A Review of IgG4-related Sclerosing Cholangitis (IgG4-SC).

IgG4-related sclerosing cholangitis (IgG4-SC) is a unique, steroid-responsive, fibroinflammatory condition that is more commonly found in older men and is strongly associated with autoimmune pancreatitis (AIP). It may pose a diagnostic challenge at times due to closely mimicking hepatobiliary diseases such as primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and cholangiocarcinoma. IgG4-SC has an excellent prognosis when promptly diagnosed and treated with steroids. Literature search strategy: The authors searched PubMed and Google Scholar, for articles with the search terms "autoimmune cholangiopathy" and "IgG4 cholangiopathy."

Biennial Endoscopic Surveillance of Gastrointestinal Metaplasia and Its Subtypes Reduces Gastric Cancer Mortality and Is Cost-Effective in a Markov State Transition Model.

OBJECTIVES: Gastric cancer in the United States has a low survival rate mainly because of the late stage of diagnosis. Furthermore, there are no well-established guidelines concerning screening and surveillance even for higher risk patients such as those with nondysplastic noncardia gastrointestinal metaplasia (GIM), and thus they are not routinely performed. This study was designed to provide new evidence-based data that can be used to support the implementation of biennial surveillance guidelines in individuals with nondysplastic noncardia GIM. This practice can help detect early malignant lesions, thereby decreasing morbidity and mortality. We evaluated the cost-effectiveness of surveillance endoscopies for noncardia gastric cancer in populations with two different pathological diagnoses: mixed GIM and incomplete GIM (iGIM). METHODS: Markov state transition models were developed using a cohort simulation of 1000 hypothetical patients. Analysis was conducted for both mixed and iGIM. Quality-adjusted life-years and transition probabilities were derived from the published medical literature. Costs associated with endoscopy, cancer care, and surgery were based on Medicare reimbursement. A willingness-to-pay threshold of $100,000 per quality-adjusted life-year was used to determine cost-effectiveness. RESULTS: Our study determined that it is significantly cost-effective to perform biennial endoscopy surveillance in patients who have been incidentally found to have noncardia mixed GIM, with a cost savings of $5783.84 per person, and in those with iGIM, with a cost savings of $8093.08 per person. CONCLUSIONS: Biennial endoscopy surveillance should be considered in all individuals found to have mixed or incomplete noncardia GIM on endoscopy. Furthermore, screening specifically for iGIM after differentiating between the two groups can lead to further cost savings. As such, we recommend that pathologists routinely differentiate between the two and recommend robust routine surveillance of iGIM.

Esophageal Cancer: An Updated Review.

The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a result, people of certain regions of the world can be more prone to a subtype. For example, squamous cell carcinoma of the esophagus has the highest incidence in eastern Africa and eastern Asia, with smoking being a major risk factor, whereas adenocarcinoma is more prevalent in North America and western Europe, with gastroesophageal reflux disease being a leading risk factor. With that being said, adenocarcinoma and squamous cell carcinoma have similar and unfortunately poor survival rates, partly because EC is prone to early metastasis given that the esophagus does not have a serosa, as well as the superficial nature of its lymphatics compared with the rest of the gastrointestinal tract. This makes early detection of the utmost importance, and certain patients have been shown to have the benefit of screening/surveillance endoscopies, including those with Barrett's esophagus, lye-induced/caustic strictures, tylosis, and Peutz-Jeghers syndrome. Until treatments significantly improve, identifying EC at the earliest stage will have the best success for patient outcomes, and further elucidation of its pathogenesis and risk factors may lead to identifying other high-risk groups that should be screened.

Obesity reduces the requirement for subsequent esophageal stricture dilation in adults with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) causes esophageal narrowing and strictures, but factors that modify the severity of strictures and requirement for subsequent dilation are not well described. The aim of this study was to identify characteristics that impact the need for repeat (> 1) esophageal dilations in EoE patients. METHODS: This was a single center retrospective cohort study over a 12-year period (September 2005-October 2017). Patients were identified using ICD9, ICD10, and CPT codes for esophageal dilation, eosinophilic esophagitis, and esophageal obstruction. Data for EoE clinical characteristics, treatments, and BMI were extracted and correlated to the number of esophageal dilations and time elapsed between dilations. RESULTS: Of the 21 patients who met inclusion criteria, 11 (52%) had at least two dilations and 9 (43%) had three dilations. There was no differences baseline demographics between patients who needed ≥ 2 vs. those who needed one dilation. However, patients with a BMI > 30 had a significantly longer median time to second dilation compared to non-obese patients (4.9 years vs. 1.8 years; p = 0.027). Stratification by either high dose PPI or inhaled steroid use did not change this result. CONCLUSIONS: EoE patients with strictures who are obese have a reduced requirement for subsequent esophageal dilation. While the mechanism for this is not clear, increased attention of non-obese patients with fibrostenotic EoE is indicated as they are at higher risk for recurrent strictures.

Acute management of pancreatitis: the key to best outcomes.

Acute pancreatitis (AP) accounts for over 230 000 US and 28 000 UK hospital admissions annually. Abdominal pain is the most common presenting symptom in AP but may not reflect severity. The clinical challenge is identifying the 20% of patients in whom AP will be severe. We summarise the common aetiologies, the risk stratification strategies including the simplified Bedside Index for Severity in Acute Pancreatitis, acute management approaches in the initial presentation setting, conditions for using advance imaging and opinions on antibiotic use. Some warning signs of impending complications are also discussed.

Diverticular Disease: The Old, the New, and the Ever-Changing View.

Our understanding of diverticular disease has evolved significantly during the last 25 years, and as such, a reexamination is in order. We performed a literature search for the years 1960-2017 of PubMed, Medline, and Google Scholar for updates regarding the epidemiology, risk factors, and therapies for traditional diverticulitis as well as the recently described subtypes of diverticular disease, segmental colitis associated with diverticulosis, and symptomatic uncomplicated diverticular disease. Although the prevalence of diverticulosis is still extremely common in the general population, the literature suggests that the incidence of diverticulitis is much less than previously believed and occurrences do not necessarily increase with age. In addition, the commonly held beliefs that low-fiber diets alone contribute to the development of diverticulosis and diverticulitis have not been verified; however, the combination of a low-fiber diet and a high red meat/high-fat diet is a risk factor for diverticulitis. Surgery continues to be the treatment for severe complications of diverticulitis, but new literature suggests that it has a poor utility in preventing a recurrence of diverticulitis in the long term; therefore, elective surgery after two episodes of diverticulitis is no longer the standard.

Hemobilia: An Uncommon But Notable Cause of Upper Gastrointestinal Bleeding.

GOAL AND BACKGROUND: A literature review to improve practitioners' knowledge and performance concerning the epidemiology, diagnosis, and management of hemobilia. STUDY: A search of Pubmed, Google Scholar, and Medline was conducted using the keyword hemobilia and relevant articles were reviewed and analyzed. The findings pertaining to hemobilia etiology, investigation, and management techniques were considered and organized by clinicians practiced in hemobilia. RESULTS: The majority of current hemobilia cases have an iatrogenic cause from either bile duct or liver manipulation. Blunt trauma is also a significant cause of hemobilia. The classic triad presentation of right upper quadrant pain, jaundice, and upper gastrointestinal bleeding is rarely seen. Computed tomography and magnetic resonance imaging are the preferred diagnostic modalities, and the preferred therapeutic management includes interventional radiology and endoscopic retrograde cholangiopancreatography. Surgery is rarely a therapeutic option. CONCLUSIONS: With advances in computed tomography and magnetic resonance imaging technology, diagnosis with these less invasive investigations are the favored option. However, traditional catheter angiography is still the gold standard. The management of significant hemobilia is still centered on arterial embolization, but arterial and biliary stents have become accepted alternative therapies.

Trends in esophageal cancer survival in United States adults from 1973 to 2009: A SEER database analysis.

BACKGROUND AND AIM: The rise in incidence of esophageal cancer (EC) in the USA over the last four decades has been well documented; however, data on trends in long-term survival and impact on modern therapies associated with survival are lacking. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients with confirmed EC. Cox proportional hazard regression was used to determine independent mortality factors. RESULTS: Of 93 167 patients diagnosed with EC between 1973 and 2009, 49% had a histologic diagnosis of esophageal adenocarcinoma (EAC). There was an increase (almost double) in the proportion of patients with adenocarcinoma from the 1970s to 2000s (n = 2,350; 35% to n = 32,212; 61%, P < 0.001). Surgery was performed for localized disease in a majority of EC regardless of type (n = 46 683; 89%). Use of surgical treatment increased significantly over the study period (49% to 64%, P < 0.001). There was also an increase in overall median survival (6 months versus 10 months, P < 0.001) and 5-year survival rate (9% to 22%, P < 0.001). Median survival increased consistently for EAC and squamous cell carcinoma (SCC) until the 1990s. After this period, median survival of EAC continued to increase more rapidly while SCC remained relatively stable. CONCLUSION: A significant survival improvement in esophageal cancer was seen from 1973 to 2009, largely because of earlier detection at a curative stage and greater utilization of treatment modalities (especially surgery). Despite the rising prevalence, patients with EAC have better long-term survival outcomes than those SCC.

Second harmonic generation imaging distinguishes both high-grade dysplasia and cancer from normal colonic mucosa.

BACKGROUND AND AIM: Second harmonic generation (SHG) is a novel imaging technology that could provide optical biopsy during endoscopy with advantages over current technology. SHG has the unique ability to evaluate the amount of extracellular matrix collagen protein and its alignment. METHODS: Hematoxylin- and eosin-stained slides from colon biopsies (normal, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and cancer) were examined with SHG imaging. Both signal intensity and collagen fiber alignment were measured. Average intensity per pixel (AIPP) was obtained, and an analyzing polarizer was used to calculate ß, an alignment parameter. RESULTS: The mean AIPP for normal mucosa was 48, LGD was 38, HGD was 42, and malignancy was 123 (p < 0.01). The AIPP ROC curve between malignant versus non-malignant tissue was 0.96 (0.93-0.99). An AIPP value of 60 can differentiate malignancy with 87 % sensitivity and 90 % specificity. The mean ß for normal tissue was 0.490, LGD was 0.379, HGD was 0.345, and cancer was 0.453 (p = 0.013), with a normal tissue mean rank of 6.5 compared to 2.5 for HGD (p = 0.029). CONCLUSIONS: SHG signal intensity can differentiate malignant from non-malignant colonic polyp tissue with high sensitivity and specificity. Anisotropic polarization can discern HGD from normal colonic polyp tissue. SHG can thus distinguish both HGD and malignant lesions in an objective numeric fashion, without contrast agents or interpretation skills. SHG could be incorporated into endoscopy equipment to enhance white light endoscopy.

Esophageal Button Battery Retrieval: Time-In May Not Be Everything.

The management of ingested foreign bodies is a challenging task because each case is unique with multiple varying factors including a patient's age, anatomical considerations, clinical presentation, and the type and location of the foreign body ingested. Additionally, concern over complications associated with button battery ingestion typically drives management decisions. The common practice is the urgent retrieval of the foreign body within two to six hours of presentation. An unusual case is presented here that demonstrated significantly delayed endoscopic removal of an ingested button battery without complication, avoiding the many risks associated with any emergent endoscopic procedure. However, this practice is a case-by-case decision because there is a lack of literature to guide the current management.

A review of the current status of endoluminal therapy as a primary approach to obesity management.

Gastroenterologists are expected to play a pivotal role in the management of the global obesity epidemic in coming years as novel endoscopic approaches become more widely available, safe, and effective. This review focuses on the recent advances in the field of endoluminal therapy as a primary approach to obesity management with the aim of providing the interventional endoscopist an overview of currently available evidence along with an insight into upcoming devices and techniques. The intragastric balloon appears to be safe and effective in the short term, especially as a bridge to bariatric surgery. Although early trials support the safety and feasibility of endoscopic gastroplasty, it is technically demanding and staple-line dehiscence continues to be a problem. Moreover, with ongoing technical innovations, most devices that have been used in published trials are no longer manufactured and results of studies using newer endoscopic suturing systems are currently awaited. The duodenojejunal bypass sleeve mimics the physiology of intestinal bypass and shares the metabolic advantages of intestinal diversion. A high rate of premature device withdrawal has been its major limiting factor. Therapeutic endoscopy may be the next paradigm of bariatric care. Combining restrictive and barrier endoscopic techniques can potentially improve efficacy and should be evaluated in the setting of appropriate clinical trials.

The potential utility of serum CA 72-4 as a marker for stage IV esophageal adenocarcinoma.

BACKGROUND: Adenocarcinoma of the esophagus has one of the fastest growing incidence rates of all cancers. The treatment and the prognosis of these patients depend mainly on the clinical stage of their disease. The purpose of this study was to see if CA72-4 can potentially be used as a marker for staging advanced esophageal adenocarcinoma. METHODS: We enrolled a consecutive sample of 21 patients with biopsy-proven esophageal adenocarcinoma. Serum CA72-4 was then obtained from all patients and compared to the clinical stage of these patients. RESULTS: CA 72-4 at cut-off value of > or = 7 U/ml has a high diagnostic performance in detecting stage IV esophageal adenocarcinoma: sensitivity (86%), specificity (93%), NPV(0.93), PPV(0.86), LR+ (12), LR- (0.15), and AUC of 8.5 (CI; 0.62-1.0). CONCLUSION: Clinicians may use serum CA72-41 levels as a predictor of stage IV disease. It may also have utility in reassessing the likelihood of metastatic disease.

Proton pump inhibitors: the good, the bad, and the unwanted.

Proton pump inhibitors (PPIs) are one of the most commonly prescribed classes of medications in the United States. By inhibiting gastric H/K adenosine triphosphatase via covalent binding to the cysteine residues of the proton pump, they provide the most potent acid suppression available. Long-term PPI use accounts for the majority of total PPI use. Absolute indications include peptic ulcer disease, chronic nonsteroidal anti-inflammatory drugs use, treatment of Helicobacter pylori, and erosive esophagitis. Although PPIs are generally considered safe, numerous adverse effects, particularly associated with long-term use have been reported. Many patients receiving chronic PPI therapy do not have clear indications for their use, prompting consideration for reduction or discontinuation of their use. This article reviews the indications for PPI use, the adverse effects/risks involved with their use, and conditions in which their use is controversial.

The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia.

Stromal cells play a central role in promoting the progression of colorectal cancer. Here, we analyze molecular changes within the epithelial and stromal compartments of dysplastic aberrant crypt foci (ACF) formed in the ascending colon, where rapidly developing interval cancers occur. We found strong activation of numerous neutrophil/monocyte chemokines, consistent with localized inflammation. The data also indicated a decrease in interferon signaling and cell-based immunity. The immune checkpoint and T-cell exhaustion gene PDCD1 was one of the most significantly upregulated genes, which was accompanied by a decrease in cytotoxic T-cell effector gene expression. In addition, CDKN2A expression was strongly upregulated in the stroma and downregulated in the epithelium, consistent with diverse changes in senescence-associated signaling on the two tissue compartments. IMPLICATIONS: Decreased CD8 T-cell infiltration within proximal colon ACF occurs within the context of a robust inflammatory response and potential stromal cell senescence, thus providing new insight into potential promotional drivers for tumors in the proximal colon.