Robert J. Huang

Acute fulminant hepatic failure associated with parvovirus B19 infection in an immunocompetent adult.

A previously healthy 21-year-old female presented with epigastric pain, nausea, vomiting, arthralgias, and decreased appetite. Three weeks before presentation, she had developed cough, fevers, chills, and coryza immediately following a similar illness in her 4-year-old daughter. Although in the interval her respiratory symptoms had resolved, she continued to experience fevers, chills, and arthralgias. Three days before presentation she began to notice mid-epigastric pain, severe headache, profound nausea, and non-bilious, non-bloody vomiting. She denied other sick exposures, alcohol use, illicit drug use, or recent travel history. At an outside hospital, an aspartate aminotransferase level (AST) of 954 U/L (normal value, 10–32 U/L), alanine aminotransferase level (ALT) of 1,300 U/L (0–30 U/L), total bilirubin level of 3.9 mg/dL (normal value, 0.2– 1.2 mg/dL), and alkaline phosphatase level of 98 U/L (normal value, 30–120 U/L) were reported. She was discharged home with instructions to return if symptoms worsened. One day later, she presented to Stanford University Medical Center with worsening symptoms. On physical examination she was visibly jaundiced, in significant distress, with right-upper to mid-epigastric tenderness to palpation, but without peritoneal signs. Repeat laboratories revealed AST of 9,348 U/L, ALT of 9,337 U/L, total bilirubin level of 2.4 mg/dL, alkaline phosphatase level of 109 U/L, and an international normalized ratio (INR) of 3.1 (normal value, 0.8–1.20), with anemia and thrombocytopenia (hemoglobin = 10.6 g/DL; platelet count =140 9 10/lL; WBC = 8.2 9 10/lL). A right-upper quadrant ultrasound revealed marked concentric gallbladder wall thickening, a nonspecific finding but suggestive of underlying hepatitis. There were no gallstones, pericholecystic fluid, or evidence of intraor extrahepatic biliary dilatation found, and portal flow was normal. The patient was admitted with a diagnosis of acute hepatitis. Antibody and serum DNA polymerase chain reaction testing for HIV, hepatitis A, B, and C were negative. DNA polymerase chain reaction testing for adenovirus, cytomegalovirus, and Epstein-Barr virus were negative, as was urine nucleic acid testing for C. trachomatis and N. gonorrhoeae. Acetaminophen level was \2.0 lg/mL (normal value, \2.0 lg/mL). Urine toxicology screen was negative. The anti-nuclear antibody result and anti-smooth muscle antibody results were negative at the laboratory detection threshold. The serum IgG level was 1,270 mg/dL (normal range, 800–1,800 mg/dL) and ceruloplasmin level was 18 mg/dL (normal range 20–35 mg/dL). Ferritin was elevated at [10,000 ng/mL (upper limit of detection), indicating an acute inflammatory process. Serum iron was normal at 117 lg/dL (normal range 50–175 lg/dL), and TIBC slightly decreased at 194 lg/dL (normal range 250–410 lg/dL). HFE gene testing for C282Y, H63D, and S65C were ultimately negative. Over the next 2 days, she symptomatically improved with supportive care. Her epigastric pain resolved, her nausea and vomiting improved, and her appetite returned. Her subjective chills, headache, and arthralgias improved as well. Her liver function tests revealed AST of 4,363, R. J. Huang (&) B. C. Varr G. Triadafilopoulos Stanford University Medical Center, Stanford, CA, USA e-mail: rjhuang@stanford.edu

Affordable Care Act and healthcare delivery: A comparison of California and Florida hospitals and emergency departments

Importance The Affordable Care Act (ACA) has expanded access to health insurance for millions of Americans, but the impact of Medicaid expansion on healthcare delivery and utilization remains uncertain. Objective To determine the early impact of the Medicaid expansion component of ACA on hospital and ED utilization in California, a state that implemented the Medicaid expansion component of ACA and Florida, a state that did not. Design Analyze all ED encounters and hospitalizations in California and Florida from 2009 to 2014 and evaluate trends by payer and diagnostic category. Data were collected from State Inpatient Databases, State Emergency Department Databases and the California Office of Statewide Health Planning and Development. Setting Hospital and ED encounters. Participants Population-based study of California and Florida state residents. Exposure Implementation of Medicaid expansion component of ACA in California in 2014. Main outcomes or measures Changes in ED visits and hospitalizations by payer, percentage of patients hospitalized after an ED encounter, top diagnostic categories for ED and hospital encounters. Results In California, Medicaid ED visits increased 33% after Medicaid expansion implementation and self-pay visits decreased by 25% compared with a 5.7% increase in the rate of Medicaid patient ED visits and a 5.1% decrease in rate of self-pay patient visits in Florida. In addition, California experienced a 15.4% increase in Medicaid inpatient stays and a 25% decrease in self pay stays. Trends in the percentage of patients admitted to the hospital from the ED were notable; a 5.4% decrease in hospital admissions originating from the ED in California, and a 2.1% decrease in Florida from 2013 to 2014. Conclusions and relevance We observed a significant shift in payer for ED visits and hospitalizations after Medicaid expansion in California without a significant change in top diagnoses or overall rate of these ED visits and hospitalizations. There appears to be a shift in reimbursement burden from patients and hospitals to the government without a dramatic shift in patterns of ED or hospital utilization.

Effects of a Brief Educational Program on Optimization of Fluoroscopy to Minimize Radiation Exposure During Endoscopic Retrograde Cholangiopancreatography

Background & Aims Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) is increasingly performed by therapeutic endoscopists, many of whom have not received formal training in modulating fluoroscopy use to minimize radiation exposure. Exposure to ionizing radiation has significant health consequences for patients and endoscopists. We aimed to evaluate whether a 20‐minute educational intervention for endoscopists would improve use of fluoroscopy and decrease ERCP‐associated exposure to radiation for patients. Methods We collected data from 583 ERCPs, performed in California from June 2010 through November 2012; 331 were performed at baseline and 252 following endoscopist education. The educational intervention comprised a 20‐minute video explaining best practices for fluoroscopy, coupled with implementation of a formal fluoroscopy time‐out protocol before the ERCP was performed. Our primary outcome was the effect of the educational intervention on direct and surrogate markers of patient radiation exposure associated with ERCPs performed by high‐volume endoscopists (HVEs) (200 or more ERCPs/year) vs low‐volume endoscopists (LVEs) (fewer than 200 ERCPs/year). Results At baseline, total radiation dose and dose area product were significantly higher for LVEs, but there was no significant difference between HVEs and LVEs following education. Education was associated with significant reductions in median fluoroscopy time (48% reduction for HVEs vs 30% reduction for LVEs), total radiation dose (28% reduction for HVEs vs 52% for LVEs) and dose area product (35% reduction for HVEs vs 48% reduction for LVEs). All endoscopists significantly increased their use of low magnification and collimation following education. Conclusions A 20‐minute educational program with emphasis on ideal use of modifiable fluoroscopy machine settings results in an immediate and significant reduction in ERCP‐associated patient radiation exposure for low‐volume and high‐volume endoscopists. Training programs should consider radiation education for advanced endoscopy fellows.

The Gastroenterology Fellowship Match: A Decade Later

Following a period of uncertainty and disorganization, the gastroenterology (GI) national leadership decided to reinstitute the fellowship match (the Match) under the auspices of the National Residency Matching Program (NRMP) in 2006. Although it has now been a decade since the rebirth of the Match, there have been limited data published regarding progress made. In this piece, we discuss reasons for the original collapse of the GI Match, including most notably a perceived oversupply of GI physicians and a poor job market. We discuss the negative impacts the absence of the Match had on programs and on applicants, as well as the impetus to reorganize the Match under the NRMP. We then utilize data published annually by the NRMP to demonstrate that in the decade since its rebirth, the GI Match has been remarkably successful in terms of attracting the participation of applicants and programs. We show that previous misguided concerns of an oversupply of GI physicians were not realized, and that GI fellowship positions remain highly competitive for internal medicine applicants. Finally, we discuss possible implications of recent changes in the healthcare landscape on the GI Match.

A prospective evaluation of radiation-free direct solitary cholangioscopy for the management of choledocholithiasis

BACKGROUND AND AIMS Endoscopy has replaced many radiologic studies for the GI tract. However, ERCP remains a hybrid endoscopic-fluoroscopic procedure, which limits its portable delivery, creates delays because of fluoroscopy room unavailability, and exposes patients and providers to radiation. We evaluated fluoroscopy/radiation-free management of patients with noncomplex choledocholithiasis using direct solitary cholangioscopy (DSC). METHODS Patients underwent fluoroscopy-free biliary cannulation, sphincterotomy, and then cholangioscopy to establish location and number/size of stones and to document distance from ampulla to bifurcation to guide balloon advancement. Stones were extracted using a marked balloon catheter advanced to the bifurcation and inflated to the bile duct diameter, documented on prior imaging. Repeat cholangioscopy was performed to confirm stone clearance. RESULTS Fluoroscopy-free biliary cannulation was successful in all 40 patients (100%). Advanced cannulation techniques were required in 5 patients. Papillary balloon dilation was performed in 8 patients and electrohydraulic lithotripsy in 3 patients. Discrete stones were visualized in 31 patients and stone debris/sludge in 8 patients. Fluoroscopy-free stone/debris/sludge extraction was successful in all these patients. Brief fluoroscopy was used in 2 patients (5%) to confirm stone clearance. No stone/debris/sludge was noted in 1 patient. Mild pancreatitis was noted in 2 patients (5%) and bleeding in 1 (2.5%). CONCLUSIONS This study establishes the feasibility of fluoroscopy/radiation-free, cholangioscopic management of noncomplex choledocholithiasis with success and adverse event rates similar to standard ERCP. DSC represents a significant procedural advance in the management of biliary disorders that does not need to be confined to the fluoroscopy suite and can be reimagined as bedside procedures in emergency department or intensive care unit settings. (Clinical trial registration number: NCT03074201.).

Colonoscopy with polypectomy is associated with a low rate of complications in patients with cirrhosis

Background and study aims: Cirrhotic patients are at a theoretically increased risk of bleeding. The safety of polypectomy in cirrhosis is poorly defined. Patients and methods: We performed a retrospective review of patients with cirrhosis who underwent colonoscopic polypectomy at a tertiary-care hospital. Patient characteristics and polyp data were collected. Development of complications including immediate bleeding, delayed bleeding, hospitalization, blood transfusion, perforation, and death were recorded to 30-day follow-up. Clinical characteristics between bleeders and non-bleeders were compared, and predictors of bleeding were determined. Results: A total of 307 colonoscopies with 638 polypectomies were identified. Immediate bleeding occurred in 7.5 % (95 % CI 4.6 % – 10.4 %) and delayed bleeding occurred in 0.3 % (95 % CI 0.0 % – 0.9 %) of colonoscopies. All cases of immediate bleeding were controlled endoscopically and none resulted in serious complication. The rate of hospitalization was 0.7 % (95 % CI 0.0 % – 1.6 %) and repeat colonoscopy 0.3 % (95 % CI 0.0 % – 0.9 %); no cases of perforation, blood transfusion, or death occurred. Lower platelet count, higher INR, presence of ascites, and presence of esophageal varices were associated with increased risk of bleeding. Use of electrocautery was associated with a lower risk of immediate bleeding. There was no significant difference between bleeding and non-bleeding polyps with regard to size, morphology, and histology. Conclusions: Colonoscopy with polypectomy appears safe in patients with cirrhosis. There is a low risk of major complications. The risk of immediate bleeding appears higher than an average risk population; however, most bleeding is self-limited or can be controlled endoscopically. Bleeding tends to occur with more advanced liver disease. Both the sequelae of portal hypertension and coagulation abnormalities are predictive of bleeding.

Isoniazid hepatotoxicity requiring liver transplantation.

A 65-year-old female Peruvian immigrant was initially evaluated for potential initiation of anti-tumor necrosis factor (TNF)-a therapy for her poorly controlled rheumatoid arthritis. The patient had a history of thyroid cancer that had required thyroidectomy and replacement levothyroxine. The patient’s quantiferon test was positive, and she also had a history of aspartate transaminase (AST) and alanine transaminase (ALT) values between 40 and 60 IU/ L for at least the previous 4 years. Previous laboratory evaluation had revealed a positive anti-nuclear antibody (ANA) titer at dilution of 1:640 with homogeneous pattern, positive anti-smooth muscle antibody, and elevated immunoglobulin G (IgG) levels at 2,310 mg/dL. The patient, however, denied any prior history of chronic liver disease; consequently, no further evaluation was pursued. Isoniazid (INH) prophylaxis for latent tuberculosis infection (LTBI), was instituted for an expected nine-month course. The patient did not take any dietary or herbal supplements and did not drink alcohol. One month after initiating INH, the patient sought evaluation for jaundice, nausea, and fatigue. Her total bilirubin level was 11.3 mg/ dL, direct bilirubin level 8.6 mg/dL, AST 1,642 IU/L, ALT 1,576 IU/L, alkaline phosphatase 246 IU/L, albumin 3.0 g/ dL, and international normalized ratio 1.2. Serologic testing for acute viral hepatitis was negative. Because of presumed INH hepatotoxicity, INH was discontinued. Two weeks later, the patient complained of worsening nausea as well as new-onset ascites and lower extremity edema. Her total bilirubin was 27.8 mg/dL, direct bilirubin 21.6 mg/ dL, AST 726 IU/L, ALT 588 IU/L, alkaline phosphatase 254 IU/L, albumin 2.4 g/dL, and international normalized ratio 1.8. Triphasic contrast CT imaging demonstrated a shrunken and nodular liver and moderate-volume ascites. The patient was treated with spironolactone, furosemide, and subcutaneous vitamin K, but continued to feel poorly. Two weeks later, she developed encephalopathy with worsening renal insufficiency and international normalized ratio rising to 2.3. She was transferred to Stanford Hospital for urgent liver transplant evaluation. Upon transfer, WBC was 14.2 K/lL, platelet count 112 K/lL, sodium level 126 mmol/L, potassium level 5.4 mmol/L, CO2 18 mmol/L, BUN 57 mg/dL, creatinine 2.9 mg/dL, AST 229 IU/L, ALT 251 IU/L, total bilirubin 26.1 mg/dL, alkaline phosphatase 502 IU/L, albumin 1.4 g/dL, and international normalized ratio 2.6. The patient’s model for end-stage liver disease (MELD) score was 40. Expedited transplant evaluation was initiated, and supportive care was provided with lactulose, rifaximin, and intravenous albumin. The patient also received intravenous vitamin K as well as fresh frozen plasma transfusions. Despite these measures, the patient experienced worsening encephalopathy, azotemia, and hepatic synthetic dysfunction. On E. Sheen (&) M. H. Nguyen Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, Stanford University, Alway Building, Room M-211, 300 Pasteur Drive, Stanford, CA 94305, USA e-mail: esheen@stanford.edu

Two Evils: Gastrocolic Fistula and Heart Failure

A 35-year old man was transferred to Stanford Hospital for further care of Crohn’s disease (CD) pancolitis complicated by fistula formation. He had no significant past medical history other than his CD, which was diagnosed three and a half years before admission. He had no prior history of heart disease and he had not experienced any recent symptoms of viral infection. He had, nevertheless, noted gradual worsening of his functional status over the year before admission, with increasing fatigue, dyspnea on exertion, and intermittent lower extremity edema. There was no family history of inflammatory bowel disease or heart failure. The patient did not smoke, drink, or use any illicit drugs, and was currently unemployed. The patient had been diagnosed with CD with terminal ileitis and perianal involvement and treated with adalimumab and methotrexate, with previous lack of response to infliximab. He had lost health insurance coverage several times after his diagnosis of CD and had thus been unable to receive anti-tumor necrosis factor (TNF)-a therapy at times. He was admitted to an outside hospital with 50 lb weight loss accompanied by post-prandial feculent emesis. Computed tomography (CT) of the abdomen revealed severe colitis and gastrocolic fistula extending from the posterior gastric wall to the distal transverse colon (Fig. 1). A left ventricular thrombus was also detected by CT imaging. Transthoracic echocardiography revealed severe left ventricular dysfunction with ejection fraction 20–25 %. The patient was subsequently empirically treated with ceftriaxone, IV heparin, peripheral parenteral nutrition (PPN), and ‘‘bowel rest’’, and transferred to Stanford Hospital to receive a higher level of care. At Stanford, the patient was afebrile, normotensive, and remained clinically stable without low output heart failure. The possibilities of viral myocarditis, familial cardiomyopathy, and substance abuse-induced cardiomyopathy were considered but there was no evidence of these etiologies. The patient was tachycardic on presentation but this was thought to be most likely a compensatory response to his heart failure. The possibility of tachycardia-induced cardiomyopathy was considered but was not supported by his disease course. Cardiac magnetic resonance imaging (MRI) revealed marked left ventricular enlargement with substantially reduced systolic function, severe diffuse ventricular hypokinesis, and estimated left ventricular ejection fraction (LVEF) of 14 % (Fig. 2). Left ventricular trabeculations were present but did not meet criteria for noncompaction cardiomyopathy. The patient was initially treated with low-dose carvedilol, digoxin, and spironolactone. Lisinopril was also initiated but was subsequently discontinued because of hypotension. Repeat echocardiogram confirmed the presence of a left ventricular thrombus necessitating anticoagulation with E. Sheen (&) Division of Gastroenterology and Hepatology, Department of Medicine, Stanford School of Medicine, Alway Building, Room M-211, 300 Pasteur Drive, Stanford, CA 94305, USA e-mail: esheen@stanford.edu

Scoping the scope: endoscopic evaluation of endoscope working channels with a new high-resolution inspection endoscope (with video)

BACKGROUND AND AIMS Outbreaks of transmission of infection related to endoscopy despite reported adherence to reprocessing guidelines warrant scrutiny of all potential contributing factors. Recent reports from ambulatory surgery centers indicated widespread significant occult damage within endoscope working channels, raising concerns regarding the potential detrimental impact of this damage on the adequacy of endoscope reprocessing. METHODS We inspected working channels of all 68 endoscopes at our academic institution using a novel flexible inspection endoscope. Inspections were recorded and videos reviewed by 3 investigators to evaluate and rate channel damage and/or debris. Working channel rinsates were obtained from all endoscopes, and adenosine triphosphate (ATP) bioluminescence was measured. RESULTS Overall endoscope working channel damage was rated as minimal and/or mild and was consistent with expected wear and tear (median 1.59 on our 5-point scale). Our predominant findings included superficial scratches (98.5%) and scratches with adherent peel (76.5%). No channel perforations, stains, or burns were detected. The extent of damage was not predicted by endoscope age. Minor punctate debris was common, and a few small drops of fluid were noted in 42.6% of endoscopes after reprocessing and drying. The presence of residual fluid predicted higher ATP bioluminescence values. The presence of visualized working channel damage or debris was not associated with elevated ATP bioluminescence values. CONCLUSION The flexible inspection endoscope enables high-resolution imaging of endoscope working channels and offers endoscopy units an additional modality for endoscope surveillance, potentially complementing bacterial cultures and ATP values. Our study, conducted in a busy academic endoscopy unit, indicated predominately mild damage to endoscope working channels, which did not correlate with elevated ATP values.

A Chance to Cut Is a Chance to Cure: Endoscopic Submucosal Dissection for Early Gastric Cancer

A 71-year-old woman who is a first-generation immigrant from North Africa with a history of insulin-dependent diabetes mellitus, essential hypertension, and medically controlled hyperlipidemia was referred for incidentally noted asymptomatic mild normocytic anemia and a positive fecal occult blood test. At the time of referral, her hemoglobin was 11.4 g/d and her hematocrit 33.6%, with a mean corpuscular volume of 91.6 fL. She reported being in her usual state of health, without melena, hematochezia, nausea, vomiting, dysphagia, abdominal pain, weight loss, fever, chills, or change in bowel habits. She recalled having undergone a colonoscopy more than 20 years prior to referral, but she had had never had an upper endoscopic evaluation. Upper endoscopic evaluation revealed a 2.5-cm elevated lesion (Paris classification type 0-IIa) arising from the lesser curvature of the antrum and extending toward the incisura angularis (Fig. 1); the proximal stomach, esophagus, and duodenum were without endoscopic abnormality; colonoscopy was unrevealing. Biopsies from the antral mass revealed fragments of low-grade dysplasia and extensive intestinal metaplasia without Helicobacter pylori (Hp) organisms seen, whereas biopsies of the stomach corpus also revealed extensive intestinal metaplasia without dysplasia or Hp. As a staging computed tomographic (CT) scan showed no evidence of regional or distant malignant disease, she was referred for endoscopic submucosal dissection (ESD) of her gastric lesion. Endoscopy demonstrated no evidence of “tethering” or other endoscopic evidence of deep invasion. The border of the lesion was then marked 5 mm from the polyp edge using a cautery (Fig. 2A). Injection just outside of the border markings was made with a solution of saline, 6% hetastarch, epinephrine (1:500,000), and indigo carmine. Following circumferential incision with a flush knife (Fig. 2B), dissection along the submucosal plane was performed utilizing an insulated tip knife (Fig. 2C), and visible vessels within the submucosa were treated with coagulation forceps. The polyp demonstrated excellent “lift” such that the underside of the mucosa was exposed during dissection with no muscularis propria injury visualized. The specimen was resected en bloc, pinned to a corkboard, and processed for histology (Fig. 2D). Histologic sections of the endoscopic dissection specimen demonstrated a 3-cm adenomatous polyp arising in gastric mucosa with intestinal metaplasia, which contained a 7-mm focus of invasive adenocarcinoma (Fig. 3A) that was poorly differentiated with invasion into the submucosa and evidence of multifocal lymphovascular invasion (Fig. 3B). The resection specimen demonstrated a mucosal (deep) resection margin of 0.9 mm and a radial resection margin of 0.1 mm. The lesion was assigned an American Joint Committee on Cancer, 8th edition, pathologic stage of pT1b (submucosal invasion without invasion into muscularis propria). Immunohistochemical testing performed on the adenocarcinoma revealed loss of expression of mismatch repair proteins MutL homolog 1 (MLH1) and post-meiotic segregation increased 2 (PMS2), and negative human epidermal growth factor receptor 2 (HER2) expression; additional testing revealed hypermethylation of the promotor region of MLH1. Following resection, she was referred to the oncologic tumor board for further management. Given the angio-lymphatic involvement, the poor differentiation of the tumor on histology, and her overall good state of health, she was offered surgical resection. One month following endoscopic * Robert J. Huang rjhuang@stanford.edu