Editorial Cheif : Shreyas Saligram, MD Title proper: Gastro-Open Jouranal Journal Initials: GOJ ISSN: 2377-8369 Subject: Medicine Publisher: Openventio Publishers Dates of publication: 2014 Frequency & Medium: Halfyearly , Online Language: English Country: India Indexed by: CROSSREF , ROAD , THE KEEPERS Title DOI of the Journal: http://doi.org/10.17140/issn-2377-8369
Call Me Anything but Thoughtless or Misguided in IBD Management
I read with interest the open access, original article, by S.K. Murthy, et al, Introduction of anti-tumor necrosis factor (TNF) therapy has not yielded expected declines in hospitalization and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study appearing in Gut 12 June 2019.1 It must first be stated that the authors are to be congratulated for the magnificent demonstration of the benefits of the Canadian healthcare system in terms of collection of healthcare data. That said, I take issue with their explanation and hypothesis: “misguided use and failure to optimize use of infliximab, particularly among patients with Crohn’s Disease (CD), as well as possible underuse of infliximab among patients with ulcerative colitis (CUC)….” In the follow-up press release, one summary recommendation was that “doctors should be more thoughtful in managing inflammatory bowel disease (IBD).” It is unfortunate, indeed, that the term “misguided use” would appear and then be translated into perhaps a deeper, and unwarranted, criticism that doctors managing IBD have been “less than thoughtful or misguided” in the use of biologics. I think the authors actually intended to report that the academic community has collected clinical trial data and offered practicing clinicians a plan for use of biologics only to find in retrospect that those recommendations were not likely to be effective given the general IBD patient population and the less than complete effectiveness of the biologics. Nonetheless, the message was certainly blurred.
Endoscopic Treatment of Refractory Variceal Bleed
A 70-year-old man with history of end-stage liver disease due to alcohol misuse disorder was admitted to the hospital with hematemesis. He had at least 5 episodes of bright red hematemesis and was feeling dizzy. He complained of epigastric pain for 3 days prior to presentation. He had noticed progressive development of dark urine, pale stools and yellow sclera. He had not consumed any non-steroidal anti-inflammatory drugs recently. His last consumption of alcohol was 3 months ago. He had a prior history of gastrointestinal (GI) bleeding and had undergone upper GI endoscopy that revealed large varices with highrisk stigmata (white nipple sign) requiring variceal band ligation. His last endoscopy was 6 weeks prior to presentation. He was noncompliant with prophylactic propranolol and was not on any other medications.
The Importance of Enzyme Substitution Therapy in Early Pancreas Exocrines of Insufficiency
Introduction Functional disorders of the digestive tract are a common occurrence in the doctor’s office. In addition to functional dyspepsia, 35% of dyspepsia are unresolved dyspepsia, which are a symptom of the early stage of pancreatic exocrine insufficiency. Aim Based on clinical experience, we can suspect and detect chronic pancreatic insufficiency at an early stage, which is the aim of this paper. Method To demonstrate the efficacy of enzyme replacement therapy in the early stage of pancreatic exocrine insufficiency using the case report of the patient. Results Results confirms significance and effectiveness of creon as an enzyme replacement therapy in the treatment of malabsorption and maldigestion. Conclusion Creon (pancreatin) showed great effect in the treatment of dyspepsia and anorexia nervosa, body mass index (BMI) for 30 days increased from 15.9 to 17.4, which leads us to the conclusion that unrecognized chronic pancreatic insufficiency can be expected in long-term dyspepsia.
What IBD Physicians Can Learn from Major League Baseball Managers
Yogi Berra philosophized, “You can observe a lot by just watching.” Physicians managing inflammatory bowel disease (IBD) patients are constantly exposed to the recent literature, the visiting pharmaceutical representatives, and to the valuable presentations by the academic experts at the annual meetings. In my opinion, these presentations too often are advanced in a vacuum of unconvincing compartmentalization rather than as a well-choreographed management strategy that considers both the impact of any IBD drug and the nearly certain likelihood of a patient’s failed response or eventual relapse. Stated another way, what is most often missed, only mentioned as an aside, and almost never clearly defined is an agent’s place within the context of management of the entire course of the disease. Twenty years into the new century with the current and evolving list of IBD drugs, it would be valuable to much more often and with authority present specific management algorithms that offer the highest likelihood of remission.1,2 Having a progressively enlarging menu of partially effective drugs is no longer satisfactory. I give you Major League Baseball (MLB).
Superior Mesenteric Artery and Nutcracker Syndromes in a Healthy 14-Year-Old Girl Requiring Surgical Intervention after Failed Conservative Management
This case report presents the diagnosis of superior mesenteric artery and nutcracker syndromes in a previously fit and well 14-yearold girl. Although these two entities usually occur in isolation, despite their related aetiology, our patient was a rare example of their occurrence together. In this case the duodenal compression of superior mesenteric artery syndrome caused intractable vomiting leading to weight loss, and her nutcracker syndrome caused severe left-sided abdominal pain and microscopic haematuria without renal compromise. Management of the superior mesenteric artery syndrome can be conservative by increasing the weight of the child which leads to improvement of retroperitoneal fat and hence the angle of the artery. The weight can be improved either by enteral feeds or parenteral nutrition. This conservative management initially helped but not in the long-term as the child started losing weight again. The next step in management is surgery (duodenojejunostomy – if the conservative management fails), which the child went through, remarkably improving their symptoms.
Decision-Making in Diagnosis and Management of Extraintestinal Manifestations of Inflammatory Bowel Disease
In the absence of certainty regarding the causes of both inflammatory bowel disease (IBD) and its extraintestinal manifestations (EIMs), there is necessarily ambiguity in both academic and clinical arenas concerning the diagnosis, classifications, and treatments of EIMs. While the “true” EIMs are considered extensions of the IBD gut pathogenesis with an immunologically mediated inflammatory consequence, other EIMs are considered to be complications of IBD itself or its treatment. A third group of IBD EIMs includes those disorders which seem to occur more often in IBD but for which an etiologic or pathophysiologic connection to IBD is highly theoretical. Patients with IBD and EIMs tend to have more severe, long-duration disease, and a reduced quality of life. EIMs presentation may or may not parallel IBD gut inflammatory activity. The clinical decision-making processes necessary for successfully managing simultaneously the gut component of IBD and its EIMs are presented. Based upon clinical experience and review of leading publications, the consensus of best practices, differential diagnoses for EIMs, and current management programs are presented with enumeration of specific decisions and considerations required for successful management of EIMs. EIMs of inflammatory bowel disease reflect the immunopathologic common ground and hence the systemic nature of the IBD. A defined decision-making process is offered which includes consultations and attention to the differential diagnosis to avoid not uncommon mistakes in diagnosis. Management of all EIMs requires assessment of both the clinical and pathologic status of the gut component of IBD combined with judicious selection of general and /or immunosuppression therapy for the EIMs.
Migration is the most common complication of placing an esophageal fully covered self-expanding metal stent (FCSEMS). Prior Studies have demonstrated high migration rates of FCSEMS leading to additional invasive procedures.1 We report a case of esophageal FCSEMS placement with endoscopic suturing which prevented migration of the stent and a successful post procedure course.
Microgenderome: An Important Variable for Developing Therapeutic Strategies?
A close association of microbiota in human health continues to emerge. Microbiota has been implicated in autoimmune disorders such as type I diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis.1 This is pointing out that early-life microbial exposure could be linked to later-life susceptibility to immune-mediated disorders. From the experimental models related to autoimmune disorders, it is known that tissue injury is prevented by alteration in microbiota or in germ-free condition. Therefore, microbial alteration can be beneficial during autoimmune disorders. However, several lines of evidence suggest the role of gender-bias, (regulation of sex-hormones by microbiota) in numerous diseases. This editorial aims to throw light on the novel, emerging triangular relationship between host microbiota, sex hormones (testosterone, progesterone and estrogen) and immune responses cumulatively termed as “Microgenderome”.
The Role of Pre-Assessment in Oesophageal Cancer Surgery
National figures for oesophagectomy mortality in the United Kingdom have been steadily dropping (12% to 9%) since the late 1990’s.1 More recently, these figures have improved significantly as shown in the 2016 annual report of the UK National Oesophago-Gastric Cancer Audit (NOGCA), revealing a post-oesophagectomy 90-day mortality rate of 3.2%.2 Despite this, surgical treatment for oesophageal cancer still carries significant morbidity, often quoted up to 64%.3 While centres of excellence maintain high standards of surgery and improved surgical techniques, with minimally invasive techniques potentially reducing physiological stresses on patients, we are perhaps being less conservative in our selection of patients for surgery; all having varying influences on the overall risks.
Analysis of the Intracellular Zinc in HCV Replicon
Aim: In patients with chronic liver injury, metabolic disturbance of zinc was frequently observed and Hepatitis C virus (HCV) replication is crucially involved with zinc metabolism. In vitro HCV replication system, HCV replicon enabled us to analyze HCV replication in vitro. Here we aimed to quantitatively analyze the zinc in a HCV-infected hepatocyte, namely HCV replicon and control. Methods: Genome-length HCV RNA-replicating cells, namely replicon cells (HCV-O cells) and control cells were treated with zinc salts and assayed their zinc content by in-air micro- PIXE analyzer. Metallothionein (MT) which is a major reserve of zinc was also analyzed by Cd-hem assay. Results: 1) Micro-PIXE analysis revealed that zinc concentration was increased more in HCV-O cells than control. Additional zinc by zinc chloride administration enhanced the peak of zinc in both control and HCV replicon cells. Furthermore, the degree of zinc increment by additional zinc is more in HCV-O cells than control. 2) Cd-hem assay also demonstrated the increase of zinc in HCV-O cells and zinc stimulation further increased the metallothionein content in HCV-O cells. Conclusion: In-air-micro-PIXE and Cd-hem assay revealed the increase of zinc and metallothionein in HCV-O. Metallothionein increased and additional zinc also increased more in HCV-O. Thus, HCV infection increased zinc at least partially through metallothionein.
Boerhaave’s syndrome or spontaneous oesophageal perforation is characterised by barogenic oesophageal injury. This leads to contamination of the pleural cavity with enteric contents and various degrees of injury.1 The syndrome is named after Herman Boerhaave, a Dutch physician, who first described it in 1724. Incidence of spontaneous rupture amongst all oesophageal ruptures varies between 15-38%.2,3 Mallory-Weiss tears are assumed to represent part of the spectrum of the spontaneous perforation, but it is likely that these mucosal injuries reflect shearing rather than barogenic trauma.4 Spontaneous oesophageal perforations are associated with the highest mortality amongst all gastrointestinal perforations with an overall rate of nearly 30%. Early diagnosis and definitive surgical management as soon as possible after the presentation of symptoms, indisputably within the first 24 hours show the best outcomes. If treatment is started within 24 hours from the onset of symptoms, mortality rate is observed to be below 10%; after 24 hours, it is approximately 65% and after 48 hours, it reaches 75%-89%. If left untreated it rises up to 100%.
Overriding Elements in Colon Cancer Progression: Some Less Known Facts
Colorectal cancer (CRC) is one of the most life threatening disease with escalating mortality and morbidity. Some known causative factors include lifestyle, alcohol etc. but there are other aspects like long standing colitis, inhibition of apoptotic proteins, chemokines and their receptors and inflammasomes which increase the chances of CRC progression. In a clinical setting of diseases like colitis and Crohn’s disease, the risk of CRC varies on degree of inflammation, expression of chemokines and cytokines and other molecular alterations. Hence, the underlying molecular inductions determine the fate of CRC progression through extent of epithelialmesenchymal transition, metastasis and invasive ability. The present view point will showcase some of the latent and notable considerations in CRC progression.
Salvage Cryotherapy for Treatment of Persistent Barrett’s Esophagus
Background: A dysplastic Barrett’s esophagus can lead to cancer if not treated by endoscopic eradication therapy. The current consensus is to eradicate the entire residual Barrett’s esophagus that is visible during endoscopy by ablation therapy. However, a section of patients are resistant to this ablation therapy. They may need a second line of ablation therapy to eradicate the visible residual Barrett’s esophagus. Aims: To evaluate the efficacy of treatment with salvage cryotherapy of persistent Barrett’s esophagus who failed to respond for ablation by radio frequency ablation. Methods: Barrett’s esophagus with high-grade dysplasia was initially treated with radiofrequency ablation (RFA) for at least 6 sessions to achieve complete eradication of Barrett’s esophagus. Barrett’s esophagus patients who failed to respond to the radiofrequency ablation was then treated with a different ablation therapy modality like a cryotherapy to achieve complete eradication of Barrett’s esophagus. Results: Two patients with Barrett’s esophagus and high-grade dysplasia were included in the case series. The Barrett’s esophagus in both the patients was treated with a mean of 6.5 sessions of radiofrequency ablation. Both the patients had persistent Barrett’s esophagus despite the treatment with radiofrequency ablation as demonstrated by surveillance endoscopic biopsies. They were then treated with a mean of 4.5 sessions of cryotherapy as a salvage therapy. Surveillance endoscopy showed persistent Barrett’s esophagus in both the patients despite being treated with cryotherapy. None of the patients had high-grade dysplasia in the surveillance endoscopy. Conclusion: Salvage cryotherapy is futile in persistent Barrett’s esophagus that had prior treatment failure with a different ablation therapy.
The Clinical or Radiographic Diagnosis of Gastroptosis: Still Relevant?
Introduction: Gastroptosis was a frequent diagnosis in former days, however in current practice it is a rare diagnosis with uncertain etiology, with only a few number of studies to support it. Gastroptosis is diagnosed on a nupper gastrointestinal (GI) study by the downward displacement of the greater curve of the stomach below the level of the iliac crests in a standing position. Gastroptosis could possibly cause GI symptoms and delayed gastric emptying, but the relation is unknown, especially in children. This study addresses the association of GI symptoms and gastroptosis in children in the Netherlands. Methods: We present a retrospective study of all children aged 6 to 18 years who underwent an upper GI study of the stomach in a 5-year period in our university children’s hospital. Sixty of one hundred sixty-one children were included in the analysis, of whom seven appeared to have a radiological diagnosis of gastroptosis. Results: GI symptoms were not significantly different between children with and without gastroptosis. Compared to the control group, there was a significant higher incidence of decreased gastric motility (p=0.004) in children with gastroptosis, as well as delayed gastric emptying (p=0.045). Conclusion: Children with gastroptosis did not have specific GI symptoms. Gastroptosis was associated with decreased gastric motility and delayed gastric emptying, which could either be the cause of the gastroptosis or a consequence. The radiologic diagnosis gastroptosis had no consequence regarding treatment. Therefore, gastroptosis on an upper GI study seems clinically irrelevant.
A Multicenter UK Study on Trainee Involvement in Clinical Audit: Is it an Effective Contribution to Service Quality Improvement or a Portfolio Generating Activity?
Aims: The primary purpose of audit is to improve quality of care, but it is also considered educationally valuable. Audits are often sought in job applications and also form annual review targets. The study aimed to examine audit activity across hospital trainees. Methods: 100 doctors, ranging from F1 to Specialty Training year 5 (ST5) level across 10 UK hospitals were invited to complete a printed or online questionnaire about audit involvement. Results: Seventy five (75%) participated, including 1 F1 (1.3%), 34 F2s (45%), 6 ST1s (8%), 14 ST2s (19%), and 20 ST3-5s and post-basic training fellows (26%). Their Specialities included: Medicine 33(44%), Surgery 29(38%), General Practice (GP) 6(8%), Anaesthesia 4(5.3%), Accident and Emergency (A&E) 2(2.6%) and Ophthalmology 1(1.3%). Seventy (93%) claimed audit involvement in the last year. Most (54, 72%) worked by themselves, with over a quarter led by others (28%). None received audit training. Most (86%) completed within 6 months. Audits focused chiefly on local practice (96%), with only 3 regional or national audits (4%). Only five were re-audits (6.7%), and just four were submitted for publication (5.3%). Most (60, 80%) were formally presented: 46 at local meetings (61%), 10 reaching regional (13%) and 4 international (5.3%) conferences. Conclusion: The positive response rate indicates that audit is a frequent trainee activity, but the results suggest that it is mainly a self-directed portfolio fulfilling exercise. Improved training and supervision may be needed to achieve the primary aim of audit, which is improved clinical practice, whilst the educational value is unproven.
Coalescent Cyclical Vomiting: A Manifestation of Narcotic Bowel Syndrome?
This illustrative case suggests mechanisms that may contribute to disease progression and complications in adults with Cyclical Vomiting Syndrome (CVS). Symptoms initially followed a characteristic pattern in the context of marijuana use and led to repeated hospitalizations. Escalating opioid use for pain control resulted in coalescence of the syndrome with more frequent and severe emetic episodes, ultimately complicated by an esophageal microperforation. While analgesic therapy may play an important role in management of acute exacerbations, ongoing use of narcotics may contribute to the development of refractory CVS. This association of disease progression with opiates suggests that coalescent CVS should be considered a foregut manifestation of narcotic bowel syndrome.
Management of Inflammatory Bowel Diseases in Jehovah’s Witness
Background: Treatment of Inflammatory Bowel Disease (IBD) patients who are known to be Jehovah’s Witness (JW) can be a unique challenge. JW accept most available medical treatments, but may not accept blood transfusions or blood products due to their religious beliefs. We looked at the experience of treating IBD in JW, their care during acute bleed and also the outcome. Methods: A retrospective review was performed to identify patients treated for IBD known to be JW between the years 2005-2009 at two University of Pittsburgh Medical Center Hospitals. Demographic data, clinical presentation, treatment during hospitalizations and outpatient clinics were abstracted from the chart. All patients were confirmed to be having IBD either by colonoscopy or by documented evidence during clinical care. JW was confirmed by documentation in the chart. We took note of complications secondary to IBD, treatment measures during emergent conditions like acute bleed, bowel obstruction and also different treatment options used for long term management of IBD. Results: Twenty two patients were identified in both the university (n=14) and community hospital (n=8). Out of them, 13 patients had ulcerative colitis and 9 had Crohn’s disease. Caucasians comprised majority of the population (68%). Mean age was 51 years. Mean time interval between initial diagnosis and most recent follow-up was 14 years. Among study subjects, 68% had documented colonoscopy reports with 6 patients (27%) showing active disease. Nine (41%) of these patients were post surgical and 6(27%) patients developed complication (clostridium difficile, abscess, fistula, colon cancer and small bowel obstruction) secondary to their IBD. Seventeen (77%) IBD patients were treated as an outpatient and 5(23%) as an inpatient. Three (14%) patients had to be admitted to Intensive Care Unit (ICU) during their inpatient stay. Hemoglobin was more than 10 g/dl in 68%, between 7 to 10 g/dl in 18% and less than 7 g/dl in 14% at baseline. After treatment with conservative measures for anemia, hemoglobin improved to more than 10 g/dl in 91%, and between 7 to 10 g/dl in 9%. One patient died with organ failure secondary to sepsis. Two patients (9%) underwent bloodless surgery with cell saver technique with no mortality. Conclusion: Management of IBD related anemia in JW has a good outcome and can be treated conservatively without blood transfusion. Complications secondary to IBD does not adversely affect the outcome.
Role of Calcium in Vomiting: Revelations from the Least Shrew Model of Emesis
Cisplatin-like chemotherapeutics cause vomiting via release of multiple neurotransmitters (dopamine, serotonin, or substance P) from the gastrointestinal enterochromaffin cells and/or the brainstem via a Calcium (Ca2+) dependent process. In addition, evidence from literature indicate that Ca2 + signaling is also triggered subsequent to activation of other emetogenic receptors including serotonergic 5-HT3, tachykinin NK1, dopamine D2, and histaminergic H1 receptors. Moreover, other emetogens such as prostaglandins, cisplatin, rotavirus NSP4 protein and bacterial toxins have the ability to induce intracellular Ca2 + elevation. Our findings demonstrate that application of the L-type Ca2+ channel (LTCC) agonist FPL-64176 or the Ca2+ mobilizing agent thapsigargin (a sarco/endoplasmic reticulum Ca2+-ATPase inhibitor) cause vomiting in the least shrew, whereas blockade of LTCC by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic activity against diverse emetogens including agonists of 5-HT3 (e.g. 5-HT or 2-Me-5-HT)-, NK1(GR73632)-, D2 (apomorphine or quinpirole)-, and M1 (McN-A343)-receptors, but can also potentiate the antiemetic efficacy of well-established antiemetic palonosetron against the non-specific emetogen, cisplatin. The transmission of emesis signals in the gastrointestinal tract and brainstem is crucially dependent on Ca2+ channels in neurons. In this review, we will examine the current knowledge on the role of Ca2+ channels and Ca2+-dependent signaling pathways in the perception and modulation of emesis.
A Double-Edged Sword and Swinging Pendulum: The Evolving Role of Percutaneous Endoscopic Gastrostomy Tubes in Patients with Advanced Dementia
Percutaneous Endoscopic Gastrostomy (PEG) tubes have been increasingly utilized in recent decades accompanying the rise in prevalence of disorders that require long-term nonoral enteral feeding such as Cerebrovascular accident (CVA), head and neck cancer and most notably advanced dementia.1,2 The population of patients with dementia is expected to increase worldwide due to shifts in aging demographics leading to an estimate of 81 million people with this condition by 2040.3 A commonly encountered challenge in adults with advanced dementia is the development of difficulty with mastication and swallowing leading to weight loss, malnutrition and risk of aspiration pneumonia.4,5 One long-term intervention to manage such malnutrition and risk of aspiration is the provision of enteral feeding through a percutaneous endoscopic gastrostomy (PEG) tube given the proposed nutritional, medication administration, and quality of life benefits.6 However such benefits are controversial given lack of randomized controlled data as well as conflicting evidence regarding the prevalence of complications of PEG tubes compared to the actual benefit received with respect to morbidity and mortality from malnutrition and dysphagia. Multiple studies have revealed that PEG tubes in nursing home residents with advanced dementia do not in fact improve survival, nor prevent or help heal decubitus ulcers in this group of patients.7-10 Additionally, risks of aspiration are not eliminated by PEG tube placement.11,12 Finally, PEG tube insertion is associated with procedure-related complications such as bleeding, wound infection, aspiration events, tube leakage and dislodgment, buriedbumper syndrome, necrotizing fasciitis and peritonitis.1,13-15 Of note, certain factors have been shown to predict the occurrence of complications following PEG insertion including low body mass index, malignancy, low serum albumin and neurologic diseases.
Percutaneous Endoscopic Gastrostomy (PEG)
Capsule Endoscopy: Indications, Findings and Complications among Patients with Suspected Small Bowel Lesions
Background/Aims: Until a few years back, evaluation of small bowel pathology was unsatisfactory because of the inability to completely visualize the small bowel mucosa with the available endoscopic and radiological techniques. Since the advent of capsule endoscopy at the beginning of the millennium it became the gold standard for the diagnosis of most diseases of the small intestine. At present capsule endoscopy still have some limitations; it lacks the ability to obtain tissue biopsy or provide endoscopic treatment and cannot be controlled remotely. But the near future foreshadows capsules that can perform drug delivery and tissue sampling. Although, capsule endoscopy is considered a simple, safe, and a non-invasive reliable technique, retention of the capsule is the main complication of the procedure. Patients and Methods: This study was conducted to assess the indications, findings, and complications of CE among patients with suspected small bowel lesions. It also studies the effect of small bowel transit time on the diagnostic yield of the capsular endoscopy and the effect of gastric transit time on complete small bowel examination. A total of 119 patients with suspected small bowel disease received CE examination at the department of gastroenterology of Ibn-sina and Fedail Hospitals in Sudan, during the period from January 2010 to June 2011. Conclusion: Capsule endoscopy is a very useful diagnostic tool, especially in the presence of a strong suspicion of small bowel pathology. The duration of small bowel transit time during capsule endoscopy does not affect its diagnostic yield. The latter is affected by the underlying indication. Capsule retention was the main complication and in 10% the capsule examination was not complete as the capsule did not reach the ileocecal valve. The gastric transit time was not associated with complete examination rate. Repeating the capsule endoscopy in patients with a previously negative capsule examination and a high suspicion of small bowel pathology may reveal additional finding in the majority of patients.
Effect of Chronic Proton Pump Inhibitor Use on Serum Magnesium Levels in Pediatric Patients
Hypomagnesemia has been reported in adult patients on Proton Pump Inhibitor (PPI) therapy. No studies have described the effect of this class on medications on Magnesium (Mg) levels in children. This was a retrospective cohort study assessing serum Mg levels in patients on PPI therapy followed by a pediatric gastroenterology service at a tertiary center. The study included 31 patients with a mean age of 7.8 years with 74 serum Mg levels. Duration of PPI therapy ranged between few days to more than 8 years. The main indication for PPI therapy was gastroesophageal reflux disease. Only 2 patients, of adult age, had Mg levels below the normal reference limit of 1.6 mg/dL. In one patient, multiple risk factors for hypomagnesemia were noted. For the entire cohort, there was no statistically significant difference in serum Mg levels over time or with chronic use (defined as more than 2 years). This study did not identify any patient less than 18 years of age with hypomagnesemia while on PPI therapy. Prospective larger long-term pediatric studies may still be needed to better assess the incidence of hypomagnesemia in children on PPI therapy.
Tenofovir Disoproxil Fumarate Treatment for Pediatric Patients with Perinatally Acquired Chronic Hepatitis B
Objectives: Infection with Hepatitis B Virus (HBV) is an important cause of chronic liver disease in children. Perinatal transmission accounts for the majority of infections. We examined the effects of Tenofovir Disoproxil Fumarate (TDF) on pediatric patients with perinatally acquired Chronic Hepatitis B (CHB). Methods: We retrospectively analyzed the data on pediatric patients with perinatally acquired CHB treated with TDF over a 72-week period. Results: 55 cases were analyzed of which 26 were treated. Fourteen (54%) had immune active hepatitis and 12(46%) were in the immune tolerant phase. In both groups, no difference in inflammation or fibrosis was found on baseline liver biopsy. Mean HBV DNA level at baseline was 9 log10 copies/mL. Levels declined to 5.9 log10 copies/mL at 40 weeks of therapy and were undetectable in 19/26(73%) of the patients by week 72. Alanine aminotransferase (ALT) levels normalized by 32 weeks in the immune active hepatitis group. No breakthrough elevations were seen in either group. Overall, 11(42%) and 9(35%) of the patients had Hepatitis B e antigen (HBeAg) clearance and Hepatitis B e antibody (anti-HBe) seroconversion respectively by 72 weeks of treatment. Conclusion: TDF is an effective therapy in pediatric patients with perinatally acquired CHB in both immune active hepatitis and immune tolerant phase patients. Response to treatment did not seem to be affected by baseline ALT levels and liver histopathology findings.
Therapeutic and Chemopreventive Effects of Ursodeoxycholic Acid (UDCA): Potential Role in Patients with Barrett’s Esophagus
Ursodeoxycholic Acid (UDCA) is widely used for the treatment of cholestatic liver diseases. Major mechanisms of this action are protection of cholangiocytes against cytotoxicity of hydrophobic bile acids, stimulation of hepatobiliary secretion, and protection of hepatocytes against bile acid induced apoptosis. UDCA has also been shown to modulate mitochondrial transmembrane potential and prevent increases in mitochondrial Reactive Oxygen Species (ROS) production. Moreover, UDCA has been shown to have a chemopreventive role in mouse models of colon cancer and in patients with primary sclerosing cholangitis and concomitant Inflammatory Bowel Disease (IBD), low dose UDCA lowers the risk of IBD-associated colorectal neoplasia. Our studies suggest that oral UDCA may protect against DNA damage induced by hydrophobic bile acids such as Deoxycholic acid (DCA) in the metaplastic mucosa of patients with Barrett’s esophagus. We have found that DCA induces carcinogenic DNA damage in Barrett’s metaplasia. UDCA which counters the DNA damaging effects of DCA therefore might have a role as a chemopreventive agent in Barrett’s metaplasia. Future clinical studies on the
Biphasic Roles of a Small G-Protein, RAC1 in Pancreatic Β-Cell
Glucose-stimulated insulin secretion (GSIS) involves cross talk between small Gproteins and their regulating factors. These interactions results in translocation of insulin-laden granules to the plasma membrane for fusion and insulin release. Vesicular transport and fusion events are tightly regulated by signals which coordinate between vesicle- and membrane-associated docking proteins. It is now being accepted that small G-protein, Rac1-mediated Reactive Oxygen Species (ROS) functions as a second messenger in islet β-cell function. Further, evidence from multiple laboratories suggests a tonic increase in ROS generation is necessary for GSIS and fatty acid-induced insulin secretion. On the other hand, Rac1-mediated NADPH oxidase-activation and subsequent generation of excessive ROS under glucolipotoxic conditions and cytokines exposure has proven to be detrimental for islet β-cell function. In this review we overview the normal physiological effects (positive role) and adverse effects (negative role) of activated small G-protein, Rac1 in pancreatic β-cells.
Brunner Gland Cyst: Two Cases of a Rare Entity and Review of the Literature
Objective: Brunner gland cysts are rare with only 14 cases reported in the literature. The term has been used to consolidate the following entities: Brunner’s gland cyst, cystic Brunner’s gland hamartoma, Brunner’s gland cystadenoma and mucocele of the Brunner gland. Methods: We present the clinico-pathological features of two cases of Brunner gland cyst along with a review of the literature. Results: Brunner gland cyst affects slightly more men than women. The age range is 30 to 72 years with an average of 55 years. The lesions range from 1 to 5 cm in size, the average being 2.3 cm in greatest dimension. The majority of lesions are found incidentally in patients with symptoms not specifically related to the lesion. They affect predominantly the first and second portion of duodenum. The majority of the lesions are single and pedunculated filling the submucosa. They can be unilocular or contain multiple cysts divided by fine septae. The epithelial lining is of columnar and clear cells with basally located nuclei. Conclusion: Brunner gland cysts are benign lesions that are usually not diagnosed pre-operatively. The cases described here add awareness of this entity among pathologists and gastroenterologists allowing for a better recognition of this rare entity.
Endoscopic Ultrasound Diagnosis of Perianal Rhabdomyosarcoma
A 27-year-old male with no significant past medical history, presented to the emergency room with symptoms of perianal pain. Additionally, the patient complained of cramps in his legs and buttocks for approximately one month. The cramps were initially minor but progressively worsened and then became constant. His vitals and physical examination were normal except for his digital rectal examination, which was painful and tender. However, no obvious mass was felt in the rectum. His initial blood tests were unremarkable which included hemoglobin-14 g/dl (Nv-13.5-16.5), white cell count-8.9 (Nv-4.5-11), platelets-324 (Nv-150- 400), blood urea nitrogen-12 (Nv-7-25), creatinine 1.2 (Nv-0.4-1.24), sodium-140 (Nv-137- 145) and potassium of 3.7 (Nv-3.5-5.1). Pelvic Computed Tomography (CT) (Figure 1) showed a mass in the perianal region measuring 12 cm with metastasis to the left iliac and obturator lymph nodes. In view of the CT findings, other lab tests like Carcinoembryonic antigen (CEA)- 0.5 (Nv-<3 ng/ml), CA 19-9-10 (Nv-<35 u/ml), Human Immunodeficiency Virus (HIV), Human papillomavirus (HPV) and Chlamydia were checked and were all within normal range. The patient then underwent lower EUS, which showed a 5 cm hypoechoic mass (Figure 2) just outside the anal canal. An FNA was obtained which showed neoplastic cells (Figure 3A). The cells were largely mononuclear, with a few binucleate and multinucleate cells. These cells had a high nuclear cytoplasmic ratio with a relatively round nucleus. Immunohistochemical stain was positive for muscle (desmin) and more precisely for striated muscle (myogenin, Figure 3B), supporting the diagnosis of Rhabdomyosarcoma. Subsequent Fluorescent in situ hybridization (FISH) performed using DNA probe specific for the FOXO1 (FKHR) gene on 13q14 showed a signal pattern suggestive of rearrangement of FOXO1 gene. Rearrangement of FOXO1 is associated with a diagnosis of Alveolar Rhabdomyosarcoma. Unfortunately, the patient was a poor candidate for curative treatment due to the presence of distal metastasis. However, he underwent adjuvant chemotherapy and radiation therapy for treatment of his cancer.
Massive Gastric Variceal Bleeding in a Patient with Chronic Pancreatitis
Left-sided portal hypertension (LSPH) is a rare form of portal hypertension that usually occurs as a result of isolated obstruction and thrombosis of the splenic vein. We present a case of a 45-year-old male patient with history of repetitive chronic pancreatitis exacerbations, who was hospitalized because of the severe gastric variceal bleeding and hemorrhagic shock, developed as a complication of the splenic vein thrombosis and LSPH. Splenectomy is the treatment of choice, but in this case, because of the patient`s severe general condition and significant risk of new surgical procedure (extensive fibrous adhesions in abdomen), transcatheter embolization of the splenic artery was undertaken as the method of “nonsurgical splenectomy”. Upper endoscopy was performed two weeks after embolization and it showed significantly reduced gastric varices, with no signs of bleeding, what brings us indirectly to a conclusion that the embolization significantly decreased pressure in the portal circulation. KEYWORDS: Left-sided portal hypertension (LSPH); Pancreatitis; Gastric varices; Bleeding; Embolization. ABBREVIATIONS: LSPH: Left-sided portal hypertension; MSCT: Multi Slice Computer Tomography; SVT: Splenic Vein Thrombosis.
Percutaneous Endoscopic Gastrostomy: Use and Abuse in Clinical Practice
Nowadays, Percutaneous Endoscopic Gastrostomy (PEG) is considered the method of choice for long-term enteral feeding, and is spreading all over the world because of its effectiveness and easy carrying out. This review encompasses indications and contraindications of PEG tube placement, and deals with the problem of the growing disconnect between scientific evidence and clinical practice. Despite the evidence shows an advantage in the outcome from PEG placement only in selected subgroups of patients, this technique is also used for questionable indications in clinical practice, such as advanced dementia, permanent vegetative state, and even in end-life patients. Such an overuse is indirectly confirmed by several studies reporting a high 30-day mortality rate after PEG placement in elderly patients. The decision of placing PEG in end-stage patients involves very complex ethical issues, and the authors of this review are not so pretentious as to think themselves capable of dealing with and solving such a dramatic issue. However, patients’ interests should be better protected by a case-by-case decision making, based not only on technical competence, but also on sympathetic awareness, avoiding to perform procedures that can be disadvantageous for the patients.
Non-alcoholic Fatty Liver Disease and the Gut Microbiota: Exploring the Connection
As the gut microbiota continues to be implicated in an increasing number of disease processes, a plethora of new literature surrounding its complexity and role in the maintenance of intestinal homeostasis has become available. Non-alcoholic fatty liver disease (NAFLD) has become the most common nonviral liver disease worldwide and a number of predisposing risk factors for NAFLD have been identified, including obesity and insulin resistance. Recent evidence supports a role for the gut microbiota in the pathogenesis of these risk factors and NAFLD, itself. Additionally, changes in the gut microbiota can lead to activation of immune responses that have the potential to promote progression of NAFLD to the more severe Nonalcoholic steatohepatitis (NASH). Furthermore, the gut microbiota may serve as a potential target for therapeutic options to treat NAFLD. This review seeks to explain the role of the gut microbiota in the pathogenesis of NAFLD and its risk factors, while also discussing potential future treatment options directed at correcting imbalances with in the gut microbiota.
Mucinous Tumour in Ileal Pouch Post Restorative Proctocolectomy and Ileal Pouch Anal Anastomosis for Familial Adenomatous Polyposis
We present a fifty-six years old female having surveillance gastroscopy and colonoscopy ten years after a restorative proctocolectomy and Ileal-pouch anal anastomosis (IPAA). This was performed for Familial Adenomatous Polyposis (FAP). The patient was found to have unusual patchy nodular areas of abnormal mucosa in the ileal pouch and at the level of the anastomosis. Magnetic Resonance Imaging (MRI) was performed which showed a large fluid collection (12x10x13 cm) within the pelvis. Histopathology from biopsy was reported as a low grade mucinous tumour with abundant mucoid material containing scattered degenerate cellular material and histiocytes. Computed Tomography (CT) of chest and pelvis did not reveal any evidence of metastatic disease. A pelvic exenteration was performed and patient underwent adjuvant radiotherapy. Histopathology showed cystic mass 50 mm × 50 mm × 30 mm in size containing mucin of intermediate nuclear grade with 0/18 nodes involved (Figure 1).