Background and Aims: Early-stage small intestinal neuroendocrine tumors (SI-NETs) are generally asymptomatic and difficult to diagnose. As a result, patients often present with late-stage incurable disease. SI-NETs originate from enterochromaffin (EC) cells, which develop enteroendocrine cell (EEC) clusters consisting of a subset of EC cells at the crypt bottom at an early stage of tumor progression. In a familial form of SI-NET, EEC clusters arise in a multifocal and polyclonal fashion. We sought to determine whether early detection and analysis of cryptal EEC clusters could provide insight into the development of SI-NETs and allow successful pre-symptomatic screening for at risk family members of patients with SI-NETs. Methods: Isolated crypts from endoscopic ileal biopsies or surgically removed specimens from 43 patients with familial SI-NET and 20 controls were formalin-fixed, immunostained for chromogranin A, and examined by confocal three-dimensional analysis for the presence of EEC cluster formations. Results: Examination of multiple areas of macroscopic tumor-free mucosa in surgically resected specimens from patients with familial SI-NET revealed widely distributed, independent, multifocal EEC micro-tumor formations of varying sizes. Consistent with this finding, randomly sampled ileal biopsy specimens identified aberrant crypt containing endocrine cell clusters (ACECs) in patients. ACECs were found exclusively in patients (23/43, 53%) and not in controls (0/20). Furthermore, analysis of positions and numbers of EECs in crypts and ACECs indicated significant increases in EECs at the crypt bottom, predominantly at positions 0 and 1′ ( p < 0.0001 compared to controls), suggesting the progression of EEC accumulation below +4 position as the early process of ACEC formation. These findings also suggested that ACECs were precursors in the development of micro-tumors and subsequent macro-tumors. Conclusion: This study indicates that SI-NETs develop from deep crypt EC cells to become ACECs, micro-tumors, and ultimately gross tumors. This process occurs widely throughout the distal small intestine in patients with familial SI-NETs consistent with but not exclusively explained by germline disease. Finally, analysis of crypts from ileal biopsies could contribute in part to earlier diagnostic screening processes avoiding late-stage presentation of incurable disease.

Saleh, Sherif MD; Dalal, Shaman MD; Desai, Aakash MD; Thomas, Charles BA; Chitsaz, Ehsan MD Author Information

Background: Response to a trial of proton pump inhibitors (PPIs) is currently accepted as a first step in the management of gastroesophageal reflux disease (GERD). However, information on the diagnostic performance of the PPI test is limited. Aim: The aim of this study was to determine the diagnostic accuracy of the PPI test in GERD and noncardiac chest pain (NCCP) and to assess the test performance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD). Methods: Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and MEDLINE were searched for studies reporting the diagnostic accuracy of the PPI test in adult patients with typical GERD and NCCP who underwent evaluation using an accepted reference standard, from January 1, 1950, through February 1, 2021. Subgroup analyses were performed, and the risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: Nineteen studies (GERD=11, NCCP=8) involving 1691 patients were included. In GERD, the PPI test had 79% pooled sensitivity [95% confidence interval (CI), 72%-84%], and 45% pooled specificity (95% CI, 40%-49%). In NCCP, pooled sensitivity and specificity were 79% (95% CI, 69%-86%) and 79% (95% CI, 69%-86%), respectively. In ERD, the PPI test had 76% pooled sensitivity (95% CI, 66%-84%) and 30% pooled specificity (95% CI, 8%-67%). In NERD, the PPI test had 79% pooled sensitivity (95% CI, 70%-86%) and 50% pooled specificity (95% CI, 39%-61%). Conclusions: The PPI test was sensitive in GERD but with suboptimal specificity. The test performed better in GERD-related NCCP. Diagnostic accuracy was comparable in ERD and NERD.

Colon cancer can present with variable clinical manifestations. An unusual finding is the direct dissemination of colon adenocarcinoma through the abdominal wall and skin. We present a rare case of complicated diverticulitis with abscess formation that demonstrates diagnosis of colonic adenocarcinoma from necrotic skin tissue upon debridement. In the modern world of widespread use of colonoscopy screening, the initial diagnosis of colon cancer is declining. This particular case, however, illustrates the value of maintaining a high index of suspicion in patients with diver-ticulitis complicated by abscess formation

Introduction: Symptomatic response to PPIs remains a popular approach to diagnosing gastroesophageal reflux disease (GERD). Meta-analyses of the “PPI test” diagnostic performance are limited and out-of-date. We conducted a comprehensive systematic review and meta-analysis to examine the diagnostic accuracy of the PPI test in GERD and non-cardiac chest pain (NCCP). Methods: Web of Science, Cochrane Controlled Register of Trials [CENTRAL] and MEDLINE were searched for studies reporting the diagnostic accuracy of the PPI test in adult patients with typical GERD and NCCP who underwent evaluation using an accepted reference standard from January 1st, 1950 through February 1st, 2021. Subgroup analyses were performed based on study design. Summary estimates of sensitivity, specificity, diagnostic odds (DOR), positive and negative likelihood ratios (LR) for the PPI test were determined using bivariate random effects model. All tests were 2 sided; P< 0.05 was considered statistically significant. The area under the receiver operating characteristic curve (AUC) was calculated. Heterogeneity was assessed by the Paule-Mandel tau square (τ2), I2 index, and Cochran’s Q test. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: Nineteen studies (GERD= 11, NCCP= 8) were included involving 1,691 patients. In GERD, the PPI test had 79% pooled sensitivity (95% CI, 72.4%-84%; I2= 59%, P= 0.14), and 45% pooled specificity (95% CI, 40%-49%; I2= 0%). Overall DOR, positive LR and negative LR were 2.30 (95% CI, 1.78-3.0, I2= 0), 1.36 (95% CI, 1.15-1.60), and 0.54 (95% CI, 0.4-0.74), respectively. In NCCP, the pooled sensitivity and specificity were 79% (95% CI, 69%-86%; I2= 29%, P= 0.23) and 79% (95% CI, 69%-86%; I2= 22% P= 0.28), respectively. Overall DOR, positive LR, and negative LR were: 17.27 (95% CI, 8.84-33.71; I2=0%), 3.91 (95% CI, 2.60-5.89) and 0.26 (95% CI, 0.17-0.39), respectively. The AUC was 0.62 and 0.85 in GERD and NCCP, respectively. Conclusion: The PPI test was highly accurate in GERD-related NCCP, sensitive in typical GERD but with suboptimal specificity.Figure 1.: Forest plots of PPI test pooled estimates of (A) sensitivity and (B) specificity in GERD and NCCP. Abbreviations: PPI, proton pump inhibitor; GERD, gastroesophageal reflux disease; NCCP, non-cardiac chest pain; CI, confidence interval; RCT, randomized clinical trials.Table 1.: Characteristics of Included Studies. Abbreviations: GERD, gastroesophageal reflux disease; NCCP: non-cardiac chest pain; BID, twice daily; NA, not available; PPI, proton pump inhibitor.

Introduction: In clinical setting, the PPI test remains a reasonable diagnostic tool for patients with suspected gastroesophageal reflux disease (GERD). Erosive reflux disease (ERD) and non-erosive reflux disease (NERD) are 2 distinct phenotypes of GERD. More information is needed about the utility of the PPI test in these 2 groups. We conducted a systematic review and meta-analysis to examine the diagnostic performance of the PPI test in patients with ERD and NERD. Methods: Web of Science, Cochrane Controlled Register of Trials [CENTRAL] and PubMed/MEDLINE were searched for studies reporting the diagnostic accuracy of the PPI test in adult patients with GERD who underwent evaluation using upper endoscopy and esophageal pH-monitoring from January 1st, 1950 through February 1st, 2021. Subgroup analyses were performed based on study design and GERD phenotype. Summary estimates of sensitivity, specificity and diagnostic odds for the PPI test were determined using bivariate random effects model. Heterogeneity was assessed by the Paule-Mandel tau square (τ2), I2 index, and Cochran’s Q test. Results: A total of 5 studies involving 127 ERD patients and 172 NERD patients were included in the final analysis. In ERD, the PPI test had 76% pooled sensitivity (95% CI, 66%-84%; I2= 0%, P= 0.28) and 30% pooled specificity (95% CI, 8%-67%; I2= 66%, P= 0.76). In NERD, the PPI test had 79% pooled sensitivity (95% CI, 70%-86%; I2= 0%, P= 0.28) and 50% pooled specificity (95% CI, 39%-61%;I2= 0%, P= 0.54).The overall diagnostic odds ratio (DOR) was 1.41 (95% CI, 0.30-0.68;I2= 57%, P= 0.10) in ERD and 3.83 (95% CI, 1.92-7.61; I2= 0%, P= 0.87) in NERD. Conclusion: The PPI test performed slightly better in NERD but with overall comparable diagnostic utility in both phenotypes. Future studies with larger cohorts stratified by GERD phenotype are needed to further investigate our findings.Figure 1.: Forest Plots of Pooled Estimates of (A) Sensitivity and (B) Specificity of The PPI test in ERD and NERD.Table 1.: Characteristics of study included in analysis. Abbreviations: No., number; PPI, proton pump inhibitor; M, male; F, female; NA, not available; pH-metry, esophageal pH-monitoring; BID, twice daily.

INTRODUCTION: Covid-19 pandemic has changed every aspect of everyday life globally and this includes performing endoscopic procedures with appropriate infection control to ensure safety of both patients and providers. Evidence suggests higher rates of transmissibility of the virus through aerosolized droplets during upper endoscopies as well as viral particles detected though feces. Initial statements by joint GI societies recommendation provided preliminary framework for infection control during procedures. However, optimal strategies in resuming endoscopies are still not fully understood. We aim to describe a protocol to uniformly test patients for upper endoscopies (including EGD, EUS, ERCP, etc) prior to the procedure date presenting to a large tertiary hospital in urban settings. METHODS: All patients referred to the Cuyahoga county hospital in Cleveland, OH for elective upper endoscopic procedures were included between 5/ 6 to 5/22/2020. Patients were screened over the phone 1–3 days prior to their procedure. This included symptom screening (cough, fevers, dyspnea or acute diarrhea), hx of exposure, or recent travel history to endemic areas. If screened negative per questionnaire, then will be referred for SARS-2 nasal swab real-time PCR 24 hours prior to the procedure. RESULTS: Over the course of 2 week period, a total of 138 asymptomatic patients were referred for real-time nasal swab PCR testing with 65% completion rate of test among them. Of those not completing the test, 6 proceeded with their procedures (and were considered as if they tested positive) and the rest were no shows for their endoscopies. A total of 3 out of 90 (3.33%) patients tested returned positive for SARS-2. CONCLUSION: Even though 3.33% positivity rate in asymptomatic patients does not seem very significant, this is a relatively high rate in the northeast Ohio were the disease prevalence was lower than national average. Detecting positive patients is not only important from PPE and proper intraprocedural infection control but also is important from public health stand point where infected patients can come into contact a larger number of patients (many of whom are at higher risk for the infection given their comorbidities), health care providers and staff, and contaminating the equipment, endoscopy rooms, etc. Therefore, standard clinical and PCR testing for asymptomatic patients tend to identify asymptomatic patients and even 24-hr prior testing seem to have a relatively good feasibility and adherence among patients.

INTRODUCTION: Non cardiac chest pain (NCCP) is among the most common conditions evaluated in theprimary and specialty outpatient clinics. Gastroesophageal Reflux Disease (GERD) is the most commoncause of NCCP. A treatment trial with proton pump inhibitor test, also known as the “PPI-test" is commonly for the diagnosis of GERD-related NCCP. However, the studies evaluating the accuracy of this diagnostic modality have shown variable results in the past due to variable definition of the PPI test as well as inconsistent inclusion of the studies. We aim to perform a meta-analysis that evaluates the accuracy of the well-defined PPI-test in diagnosing NCCP using only controlled clinical trials. METHODS: We performed a systematic review of the controlled clinical trials examining a short course (1, 2 or 4 weeks) of high dose PPI as a diagnostic test for patients with suspected GERD that were published between Jan 01, 1950 and Feb 01, 2020. MEDLine, Web of Science, and Cochrane Controlled Register ofTrials (CENTRAL) were systematically searched with controlled vocabulary as well as key word searching. Hand searching and cross reference checking was performed. A total of 3874 studies were screened and 14 studies were included in the final analysis. We calculated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), pooled Diagnostic Odds Ratio (DOR), and pooled positive predictive value (PPV) and negative predictive values (NPV )and SROC curves were examined. We used randomeffects model in Meta- DiSc Version 1.4 to calculate pooled estimates and the corresponding 95%confidence intervals. RESULTS: A total of 8 studies that included. 285 patients met the inclusion criteria. The pooled estimates forboth sensitivity and specificity of PPI test were 78% (70%-84%) and corresponding positive and negative likelihood ratios were estimated at 3.21 (2.36–4.36) and 0.30 (0.20–0.43) respectively and diagnostic odds ratio (DOR) was 17.2 (8.84–33.7). After sensitivity analysis, and removal of a study with suboptimal randomization, the heterogeneity index I 2 markedly decreased from 39% to 0% and the respective pooled estimates indicated sensitivity of 82%, specificity of 78%, positive likelihood ratio of 3.31, negative likelihood ratio of 0.25, and diagnostic odds ratio of 21.24. CONCLUSION: PPI-test, defined as clinical response to diagnostic trial with high dose PPI for 1-4 weeksconfers high diagnostic accuracy for GERD-related non-cardiac chest pain.Figure 1.: Pooled sensitivity and specificity of PPI test in diagnosing GERD-related non-cardiac chest pain.Figure 2.: Pooled Diagnostic Odds ratio (DOR) and summary receiver operating characteristics (SROC) of PPI test in diagnosing GERD-related non-cardiac chest pain.

INTRODUCTION: Clinical response to a trial of proton pump inhibitors (PPI) in patients with suspected GERD is commonly used in clinical practice to diagnose GERD. Despite its pivotal role as a widely used approach as the first line in clinical practice, its diagnostic utility has been discredited mainly due to a prior commonly cited meta-analysis that did not show high diagnostic performance for the PPI-test. However, this study had major methodological issues including using an inconsistent/variable definition of the PPI test, including non-GERD trials, as well as using GERD treatment efficacy trials (rather than diagnostic trials) among the studies included in the meta-analysis. METHODS: We performed a systematic review of the controlled clinical trials examining a short course (1, 2 or 4 weeks) of high dose PPI as a diagnostic test for patients with suspected GERD that were published between Jan 01, 1950 and Feb 01, 2020. MEDLine, Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) were systematically searched with controlled vocabulary as well as key word searching. Hand searching and cross reference checking was performed. A total of 3874 studies were screened and 14 studies were included in the final analysis. We calculated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), pooled Diagnostic Odds Ratio (DOR), and pooled positive predictive value (PPV) and negative predictive values (NPV) and SROC curves were examined. We used random effects model in Meta-DiSc Version 1.4 to calculate pooled estimates and the corresponding 95% confidence intervals. RESULTS: GERD was diagnosed in all studies by the presence of abnormal endoscopic findings and/or an abnormal 24-hour ambulatory esophageal pH metry. Of the total of 1642 patients with GERD symptoms, the pooled estimates revealed sensitivity of 71.4% (68.6%–74.1%), specificity 49.3% (45.1%–53.5%), DOR 2.71 (2.07–3.66), positive LR 1.38, negative LR 5.52, PPV 72.2%, and NPV 48.3%. There was a significant heterogeneity between studies signified by I 2 = 79.5% and chi-squared 63.5 (P < 0.001). After sensitivity analysis with 12 studies, the pooled sensitivity, specificity, positive LR, negative LR, and DOR were 75%, 45%, 1.32, 0.58 and 2.36 respectively. CONCLUSION: The PPI test shows high sensitivity in diagnosing GERD but low specificity which may be due to positive response of conditions other than GERD including reflux hypersensitivity.Figure 1.: Pooled sensitivity and specificity of PPI test in diagnosing GERD.Figure 2.: Pooled Diagnostic Odds ratio (DOR) and summary receiver operating characteristics (SROC) of PPI test in diagnosing GERD.

Background and Aims Autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED), caused by autoimmune regulator (AIRE) mutations, manifests with chronic mucocutaneous candidiasis (CMC) and multisystem autoimmunity, most often hypoparathyroidism (HP) and adrenal insufficiency (AI). European cohorts previously reported a ~10% prevalence of APECED‐associated hepatitis (APAH) with presentations ranging from asymptomatic laboratory derangements to fatal fulminant hepatic failure. Herein, we characterized APAH in a large APECED cohort from the Americas. Approach and Results Forty‐five consecutive patients with APECED were evaluated (2013‐2015) at the National Institutes of Health (NIH; NCT01386437). Hepatology consultation assessed hepatic and autoimmune biomarkers and liver ultrasound in all patients. Liver biopsies evaluated autoimmune features and fibrosis. The 16S ribosomal RNA (rRNA) sequencing was performed in 35 patients’ stools (12 with and 23 without APAH). Among 43 evaluable patients, 18 (42%) had APAH; in 33.3% of those with APAH, APAH occurred before developing classic APECED diagnostic criteria. At APAH diagnosis, the median age was 7.8 years, and patients manifested with aminotransferase elevation and/or hyperbilirubinemia. All patients with APAH were in clinical remission during their NIH evaluation while receiving immunomodulatory treatment. We found no difference in age, sex, or prevalence of CMC, AI, or HP between patients with or without APAH. Autoantibody positivity against aromatic L‐amino acid decarboxylase, cytochrome P450 family 1 subfamily A member 2, histidine decarboxylase (HDC), bactericidal/permeability‐increasing fold‐containing B1, tryptophan hydroxlase, and 21‐hydroxylase (21‐OH), and the homozygous c.967_979del13 AIRE mutation were associated with APAH development. Classical serological biomarkers of autoimmune hepatitis (AIH) were only sporadically positive. AIH‐like lymphoplasmacytic inflammation with mild fibrosis was the predominant histological feature. Stool microbiome analysis found Slackia and Acidaminococcus in greater abundance in patients with APAH. Conclusions APAH is more common than previously described, may present early before classic APECED manifestations, and most often manifests with milder, treatment‐responsive disease. Several APECED‐associated autoantibodies, but not standard AIH‐associated biomarkers, correlate with APAH.

INTRODUCTION: Acute on chronic mesenteric ischemia resulting in cecal/terminal ileum perforation in a symptomatic patient. This is an important differential to consider with unknown etiology of abdominal pain, weight loss, and diarrhea. CASE DESCRIPTION/METHODS: A 61 year-old man initially presented with diarrhea (up to 15 bowel movements per day, non-bloody with nocturnal episodes), intermittent abdominal pain, weight loss (40 pounds), and dyspepsia. He had a history of reflux symptoms for a couple years, and was recently started on a proton pump inhibitor with minimal improvement. Initial EGD and colonoscopy were unremarkable including normal biopsies of the stomach. Labs consisted of normal celiac serologies, negative stool cultures and Clostridium difficile, and normal TSH, hemoglobin, pancreatic elastase, and ESR/CRP. A CT abdomen/pelvis was also unremarkable except for atherosclerotic calcifications within the celiac axis and SMA. He was placed on a combination of a proton pump inhibitor, dicyclomine, diphenoxylate/atropine, loperamide, duloxetine, and eluxadoline. A repeat CT scan of the abdomen revealed small splenic infarcts, with unremarkable hematologic work-up. Repeat EGD and colonoscopy were negative including biopsies. Video capsule endoscopy showed multiple ulcerations in the jejunum which were subsequently biopsied. Histology revealed superficial ulceration, active inflammation, and eosinophilia. Tissue culture including AFB was unremarkable. Worsening abdominal pain prompted a CT scan which showed a dilated cecum and pneumatosis in the setting of sepsis. Exploratory laparotomy was performed which revealed a necrotic cecum and distal ileum with an absent SMA pulse. Resection of necrotic small bowel and cecum with SMA bypass and antegrade anastomosis was completed. Final pathology of the resected tissue showed ischemic enterocolitis with focal mucosal ulceration, transmural acute and chronic inflammation, and acute serositis. DISCUSSION: The clinical presentation of weight loss, diarrhea, dyspepsia and abdominal pain was initially treated as GERD and IBS (diarrhea predominant). The patient presented to the emergency room prior to the final diagnosis of acute on chronic mesenteric ischemia, which is usually made by CT or MR angiography. In a patient with risk factors for mesenteric ischemia, including atherosclerosis and splenic infarcts, this should prompt additional work-up accordingly.Figure 1.: Ischemic enterocolitis: mucosal ulceration and associated purulent exudate, transmural acute and chronic inflammation, and acute serositis.Figure 2.: Cecal dilation with pneumatosis.Figure 3.: Ulcerated lesion with central clean base and adjacent erythema and dilated lacteals located in the jejunum.

Question: A 56-year-old man with no significant past medical history presented for age-appropriate average-risk screening colonoscopy. Gastrointestinal review of systems was negative for abdominal pain, diarrhea, constipation, weight loss, or blood in the stool. Laboratory data showed normal hemoglobin of 13.8 g/dL, mean corpuscular volume of 93 fL, and white blood cell count of 5.9 with normal neutrophils, lymphocytes, and eosinophils. During colonoscopy and upon intubation of cecum, innumerable “small white strands” were noted on the mucosa of colon and terminal ileum on both white light as well as narrow band imaging (Figure A–D). The patient is a Mexican immigrant who, for the past 10 years, has lived and worked on a farm in the mid-Atlantic region of the United States with exposure to livestock, dogs, and rodents. He denied any close sick contacts recently. However, he reported history of parasitic infection in 5 of his children back in Mexico more than a decade ago for which the entire family received medical treatment. He denied any close contact with his family since he migrated to the United States. The fluid in the lumen of colon was aspirated and the microscopic analysis is depicted in Figure A–D. What is the diagnosis and what would be the best management? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The gross anatomy of the aspirated fluid revealed thread-like tape worms. Light microscopy confirmed the diagnosis of Hymenolepis nana (“dwarf tapeworm”) with presence of gravid proglottids and eggs being released from the adult worm (Figure E-G). H nana is the most common human cestode. It is more common in populations living with poor hygiene and inadequate sanitation and particularly where fleas and rodents are present.1Tanaka K. Hamada Y. Nakamura M. et al.Hymenolepis nana infection detected by magnifying colonoscopy with narrow-band imaging (with video).Gastrointest Endosc. 2017; 86: 923-924Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar The adult worms usually measure 15 to 40 mm and have a short life span of 4 to 6 weeks. They may be mistaken with Enterobius vermicularis (pinworms), which are the most common human nematodes. Rodents are the primary definitive hosts with the intermediate hosts being arthropods such as grain beetles and fleas. Human beings can be infected either with incidental ingestion of parasitized intermediate insects or through the fecal–oral cycle by direct ingestion of eggs present in soil or contaminated food. Ingested eggs usually open in the duodenum and oncospheres invade the mucosal villi to evolve into cysticercoids. Then, they are released upon rupture of villi and complete the life cycle to produce adult worms, which then attach to mucosa in the distal small bowel. The majority of the infections are clinically silent; however, patients with heavy infections may become symptomatic and present with abdominal pain, diarrhea, nausea, weight loss, or pruritus ani. The diagnosis is usually made through identification of worms or eggs in the stool specimen and recommended treatment is 1-time dose of praziquantel with a repeat dose in 10 days. Case reports from Korea, Japan, and Saudi Arabia describe detection of H nana infection on colonoscopy in 3 patients (2 of these patients manifested gastrointestinal symptoms).2Cho S.C. Lee H.L. Lee O.Y. et al.Hymenolepis nana infection of the colon in an adult male.Gastrointest Endosc. 2009; 70: 784-785Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Parasitic infections have low prevalence in the United States and the detection of parasites on screening colonoscopy is even more rare. This patient represents a rare case of H Nana infection diagnosed on screening colonoscopy in an asymptomatic farmer with potential exposure to fleas and with poor sanitation in his living condition. Careful mucosal examination during colonoscopy even among asymptomatic patients but with appropriate risk profile leads to the timely diagnosis and treatment of infected individuals.

Question: A 65-year-old Caucasian woman with a history of severe aplastic anemia status post hematopoietic stem cell transplant was referred for the evaluation of unexplained thrombocytopenia and esophageal varices identified during a surveillance computed tomography scan. Serologic workup was unrevealing for viral hepatitides and other etiologies of chronic liver disease. Given the lack of a clinical diagnosis, with evidence of portal hypertension, the patient underwent a transjugular liver biopsy (TJLB) and hepatic venous pressure gradient measurements followed by esophagogastroduodenoscopy (EGD) to confirm the presence of varices during the same procedural session. The TJLB was performed using carbon dioxide (CO2) angiography, owing to the patient’s history of severe iodinated contrast allergy. Hepatic vein catheterization, hepatoportal pressure measurements and liver biopsy (Figure A) were technically successful without evidence of immediate intraprocedural complications. EGD was performed immediately after TJLB, which was notable for nonbleeding large esophageal varices, normal stomach, and normal duodenal bulb (Figure B). However, upon entry into the second portion of duodenum, the lumen was filled with a considerable amount of black-colored fluid, intraluminal “smoke,” floating bubbles of gas, and small streaks of red blood in the examined portion of duodenum (Figure C). What are the black fluid and intraluminal smoke and what is the etiology of these findings in duodenum? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. With concern for post liver biopsy bleeding and resultant hemobilia, the patient was admitted for observation. Her hemoglobin decreased to 11.7 from preprocedural levels of 13.3. However, there was no overt gastrointestinal bleeding, melena, or hematemesis, and the patient remained hemodynamically stable with no requirement for transfusion of blood products. The incidence of bleeding, including hemobilia, after liver biopsy is <1%.1Rogart J. Aslanian H. massive hemobilia after transjugular liver biopsy treated endoscopically and angiographically.Clin Gastroenterol Hepatol. 2008; 6: A30Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar It can occur immediately or up to 1 week after biopsy. Acute bleeding usually presents with the bright red color of fresh blood. Blood color alters in the acidic environment of the stomach with the heme-iron being oxidized, creating a coffee grounds appearance or through enzymatic alteration by digestive enzymes or intestinal bacteria rendering a melena—dark black appearance in the distal small bowel or colon with a long transit time.2Walker B. Colledge N. Ralston S. Davidson's principles and practice of medicine. 22nd ed. Churchill Livingstone, Edinburgh2014: 854Google Scholar Carbaminohemoglobin, a product of direct reaction of hemoglobin with CO2 results in the uncoupling of oxygen and hemoglobin and hence the dark blue/purple appearance of venous blood. However, in normal circumstances, only 10% to 20% of CO2 is transported bound to hemoglobin while the remainder is transported as dissolved CO2-bicarbonate resulting in the very mild color changes of venous blood.3Hall J. Guyton and Hall textbook of medical physiology.13th ed. Saunders, Philadelphia2015: 534Google Scholar Our patient represents a rare case of immediate post biopsy hemobilia. Although fresh blood in the duodenum and specifically hemobilia are expected to have a bright red color, the use of CO2 in our case and hence the abundant intravascular and intraluminal CO2 gas concentration caused the instantaneous production of large quantities of carbaminohemoglobin resulting in the unique black color of the fresh blood as well as appearance of smoke in the bowel lumen. Although use of CO2 contrast is not uncommon and post biopsy bleeds are not too rare, performing EGD immediately after TJLB in our case allowed for timely detection of uniquely discolored hemobilia.

Table 1.Outcomes per 1000 40-year-olds for screening strategies with similar age to start and age to stop screening as the selected benchmark colonoscopy strategy.