Esophagus
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Esophagus connects the pharynx to the stomach. It is afflicted by tumours on occasion. Probably the most common affliction is gastroesophageal reflux disease (GERD). Most biopsies revolve around the questions: 1. intestinal metaplasia? 2. dysplasia? and 3. cancer?
Normal esophagus
General:
- Stratified squamous non-keratinized epithelium.
Normal (esophageal) squamous epithelium:
- Should "mature" to the surface like good stratified squamous epithelium does.
- No nuclei at luminal surface.
- Cells should become less hyperchromatic as you go toward the lumen.
- Mitoses should be rare and should NOT be above the basal layer.
- Inflammatory cells should be very rare.
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ESOPHAGUS, DISTAL, BIOPSY: - COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION. - REACTIVE SQUAMOUS EPITHELIUM. - NEGATIVE FOR INTESTINAL METAPLASIA. - NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
Diagnoses
Common
- Normal.
- Metaplasia (Barrett's esophagus).
- Dysplasia.
- Adenocarcinoma.
Less common
- Squamous cell carcinoma.
- Eosinophilic esophagitis.
- Candidiasis.
- CMV esophagitis.
Tabular summary
Simplified overview
| Entity | Key feature | Other features | IHC/Special | Clinical | Image |
| Normal | squamous epi. matures to surface | no inflammation, no atypia | - | - | |
| GERD | inflammation (eosinophils, lymphocytes) | elongated (epithelial) papillae, basal cell hyperplasia | incr. risk of Barrett's | ||
| Eosinophilic esophagitis | abundant eosinophils | elongated (epithelial) papillae, basal cell hyperplasia, lymphocytes | unresponsive to PPIs | ||
| Barrett's type change | goblet cells | no dysplasia | Alcian blue +ve | incr. risk of adenocarcinoma | |
| Dysplasia, low grade | nuclear crowding at surface | hyperchromasia, mild arch. complexity, no necrosis | incr. risk of carcinoma | ||
| Dysplasia, high grade | cribriforming and/or necrosis | nuclei often round & large, hyperchromasia | marked incr. risk of carcinoma |
Columnar dysplasia
| Entity | Surface maturation | Architecture | Cytology | Other | Clinical | Image |
| Normal | matures | round glands | no nuclear atypia | - | - | Image |
| Barrett's esophagus | matures | round glands, normal gland density | +/-scant nuclear atypia | goblet cells | clinical diagnosis | Image |
| Indefinite for columnar dysplasia | minimal maturation or cannot see surface | round glands, normal gland density | mild nuclear atypia, nuclear pseudostratification, no necrosis | - | follow-up | Image |
| Low-grade columnar dysplasia | minimal-to-scant maturation | round glands, +/-rare budding, increased gland density | mild-to-moderate nuclear atypia, nuclear pseudostratification, no necrosis | - | follow-up | Image |
| High-grade columnar dysplasia | no maturation | incr. density of irregular glands with budding and/or rare cribriforming and/or gland dilation | moderate-to-marked nuclear atypia (usu. plump round nuclei), hyperchromasia, +/-necrosis | - | EMR, surgery | Image |
| Intramucosal adenocarcinoma | no maturation | single cells or back-to-back irregular glands with budding and/or cribriforming and/or gland dilation or glands with long axis along muscularis mucosae | moderate-to-marked nuclear atypia - usu. round large nuclei, hyperchromasia, +/-necrosis | - | EMR, surgery | Image |
Columnar dysplasia - another table
| Feature | Indefinite for columnar dysplasia | Low-grade columnar dysplasia | High-grade columnar dysplasia | Intramucosal carcinoma (IMCa) | Utility |
|---|---|---|---|---|---|
| Depth of glands | superficial only | superficial only | superficial/deep | deep | low vs. high |
| Gland density | normal | near normal | increased | back-to-back | low vs. high vs. IMCa |
| Gland morphology | round | round | irregular/rare cribriforming | irregular/cribriform/sheeting | low vs. high vs. IMCa |
| Necrosis | none | none | may be present | may be present | low vs. high & IMCa |
| Hyperchromasia | +/- | present | present | present | indef. vs. low |
| Palisaded/crowded nuclei | present | present | absent/present | uncommon | low vs. high |
| Round nuclei + enlargement | absent | absent | present/absent | present | low vs. high |
| Desmoplasia | absent | absent | absent | +/- (uncommon) | high vs. IMCa |
| Surface involvement | present (required) | present (required) | +/- | +/- | low vs. high |
Decision tree for columnar dysplasia
Odze has made an algorithm - see: Diagnostic algorithm (nih.gov).[1]
Indications
- Pyrosis = heartburn.[2]
Infectious esophagitis
Main article: Microorganisms
Is a relatively common problem, especially in those that live at the margins (EtOH abusers) and immunosuppressed individuals (HIV/AIDS).
Useful stains
- PAS.
- Gram stain.
Overview
Candida esophagitis
Main article: Candidiasis
- AKA esophageal candidiasis.
Gross (endoscopic)
Features:
- White patches.
DDx (endoscopic):[3]
Microscopic
Features:
- Worm-like micro-organisms - key feature.
- Pseudohyphae (single cells).
- Thickness ~ 1/3-1/2 of squamous cell nucleus.
- Should be within (squamous) epithelium.
- Superficial inflammation - esp. neutrophils - important.
Notes:
- On top of epithelium does not count,[4] i.e. it is likely an artifact.
- Bacilli and cocci may accompany the candida. They are typically ignored.
DDx:
- Acute esophagitis - no candida seen.
Image
Esophageal candidiasis. (WC)
_PAS_stain.jpg)
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ESOPHAGUS, BIOPSY: - ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
ESOPHAGUS, BIOPSY: - ACUTE ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA. - NEGATIVE FOR INTESTINAL METAPLASIA. - NEGATIVE FOR DYSPLASIA.
Cytomegalovirus esophagitis
Microscopic
Features:
- Classically at the base of the ulcer; within endothelial cells - key point.
Note:
- Biopsying the the base of an ulcer usually just yields (non-diagnostic) necrotic debris; so, clinicians are told to biopsy the edge of the lesion. A suspected CMV infection is the exception to this rule!
Herpes esophagitis
General
Etiology:
Gross/endoscopic
Features:
- Ulcers with a "punched-out" appearance with a brown/red edge.
Images
Herpes esophagitis - endoscopy. (WC)
www:
Microscopic
Features (3 Ms):
- Moulding.
- Multinucleation.
- Margination of chromatin.
Images
HSV esophagitis - very high mag. (WC/Nephron)
HSV esophagitis - intermed. mag. (WC/Nephron)
IHC
- HSV-1 +ve.[5]
- Occasionally HSV-2 +ve.
Human papillomavirus esophagitis
General:
Microscopic
Features:
- Koilocytes:
- Perinuclear clearing.
- Nuclear changes.
- Size similar (or larger) to those in the basal layer of the epithelium.
- Nuclear enlargement should be evident on low power, i.e. 25x. [7]
- Central location - nucleus should be smack in the middle of the cell.
Images:
Other
The group of conditions doesn't fit neatly with the others. It is a mixture of different non-neoplastic conditions.
Gastroesophageal reflux disease
- Abbreviated GERD or GORD (gastro-oesophageal reflux disease).
- AKA reflux esophagitis.
Main article: Gastroesophageal reflux disease
Eosinophilic esophagitis
- Abbreviated EE.
Main article: Eosinophilic esophagitis
Erosive esophagitis
DDx
- Infections.
- Crohn's disease.
- Pill esophagitis.
Work-up
Pill esophagitis
Classic causes:
- Alendronate (Fosamax) - for osteoporosis.
- Iron - can be demonstrated with Prussian blue stain.
- Doxycycline.
Esophageal varices
Main article: Esophageal varices
Acute esophagitis
Main article: Acute esophagitis
Benign esophageal stricture
Main article: Esophageal stricture
Preneoplastic
Barrett esophagus
Main article: Barrett esophagus
Neoplastic
Columnar dysplasia of the esophagus
- AKA esophageal columnar dysplasia, abbreviated ECD.[6]
- AKA dysplasia in the columnar-lined esophagus.[7]
- AKA columnar epithelial dysplasia.[8]
General
- Arises in the setting of Barrett esophagus.
Classification
- Indefinite for dysplasia.
- Low grade dysplasia.
- High grade dysplasia.
Management
Low grade dysplasia & indefinite for dysplasia:
- Follow-up.
High grade dysplasia:
- Endoscopic mucosal resection.[9]
- Surgical resection (esophagectomy).
Microscopic
Features to assess:[10]
- Lack of surface maturation - very common, occasionally absent.[11]
- Lack of lighter staining at surface.
- Nuclear crowding at surface.
- Nuclei at the surface not smaller.
- Architecture - esp. at low power.
- Glands not round.
- Low-grade feature: gland budding.
- High-grade features: cribriforming, cystic dilation, necrotic debris.
- Gland density:
- Increased & round - think low-grade dysplasia.
- Increased & irregular - think high-grade dysplasia.
- Glands not round.
- Cytology, esp. at high magnification.
- Nuclear abnormalities in: size, staining, shape.
- Loss of "nuclear polarity" = high-grade feature
- Loss of palisaded appearance, rounding-up of nuclei.
- Inflammation, erosions & ulceration.
- Marked inflammation should prompt consideration of knocking down the diagnosis one step, i.e. low-grade becomes indefinite or high-grade becomes low-grade.
Negatives:
- No desmoplasia.
- Stromal fibrotic reaction to the tumour.
- Desmoplasia is rare in the superficial esophagus.[12]
- Stromal fibrotic reaction to the tumour.
- No single cells.
- No extensive back-to-back glands.
Notes:
- Changes similar to those see in colorectal tubular adenomas; however, what would be low-grade dysplasia in the rectum is high-grade dysplasia in the esophagus.
- Presence of goblet cells suggests it is not dysplasia.[13]
- Desmoplasia present = invasive adenocarcinoma.[14]
- Some literature suggests community pathologists should not make this call, i.e. it should be diagnosed by an expert.[15]
DDx:
Images
No dysplasia - only intestinal metaplasia:
Indefinite for columnar dysplasia:
Low-grade columnar dysplasia:
High-grade columnar dysplasia:
- High-grade columnar dysplasia (nature.com).[16]
- High-grade columnar dysplasia (nature.com).[17]
- High-grade columnar dysplasia (nih.gov).[1]
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ESOPHAGUS, DISTAL, BIOPSY: - LOW-GRADE COLUMNAR EPITHELIAL DYSPLASIA, SEE COMMENT. - COLUMNAR EPITHELIUM WITH GOBLET CELL METAPLASIA. - REACTIVE SQUAMOUS EPITHELIUM. COMMENT: This was reviewed with Dr. X and they agree with the diagnosis.
Alternate
ESOPHAGUS, 30 CM, BIOPSY: - LOW-GRADE COLUMNAR DYSPLASIA WITH INTESTINAL METAPLASIA AND MILD CHRONIC INFLAMMATION. - NEGATIVE FOR MALIGNANCY.
Squamous dysplasia of the esophagus
- AKA eosphageal squamous dysplasia.
General
- Precursor of esophageal squamous cell carcinoma.[18]
- Common in China.[18]
- Not very common in North America.
Microscopic
Features:
- Squamous cell nuclear atypia.
- Lack of maturation to the surface.
Note:
- Grading differences between Western pathologists and those of the east.[18]
DDx:
- Reactive changes.
- Esophageal squamous cell carcinoma.
Images
A set of cases from Japan:[19]
- Mild squamous dysplasia (nih.gov).
- Moderate squamous dysplasia (nih.gov).
- Severe squamous dysplasia (nih.gov).
- Carcinoma in situ (nih.gov).
- Squamous cell carcinoma of the esophagus (nih.gov).
IHC
- Ki-67 may be useful:[20]
- Reactive changes/normal: ~98% negative, ~2% intermediate.
- Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
- High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.
Definitions:[20]
- Negative defined as: < 25% of epithelium +ve and staining only in lower quarter of epithelium.
- Intermediate defined: >=25% and <=50% of epithelium +ve and only in the lower half of the epithelium.
- Strong defined: >50% of epithelium +ve or upper half of epithelium.
Leiomyoma of the esophagus
Main article: Leiomyoma
General
- Benign.
- Uncommon.
- Before the time of GISTs - this was a relatively common diagnosis.
- Like leiomyomas elswhere.
Microscopic
- See: Leiomyoma.
DDx:
Gastrointestinal stromal tumour
Main article: Gastrointestinal stromal tumour
Cancer
General
- Proximal esophagus: squamous cell carcinoma.
- Distal esophagus: adenocarcinoma arising from Barrett's esophagus.
Risks:
Squamous cell carcinoma of the esophagus
- AKA esophageal squamous cell carcinoma, abbreviated esophageal SCC.
Main article: Squamous cell carcinoma of the esophagus
Esophageal adenocarcinoma
- AKA adenocarcinoma of the esophagus.
Main article: Esophageal adenocarcinoma
Weird stuff
- Inflammatory polyp - assoc. trauma/previous intervention.
- Giant fibrovascular polyp - loose connective tissue covered with squamous epithelium.
- Granular cell tumour.
- Squamous papilloma - koilocytes.
- Heterotopic gastric mucosa ("inlet patch") - benign appearing gastric mucosa.
Granular cell tumour
Main article: Granular cell tumour
Microscopic
Features:
- Abundant eosinophilic granular cytoplasm key feature.
- Granules:
- Size: 1-3 micrometers.
- Poorly demarcated.
- Granules:
- Usu. bland (cytologically non-malignant) nuclei.
Images
Esophagitis dissecans superficials
General
- Rare & benign condition that resolves without lasting pathology.[21]
- Case report - chronic with strictures.[22]
- Sloughing of large fragments of the esophageal mucosa - seen on endoscopy.
Microscopic
Features:[21]
- Flaking of superficial squamous epithelium.
- Focal bullous separation of the layers.
- Parakeratosis.
- Variable acute or chronic inflammation.
Glycogenic acanthosis of the esophagus
General
- Uncommon.
- Benign.
- Possible association with ingestion of hot liquids.[23]
Gross/endoscopic
- Distinctive endoscopic appearance - grey/white raised lesion.[23]
Image:
Microscopic
Features:[23]
- Squamous epithelium with:
- Superficial clearing of the cytoplasm.
- Thickening.
Images:
Achalasia
General
- Uncommon.
- Risk factor for squamous cell carcinoma (in men and women) and adenocarcinoma (in men).[24]
- Due to loss of ganglion cells.[25]
Clinical:
- Dysphagia (difficulty swallowing) liquids and solids.[25]
DDx:
- Chagas disease - classically with dilation of the esophagus.[26]
Microscopic
Features:[27]
- Mucosa typically normal - even in long-standing achalasia.
Note:[27]
- Achalasia seen in the context of a resection usually has inflammation.
- Post-Heller myotomy often has inflammation.
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ESOPHAGUS, BIOPSY: - SQUAMOUS EPITHELIUM WITH A MILD DEEP LYMPHOCYTIC INFILTRATE, EDEMA, AND REACTIVE CHANGES, NO EOSINOPHILS APPARENT. - SCANT COLUMNAR EPITHELIUM WITH MINIMAL STROMA, NO APPARENT SIGNIFICANT PATHOLOGY. - NEGATIVE FOR INTESTINAL METAPLASIA. - NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
Alternate
GASTROESOPHAGEAL JUNCTION, BIOPSY: - COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION. - REACTIVE SQUAMOUS EPITHELIUM. - NEGATIVE FOR INTESTINAL METAPLASIA. - NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
Esophageal inlet patch
General
- Benign and likely not of any significance.[28]
Gross
- Proximal esophagus - salmon coloured lesion.[28]
Microscopic
Features:
- Gastric mucosa.[29]
Image:
Squamous papilloma of the eosphagus
- AKA esophageal squamous papilloma.
General
- Uncommon.
Microscopic
Features:
- Papillomaous projections - low power.
Image
www:
SP of the esophagus. (WC)
SP of the esophagus. (WC)
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See also
References
- ↑ 1.0 1.1 1.2 1.3 Odze, RD. (Oct 2006). "Diagnosis and grading of dysplasia in Barrett's oesophagus.". J Clin Pathol 59 (10): 1029-38. doi:10.1136/jcp.2005.035337. PMID 17021130.
- ↑ URL: http://dictionary.reference.com/browse/pyrosis. Accessed on: 21 June 2010.
- ↑ Odze, Robert D.; Goldblum, John R. (2009). Surgical pathology of the GI tract, liver, biliary tract and pancreas (2nd ed.). Saunders. pp. 244. ISBN 978-1416040590.
- ↑ ALS. 4 October 2010.
- ↑ Canalejo Castrillero, E.; García Durán, F.; Cabello, N.; García Martínez, J. (Jul 2010). "Herpes esophagitis in healthy adults and adolescents: report of 3 cases and review of the literature.". Medicine (Baltimore) 89 (4): 204-10. doi:10.1097/MD.0b013e3181e949ed. PMID 20616659.
- ↑ Feng, W.; Zhou, Z.; Peters, JH.; Khoury, T.; Zhai, Q.; Wei, Q.; Truong, CD.; Song, SW. et al. (Aug 2011). "Expression of insulin-like growth factor II mRNA-binding protein 3 in human esophageal adenocarcinoma and its precursor lesions.". Arch Pathol Lab Med 135 (8): 1024-31. doi:10.5858/2009-0617-OAR2. PMID 21809994.
- ↑ Levine, DS. (Sep 1997). "Management of dysplasia in the columnar-lined esophagus.". Gastroenterol Clin North Am 26 (3): 613-34. PMID 9309409.
- ↑ Hamilton, SR.; Smith, RR. (Mar 1987). "The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett's esophagus.". Am J Clin Pathol 87 (3): 301-12. PMID 3825997.
- ↑ Sampliner RE (March 2009). "Endoscopic Therapy for Barrett's Esophagus". Clin. Gastroenterol. Hepatol.. doi:10.1016/j.cgh.2009.03.011. PMID 19306943.
- ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 46. ISBN 978-0443066573.
- ↑ Lomo, LC.; Blount, PL.; Sanchez, CA.; Li, X.; Galipeau, PC.; Cowan, DS.; Ayub, K.; Rabinovitch, PS. et al. (Apr 2006). "Crypt dysplasia with surface maturation: a clinical, pathologic, and molecular study of a Barrett's esophagus cohort.". Am J Surg Pathol 30 (4): 423-35. PMID 16625087.
- ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 49. ISBN 978-0443066573.
- ↑ GAG. January 2009.
- ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 54. ISBN 978-0443066573.
- ↑ Alikhan, M.; Rex, D.; Khan, A.; Rahmani, E.; Cummings, O.; Ulbright, TM. (Jul 1999). "Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice.". Gastrointest Endosc 50 (1): 23-6. PMID 10385717.
- ↑ 16.0 16.1 Odze, RD. (Aug 2009). "Barrett esophagus: histology and pathology for the clinician.". Nat Rev Gastroenterol Hepatol 6 (8): 478-90. doi:10.1038/nrgastro.2009.103. PMID 19581906.
- ↑ Riddell, RH.; Odze, RD. (Oct 2009). "Definition of Barrett's esophagus: time for a rethink--is intestinal metaplasia dead?". Am J Gastroenterol 104 (10): 2588-94. doi:10.1038/ajg.2009.390. PMID 19623166.
- ↑ 18.0 18.1 18.2 Dry, SM.; Lewin, KJ. (Feb 2002). "Esophageal squamous dysplasia.". Semin Diagn Pathol 19 (1): 2-11. PMID 11936262.
- ↑ 19.0 19.1 19.2 Terada, T. (2013). "A clinicopathologic study of esophageal 860 benign and malignant lesions in 910 cases of consecutive esophageal biopsies.". Int J Clin Exp Pathol 6 (2): 191-8. PMID 23330004.
- ↑ 20.0 20.1 Wang, WC.; Wu, TT.; Chandan, VS.; Lohse, CM.; Zhang, L. (Oct 2011). "Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia.". Hum Pathol 42 (10): 1430-7. doi:10.1016/j.humpath.2010.12.009. PMID 21420715.
- ↑ 21.0 21.1 21.2 Carmack, SW.; Vemulapalli, R.; Spechler, SJ.; Genta, RM. (Dec 2009). "Esophagitis dissecans superficialis ("sloughing esophagitis"): a clinicopathologic study of 12 cases.". Am J Surg Pathol 33 (12): 1789-94. doi:10.1097/PAS.0b013e3181b7ce21. PMID 19809273.
- ↑ Coppola, D.; Lu, L.; Boyce, HW. (Oct 2000). "Chronic esophagitis dissecans presenting with esophageal strictures: a case report.". Hum Pathol 31 (10): 1313-7. doi:10.1053/hupa.2000.18470. PMID 11070124.
- ↑ 23.0 23.1 23.2 Lopes, S.; Figueiredo, P.; Amaro, P.; Freire, P.; Alves, S.; Cipriano, MA.; Gouveia, H.; Sofia, C. et al. (May 2010). "Glycogenic acanthosis of the esophagus: an unusually endoscopic appearance.". Rev Esp Enferm Dig 102 (5): 341-2. PMID 20524767.
- ↑ Zendehdel, K.; Nyrén, O.; Edberg, A.; Ye, W. (Jan 2011). "Risk of esophageal adenocarcinoma in achalasia patients, a retrospective cohort study in Sweden.". Am J Gastroenterol 106 (1): 57-61. doi:10.1038/ajg.2010.449. PMID 21212754.
- ↑ 25.0 25.1 Blatnik, JA.; Ponsky, JL. (Jan 2014). "Advances in the Treatment of Achalasia.". Curr Treat Options Gastroenterol. doi:10.1007/s11938-013-0007-2. PMID 24395614.
- ↑ Pantanali, CA.; Herbella, FA.; Henry, MA.; Mattos Farah, JF.; Patti, MG. (Jan 2013). "Laparoscopic Heller myotomy and fundoplication in patients with Chagas' disease achalasia and massively dilated esophagus.". Am Surg 79 (1): 72-5. PMID 23317615.
- ↑ 27.0 27.1 Kjellin, AP.; Ost, AE.; Pope, CE. (2005). "Histology of esophageal mucosa from patients with achalasia.". Dis Esophagus 18 (4): 257-61. doi:10.1111/j.1442-2050.2005.00478.x. PMID 16128783.
- ↑ 28.0 28.1 Chong, VH. (Jan 2013). "Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus.". World J Gastroenterol 19 (3): 331-8. doi:10.3748/wjg.v19.i3.331. PMID 23372354.
- ↑ 29.0 29.1 Behrens, C.; Yen, PP. (2011). "Esophageal inlet patch.". Radiol Res Pract 2011: 460890. doi:10.1155/2011/460890. PMID 22091379.