Gastric mucosal lesion (GML) is a common gastrointestinal disorder with multiple pathogenic mechanisms in clinical practice. In traditional Chinese medicine (TCM), electroacupuncture (EA) treatment has been proven as an effective therapy for GML, although the underlying healing mechanism is not yet clear. Here, we used proton nuclear magnetic resonance- ((1)H NMR-) based metabolomic method to investigate the metabolic perturbation induced by GML and the therapeutic effect of EA treatment on stomach meridian (SM) acupoints. Clear metabolic differences were observed between GML and control groups, and related metabolic pathways were discussed by means of online metabolic network analysis toolbox. By comparing the endogenous metabolites from GML and GML-SM groups, the disturbed pathways were partly recovered towards healthy state via EA treated on SM acupoints. Further comparison of the metabolic variations induced by EA stimulated on SM and the control gallbladder meridian (GM) acupoints showed a quite similar metabolite composition except for increased phenylacetylglycine, 3,4-dihydroxymandelate, and meta-hydroxyphenylacetate and decreased N-methylnicotinamide in urine from rats with EA treated on SM acupoints. The current study showed the potential application of metabolomics in providing further insight into the molecular mechanism of acupuncture.
Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.
Cold snare polypectomy (CSP) should be performed for benign lesions, though an accurate diagnosis is sometimes difficult with only white light observation. Irregular findings by narrow-band imaging (NBI) are useful for differentiating malignant lesions from benign lesions, and cases with this finding are not expected for CSP. We present a diminutive T1 cancer resected by CSP as a reflection case. A 68-year-old man underwent colonoscopy for surveillance after polypectomy. A reddish polyp 4 mm in size was detected at the rectum. White light observation showed no depression, but a slight, heterogeneous color change. NBI magnification showed irregular vessel and surface patterns. The polyp was diagnosed as intramucosal cancer. Even though cancerous lesions are regularly resected by endoscopic mucosal resection (EMR), this polyp was resected by CSP in daycare surgery because the patient requested not to be treated by EMR but by CSP, which needed an admission to our institution. The surgeon thought the polyp could be completely resected by CSP. It was thoroughly resected, and a histological examination showed submucosal cancer with a positive vertical margin. Additional surgical resection was not accepted by the patient, since he had received total gastrectomy for gastric cancer and a right hemicolectomy for colonic cancer in the past 7 years. He underwent follow-up colonoscopy 2 months after the CSP. Although there were no recurrent endoscopic findings, endoscopic submucosal dissection was performed to the scar area. The histological examination showed no residual tumor. In conclusion, CSP should only be adopted for benign cases, as cancerous lesions have a possibility for invading the submucosa, like in our case.
Incidence rates of gastric cancer in Malaysia has declined by 48% among males and 31% among females in the latest reporting period of 13 years. Malays used to have age-standardized-rates only a fifth of those in Chinese and Indians, but the incidence among them is slightly rising even as the rates drop in the other races. Besides ethnicity, a low level of education, high intake of salted fish and vegetables, H pylori infection and smoking are risk factors. Consumption of fresh fruit and vegetable is protective. Variation in the strains of H pylori infection affect gastric cancer risk, with hspEAsia isolates among Chinese appearing linked to a high incidence than with hpAsia2 or hpEurope strains among Indians and Malays. It was reported in the 1980s that only about 3% of patients presented with early gastric cancer, but more encouraging rates reaching 27% with Stage 1 and 2 disease have been reported in the twenty-first century from leading centres. More tumours occur in the distal stomach except in Kelantan, where the incidence is low and main site is the cardia. Prompt endoscopy is advocated and open access, with direct referrals, to such services using a weighted scoring system should be more utilized. In view of the high rate of late disease laparoscopic staging unnecessary laparotomy needs to be avoided. Late presentation of gastric cancer however, is still predominant and the mortality to incidence ratio is relatively high. Besides seeking to reduce risk factors and achieve early detection, implementation of improved care for patients with late disease must be promoted in Malaysia.
Zinc is a naturally occurring element with roles in wound healing and rescuing tissue integrity, particularly in the gastrointestinal system, where it can be detected in the mucosal and submucosal layers. Zinc chelates are known to have beneficial effects on the gastrointestinal mucosa and in cases of gastric ulcer. We synthesized complexes of zinc featuring a heterocyclic amine binding amino acids then investigated their ability to enhance the gastric self-repair. Zinc-morpholine complex, Zn(L)SCN, namely showed strong free-radical scavenging, promotion of the DNA and RNA polymerases reconstruction and suppression of cell damage. The complex's mode of action is proposed to involve hydrogen bond formation via its bis(thiocyanato-k)zinc moiety. Zn(L)SCN complex had potent effects on gastric enzymatic activity both in vitro and in vivo. The complex disrupted the ulcerative process as demonstrated by changes in the intermediate metabolites of the oxidative pathway - specifically, reduction in the MDA levels and elevation of reduced glutathione together with an attenuation of oxidative DNA damage. Additionally, Zn(L)SCN restored the gastric mucosa, inhibited the production of pro-inflammatory cytokines (IL-6, TNF and the caspases), and preserved the gastric mucous balance. Zn(L)SCN thus exhibited anti-oxidative, anti-inflammatory and anti-apoptotic activities, all of which have cytoprotective effects on the gastric lining.
Gastric volvulus is an uncommon disorder with an unknown incidence, unless it stays in the back of the diagnostician's mind, diagnosis of gastric volvulus, which can have significant morbidity and mortality associated with it, can be easily missed and can present either in the acute or chronic setting with variable symptoms. When it occurs in the acute scenario, patients present with severe epigastric pain and retching without vomiting. Together with inability to pass nasogastric tube, they constitute Borchardt's triad. The presence of a hiatal hernia with persistent vomiting despite initial antiemetic treatment should trigger one to think of gastric volvulus, despite the patient appearing very stable. We report a case which presented in our hospital with abdominal pain and vomiting. As Oesophagogastroduodenoscopy shows hiatal hernia and peptic ulcer. Primary gastric volvulus occurs in the absence of any defect in the diaphragm or adjacent organ pathology and may be caused by weakening of gastric supports. As conclusion; Gastric volvulus is a surgical case, requiring early diagnosis and aggressive management, as a delay results into complications like gangrene and perforation which substantially increase the morbidity and mortality in these patients, and contrast enhanced computed tomography (CECT) is the best modality for diagnosis of gastric volvulus.
A 103 year old patient was admitted with pain in the right iliac fossa. There was no response to conservative treatment. Subsequent laparatomy showed the presence of a perforated ulcer in the pyloric region. The condition improved gradually after the surgical management.
Rats exposed to stress developed various changes in the gastrointestinal tract and hormones. The present study was designed to compare the impact of tocopherol and tocotrienol on changes that influence gastric and hormonal parameters important in maintaining gastric mucosal integrity in rats exposed to restrain stress. These include gastric acidity, gastric tissue content of parameters such as malondialdehyde, prostaglandin (PGE(2)), serum levels of gastrin and glucagon-like peptide-1 (GLP-1). Sixty male Sprague-Dawley rats (200-250 g) were randomly divided into three equal sized groups, a control group which received a normal rat diet (RC) and two treatment groups each receiving a vitamin deficient diet with oral supplementation of either tocopherol (TF) or tocotrienol (TT) at 60 mg/kg body weight. Blood samples were taken from half the number of rats (non-stressed group) after a treatment period of 28 days before they were killed. The remaining half was subjected to experimental restraint-stress, at 2 hours daily for 4 consecutive days (stressed groups), on the fourth day, blood samples were taken and the rats killed. The findings showed that the gastric acid concentration and serum gastrin level in stressed rats were significantly (P<0.05) reduced compared to the non-stressed rats in the control and TF groups. However, the gastric acidity and gastrin levels in the TT group were comparable in stressed and non-stressed rats. These findings suggest that tocotrienol is able to preserve the gastric acidity and serum gastrin level which are usually altered in stressed conditions. The PGE(2) content and the plasma GLP-1 level were, however, comparable in all stressed and non-stressed groups indicating that these parameters were not altered in stress and that supplementation with TF or TT had no effect on the gastric PGE2 content or the GLP-1 level. The malondialdehyde, an indicator of lipid peroxidation was higher from gastric tissues in the stressed groups compared to the non-stressed groups. These findings implicated that free radicals may play a role in the development of gastric injury in stress and supplementation with either TF or TT was able to reduce the lipid peroxidation levels compared to the control rats. We conclude that both tocopherol and tocotrienol are comparable in their gastro-protective ability against damage by free radicals generated in stress conditions, but only tocotrienol has the ability to block the stress-induced changes in the gastric acidity and gastrin level.
Gastrointestinal myxosporean parasites from the genus Enteromyxum are known to cause severe disease, resulting in high mortalities in numerous species of cultured marine fishes globally. Originally described as Myxidium spp., they were transferred to a new genus, Enteromyxum, to emphasize their novel characteristics. Their retention in the family Myxidiidae at the time was warranted, but more comprehensive phylogenetic analyses have since demonstrated the need for a new family for these parasites. We discovered a novel Enteromyxum in wild fish from Malaysia and herein describe the fourth species in the genus and erect a new family, the Enteromyxidae n. fam., to accommodate them. Enteromyxum caesio n. sp. is described infecting the tissues of the stomach in the redbelly yellowtail fusilier, Caesio cuning, from Malaysia. The new species is distinct from all others in the genus, as the myxospores although morphologically similar, are significantly smaller in size. Furthermore, small subunit ribosomal DNA sequence data reveal that E. caesio is <84% similar to others in the genus, but collectively they form a robust and discrete clade, the Enteromyxidae n. fam., which is placed as a sister taxon to other histozoic marine myxosporeans. In addition, we describe, using transmission electron microscopy, the epicellular stages of Enteromyxum fugu and show a scanning electron micrograph of a mature myxospore of E. caesio detailing the otherwise indistinct sutural line, features of the polar capsules and spore valve ridges. The Enteromyxidae n. fam. is a commercially important group of parasites infecting the gastrointestinal tract of marine fishes and the histozoic species can cause the disease enteromyxosis in intensive finfish aquaculture facilities. Epicellular and sloughed histozoic stages are responsible for fish-to-fish transmission in net pen aquaculture systems but actinospores from an annelid host are thought to be necessary for transmission to fish in the wild.
Gastro-peritoneal fistula is a rare but serious complication of laparoscopic sleeve gastrectomy with significant morbidity and mortality. We present the case of a 42-year-old man who underwent laparoscopic sleeve gastrectomy for morbid obesity and presented later with a history of chronic epigastric pain and severe reflux. Upper gastrointestinal series showed the presence of a communicating fistula between the stomach and the left hemi-diaphragm and peri-splenic area.
Introduction: Gastrointestinal stromal tumour (GIST) is relatively rare. The clinical behaviour of GIST ranges
from benign to frank sarcoma. The diagnosis is established through histopathological examination and
immunohistochemistry profile. In Malaysia, the number of publications related to GIST is relatively rare. This
study was therefore conducted to examine the demographic, histopathological and immunohistochemical
features of GIST cases diagnosed in the Department of Pathology, Hospital Tengku Ampuan Afzan, Kuantan,
Pahang from 2009 until 2014. Methods: Past histopathological records were reviewed. Demographic and
histopathological and immunohistochemical data of patients diagnosed were collected. Results: There were
28 cases (14 males and 14 females) diagnosed as GIST. Mean age was 56.4 years, and the majority were
above 40 years of age (85.7%). Stomach was the most common location (42.9%), followed by small intestine
(28.6%). In 23 cases (82%), the tumours exhibited spindle cell morphology, while epithelioid cell and mixed
cell types were seen in 3 cases (11%) and 2 cases (7%), respectively. Five cases were categorised as very low
risk to low risk behaviour, while 18 cases were intermediate to high. None of the histological parameters
analysed which include tumour morphology, necrosis, haemorrhage, nuclear atypia and mean number of
mitoses showed significance difference between the different risk behaviour groups. Positivity with KIT
(CD117), considered to be the defining immunohistochemistry feature, was negative in 2 cases. Conclusion:
Although this study is a retrospective study, the findings contribute to the knowledge on GISTS in Malaysia.
Future research related to GISTs in Malaysia should focus on molecular analyses for KIT and PDGFRA
mutations for diagnostic confirmation especially in KIT-negative cases and also for the purpose of
therapeutic response correlations.
Aim. Helicobacter pylori (H. pylori) infection is exceptionally rare in population from the north-eastern region of Peninsular Malaysia. This provides us an opportunity to contemplate the future without H. pylori in acute non-variceal upper gastrointestinal (GI) bleeding. Methods. All cases in the GI registry with GI bleeding between 2003 and 2006 were reviewed. Cases with confirmed non-variceal aetiology were analysed. Rockall score > 5 was considered high risk for bleeding and primary outcomes studied were in-hospital mortality, recurrent bleeding and need for surgery. Results. The incidence of non-variceal upper GI bleeding was 2.2/100,000 person-years. Peptic ulcer bleeding was the most common aetiology (1.8/100,000 person-years). In-hospital mortality (3.6%), recurrent bleeding (9.6%) and need for surgery (4.0%) were uncommon in this population with a largely low risk score (85.2% with score ≤5). Elderly were at greater risk for bleeding (mean 68.5 years, P = 0.01) especially in the presence of duodenal ulcers (P = 0.04) despite gastric ulcers being more common. NSAIDs, aspirin and co-morbidities were the main risk factors. Conclusions. The absence of H. pylori infection may not reduce the risk of peptic ulcer bleeding in the presence of risk factors especially offending drugs in the elderly.
Mathematically, the human alimentary tract organs were simplified in the model structure as separate compartments with
pathways of transfer that are kinetically homogenous and equally distributed. The development of gastro-compartment
model follows the first order kinetics of differential equations to describe cadmium absorption, distribution and elimination
in the human digestive system. With the aid of in vitro DIN assay, an artificial gastric and gastrointestinal fluid were
prepared using water leach purification (WLP) residue as a sample that contained toxic metals cadmium. The Simulation,
Analysis and Modelling II (SAAM II) V2.1 software is employed to design models easily, simulate experiments quickly and
analyze data accurately. Based on the experimental inputs and fractional transfer rates parameter incorporated to the
gastro-compartment model, the concentration of cadmium against time profile curves were plotted as the model output.
The curve presented concentration of cadmium in both gastric and gastrointestinal fluid where initially absorption phase
(first hour) occurred followed by the distribution phase (second to third hours) and elimination process (third to fifth
hours). The concentration of cadmium obtained from the simulated model structures was in good agreement with the
fitted model predicted measurements as statistical t-test conducted showed the values were not significantly different.
Therefore, modeling approach with SAAM II software gave realistic and better estimation of cadmium dissolution into
the human gastrointestinal tract.
Manganese is a crucial element for health. In this study, the gastroprotective efficacy of Mn (II) complex (MDLA) against acidified ethanol (HCl/Ethanol)-induced gastric ulceration in rats was evaluated. The animals were distributed into 5 groups. Groups 1 and 2 received carboxymethylcellulose (CMC), group 3 was pretreated with omeprazole, and groups 4 and 5 were given 10 and 20 mg/kg of MDLA, respectively. After one hour, CMC and HCl/Ethanol were given to groups 2-5 whilst the animals in group 1 were ingested with CMC. After sacrifice, gastric lesions were evaluated by wall mucus, gross appearance, histology, antioxidant enzymes and immunohistochemistry. Group 2 displayed severe gastric damage with a significant reduction in wall mucus. Conversely, gastric lesions were reduced in groups 3-5 by 85.72%, 56.51% and 65.93%, respectively. The rats in groups 3-5 showed up-regulation of heat shock protein 70 (Hsp70) with down-regulation of Bcl-2-associated protein x (Bax). Pretreatment with omeprazole or MDLA led to an increase in the uptake of Periodic Acid Schiff (PAS) stain in the glandular part of the gastric tissue, raised levels of prostaglandin E2 (PGE2) and superoxide dismutase (SOD), and a reduction in malondialdehyde (MDA) concentrations. These results suggested the gastroprotective action of Mn (II) complex.
A case of acute gastric volvulus associated with eventration of the diaphragm in a previously well 6 year old child is reported. The child presented with acute abdominal pain, abdominal distension and vomiting. At operation, mesentero-axial type gastric volvulus was found, associated with laxity of the gastro-splenic, gastrohepatic and gastrocolic ligaments and eventration of the left hemidiaphragm. Rapid recovery followed surgery that included release of distension and fixation of the stomach to the anterior abdominal wall. There has been no evidence of recurrence on a 2 year follow-up.