Primary biliary cholangitis (PBC) is a slowly progressing, cholestatic, autoimmune liver disease characterized by the presence of extremely specific antimitochondrial (AMAs) and antinuclear antibodies (ANAs) in the patients serum. We also observe higher concentration of alkaline phosphatase, ƴ-glutamylotranspeptidase and bilirubin. AMAs are detectable in about 90% of patients with PBC. PBC-specific ANAs can be used to confirm the diagnosis of PBC, especially in AMA-negative cases. Some of ANAs targets promyelocytic leukemia protein (PML) nuclear body components such as Sp100, PML and Sp140, part of them targets the nuclear envelope (NE) proteins like anti-gp210, anti-p62, anti-LBR. They are present in 30-50% PBC patients,in AMA –negative group at a frequency over 55% . The specificity of all tests for determination of these different autoantibodies are about 95-99%. Particularly antibodies against the nuclear envelope gp210 and p62 have been indicated as significant prognostic markers. We find an association of presence of auto antibodies against nucleoporin p62 with higher concentration of bilirubin and liver fibrosis. Some of recent data suggest that the presence of antinuclear envelope protein antibodies especially anti-gp210 correlate with an unfavorable disease course and more rapid progression. The new potential auto antigens are the kelch-like 12 (KLHL12) proteins and hexokinase 1. The combination of anti-KLHL12 and anti-hexokinase 1 antibodies with other markers can also increase the diagnostic sensitivity on PBC. The very frequent coexistence of different antibodies suggests an autoimmune reaction against multiple nuclear components in some of PBC patients. The ability to detect them expands the diagnostic armamentarium of PBC-specific markers.
Dr Alicja Bauer is a senior lecturer at the Centre of Postgraduate Medical Education in Poland. She gives a lecture for physicians and laboratory workers. She is the scientific director of specialist and practical courses of autoimmune diseases, chronic liver and intestinal diseases. She has been interested in the diagnosis of primary biliary cholangitis (PBC) and cooperate with the Clinic of Gastroenterology and Hepatology, working in the project “Primary biliary cirrhosis (PBC) in Poland – clinical characteristics, analysis of relationships between genetic and molecular variants and disease phenotypes”, which could determine the helpful prognostic factors in PBC.
Upper endoscopy is the method of choice to diagnose gastrointestinal opportunistic diseases and malignancies in HIV-infected patients. In the beginning of highly active antiretroviral therapy (HAART) era, dyspeptic symptoms were very prevalent among HIV+ patients and were the main indication to endoscopy. Gastroduodenal alterations were frequently seen in these patients, mainly gastritis. However, most of the endoscopic lesions in dyspeptic patients under HAART were not related to AIDS, and gastroduodenal opportunistic infections and malignancies were rarely seen. Also, HAART did not seem to play an addictive effect on GI mucosa wounding by the use of antibiotics and/or other drugs. The prevalence of Helicobacter pylori infection was also low in these patients, especially in those with advanced immunodeficiency. It was concluded that most of dyspeptic symptoms were more related to adverse effect of HAART. Dr. Werneck-Silva observed a change in the indications of endoscopy along 22 years of HAART. Instead of dyspeptic symptoms, screening of esophageal varices has become the main indication to endoscopy. This change reflects an improvement in patient’s tolerability to newer HAART regimens and an increase in liver disease that is currently a major cause of morbidity and mortality in HIV+ patients.
Dr. Ana Luiza Werneck-Silva holds PhD degrees in Gastroenterology and in Pathology from the University of São Paulo, Brazil. She works at the University of São Paulo, where she performs endoscopic procedures and teaches the practice of endoscopy to residents. She is the head of the Endoscopy Unit at Casa da AIDS, an outpatient Unit belonging to the University of São Paulo. Dr. Werneck-Silva has had the unique opportunity to observe and collect data on the impact of the HIV, opportunistic diseases, and HAART on the gastrointestinal tract as well as the evolution of the HIV disease in Brazil over the last 22 years.
Helicobacter pylori is a gram negative bacterium that inhabits the gastric mucosa of most people in the world and is considered a preponderant factor in gastric cancer development. Despite the significance of this infection in the carcinogenesis, other factors, like host characteristics, are also important. During H. pylori colonization, some host cytokines seem to be linked to the development of gastric mucosal lesions and in cell malignant transformation. Various host peculiarities, such as the age of the infected patients and polymorphisms in genes that encode cytokines, influence in the profile of cytokines present in the gastric environment. Several studies have demonstrated that the gastric lesions caused by H. pylori infection in childhood tend to be milder than in adulthood. H. pylori-positive children tend to present a regulatory profile of cytokines in gastric mucosa, with higher levels of IL-10 and TGF-β1 when compared to adults. On the other side, infected adults are more likely to present higher concentrations of IL-17 and Th1 cytokines than younger individuals, what contributes to an inflammatory response that might add to the development of gastric lesions, which can lead to gastric carcinogenesis. Furthermore, polymorphisms in genes that encode cytokines such as IL-1β, IL-8, IL-10 and TNF-α have been associated with the severity of gastric mucosa inflammation and carcinogenesis. In conclusion, knowledge about how do these different immune modulations reverberate on neoplastic processes are important to enable a better understanding of the pathophysiology and risk factors related to gastric carcinogenesis.
Fabrício Freire de Melo has completed his PhD and postdoctoral studies from Universidade Federal de Minas Gerais, Brazil. He is professor of medicine and the Research and Extension coordinator from the Multidisciplinary Institute in Health of Universidade Federal da Bahia, Brazil. He has published more than 20 papers in reputed journals and has been serving as an reviewer in 5 journals.
Heterotopic pancreas, or pancreatic tissue found outside the normal location of the pancreas, is a rare and usually asymptomatic anatomical variation. It may become symptomatic either due to complications relating to its atypical location within the gastrointestinal tract, or if disease of the heterotopic tissue including ulceration, bleeding, pancreatitis or malignant transformation develops. Here we present a case of heterotopic pancreas discovered as an incidental finding during laparoscopic cholecystectomy. This was in a patient previously presenting with two episodes of gallstone pancreatitis who went on to have a laparoscopic cholecystectomy, where an incidental finding was made of a lesion in the stomach that had previously not been noted on imaging. She went on to have a CT scan as well as endoscopic ultrasound and biopsy (images) and this lesion was found to be heterotopic pancreatic tissue, requiring no further treatment. As well as discussion of this case and the diagnostic challenges relating to heterotopic pancreas we also present a review of the literature where other interesting presentations of this anatomical variant are reviewed. We conclude that heterotopic pancreas should be considered as a differential in sub mucosal gastrointestinal lesions, and that endoscopic ultrasound and biopsy in order to establish tissue diagnosis may avoid unnecessary surgical intervention.
Gemma Wells is a Foundation Trainee currently working in the Department of General Surgery at North Middlesex University Hospital. She obtained her medical degree and intercalated BSc in Human Genetics from University College London in 2018.
Objective: In order to generate a better surgical space in laparoscopic surgery we aim to develop a Laparoscopic Operation Field Formation (LOFF) device without pneumoperitoneum and study its feasibility, safety and effectiveness in clinical application, and explore the advantages and disadvantage of this device by comparing it with laparoendoscopic Single-site Surgery(LESS). Methods: With the consideration of generating laparoscopic surgery field by using built-in device and inflating in the body, we designed the single-port gasless laparoscopic operation platform. Based on the results of animal experiments, in clinical trials, 280 patients were elected and divided them into 2 groups for which LOFF-LESS and LESS were performed to compare the operation time, intraoperative blood loss, surgical complications, postoperative incision pain, shoulder pain, satisfaction of cosmetic incision and long-term complications of operation. Results: Based on the in vivo and in vitro experiments, Comparing the LOFF-LESS with LESS surgery, there was no time difference on establishing the operation field, and both of them have more obvious advantages than the GLESS, in sufficient operation field and shorter operation time. In clinical trials, there were no significant differences in terms of field establishing time, gallbladder removal time, intraoperative blood loss, length of stay, incision pain and satisfaction of cosmetic incision between LOFF-LESS and LESS. However, the LOFF-LESS has obviously reduced the occurrence rate of postoperative shoulder-back pain in comparison with LESS. In terms of arterial blood gas analysis LOFF-LESS leaded to lower PCO2 than LESS did at the 20th minute after surgery comparing with pre-operation, and consequently reduced potential negative influence on patients’ cardiopulmonary function that the intraoperative CO2 pneumoperitoneum made. Conclusion: LOFF is a built-in, inflatable single-port gasless operation platform. The clinical trial shows that the application of LOFF-LESS is safe, effective and feasible. LOFF-LESS has the advantages of less postoperative pain, quicker recovery and excellent cosmetic effect that LESS has, and it can also reduce the pneumoperitoneum complications.
Objectives : This study is designed to identify the responses of autonomic nervous system and gastrointestinal function which are induced by acupuncture at abdominal anterior cutaneous nerve. Methods : This study is one group before and after pilot study. Subjects were treated once, after having been fasting six hours. They had before tests, labeling points for acupuncture, acupuncture, and after tests in order. The points of acupuncture were motor points of rectus abdominis where the abdominal anterior cutaneous nerve came to the skin from abdominal wall. Before and after tests were consisted of three things: Digital Infrared Thermographic Imaging(D.I.T.I.), Heart Rate Variability(HRV), and Recording of bowel sounds. Results : There were significant differences on the skin temperature of upper body and the frequency of bowel sounds(p<0.001, p<0.001). The HRV parameters and volume of bowel sounds had no significant differences(p>0.05, p>0.05). Conclusion : Even though no significant differences in HRV parameters, the significant differences of skin temperature of upper body and frequency of bowel sounds could mean acupuncture at abdominal anterior cutaneous nerve could affect the autonomic nervous system and gastrointestinal function. However, this study had no group to compare with. Future randomized project should address this issue.
Dongho Keum has completed his PhD from Kyeonghee University, Korea. He was former head of The Society of Korean Medicine Rehabilitation. He has published more than 25 papers in Rehabilitation Medicine journals. Seohyun Park has studied Korean Medicine from Dongguk University, Korea. She has made a speciality of Rehabilitation Medicine of Korean Medicine and has been studing for doctorate.
The prescription of therapeutic monoclonal antibodies (mAbs) is steadily increasing. Several studies suggested the interest of mAbs therapeutic drug monitoring (TDM) to improve clinical or biological response rate. Proofs of concept of mAbs quantification by liquid chromatography mass spectrometry (LC-MS/MS) emerged, but a multiplex, specific and reliable routine-suited quantification method is still needed to facilitate mAbs TDM. We have developed a multiplex and easy-to-perform LC-MS/MS method for the quantification of several mAbs including adalimumab and infliximab, used in inflammatory diseases. Plasma sample preparation was performed using protein-G purification and trypsin digestion to obtain proteotypic peptides that were quantified by electro spray ionization LC-MS/MS. This method was reproducible, repeatable and accurate (coefficient of variation and bias <15%) with no cross contamination. We have then determined, in two independent cohorts of patients with inflammatory bowel disease (IBD), the therapeutic cut-off for the infliximab and adalimumab trough concentration (Cmin) associated with biological remission (defined as a plasma CRP level < 5 mg/ L and fecal calprotectin level < 150 µg /g stool). Compared to patients without biological response, infliximab and adalimumab median concentrations were higher in patients with biological remission. Cut-off concentration set to 6.2 mg/L for infliximab (sensitivity = 75%; specificity = 61%) and set to 8.0 mg/L for adalimumab (sensitivity: 74.1%, specificity: 57.9%) discriminated patients with or without biological remission. Our works demonstrated that the measures of infliximab or adalimumab Cmin by a LC-MS/MS method and the determination of new thresholds of Cmin associated with biological remission are new steps towards infliximab or adalimumab treatment personalization in patients with IBD.
Background & objectives Patients with Iron Deficiency Anemia (IDA) have been reported to have increased incidence of gall stones. Mean Platelet volume (MPV) reflects both size and platelet activation in inflammatory disease. Review of Literature shows that MPV in Acute Cholecystitis can range from 6.5 to 8.8 femto liters (fl) Objectives: 1. To evaluate MPV alterations in subjects with Acute Cholecystitis alone, Acute Cholecystitis coexisting IDA and also those with IDA. 2. Biochemical analysis of gall stones in the cholecystectomy specimen. Methods: One year cross sectional prospective study of 52 patients who underwent Cholecystectomy, imaging suggested Cholelithiasis ,Histopathological examinaton of gall bladder done. Heamogram including complete blood picture, Hemoglobin, Cell counts and Mean Platelet Volume, Serum Cholesterol, Serum Iron was done on fasting venous sample taken the day previous to the surgery. All tests were done fully automated Hematology and Biochemistry analysers. Biochemical analysis of one stone from each cholecystectomy specimen was done by manual semi-quantitative titrimetric and colorimetric methods. Results: 62% of the gall stones were of the cholesterol type. Serum Iron reduced in 38.46%. Serum cholesterol was raised in 86.54%. Mean Platelet Volume (MPV) was lower in individuals with Acute Cholecystitis in the background of Iron Deficiency Anemia (IDA): 6.5 + 0.4 femto liters (fl) compared to that in those with Acute cholecystitis alone : 6.6 + 0.2 fl while the group with IDA had the lowest value 6.4 + 0.6 fl. Conclusion: Mean Platelet volume(MPV) may not be a reliable inflammatory marker in subjects with Acute Cholecystitis who have co-existing Iron deficiency Anemia (IDA). As IDA is not only implicated in cholesterol stone formation but also influences MPV.
Nutritional studies are greatly hampered by a paucity of proper models. Previous studies regarding nutrition studies have employed conventional cell lines and in vivo models to gain a better understanding of the field. Cell models only contain single cell type, grow as a monolayer, and thus fail to mimic sophisticated physiological responses in the body. The in vivo models are often difficult to implement, contain complicated interactions inter-tissues, which makes them difficult to dissect mechanism based studies. Animal models are also challenging animal welfare and ethics. These inherent shortcomings impede their applications in nutritional studies. As a new in vitro biological model, 3D enteroids are cultured from intestinal stem cells and include enterocytes, enteroendocrine cells, goblet cells, Paneth cells, and stem cells, which mimic hallmarks of in vivo epithelium and support long-term culture without genetic or physiological changes. Furthermore, enteroids can be cryopreserved, and are suitable for various molecular assays including lentiviral transfection, immunohistochemistry, and immunofluorescence, and so on. Enteroids have been used as models to study pathogenesis of viruses and bacteria, antiviral and feed additive development, and nutritional studies including the effects of diet and nutrients on intestinal growth and development, ion and nutrient transport, secretory and absorption functions, the intestinal barrier, and location-specific functions of the intestine. Of note, this novel model can be used for personalized medicine and precise nutrition studies. Therefore, we suggest that enteroids can serve as a potential model system to be exploited in nutritional studies.
Prof. Yu-long Yin has completed his PhD from Queen's University Belfast, KU and visiting researcher in Max Planck institute, Germany. He is the director of Animal husbandry farming center, Institute of Subtropical and Agriculture, China Academy of Sciences, and vice chairman of Hunan Science Association, China. He has published more than 350 papers in reputed journals and has been serving as a Chief Editor of Animal Nutrition, and an editorial board member of Journal of Animal Science.