there is a variation in the care provided by specialists. Therefore, it is necessary to develop well defined quality indicators to assure the delivery of an adequate care to these patients. The delivery of healthcare for IBD patients is often complex and requires multidisciplinary teams. The ultimate objectives in the treatment of IBD should be to prevent bowel damage, reduce long-term disability and maintain a normal quality of life.

Background: The chronic inflammation of the intestinal mucosa, the extra-intestinal manifestations of the disease and the immunosuppressive treatment of inflammatory bowel disease may increase cancer risk. Aim: To report the demographic and clinical features of patients with IBD who developed a malignant tumor. Material and Methods: Retrospective analysis of an IBD patient registry of a private clinic, diagnosed between 1976 and 2014. Results: 437 subjects were included, aged 15-88 years (58% women). Seventy two percent of patients had ulcerative colitis. The median time of follow up was 6 years. Ten patients (2.3%) developed a malignant tumor. In four, the tumor could be related to IBD (two colorectal cancers, one cholangiocarcinoma and one chronic myeloid leukemia (CML)). Two of 45 patients treated with biological therapy developed a tumor (CML and hypernephroma). Three of 170 patients on immunosuppressive treatment developed tumors. Only one had a tumor possibly related with the use of azathioprine (non-melanoma skin cancer). In only two patients, the treatment was changed at the time of their cancer diagnosis, from immunosuppressive medications to mesalamine. Conclusions: Only a small proportion of these patients with IBD developed a malignant tumor. The treatment of IBD has to be determined by the severity of the disease and not by the fear of developing a neoplasia. Following recommendations is fundamental to decrease the possibility of developing this complication.