Continuing Medical Education Questions: April 2024.

Article Title: The Spigelman Staging System and the Risk of Duodenal and Papillary Cancer in Familial Adenomatous Polyposis. A Systematic Review and Meta-Analysis.

Endoscopic submucosal dissection for the treatment of a large inflammatory fibroid polyp in the gastric antrum prolapsing into the duodenum: A case report.

RATIONALE: Inflammatory fibroid polyp (IFP), also known as Vanek tumor, is a rare, benign gastrointestinal lesion characterized by its inflammatory and fibroid histological features. IFP is often discovered incidentally during endoscopic examinations. It is exceedingly rare for an IFP to prolapse into the duodenum and results in incomplete obstruction of the pylorus. PATIENT CONCERNS: A 64-year-old male patient was admitted to the hospital with recurrent episodes of melena over a 6-month period, along with complaints of dizziness and fatigue in the past 10 days. DIAGNOSES: Gastroscopy showed a giant polypoid mass on the posterior wall of the gastric antrum, prolapsing into the duodenum. Abdominal computer tomography (CT) confirmed the tumor protruding into the duodenum. Pathologic examination of the resected specimen confirmed the IFP diagnosis. INTERVENTIONS: The giant tumor was completely and successfully excised using endoscopic submucosal dissection (ESD). After the surgery, the patient underwent acid suppression and fluid replenishment therapy. OUTCOMES: The patient responded well to ESD and was discharged in stable condition. As of the submission of the case report, there has been no recurrence of the tumor after a 5-month follow-up, and the patient is still under follow-up. LESSONS: While IFPs have traditionally been managed surgically, ESD demonstrates promising treatment outcomes, avoiding the need for surgical distal gastrectomy, and emerges as a safe and effective treatment option.

[Early Duodenal Cancer Resected by Using Laparoscopic and Endoscopic Assistance Surgery in a Patient with Peutz-Jeghers Syndrome].

A 28-year-old female with a history of treatment for small intestinal polyps and characteristic pigmentation of her lip was clinically diagnosed with Peutz-Jeghers syndrome(PJS). Her sister had the pathogenic variant of STK11 upon genetic testing. A 20-mm polyp was identified in the second part the patient's duodenum on routine gastrointestinal surveillance, and biopsy revealed a well-differentiated adenocarcinoma. Laparoscopic partial duodenectomy with endoscopy was planned. After confirming the location of the tumor and Kocherization using a laparoscope, the polyp was resected via submucosal dissection under direct visualization with a small incision. The polyp was diagnosed as well-differentiated adenocarcinoma in situ and was resected without remnants. PJS is characterized by a high incidence of malignant tumors, and lifelong surveillance for gastrointestinal and extra-gastrointestinal tumors is necessary. The incidence of duodenal cancer is not high among patients with PJS. However, surgery for advanced cancer is highly invasive. It is desirable to detect the tumors at an early stage so that they can be resected via a less invasive treatment method such as endoscopic resection or laparoscopic surgery with an endoscope.

Life-threatening Gastrointestinal Bleeding from a Dieulafoy's Lesion in the Duodenum: A Case Report.

Dieulafoy's lesion is a rare cause of gastrointestinal bleeding, accounting for approximately 1-2% of all cases of gastrointestinal bleeding. Dieulafoy's lesion usually occurs in the lesser curvature of the stomach within six centimeters of the gastroesophageal junction. On the other hand, extragastric Dieulafoy's lesions are uncommon. Diagnosing an extragastric Dieulafoy's lesion by endoscopy can be challenging because of its small size and obscure location. The key elements for an accurate diagnosis include heightened awareness and a careful early endoscopic evaluation following a bleeding episode. Various endoscopic hemostatic techniques can be used for treatment. This paper presents a case of successful hemostasis using argon plasma coagulation for a life-threatening duodenal Dieulafoy's lesion.

Intestinal mRNA expression analysis of polarity-related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease.

BACKGROUND: Celiac disease (CD) is a chronic autoimmune disorder characterized by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. It is well established that the integrity of epithelial tight junctions (TJs) and adherens junctions (AJs) plays a crucial role in the pathogenesis of CD. These junctional complexes contribute to the apical-basal polarity of the intestinal epithelial cells, which is crucial for their proper functioning. METHODS: Sixty CD subjects, and 50 controls were enrolled in the current study. Mucosal samples were obtained from the distal duodenum, total RNA was extracted and complementary DNA was synthesized. The relative expression levels of the desired genes were evaluated by quantitative real-time polymerase chain reaction based on ΔΔCt method. The gene-gene interaction network was also constructed using GeneMANIA. RESULTS: CRB3 (p = .0005), LKB1 (p < .0001), and SCRIB (p = .0005) had lower expression in CD patients compared to controls, while PRKCZ expression did not differ between groups (p > .05). CRB3 represented a significant diagnostic value for differentiating CD patients from the control group (p = .02). CONCLUSION: The aim of the current study was to evaluate the changes in the mRNA expression levels of SCRIB, PRKCZ, LKB1, and CRB3 genes in the small intestinal biopsy samples of CD patients in comparison to the healthy control subjects. Our data uncover the importance of polarity-related genes (especially CRB3) in CD pahtomechanism, that may facilitate the planning of the future studies looking for finding innovative diagnostic and therapeutic strategies for CD.

Unusual case of retroperitoneal hematoma and duodenal ulcerative bleeding after nephrectomy: Case report.

RATIONALE: Retroperitoneal hematomas are relatively common in patients undergoing nephrectomy. Herein, we report an unusual case involving a giant retroperitoneal hematoma and subsequent duodenal ulcerative bleeding following a radical nephrectomy. PATIENT CONCERNS: A 77-year-old woman was admitted to our hospital for lower back pain, and she had severe right hydronephrosis and a urinary tract infection. DIAGNOSES: The patient was diagnosed and confirmed as high-grade urothelial carcinoma. INTERVENTIONS: After ineffective conservative treatments, a right radical nephrectomy and ureteral stump resection were performed. The patient received proton pump inhibitors to prevent stress ulcer formation and bleeding. On the first day post-surgery, she had normal gastrointestinal (GI) endoscopy findings. On the second day post-surgery, abdominal computed tomography revealed a retroperitoneal hematoma. Notably, 14 days post-surgery, massive GI bleeding occurred, and GI endoscopy identified an almost perforated ulcer in the bulbar and descending duodenum. OUTCOMES: The patient died on day 15 after surgery. LESSONS: Duodenal ulceration and bleeding might occur following a retroperitoneal hematoma in patients treated with nephrectomy. Timely intervention may prevent duodenal ulcers and complications, and thus could be a promising life-saving intercession.

Efficacy and safety of precutting endoscopic mucosal resection versus endoscopic submucosal dissection for non-ampullary superficial duodenal lesions.

BACKGROUND: Endoscopic treatments for non-ampullary superficial duodenal lesions (NASDLs) are yet to be standardized. Endoscopic submucosal dissection (ESD) for NASDLs demands advanced techniques and a long procedure time to prevent perforation and bleeding. Precutting endoscopic mucosal resection (EMR) is a technical modification of ESD that overcomes the limitations of ESD. This study aimed to compare the efficacy and safety of precutting EMR versus ESD for NASDLs. METHODS: We conducted a retrospective analysis of patients with NASDLs treated with either precutting EMR or ESD from January 2015 to March 2023. RESULTS: A total of 90 patients with NASDLs were analyzed, with 44 patients in the precutting EMR group and 46 patients in the ESD group. The endoscopic procedure achieved satisfactory outcomes in both groups, with en block resection rate of 100.0 %. The R0 resection rates in the precutting EMR and ESD groups were 95.5 % and 93.5 %, respectively. No delayed perforation occurred postoperatively in either group. There were no significant differences between the two groups in age, gender, lesion location, layer of lesion origin, macroscopic type, and lesion size. The procedure time was significantly shorter in the precutting EMR group than in the ESD group (22.9 ± 7.1 min vs 36.0 ± 10.6 min, p<0.001). The intraoperative perforation rate was significantly lower in the precutting EMR group compared to ESD group (4.5% vs 19.6 %, p = 0.030). CONCLUSIONS: Precutting EMR is comparable to ESD for NASDLs, demonstrating a lower intraoperative perforation rate and shorter procedure time compared to ESD.

Reduced expression of Ankyrin-G and E-cadherin in duodenal mucosal biopsy of subjects with celiac disease.

Confirmatory diagnosis of celiac disease (CD) include histopathology of duodenal biopsy and tissue trans-glutaminase-IgA. Identification of tissue-specific histological markers is warranted to improve the diagnosis. A genetic study in CD identified the association of ankyrin-G that connects E-cadherin with ß2-spectrin in epithelial cells of the duodenal tissue. We attempted to investigate the differential expression of ankyrin-G, E-cadherin and ß2-spectrin in duodenal biopsy of CD subjects compared to non-CD controls. Duodenal tissue was collected from 83 study participants, of which 50 were CD, and 33 were non-CD controls. Whole RNA was isolated from 32 CD and 23 non-CD controls from available tissues, and differential mRNA expression was measured using real-time PCR. Tissue sections from 18 CD cases and 10 non-CD controls were immunostained using monoclonal antibodies. Tissue immunohistochemistry were evaluated for differential expression and pattern of expression. RT-PCR revealed significantly reduced expression of ankyrin-G (fold change=0.63; p=0.03) and E-cadherin (fold change=0.50; p=0.02) among CD subjects compared to non-CD controls. Tissue immunohistochemistry confirmed the reduced expression of ankyrin-G and E-cadherin in CD. Differential expression is grossly limited within the outer columnar epithelial cell layer. Expression fold change of E-cadherin was seen to partially correlate with the serum tTG level (r=0.4; p=0.04). In CD, reduced expression of two key cytoskeletal proteins (ankyrin-G and E-cadherin) in duodenum mucosa was observed, which indicates its implication in disease biology and could be tested as a tissue-specific biomarker for CD. Functional studies may unravel the specific contribution of these proteins in CD pathophysiology.

The Spigelman Staging System and the Risk of Duodenal and Papillary Cancer in Familial Adenomatous Polyposis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Individuals with familial adenomatous polyposis (FAP) have an almost 20% lifetime risk of duodenal adenocarcinoma, currently the leading cause of death in FAP. The Spigelman staging system provides guidance on the surveillance intervals and timing of prophylactic surgery. Still, its accuracy in predicting duodenal and papillary cancer development has not been systematically evaluated. We investigated the sensitivity and cancer risk of the Spigelman stages. METHODS: We performed a systematic review on PubMed, MEDLINE, EMBASE, and Cochrane and used a random-effects model to pool effect sizes. RESULTS: After removing duplicate entries, we screened 1,170 records and included 27 studies for quantitative analysis. Once duodenal polyposis reaches Spigelman stage IV, the risk of duodenal and papillary cancers increased to 25% (95% confidence interval [CI] 12%-45%). However, the sensitivity of Spigelman stage IV for these cancers was low (51%, 95% CI 42%-60%), especially for papillary adenocarcinoma (39%, 95% CI 16%-68%). We investigated the reasons behind these low values and observed that duodenal cancer risk factors included polyps >10 mm, polyp count >20, and polyps with high-grade dysplasia. Risk factors associated with papillary cancer included a papilla with high-grade dysplasia or >10 mm. The evidence on other risk factors was inconclusive. DISCUSSION: The current Spigelman staging system had a low sensitivity for duodenal and papillary adenocarcinomas. Two Spigelman variables (duodenal villous histology and polyp count) and the lack of papilla-specific variables likely contributed to the low sensitivity values for duodenal and papillary cancers, respectively. While clinicians may be familiar with its current form, there is an urgent need to update it.

Markedly increased duodenal villous surface apoptosis in patients taking pre-exposure prophylaxis (PrEP) against human immunodeficiency virus.

AIMS: Pre-exposure prophylaxis (PrEP) consists of combination antiretroviral therapy and is increasingly utilized to prevent human immunodeficiency virus (HIV) in high-risk populations. Two index cases noted during routine care showed markedly increased duodenal villous surface apoptosis in patients on PrEP. We sought to examine the prevalence of this finding and identify any clinicopathologic correlations. METHODS: Gastrointestinal biopsy specimens from 23 male patients aged 18-40 years taking PrEP and 23 control patients were reviewed. Patients with HIV, inflammatory gastrointestinal diseases, and celiac disease were excluded. Apoptoses were counted on surface epithelium and deep crypts. The highest apoptotic body count per tissue fragment was recorded. Clusters were defined as groups of ≥5 apoptoses. Apoptotic counts between patients taking PrEP and controls were compared using t-tests. RESULTS: In PrEP patients, the median age was 35 years (range 25-40) and 83% (19/23) were white. The control patients were demographically similar (median age: 32 years [range 23-40]; 70% [16/23] white). Duodenal apoptosis in villous surface epithelium was increased in PrEP patients, with 14/23 (60.9%) patients having ≥10 surface apoptoses compared to 2/23 (8.7%) controls (P = 2.1 × 10-3 ) and 14/23 (61%) having clusters compared to 3/23 (13%) controls (P = 2.0 × 10-3 ). There was no significant association between increased surface apoptosis or clusters and clinical symptoms or duration of PrEP use. CONCLUSION: Markedly increased villous surface apoptosis, particularly in clusters, is often seen in the duodenum of patients taking PrEP. Although the mechanism and significance are unknown, knowledge of this peculiar finding may prevent unnecessary additional testing.

Endoloop pre-ligation assisted resection of a giant Brunner's gland adenoma of the duodenal bulb.

Brunner's gland adenoma (BGA), also known as Brunneroma or polypoid hamartoma, is a rare benign duodenal tumor that proliferates from Brunner's glands of the duodenum. They are usually asymptomatic and discovered by chance during endoscopy. Some giant lesions can sometimes present with chronic abdominal pain, nausea, vomiting, and anemia, including gastrointestinal bleeding and obstructive symptoms, and need to be resected by surgery or endoscopy. Here we report a giant BGA that was easily and safely removed by Endoloop pre-ligation assisted resection.

Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

Clinical and Pathological Correlation in Concomitant Celiac Disease and Eosinophilic Esophagitis Suggests Separate Etiologies.

Introduction. Recently, an increased risk of celiac disease or eosinophilic esophagitis has been postulated among patients with either of these disorders, prompting some to suggest a common underlying mechanism, whereas others maintain that their co-existence is coincidental. Methods. We compared clinical and pathological features of 29 patients meeting criteria for both celiac disease and eosinophilic esophagitis to 26 celiac disease and 26 eosinophilic esophagitis controls to determine whether any distinguished study patients from controls. Results. Eight (28%) study patients presented with symptoms of both celiac disease and eosinophilic esophagitis, whereas 14 (48%) had celiac disease symptoms only and 5 had (17%) esophageal symptoms only. Study patients had similar autoimmune and atopic conditions seen in both control groups. Histological severity of disease, including Marsh II-III duodenal histology (study specimens: 87%; controls: 89%), mean peak esophageal eosinophil counts (study specimens: 55/400x field; controls: 80/400X field, P = .1), and presence of eosinophil microabscesses, scale crust, and subepithelial fibrosis were also similar to controls. Gluten-free diet resolved celiac disease-related symptoms (19 of 20, 95%) and histology (10 of 12, 83%), but not esophageal symptoms or eosinophilia in most study patients. Conclusion. Patients with concomitant celiac disease and eosinophilic esophagitis lack distinguishing features compared to controls with celiac disease or eosinophilic esophagitis alone. The occurrence of both disorders is likely coincidental in most cases.

Intramural Duodenal Hematoma in a Case of Hyper IgM Syndrome.

Three-year-old boy who presented with colicky abdominal pain, diarrhoea and vomiting was investigated with computed tomography which revealed a mass in the peripancreatic region. An imaging possibility of duodenal intramural hematoma was considered after reassessment with ultrasound which was subsequently confirmed by magnetic resonance imaging. The development of a spontaneous duodenal hematoma lead to further evaluation of the patient and revealed X linked hyper IgM syndrome.

Giardia lamblia Diagnosed During Upper Gastrointestinal Endoscopy: Clinical Manifestation, Histopathologic Findings and the Association With Celiac Disease.

BACKGROUND: Giardia lamblia may be found incidentally during upper gastrointestinal (GI) endoscopy, including when biopsies are taken for celiac disease (CeD) diagnosis. We aimed to study the clinical presentation and histopathology of G. lamblia and determine its association with CeD. METHODS: A retrospective case series of pediatric patients diagnosed with G. lamblia based on intestinal biopsies between January 1999 and January 2023. Baseline data; demographics, symptoms, celiac serology, stool testing, macroscopic and histopathologic findings. Follow-up data; treatment and repeated celiac serology. RESULTS: Of 38 patients with G. lamblia , 15 (39.5%) were female, mean age of 6.7 (±4.8 SD) years. Clinical symptoms; GI 19/38 (50%), growth retardation and/or iron deficiency anemia 8/38 (21.1%) or a combination 11/38 (28.9%). Celiac serology was positive in 13/38 (34.2%). Duodenal endoscopic findings; normal (n = 23, 60.5%), nodularity (n = 12, 32.4%), erosions in 2 (5.4%) and scalloping in 1 (2.7%). Histopathology; normal villi 24/38 (63.2%), villous shortening with increased intraepithelial lymphocytes (IEL) 5/38 (13.2%), isolated IEL 3/38 (7.9%) and duodenitis in 6/38 (15.8%). Children with positive CeD serology were younger (4 vs. 8.1 years, P = 0.019), had fewer GI symptoms (23.1% vs. 64%, P = 0.017) and a higher rate of villous shortening with increased IEL (38.5% vs. 0, P < 0.001) versus children with negative serology. On follow-up, metronidazole treatment was recommended to all but was documented to be given in 22/38 (57.9%). Among the 13 children with positive CeD serology, serology normalized in 10 (77%). CONCLUSIONS: G. lamblia is a rare histopathologic finding in children. It may be an incidental finding in CeD or may cause false positive celiac serology.

Clinical Data Do Not Reliably Predict Duodenal Histology at Follow-up in Celiac Disease: A 13 Center Correlative Study.

Validated nonbiopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma. Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The reliability of such surrogates to predict mucosal recovery has been incompletely evaluated. The aim of this study was to rigorously assess patterns of histologic mucosal recovery at follow-up in celiac disease and to correlate findings with clinical data. Gastrointestinal pathologists from 13 centers evaluated initial and follow-up duodenal biopsies from 181 celiac disease patients. Marsh scores and intraepithelial lymphocytes (IELs)/100 enterocytes were assessed blindly. Histology at follow-up was correlated with symptoms, immunoglobulin A anti-tissue transglutaminase titers and gluten-free diet adherence. Fifty-six/181 (31%) patients had persistent villous blunting and 46/181 (25%) patients had just persistently elevated IELs at follow-up, with only 79/181 (44%) patients having complete histologic remission. IEL normalization (82/181; 45%) lagged villous recovery (125/181;69%). In a minority of patients, villous blunting was limited to proximal duodenal biopsies. No correlation was found between Marsh scores and symptoms, normalization of immunoglobulin A anti-tissue transglutaminase serology, or diet adherence. Children showed greater recovery of Marsh score ( P <0.001) and IELs ( P <0.01) than adults. Persistent mucosal injury is common in celiac disease, with discordant villous/IEL normalization. Pathologist awareness of expected findings in celiac disease follow-up biopsies, including their frequent lack of correlation with clinical data, is important for patient management, and has implications for eligibility criteria for therapeutics currently in development.

Standardized Quantification of Mast Cells in the Gastrointestinal Tract in Adults.

BACKGROUND: Current data on the normal quantity of mast cells throughout the adult gastrointestinal tract are limited in several domains. These include microanatomic localization of mast cells, standardization of staining and counting methods, and reporting of microscope field of view. OBJECTIVE: To address this lack of reliable reference ranges to facilitate the study of and diagnosis of emerging mast cell-mediated diseases. METHODS: We examined biopsies obtained from the esophagus, stomach, duodenum, and colon from an unselected cohort. Mean and peak mast cell density were determined on slides stained for tryptase and CD117, and were expressed per high power field (hpf) and surface area (mm2), thus deriving reference ranges (average ± 2 SDs). RESULTS: For the most common hpf surface area (0.238 mm2), upper limits of the derived reference ranges for average/peak mast cells were 0.15/3.67 (esophagus, tryptase), 0.70/5.98 (esophagus, CD117), 22.56/35.30 (stomach, tryptase), 31.32/53.10 (stomach, CD117), 30.28/49.77 (duodenal crypts, tryptase), 41.96/65.26 (duodenal crypts, CD117), 4.98/11.56 (duodenal villi, tryptase), 8.38/14.17 (duodenal villi, CD117), 26.58/41.08 (colon, tryptase), and 35.57/57.92 (colon, CD117). Interobserver variability was moderate to good. There was significant correlation between average and peak mast cell counts. CONCLUSIONS: These data help standardize mast cell reference ranges throughout the gastrointestinal tract in adults, which can be used to determine whether abnormal levels of mast cells are present in patients with suspected mast cell-mediated disease. Our data show that the commonly used cutoff of 20 mast cells per hpf irrespective of the gastrointestinal tract segment is an underestimate of an appropriate cutoff in stomach, duodenum (crypt area), and colon.