Tailoring freshwater diets towards boosted immunity and pancreas disease infection robustness in Atlantic salmon post smolts.

The aim of the current study was to investigate how freshwater diets impact on immunity in Atlantic salmon smolts in freshwater, during transfer to seawater and in post smolts during the seawater stage with and without pancreas disease (PD) infection. Three specific freshwater diets were prepared: (i) A diet similar in composition to commercial salmon freshwater diets (Standard diet); (ii) A diet composed of vegetable oils (rapeseed, palm and linseed oils) mimicking the fat composition in aquatic insects - the natural diet of wild salmon in freshwater (Fatty acid diet); (iii) A diet enriched with possible immune modulating amino acids including dl-methionine, l-lysine, l-threonine and taurine (Amino acid diet). After seawater transfer, all fish were fed the same commercial diet. Head kidneys were extracted, and their leukocytes isolated from smolts right before transfer to seawater, from post smolts one and six weeks after transfer to seawater, and from post smolts in seawater after 8 weeks of ongoing PD infection. In addition, to provoke bacterial or virus induced inflammation in vitro, the individual leukocyte suspension from all fish were stimulated by lipopolysaccharide (LPS) or polyinosinic acid: polycytidylic acid (PIC). The transfer of smolts from fresh-to seawater changed the transcription of several types of genes. Particularly in isolates from fish fed the Standard or Fatty acid diet in freshwater, overall gene transcription (IL-1ß, CD83, INF-γ, cox2, cd36, MGAT2, catalase) declined. However, the Amino acid diet stimulated the LPS induced gene transcription of IL-1ß, CD83, Cox2, and INF-γ at this stage. In freshwater smolts, PIC stimulated leukocytes showed higher transcription level of Mx and viperin in the Fatty acid and Amino acid diet groups compared to the Standard diet group. In seawater post smolts, Mx and viperin responded similarly to PIC challenge in all diet groups. Furthermore, leukocytes isolated from PD infected fish, continued responding to PIC, regardless of freshwater diet.

Characterization of Oral Microbiome and Exploration of Potential Biomarkers in Patients with Pancreatic Cancer.

Pancreatic cancer (PC) is highly malignant and lacks an effective therapeutic schedule, hence that early diagnosis is of great importance to achieve a good prognosis. Oral bacteria have been proved to be associated with pancreatic cancer, but the specific mechanism has not been comprehensively illustrated. In our study, thirty-seven saliva samples in total were collected with ten from PC patients, seventeen from benign pancreatic disease (BPD) patients, and ten from healthy controls (HC). The oral bacterial community of HC, PC, and BPD groups was profiled by 16S rDNA high-throughput sequencing and bioinformatic methods. As shown by Simpson, Inverse Simpson, Shannon and Heip, oral microbiome diversity of HC, BPD and PC groups is in increasing order with the BPD and PC groups significantly higher than the HC group. Principal coordinate analysis (PCoA) suggested that grouping by PC, BPD and HC was statistically significant. The linear discriminant analysis effect size (LEfSe) identified high concentrations of Fusobacterium periodonticum and low concentrations of Neisseria mucosa as specific risk factors for PC. Furthermore, predicted functions showed changes such as RNA processing and modification as well as the pathway of NOD-like receptor signaling occurred in both PC and HC groups. Conclusively, our findings have confirmed the destruction of oral bacterial community balance among patients with PC and BPD and indicated the potential of Fusobacterium periodonticum and Neisseria mucosa as diagnostic biomarkers of PC.

Quantitative diffusion-weighted magnetic resonance imaging for prediction of early infection in pancreatic collections: Results of a pilot study.

BACKGROUND/AIMS: The development of infection in pancreatitis increases the mortality rate up to 32%. Therefore, it is important to identify patients who are at high risk of developing infection, at an early stage. The objectives of the study were (a) to analyze the quantitative parameters of diffusion-weighted magnetic resonance imaging (DW-MRI) and apparent diffusion coefficient (ADC) in infected as well as sterile pancreatic collections (b) to establish "cut-off" values for ADC that can identify infected pancreatic collections. MATERIALS AND METHODS: Prospective observational study of pancreatitis cases who underwent DW-MRI from August 2018 to July 2019 were enrolled in the study. The collections were analyzed for diffusion restriction. The average of the three ADC values from the wall and center of collection was noted. RESULTS: Infected collections were seen in 7 and sterile collections observed in 11 cases. The optimal cut-off ADC value to differentiate sterile and infected collection in our study was 1.651 × 10-3 mm2/s (sensitivity of 81.8%; specificity of 100.0%). ROC curve for mean ADC from the wall showed a significant diagnostic accuracy with AUC: 0.91; 95% CI: 0.77-1.0 (P = 0.004). CONCLUSION: DW-MRI is a reliable noninvasive technique to differentiate sterile and infected pancreatic collections. ADC values from the periphery of the collection can predict infected pancreatic collections at an early stage. DW-MRI should not be considered as a substitute for aspiration cytology in patients with septic symptoms and absent diffusion restriction on MRI.

Nonalcoholic Fatty Pancreas Disease: Clinical Consequences.

Metabolic syndrome and its components such as obesity, hypertriglyceridemia, type-2 diabetes mellitus (DM-T2), and arterial hypertension are unequivocally serious problems for every society. This is especially true in economically developed countries where the imbalance in lifestyle between caloric intake and caloric output still gets greater and greater. This fact is not only a concern for the adult population but for children as well. However, metabolic syndrome does not only affect society and health in regards to cardiovascular diseases, it significantly concerns gastroenterology where it is classified as nonalcoholic fatty pancreas disease (NAFPD). The data gained from several trials show that the prevalence of NAFDP is 33% (95% CI 24-41%). When it comes to the diagnostic procedures concerning the presence of pancreatic fat, a whole spectrum of suitable methods are recommended. Probably, the most exact method is the use of magnetic resonance imaging. However, for common clinical practice, the abdominal sonographic examination based on the comparison of the pancreatic parenchymatous echogenity versus renal or hepatic echogenity is used. The clinical consequences of pancreatic steatosis and steatopancreatitis are significant. These diseases are connected with DM-T2 and insulin resistance. In recent years, changes of exocrine pancreatic function, particularly its decrease, have also been described. It is known that there is a close correlation between NAFPD and nonalcoholic hepatic steatosis and also with the increased thickness of aortic intima-media. There is also an important relationship between NAFPD and pancreatic carcinoma. Pancreatic steatosis, and especially its NAFPD form, is a serious state which can be treatable by the possible effective management of metabolic syndrome parameters, including obesity.

Pancreatic tuberculosis in immunocompetent patients. At the University Hospital in Kingdom of Saudi Arabia.

OBJECTIVES: To raise awareness of practitioners on benign treatable conditions such as pancreatic tuberculosis (TB). Methods: A retrospective study at King Khaled University Hospital, Riyadh, Saudi Arabia of all patient charts presented with pancreatic mass for a period of 10 years (2007-2017) with a study duration of 4 years between 2013 and 2017. Patients with confirmed diagnosis of pancreatic cancer were excluded. A written ethical approval was obtained accordingly. Results: All adult patient charts were retrospectively reviewed with a pancreatic mass for a period of 10 years (2007-2017). Nine patients were identified with proven diagnosis of TB. The data were obtained based on demographic features, sign and symptoms, duration of illness, imaging, ultrasound, contrast enhanced computed tomography scan, cytology or histopathology, polymerase chain reaction, culture and follow up with anti-tuberculous therapy and samples for cytology or histology. The histological findings of granuloma with caseation or positive culture were used confirming the diagnosis of TB. All patients were immunocompetent and screened for human immunodeficiency viruses before starting anti-TB treatment. Results were negative. All patients who underwent fine needle aspiration (FNA) and endoscopic ultrasound (EUS) for suspicious pancreatic mass were provided trial of antibiotics as cases of pancreatic tuberculosis showed dramatic improvement during follow up and cured from the disease. Conclusion: The EUS and FNA are good tools to confirm malignancy and rule out benign treatable conditions like TB for any patient with a pancreatic mass suspicious for carcinoma.

[Diagnosis and treatment of pancreatic tuberculosis: experiences of 10 cases].

Objectives: To study the clinical characteristics of pancreatic tuberculosis, and therefore to improve the diagnosis and treatment of this disease. Methods: The clinical data of 10 patients with pancreatic tuberculosis form 1990 to 2017 were reviewed, including clinical characteristics, laboratory tests and imaging features. Results: The ten patients aged 28 to 71 (median 56) years. All of them presented varying degrees of abdominal pain and weight loss (3 to 8 kg). Hypo-echoic pancreatic masses were shown by abdominal ultra-sound in 7 cases, and cystic-solid masses with thick wall was shown by abdominal CT scan in 4 cases, but dilatation of the pancreatic duct was found in none of the 10 cases. Hemoglobin levels lower than 12 g/L were found in 6 cases, and ESR more than 20 mm/1 h was present in 7 cases. Four cases received PPD test, but only one was positive. CA19-9 was found to be higher than normal (27 IU/ml) in 3 cases (39.2 IU/ml, 125.7 IU/ml, 88.9 IU/ml respectively). Three cases received T-spot.TB tests, and all the results were positive. Seven cases received laparotomy, and the other 3 received endoscopic ultrasound-guided biopsy. Caseous necrosis and Langerhans cells were found in all the 10 cases. Nine patients were treated by 6 to 12 months' anti-tuberculosis therapies, and at 1-5 years' follow-up, 8 were cured and 1 improved. Conclusions: The manifestations of pancreatic tuberculosis were easy to be confused with other diseases, and therefore a comprehensive understanding of history and careful examinations were important for a correct diagnosis. Once the diagnosis was made, prompt standard anti-tuberculosis therapy could lead to a favorable outcome.

The Gut Microbiome in Pancreatic Disease.

The gut microbiome increasingly is recognized for its role in human health and disease. Initial evidence has indicated that gut microbial dysbiosis is associated with several pancreatic diseases. Although it is not known if these associations are causative, gut dysbiosis is hypothesized to mediate chronic proinflammatory changes in the pancreas. Further mechanistic and epidemiologic studies of the microbiome are needed. Ultimately, targeted modulation of the microbiota could have therapeutic value.

Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders.

Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders.

The potential role of gut microbiota in pancreatic disease: A systematic review.

BACKGROUND: Several studies have suggested a link between microbiota imbalance and some gastrointestinal, inflammatory and neoplastic diseases. However, the role in pancreatic diseases remain unclear. To evaluate the available evidence for pancreatic diseases, we undertook a systematic review. METHODS: OVID Medline (1946-2017), EMBASE (1980-2017) and the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2017) were searched for studies on microbiota in pancreatic disease. We also searched the reference lists of retrieved papers, and conference proceedings. We excluded animal studies, reviews, and case reports. RESULTS: A total of 2833 articles were retrieved. After screening and applying the exclusion criteria, 10 studies were included. Three studies showed lower levels of Bifidobacterium or Lactobacillus and higher levels of Enterobacteriaceae in chronic pancreatitis. Two of these studies were uncontrolled, and the third (controlled) study which compared patients with endocrine and exocrine insufficiency, reported that Bacteroidetes levels were lower in those patients without diabetes, while Bifidobacteria levels were higher in those without exocrine insufficiency. Only one study investigated acute pancreatitis, showing higher levels of Enterococcus and lower levels of Bifidobacterium versus healthy participants. There was an overall association between pancreatic cancer and lower levels of Neisseria elongate, Streptococcus mitis and higher levels of Porphyromonas gingivalis and Granulicatella adiacens. CONCLUSIONS: Current evidence suggests a possible link between microbiota imbalance and pancreatic cancer. Regarding acute and chronic pancreatitis, data are scarce, dysbiosis appears to be present in both conditions. However, further investigation is required to confirm these findings and to explore therapeutic possibilities.

Pancreatic Abscess in a cat due to Staphylococcus aureus infection.

A 16-year-old spayed female American Shorthair cat was presented with lethargy, anorexia, and wamble. Physical and blood examination did not reveal any remarkable findings. Abdominal ultrasonography identified the presence of a localized anechoic structure with a thick wall in contact with the small intestine and adjacent to the liver. Ultrasound-guided fine-needle aspiration of the structure revealed fluid containing numerous cocci and neutrophils. Two days after antibiotic treatment, exploratory laparotomy was performed and the content of the structure was removed before multiple lavages. The pathological and bacteriological examination results supported a confirmatory diagnosis of pancreatic abscess due to Staphylococcus aureus infection, making this the first such report in a cat. The cat remained healthy thereafter with no disease recurrence.

Gut microbiota and pancreatic diseases.

Changes in diet, lifestyle, and exposure to environmental risk factors account for the increased incidence of pancreatic disorders, including acute and chronic pancreatitis, and pancreatic cancer. The role of the microbiota in the development of pancreatic disorders is increasingly acknowledged. The translocation of gut bacteria and endotoxins following gut barrier failure is a key event contributing to the severity of acute pancreatitis, while small intestine bacterial overgrowth is common in patients with chronic pancreatitis and further worsens their symptoms and malnutrition. Specific molecular mimicry link the microbiota and Helicobacter pylori with autoimmune pancreatitis. Changes in the oral microbiota typical of periodontitis seem to be associated with an increased risk of developing pancreatic cancer. The composition of the gut microbiota is also unbalanced in the presence of risk factors for pancreatic cancer, such as obesity, smoking and diabetes. Helicobacter pylori infection, atrophic body gastritis and related decreased gastric acid secretion also seem associated with the risk of pancreatic cancer, although this area needs further research. The link between dysbiosis, immune response and proinflammatory status is most likely the key for these associations. The present review article will discuss current available evidence on the role of gut microbiota in pancreatic disorders, highlighting potential areas for future research.

[A CASE OF PULMONARY TUBERCULOSIS WITH PANCREATIC LESION].

A 52-year-old woman was referred to our hospital presenting with epigastric pain and weight loss. A contrast- enhanced abdominal computed tomography (CT) scan showed a low-density mass in the body of the pancreas, indicative of a malignancy. Endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass was performed three times and showed no specific findings. A distal pancreatectomy was performed, and a pathological examination revealed epitheli- oid cell granulomas and necrosis. Ziehl-Neelsen staining did not reveal acid-fast bacilli in the pancreatic mass. A diagnosis of tuberculosis or sarcoidosis of the pancreas was con- sidered; however, the patient chose to undergo a follow-up examination without therapeutic intervention because the pancreatic mass had been removed completely and she had recovered well. Four months after the operation, the patient was readmitted to our hospital for insulin therapy for pancreatic diabetes. She presented with a fever and a productive cough, and a chest CT scan showed multiple nodules in both upper lobes. A bronchoscopy was performed and bronchoalveolar lavage fluid cultures for Mycobacterium tuberculosis were positive. The patient received antitubercular quadri-therapy and showed symptomatic and radiologic improvement. At the initial examination, we had been unable to establish the correct diagnosis; however, the detection of pulmonary lesions led to the time-delayed diagnosis of pancreatic tuber- culosis. Owing to its rarity, it is difficult to diagnose pancreatic tuberculosis using clinical symptoms and radiological imaging modalities; thus, pathologic and bacteriologic confirmation is essential. To avoid performing an unnecessary laparotomy in patients with pancreatic tuberculosis, increased vigilance and an accurate diagnostic approach are required.

Pancreatic hyperenzymemia is associated with bacterial culture positivity, more severe and right-sided colitis.

BACKGROUND/AIM: Several studies reported pancreatic hyperenzymemia (PHE) related to acute colitis. However, there is no consensus on its clinical significance. This study was addressed to find the clinical significance of PHE in acute colitis. METHODS: Pancreatic hyperenzymemia was defined as abnormal increase in serum concentrations of the pancreatic enzymes by three times of normal upper range without definite pancreatic symptoms and evidence of pancreatitis at abdominal CT imaging of pancreatic disease. And clinical and laboratory and biologic parameters of PHE group and normal pancreatic enzymemia (NPE) group were compared. RESULTS: A total of 1,069 patients admitted to hospitals due to acute colitis were analyzed. Of these patients, 2.99 % (32/1,069) showed PHE. PHE group showed more severe symptoms and had longer hospital stays than the NPE group (12.15 vs. 4.59 days; P < 0.001). Multivariable analysis showed that right-sided colitis (OR 2.846; 95 % CI 1.122-7.224; P = 0.028) and culture positivity (OR 3.346; 95 % CI 1.119-10.008; P = 0.031) are associated with PHE during acute colitis. Also, PHE group was more common when a microorganism could be identified in the cultures (28.1 vs. 7.0 %; P = 0.003), especially blood culture. Among patients with positive cultures, Salmonella spp. had a positive correlation with the right-sided colitis and PHE (amylase P = 0.002; lipase P = 0.029), Salmonella serovar typhimurium (group B) was especially related to increased serum lipase but not to increased serum amylase (lipase; P = 0.041: amylase; P = 0.485). CONCLUSION: Pancreatic hyperenzymemia is associated with right-sided colitis, bacterial culture positivity, and severe acute colitis.

Infantile splenorenopancreatic mucormycosis complicating neuroblastoma.

Herein is described the first case of an infant with neuroblastoma who developed isolated splenorenopancreatic mucormycosis. An 18-month-old boy with neuroblastoma who was on intensive chemotherapy was admitted with febrile neutropenia. On abdominal computed tomography, multiple hypodense lesions in the spleen with invasion to the upper pole of the left kidney were demonstrated. Enlargement of splenic lesions with a complete hypoechoic pattern replacing the whole spleen, consistent with splenic abscess were observed on serial ultrasound. On splenectomy the resected spleen appeared to be severely fragmented and necrotic. On pathology, massive infiltration of broad, non-septate hyphal fragments identified as Mucor with invasion to all blood vessels was seen. Histologically, a piece of the tail of the pancreas also showed involvement by the filamentous Mucor. The present case highlights the necessity of high index of suspicion in susceptible patients, early diagnosis and appropriate management in order to minimize the mortality rate.

Enterohepatic Helicobacter other than Helicobacter pylori.

The Helicobacter genus includes Gram negative bacteria which were originally considered to belong to the Campylobacter genus. They have been classified in a separate genus since 1989 because they have different biochemical characteristics, with more than 24 species having been identified and more still being studied.H. pylori is the best known. It has an important etiopathogenic role in peptic ulcer disease and gastric cancer. Enterohepatic Helicobacters (EHH) other than H. pylori colonize the bowel, biliary tree and liver of animals and human beings with pathogenic potential. The difficulties existing to correctly isolate these microorganisms limit the description of their true prevalence and of the diseases they cause. Many studies have tried to discover the different clinical implications of EHH. Diseases like chronic liver disease, autoimmune hepatitis, hepatocarcinoma, autoimmune hepatobiliary disease, biliary lithiasis, cholangiocarcinoma and gallbladder cancer, Meckel´s diverticulum, acute appendicitis and inflammatory bowel disease have been related with different EHH species with different results, although their prevalence is greater than in healthy subjects. However, these data are currently not sufficient to draw definitive conclusions. Finally, the best known role of EHH in bowel disease is production of acute and chronic diarrhea pictures initially referred to as Campylobacter. H. pullorum has been identified in patients with acute gastroenteritis. The correct identification of EHH as producers of infectious gastroenteritis is found in its antibiotic susceptibility. It is generally macrolide-susceptible and quinolone-resistant.