Reflux-Associated Cholecystopathy

Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma

Takashi Muraki, Bahar Memis, Michelle D. Reid, Takeshi Uehara, Tetsuya Ito, Osamu Hasebe, Shinji Okaniwa, Naoto Horigome, Takeshi Hisa, Pardeep Kumar Mittal, Alexa Freedman, Shishir Maithel, Juan M. Sarmiento, Alyssa Krasinskas, Jill Koshiol, Volkan Adsay

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

Original languageEnglish (US)
Pages (from-to)1167-1177
Number of pages11
JournalAmerican Journal of Surgical Pathology
Volume41
Issue number9
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Pancreatic Ducts
Common Bile Duct
Gallbladder
Hyperplasia
Carcinoma
Metaplasia
Japan
Biliary Tract Neoplasms
Sphincter of Oddi
Chemical Models
Gallbladder Neoplasms
Pancreatic Juice
Hyalin
Cholelithiasis
Cholecystectomy
Gallstones
Gastric Mucosa
Bile Ducts
Amyloid
Pancreatitis

Keywords

  • anomaly
  • carcinoma
  • cholecystopathy
  • gall bladder
  • hyperplasia
  • pancreatobiliary maljunction
  • reflux

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Reflux-Associated Cholecystopathy : Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma. / Muraki, Takashi; Memis, Bahar; Reid, Michelle D.; Uehara, Takeshi; Ito, Tetsuya; Hasebe, Osamu; Okaniwa, Shinji; Horigome, Naoto; Hisa, Takeshi; Mittal, Pardeep Kumar; Freedman, Alexa; Maithel, Shishir; Sarmiento, Juan M.; Krasinskas, Alyssa; Koshiol, Jill; Adsay, Volkan.

In: American Journal of Surgical Pathology, Vol. 41, No. 9, 01.01.2017, p. 1167-1177.

Research output: Contribution to journalArticle

Muraki, Takashi ; Memis, Bahar ; Reid, Michelle D. ; Uehara, Takeshi ; Ito, Tetsuya ; Hasebe, Osamu ; Okaniwa, Shinji ; Horigome, Naoto ; Hisa, Takeshi ; Mittal, Pardeep Kumar ; Freedman, Alexa ; Maithel, Shishir ; Sarmiento, Juan M. ; Krasinskas, Alyssa ; Koshiol, Jill ; Adsay, Volkan. / Reflux-Associated Cholecystopathy : Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma. In: American Journal of Surgical Pathology. 2017 ; Vol. 41, No. 9. pp. 1167-1177.
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abstract = "Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16{\%} vs. 80{\%} in non-PBM, P<0.01) whereas cholesterolosis was more common (49{\%} vs. 29{\%}, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82{\%} vs. 42{\%}, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68{\%} vs. 47{\%}, P=0.01), bulbous dilatation (52{\%} vs. 21{\%}, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56{\%} vs. 15{\%}, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70{\%} vs. 48{\%}, P=0.01) and intestinal metaplasia (24{\%} vs. 6{\%}, P<0.01). Invasive gallbladder carcinoma was present in 22 (29{\%}) of the cases with 6 of these (27{\%}) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as {"}reflux-associated cholecystopathy.{"} Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.",
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T1 - Reflux-Associated Cholecystopathy

T2 - Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma

AU - Muraki, Takashi

AU - Memis, Bahar

AU - Reid, Michelle D.

AU - Uehara, Takeshi

AU - Ito, Tetsuya

AU - Hasebe, Osamu

AU - Okaniwa, Shinji

AU - Horigome, Naoto

AU - Hisa, Takeshi

AU - Mittal, Pardeep Kumar

AU - Freedman, Alexa

AU - Maithel, Shishir

AU - Sarmiento, Juan M.

AU - Krasinskas, Alyssa

AU - Koshiol, Jill

AU - Adsay, Volkan

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

AB - Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

KW - anomaly

KW - carcinoma

KW - cholecystopathy

KW - gall bladder

KW - hyperplasia

KW - pancreatobiliary maljunction

KW - reflux

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