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.

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.

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).

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.

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.

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.

NOD2/CARD15: geographic differences in the Spanish population and clinical applications in Crohn's disease.

Crohn's disease (CD) is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide), though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, at present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.

Gastrointestinal stromal tumors (GISTs) of the colon.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Although they may arise anywhere of GI tract, colonic presentation is infrequent. We report 2 new cases of colonic GISTs localized at descending and sigmoid colon. Endoscopic biopsies were diagnostic for GISTs and no distant metastasis were observed. Both cases underwent resective surgery as the only treatment. No recurrence was observed during the follow-up period. In this clinical note we review the diagnosis, management and therapeutical options in colonic GISTs, according to literature. KIT immunoreactivity is the base for diagnosis. Risk of malignancy is based on the primary tumor diameter and the mitotic count. Anatomic localization is not an independent prognostic factor. Surgery is the standard treatment for localized primary disease and imatinib is indicated if metastatic or unresectable GISTs.

Viral and host factors related with histopathologic activity in patients with chronic hepatitis B and moderate or intermittently elevated alanine aminotransferase levels.

OBJECTIVE: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. PATIENTS AND METHODS: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/ml)] and/or DNA-HBV > 2 x 10³ IU/ml in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS) > 7 and histological lesion indicating treatment, lobular inflammation ≥2 or fibrosis ≥2 according to Scheuer Classification. RESULTS: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p < 0.05). Frequency of advanced lesion indicating treatment was upper in patients with ALT levels > ULN (69.1 vs. 47.1%, p = 0.04). There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNA-HBV > 2 x 10³ IU/ml viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p < 0.05). CONCLUSION: upper frequency of advanced histological lesion in chronic hepatitis B patients with moderate or intermittently elevated ALT levels make recommended liver biopsy, independent of viral load and serological status HBeAg. Other factors like age, gender or genotype can help to indicate biopsy in individual cases.

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.

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.

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.

Psychological impact of Crohn's disease on patients in remission: anxiety and depression risks.

BACKGROUND: the role of anxiety and depression in CD patients in remission has been poorly investigated. OBJECTIVE: the aim of the study was to evaluate the frequency of anxiety and depression symptoms in CD patients in remission, and potential factors influencing the development of these symptoms. METHODS: CD patients older than 18 years in remission for at least 6 months before study entry were included. CD remission was defined as a Crohn s Disease Activity Index (CDAI) < 150 points together with C-reactive protein < 5 mg/L. A demographic questionnaire was filled in, and all patients were clinically classified. The therapy maintaining remission was also recorded. A Hospital Anxiety and Depression scale (HAD) was administered to all patients. Results are shown as OR and 95% CI, and analyzed by logistic regression. RESULTS: 92 consecutive patients were included (48 male, mean age 37 years, range from 18 to 71 years). One patient failed to correctly fill in the questionnaire. Anxiety and depression symptoms were present in 36 (39%) and 22 (24%) patients, respectively. Infliximab therapy was the only factor associated with anxiety (OR = 3.11; 95% CI: 1.03-9.43; p < 0.05). In contrast, the presence of depressive symptoms is less frequent in patients under infliximab therapy (OR = 0.16; 95% CI: 0.02-0.97; p < 0.05). CONCLUSIONS: despite clinical remission, an important number of CD patients present with anxiety or depressive symptoms. Infliximab therapy in CD patients is associated to more anxiety but fewer depressive symptoms. CD patients in remission would probably benefit from psychological support.

Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer.

Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS) appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

Pancreatitis and systemic lupus erythematosus.

Gastrointestinal symptoms in patients with SLE are common, specifically abdominal pain. However, the rate of pancreatic diseases is much lower and does not reach 5% according to published series in Europe and the USA. This association between SLE and pancreatic disease is basically at the expense of episodes of acute pancreatitis. An association with chronic pancreatitis is much more uncommon, and only four articles have been published showing this relationship. Three cases of SLE-associated pancreatitis are described, and disease onset, etiological factors, and clinical progression are analyzed. A review of the literature and a brief discussion about pathophysiological mechanisms and the role of corticosteroids are also included.

Second-generation endoscopic ultrasound elastography in the differential diagnosis of solid pancreatic masses. Pancreatic cancer vs. inflammatory mass in chronic pancreatitis.

Endoscopic ultrasonography (EUS) is considered one of the most accurate methods for the diagnosis and staging of pancreatic tumors. EUS-guided fine-needle aspiration (FNA) allows to increase the diagnostic accuracy of EUS in this setting; however, it is technically demanding (a pathologist is also essential) and is furthermore associated with small, but not insignificant morbidity. EUS pancreatic elastography, by analyzing tissue stiffness, arises as a new and very useful tool for the differential diagnosis of solid pancreatic masses. Elastography provides specific patterns supporting the benign or malignant nature of the disease. However, there is a handicap related to the subjective interpretation of images. Second-generation elastography has been recently developed, and allows a quantitative analysis of tissue stiffness. It is based on the determination of a strain ratio (obtained after comparing the strain value of the mass to a strain value from a control area in the region under study). We present two cases reflecting the usefulness of second-generation elastography in the differential diagnosis between pancreatic adenocarcinoma and an inflammatory mass in the context of chronic pancreatitis. We found significant differences between both masses in the strain ratio values (25.46% in the pancreatic adenocarcinoma vs. 2.35% in the inflammatory mass). Second-generation elastography is a very useful tool for the differential diagnosis of solid pancreatic masses.

Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors.

In the presence of a pancreatic tumor, the main diagnostic problem is to determine the benign o malignant nature of the lesion, and then to evaluate its resectability. A preoperative biopsy was usually rejected based on the fact that negative results do not exclude malignancy, that such biopsy may hamper the possibility of curative surgery because of potential seeding along the biopsy s trajectory, that surgical morbidity and mortality are low, and also because of the high diagnostic sensitivity of the various imaging techniques. Biopsy for solid pancreatic tumors was limited to irresectable tumors, and isolated cases with suspicion of tuberculosis, lymphoma or neuroendocrine tumors. Nowadays the performance of a pancreatic biopsy is becoming essential for the correct management of solid lesions, and is useful not only to establish malignancy, but also for a better knowledge of all kind of pathologies and, thus, for better therapeutic management. In this context, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has proven a safe technique with a low rate of complications and a diagnostic accuracy superior to other procedures, this being considered the method of choice for the study of solid pancreatic lesions. An illustrative example is the case we report in this article -a patient diagnosed of a solid, locally advanced-stage pancreatic tumor with imaging techniques (abdominal ultrasounds and EUS) under EUS-guided FNA; the procedure could establish a final diagnosis of pancreatic fusocellular sarcoma.

[Adult gastric duplication cyst: diagnosis by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)]. / Quiste de duplicación gástrico: diagnóstico por punción-aspiración guiada por ecoendoscopia.

Duplication cysts are rare gastrointestinal congenital abnormalities. They can occur anywhere throughout the gastrointestinal tract, and gastric duplication cysts are most uncommon, representing only 4-8% of all gastrointestinal duplication cysts. Nowadays several theories try to explain the pathogenic mechanisms involved. These cysts are usually diagnosed during early childhood, and very rarely are detected in adults, mostly incidentally due to a lack of symptoms. Close to 50% of gastric cysts are associated with other abnormalities. It is extremely important that a meticulous differential diagnosis is performed regarding other diseases, mainly malignancies with a cystic component. Although extremely uncommon, a malignant transformation of these lesions has been reported, which highlights the importance of a correct diagnosis. Herein we report the case of a duplication cyst in an adult, which was detected by endoscopic ultrasound-guided fine-needle aspiration, recently proposed as the most accurate technique for the identification of these lesions.