Multidisciplinary consensus statement on the clinical management of patients with pancreatic cancer.

Pancreatic cancer (PC) remains one of the most aggressive tumors with an increasing incidence rate and reduced survival. Although surgical resection is the only potentially curative treatment for PC, only 15-20% of patients are resectable at diagnosis. To select the most appropriate treatment and thus improve outcomes, the diagnostic and therapeutic strategy for each patient with PC should be discussed within a multidisciplinary expert team. Clinical decision-making should be evidence-based, considering the staging of the tumor, the performance status and preferences of the patient. The aim of this guideline is to provide practical and evidence-based recommendations for the management of PC.

Platypnea-orthodeoxia syndrome: Importance of patient position for correct diagnosis at the time of (99m)Tc-MAA injection.

A 65-year-old male presented with unexplained hypoxia that became exacerbated by an upright posture (platypnea-orthodeoxia syndrome) secondary to hepatopulmonary syndrome (HPS). A (99m)Tc-macroaggregated albumin pulmonary perfusion scan revealed a right to left shunt of 29% in the sitting position, which had not been previously detected when the radiotracer injection was performed with the patient in supine position, nor was it diagnosed using another non-invasive imaging method (transthoracic contrast echocardiography and angio-CT). A transesophageal echocardiography was contraindicated due to the presence of esophageal varices. The administration of the radiopharmaceutical in sitting position for the study of the pulmonary perfusion allowed us to confirm the presence of the shunt and consider the patient a candidate for liver transplantation.

A Spanish multicenter study to estimate the prevalence and incidence of chronic pancreatitis and its complications.

BACKGROUND AND OBJECTIVE: No nation-wide epidemiological study on the incidence and prevalence of chronic pancreatitis (CP) had been thus far carried out in Spain. Our goal is to estimate the prevalence and incidence of CP, as well as to determine the diagnostic and therapeutic criteria used in Spanish pancreas units. METHODS: An observational, descriptive study of hospital pancreas units in Spain. CP-related epidemiology, etiology, manifestations, diagnostic tests, functional complications, and treatments were all assessed using a structured questionnaire. Overall results were estimated by weighting cases in each site. RESULTS: Information was collected from six pancreas units with a sample frame of 1,900,751 inhabitants. Overall prevalence was 49.3 cases per 105 population (95 % CI, 46 to 52) and incidence was 5.5 cases per 105 inhabitant-years (95 % CI, 5.4 to 5.6). Most common etiologies included tobacco and alcoholism, which were associated with three in every four cases. The most prevalent symptoms were recurring pain (48.8 %) and chronic abdominal pain (30.6 %). The most widely used diagnostic method was echoendoscopy (79.8 %), CT (computerized tomography) (58.7 %), and MRI (magnetic resonance imaging)/MRCP (magnetic resonance cholangiopancreatography) (55.9 %). Most prevalent morphologic findings included calcifications (35 %) and pseudocysts (27 %). Exocrine (38.8 %) and endocrine (35.2 %) pancreatic insufficiency had both a similar frequency. Treatments used were rather heterogeneous among sites, with enzyme replacement therapy (40.7 %) and insulin (30.9 %) being most commonly used. CONCLUSIONS: Pancreas units amass a significant number of both prevalent and incident CP cases. Patients seen in these units share a similar typology, and differences between units are greater regarding diagnostic and therapeutic strategies.

Early and/or immediately full caloric diet versus standard refeeding in mild acute pancreatitis: a randomized open-label trial.

UNLABELLED: Refeeding after acute pancreatitis (AP) is traditionally started in a successively increasing manner when abdominal pain is absent and pancreatic enzymes are decreasing. We aimed to evaluate length of hospital stay (LOHS) and refeeding tolerance for early refeeding and/or immediately full caloric intake in patients recovering from AP. METHODS: In this randomized, open-label trial, patients with AP were randomized into four different refeeding protocols. Group 1 and 2 received a stepwise increasing diet during three days while 3 and 4 received an immediately full caloric, low fat diet. Group 2 and 4 started refeeding early (once bowel sounds returned) and 1 and 3 started at standard time (bowel sounds present, no abdominal pain, no fever, leucocytes and pancreatic enzymes decreasing). Main outcomes measurements were LOHS and tolerance (ability to ingest >50% of meals without severe pain, nausea or AP relapse). RESULTS: Eighty patients were evaluated and 72 randomized (median age 60 years, range 24-85, 33 male). LOHS was significantly reduced after early refeeding (median 5 versus 7 days (p = 0.001)) but not in patients receiving immediately full caloric diet, compared to standard management (6 versus 6 days (p = 0.12)). There was no difference in refeeding tolerance comparing immediately full caloric diet versus stepwise increasing diet (31/35 (89%) versus 33/37 (89%) patients tolerating the treatment, p = 1.00) or early versus standard time for refeeding (33/37 (89%) versus 31/35 (89%), (p = 1.00)). CONCLUSIONS: Refeeding after AP when bowel sounds are present with immediately full caloric diet is safe and well tolerated. Early refeeding shortens LOHS.

Psychological factors are associated with changes in the health-related quality of life in inflammatory bowel disease.

BACKGROUND: The effect of different sociodemographic and clinical variables on the health-related quality of life (HRQOL) of patients with inflammatory bowel disease (IBD) is currently known, but the influence of psychological factors has not been sufficiently explored. The objective of this study was to identify psychological predictors of HRQOL in patients with IBD. METHODS: A cross-sectional prospective study was undertaken including 875 consecutive IBD patients. Independent variables were measured using a sociodemographic and clinical questionnaire, the Hospital Anxiety and Depression Scale (HADS) questionnaire, the Perceived Stress Scale (PSS) questionnaire, and the COPE questionnaire. Dependent variables were measured using the Short Form 36 Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ-36). Logistic regression was performed to identify factors associated with HRQOL. RESULTS: The participation rate was 91.3%. Patients with IBD had a poorer HRQOL than the general population except on the Physical Function, Social Function, and Emotional Function Scale. Moreover, high levels of anxiety, depression, and stress were found to be associated with low levels in all quality of life measurements. No significant relationship was found between HRQOL and coping strategies. CONCLUSIONS: In patients with IBD, stress, anxiety and depression are important determinants of HRQOL and should therefore be considered in the management of this patient population.

The role of high fat diet in the development of complications of chronic pancreatitis.

BACKGROUND: Little is known about risk factors for complications in chronic pancreatitis (CP). High fat diet (HFD) has been demonstrated to aggravate pancreatic injury in animal models. The aim of this study was to investigate the role of HFD in age at diagnosis of CP and probability of CP related complications. METHODS: A cross-sectional case-case study was performed within a prospectively collected cohort of patients with CP. Diagnosis and morphological severity of CP was established by endoscopic ultrasound. Pancreatic exocrine insufficiency (PEI) was diagnosed by ¹³C mixed triglyceride breath test. Fat intake was assessed by a specific nutritional questionnaire. Odds ratios (OR) for CP related complications were estimated by multivariate logistic regression analysis. RESULTS: 168 patients were included (128 (76.2%) men, mean age 44 years (SD 13.5)). Etiology of CP was alcohol abuse in 89 patients (53.0%), other causes in 30 (17.9%) and idiopathic in the remaining 49 subjects (29.2%). 24 patients (14.3%) had a HFD. 68 patients (40.5%) had continuous abdominal pain, 39 (23.2%) PEI and 43 (25.7%) morphologically severe CP. HFD was associated with an increased probability for continuous abdominal pain (OR = 2.84 (95% CI, 1.06-7.61)), and a younger age at diagnosis (37.0 ± 13.9 versus 45.8 ± 13.0 years, p = 0.03) but not with CP related complications after adjusting for sex, years of follow-up, alcohol and tobacco consumption, etiology and body mass index. CONCLUSIONS: Compared with a normal fat diet, HFD is associated with a younger age at diagnosis of CP and continuous abdominal pain, but not with severity and complications of the disease.

The actual management of early pancreatic cancer.

Pancreatic cancer (PC) is a highly lethal disease. Early diagnosis remains the only possibility nowadays for an intention to cure the disease, since prognosis of PC is significantly better in patients diagnosed of small (<2 cm), well differentiated, stages I and II pancreatic tumors. However, the best approach would be to detect precursor lesions, like Intraductal papillary mucinous neoplasm (IPMN) or PanIN lesions. In this setting the best technique to diagnose either small PC and/or IPMN and PanIN lesions is clearly endoscopic ultrasound. However, detection of these lesions is very difficult, hampered by the absence of clinical manifestations of PC at these early stages. The implementation of screening programs, which - given the incidence of PC - is not cost effective for the general population, in high-risk individuals, may lead to increase the detection of PC an early stages as well as precursor lesion. When focusing on treatment, PC patients are best cared by multidisciplinary teams. For patients with resectable disease surgery remains the treatment of choice, followed by postoperative treatment. When precursor lesions are detected, mainly IPMN, treatment should be individualized, following latest international guidelines.

Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

BACKGROUND AND AIMS: Clarification of the position of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the interventional options available for treating patients with chronic pancreatitis. METHODS: Systematic literature search to answer explicit key questions with levels of evidence serving to determine recommendation grades. The ESGE funded development of the Guideline. SUMMARY OF SELECTED RECOMMENDATIONS: For treating painful uncomplicated chronic pancreatitis, the ESGE recommends extracorporeal shockwave lithotripsy/endoscopic retrograde cholangiopancreatography as the first-line interventional option. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team. Surgical options should be considered, in particular in patients with a predicted poor outcome following endoscopic therapy (Recommendation grade B). For treating chronic pancreatitis associated with radiopaque stones ≥ 5 mm that obstruct the main pancreatic duct, the ESGE recommends extracorporeal shockwave lithotripsy as a first step, combined or not with endoscopic extraction of stone fragments depending on the expertise of the center (Recommendation grade B). For treating chronic pancreatitis associated with a dominant stricture of the main pancreatic duct, the ESGE recommends inserting a single 10-Fr plastic stent, with stent exchange planned within 1 year (Recommendation grade C). In patients with ductal strictures persisting after 12 months of single plastic stenting, the ESGE recommends that available options (e. g., endoscopic placement of multiple pancreatic stents, surgery) be discussed in a multidisciplinary team (Recommendation grade D).For treating uncomplicated chronic pancreatic pseudocysts that are within endoscopic reach, the ESGE recommends endoscopic drainage as a first-line therapy (Recommendation grade A).For treating chronic pancreatitis-related biliary strictures, the choice between endoscopic and surgical therapy should rely on local expertise, patient co-morbidities and expected patient compliance with repeat endoscopic procedures (Recommendation grade D). If endoscopy is elected, the ESGE recommends temporary placement of multiple, side-by-side, plastic biliary stents (Recommendation grade A).

Emigration to western industrialized countries: A risk factor for developing inflammatory bowel disease.

BACKGROUND: A higher incidence of inflammatory bowel disease (IBD) in industrialized areas has been previously reported, but the effect of emigrating to western industrialized countries for a period of time and returning to the country of origin is unknown. Aim of the study was to evaluate the effect of emigrating to another country and returning to the place of origin on the risk of IBD. METHODS: A prospective case-control study was performed. Inclusion criteria were all patients >18 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) in the last 10 years. Healthy, unrelated controls, matched by sex, age and smoking habits, with no family history of IBD were included. All patients and controls were interviewed and emigration was defined as living for at least one year in another country. RESULTS: 242 consecutive patients with IBD (105 CD and 137 UC) and 242 controls were included. Patients who had previously emigrated developed more frequently IBD than controls (OR 1.93, 95%CI 1.19-3.15, p<0.01). Patients who emigrated to European countries developed more frequently IBD than controls (OR 1.91, 95%CI 1.07-3.47, p=0.02), but not those who had emigrated to Latin America (OR 1.48, 95%CI 0.67-3.27, p=0.32). Emigration plays a significant role in the development of UC (OR 2.24, 95%CI:1.29-3.88, p<0.01), but not in CD (OR 1.56, 95%IC:0.83-2.92, p=0.15). CONCLUSIONS: People who emigrate to westernised countries have a higher risk for developing IBD, especially UC. Environmental factors related with industrialization seem to play an important role in the pathogenesis of these diseases.

Percutaneous endoscopic suturing is an alternative treatment for persistent gastrocutaneous post-PEG fistula.

Persistent gastrocutaneous fistula after the removal of a gastrostomy tube is an unusual complication associated with percutaneous endoscopic gastrostomy (PEG). Surgical closure has been usually the treatment of choice. Several endoscopic methods have been previously attempted to close the fistula, usually with poor results. We report a successful case of percutaneous endoscopic suturing of a persistent gastrocutaneous post-PEG fistula, using a monofilament absorbable suture. A biopsy forceps was used to deepithelialize both ends of the fistulous tract to promote granulation tissue formation. The gastrocutaneous fistula closed completely after the procedure and there were no complications during the follow-up.

Early diagnosis of pancreatic cancer, time to screen high-risk individuals?

Pancreatic cancer (PC) is considered as one of the malignant tumors with poorest survival rate (less than 5% 5-year survival). Despite new developments in imaging techniques, surgery and oncologic treatments, survival rate remains unchanged. In order to improve the outcome of this disease, it would be of interest the development of a screening program trying to detect small asymptomatic tumors or precursor lesions at the time when the disease is still at a curable stage. Although screening in general population is not feasible nowadays, screening programs in high risk individuals may be of help in this setting. A specific population has been defined to be screened, those with a >10-fold increased risk for developing the disease (inherited PC syndromes due to inherited gene mutations and individuals with a strong family history of PC with at least 2 first-degree relatives affected, but without a known genetic defect). Regarding the methods for screening, endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) appears to be the most accurate, mainly based in their ability to detect those small pancreatic tumors and precursor lesions (like IPMN and PanIN lesions). In these patients screening should start at the age of 45, or 15 years earlier than the earliest occurrence of PC in the family, whichever is the earlier age. Explorations should be schedule every 1 to 3 years, depending on initial findings.

Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency: when is it indicated, what is the goal and how to do it?

Pancreatic exocrine insufficiency with steatorrhea is a major consequence of pancreatic diseases (e.g. chronic pancreatitis, cystic fibrosis, severe acute necrotizing pancreatitis, pancreatic cancer), extrapancreatic diseases like celiac disease and Crohn's disease, and gastrointestinal and pancreatic surgical resections. Recognition of this entity is highly relevant to avoid malnutrition-related morbidity and mortality. Therapy of pancreatic exocrine insufficiency is based on the oral administration of pancreatic enzymes aiming at providing the duodenal lumen with sufficient amount of active lipase at the time of gastric emptying of nutrients. Administration of enzymes in form of enteric-coated minimicrospheres avoids acid-mediated lipase inactivation and ensures gastric emptying of enzymes in parallel with nutrients. Despite that, factors like an acidic intestinal pH and bacterial overgrowth may prevent normalization of fat digestion even in compliant patients. The present article critically reviews current therapeutic approaches to pancreatic exocrine insufficiency.

Health related quality of life in patients with Cohn´s disease in remission.

BACKGROUND: Crohn's disease (CD) affects Health Related Quality of Life (HRQoL) especially in patients with clinical activity but their impact over the disease during periods of remission has not been sufficiently studied. OBJECTIVE: To evaluate HRQoL in CD patients in remission and to identify socio-demographic and clinical factors related. METHODS: We included patients with CD in remission for at least 6 months, defined as a CDAI < 150 and a CRP < 5 mg/L. Socio-demographic and clinical parameters were recorded. HRQoL was evaluated with Short Form 36 Questionnaire (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Results were analyzed using multiple regressions with a confidence interval of 95%. RESULTS: Nine two patients (X = 37 +- 11.4 years, 52.2% men) were consecutively included. Two patients failed to fill correctly the questionnaire and were excluded. Scores on the SF-36 were lower than in the general population of similar age and sex. The most affected dimension in the SF-36 was General Health (47.98 +- 19.58) and the IBDQ Systemic Symptoms (5.15 +- 1.27). Age, colonic location and previous surgery was related with worse HRQoL, while higher educational status, more time since diagnosis, steroid-resistance and inflammatory behavior, was associated with better HRQoL. CONCLUSIONS: Despite being in remission, CD patients had affected their HRQoL, so we must continue working to achieve improvement in HRQL of these patients during these periods of the disease.

NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn's disease: a preliminary report.

INTRODUCTION: Adalimumab is a recombinant fully-human monoclonal immunoglobulin (IgG1) antibody utilized in the treatment of Crohn's disease. Unfortunately no clinical or genetic markers exist to predict response to anti-tumor necrosis factor-alpha (TNF) therapy. The aim of this study was to evaluate the association between selected genes involved in cytokine regulation and response to adalimumab treatment in Crohn's disease. METHODS: twenty-four patients with Crohn's disease either naïve (n = 8) or had lost response or were unable to tolerate the chimeric anti-TNF antibody infliximab (n=16) were enrolled in the study. Patients were genotyped for main polymorphisms in NOD2, CD14 and TLR4 genes. Response to adalimumab treatment was defined as a decrease of Crohn's disease activity index of at least 100 points or a closure of at least 50% of fistulas in case of fistulizing Crohn's disease. RESULTS: overall, 75% of patients did respond to treatment. However, no statistically significant association was found between any of the genotypes and the response to adalimumab. CONCLUSIONS: In our small study group no association between the studied polymorphisms and response to adalimumab was apparent. Systematic studies to search for genetic markers of response to anti-TNF therapy are necessary.

Calidad de vida en pacientes con enfermedad de Crohn en remisión / No disponible

Introducción: La enfermedad de Crohn (EC) afecta la Calidad de Vida Relacionada con la Salud (CVRS) en las fases de actividad pero el impacto de esta enfermedad en la CVRS durante los períodos de remisión no ha sido suficientemente estudiada. Objetivo: Evaluar la CVRS en pacientes con EC en remisión e identificar los factores sociodemográficos y clínicos relacionados. Métodos: Se incluyeron pacientes adultos con EC en remisión durante al menos 6 meses, definida con un CDAI < 150 y una PCR < 5 mg/l. Se recogieron datos sociodemográficos, clínicos y de CVRS con los cuestionarios Short Form 36 Questionnaire (SF-36) y The Inflammatory Bowel Disease Questionnaire (IBDQ). Los resultados fueron analizados mediante regresión múltiple con un intervalo de confianza del 95%. Resultados: Se incluyeron consecutivamente 92 pacientes (X – = 37 ± 11,4 años; 52,2% varones). 2 pacientes no cumplimentaron adecuadamente los cuestionarios. Las puntuaciones en el SF-36 fueron inferiores a las de la población general de similar edad y sexo. La dimensión más afectada en el SF-36 fue Salud General (47,98 ±19,58) y en el IBDQ Síntomas Sistémicos (5,15 ± 1,27). La mayor edad, la localización colónica y la cirugía previa se relacionaron con una peor CVRS, mientras que mayor nivel de estudios, mayor tiempo desde el diagnóstico, patrón inflamatorio y corticorresistencia se asociaron con una mejor CVRS. Conclusiones: A pesar de encontrarse en período de remisión los pacientes EC presentan afectada su CVRS, por lo que se debe continuar trabajando en la consecución de la mejora en la CVRS de estos enfermos durante esta fase de la enfermedad(AU)

Background: Crohn’s disease (CD) affects Health Related Quality of Life (HRQoL) especially in patients with clinical activity but their impact over the disease during periods of remission has not been sufficiently studied. Objective: To evaluate HRQoL in CD patients in remission and to identify socio-demographic and clinical factors related. Methods: We included patients with CD in remission for at least 6 months, defined as a CDAI < 150 and a CRP < 5 mg/L. Socio-demographic and clinical parameters were recorded. HRQoL was evaluated with Short Form 36 Questionnaire (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Results were analyzed using multiple regressions with a confidence interval of 95%. Results: Nine two patients (X – = 37 ± 11.4 years, 52.2% men) were consecutively included. Two patients failed to fill correctly the questionnaire and were excluded. Scores on the SF-36 were lower than in the general population of similar age and sex. The most affected dimension in the SF-36 was General Health (47.98 ± 19.58) and the IBDQ Systemic Symptoms (5.15 ± 1.27). Age, colonic location and previous surgery was related with worse HRQoL, while higher educational status, more time since diagnosis, steroid-resistance and inflammatory behavior, was associated with better HRQoL. Conclusions: Despite being in remission, CD patients had affected their HRQoL, so we must continue working to achieve improvement in HRQL of these patients during these periods of the disease(AU)