今日の臨床サポート

胆のう癌

著者: 加藤厚 国際医療福祉大学附属三田病院 消化器センター

著者: 宮崎勝 国際医療福祉大学附属三田病院 消化器センター

監修: 田妻進 広島大学病院 総合内科・総合診療科

著者校正/監修レビュー済:2019/11/29
患者向け説明資料

概要・推奨   

  1. 膵・胆管合流異常は胆のう癌の危険因子であり、予防的な手術が必要である。胆管非拡張型には胆のう摘出術が、胆管拡張型には胆のう摘出術+胆外胆管切除+胆道再建が推奨される(推奨度2)
  1. 胆のうポリープは大きさが10mm以上、大きさにかかわらず広基性、画像上増大傾向を認める場合には胆のう癌の可能性があり、胆のう摘出術が推奨される(推奨度2)
  1. 胆のう癌の鑑別診断および進展度診断には、超音波内視鏡(EUS)が有用である(推奨度2)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
加藤厚 : 未申告[2021年]
宮崎勝 : 特に申告事項無し[2021年]
監修:田妻進 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 胆道癌診療ガイドライン改訂第3版に基づき、肝外胆管に直接浸潤のない胆のう癌において、リンパ節郭清を目的に、あるいは潜在的な組織学的癌浸潤を考慮して予防的肝外胆管切除が推奨されてきたが、肝外胆管切除の有無は予後因子とならないことなどから、予防的肝外胆管切除は原則として行わないことと改訂した。
  1. 胆道癌診療ガイドライン改訂第3版に基づき、肝浸潤を疑う胆のう癌において、胆のう床切除と系統的肝切除(肝S4a+S5切除)の予後に差がないことから、十分なsurgical marginを確保した胆のう床切除を行うことでよいと、改訂を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 胆のう癌は(肝外)胆管癌、(十二指腸)乳頭部癌とともに胆道癌取扱い規約で胆道癌として扱われている。
  1. 好発年齢は70歳代で、男女比は3:4と女性に多い。
  1. 胆のう癌に胆のう結石症を合併する頻度は高く40~75%と報告されているが、胆のう結石症の長期観察症例において、胆のう癌の発生頻度が増加しないという報告もあり、胆石症と胆のう癌の直接的因果関係は証明されていない。
  1. 膵・胆管合流異常は胆のう癌発症の危険因子の1つである。
  1. 胆のうポリープは大きさが10mm以上、大きさにかかわらず広基性、画像上増大傾向を認める場合には胆のう癌の可能性がある。
  1. 黄色肉芽腫性胆のう炎、胆のう腺筋症、慢性胆のう炎など、しばしば胆のう癌との鑑別が困難な場合がある。
  1. 胆のう結石症に対する胆のう摘出術により偶然、胆のう癌と診断される頻度は0.2~1.0%と報告されている。
  1. 治療は外科切除が唯一の根治的治療法であり、症例ごとにその進展様式に応じた術式を選択して、根治切除を目指すことが重要である。
  1. 胆のう癌切除後の予後因子として壁深達度、リンパ節転移の有無、壁外進展とくに肝十二指腸間膜浸潤の有無などが挙げられる。
  1. 切除不能胆のう癌に対しては化学療法が治療の主体となる。
 
  1. 胆のうポリープは大きさが10mm以上、大きさにかかわらず広基性、画像上増大傾向を認める場合には胆のう癌の可能性があり、胆のう摘出術が推奨される(推奨度2)
  1. まとめ:胆のう癌の発生母地病変として腺腫や異型上皮、腸上皮化生の関与が報告されており、胆のうポリープは異型上皮を認めることがあり、また径が大きいものはがん化しているものが多かったことが報告されている。
  1. 事例:胆のう癌周囲の胆のう粘膜には高率に異型上皮や腸上皮化生が存在することが報告されており、こうした病変が胆のう癌の発生母地として関与していることが示唆されている。また胆のう切除例1,280例の検討で、15例に腺腫を認め、このうちがん化は径が0.7cmから6.5cmのものにみられ、2cmを超えるとほとんどはがん化していたことが報告されている。また、胆のうポリープの形状が広基性、径が10mm以上、増大傾向を認める場合には癌の可能性が高いと報告されている。一方、胆嚢のポリープ様病変36例の検討で、大きさが5mm未満の11例には癌を認めなかったと報告されている。
  1. 結論:胆のうポリープは径が10mm以上、増大傾向、広基性の場合には胆のう癌の頻度が高く、胆のう摘出術が推奨される。
  1. 追記:胆のう癌と異型上皮、腸上皮化生などの関連を検討するために、遺伝子変異が基礎的、臨床的に検討されている。
問診・診察のポイント  
問診:
  1. 併存する胆のう結石症や胆のう炎による症状が現れることがあるが、初期においては特有の症状はないため、進行した状態で発見されることが多い。

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文献 

著者: Seiki Tashiro, T Imaizumi, H Ohkawa, A Okada, T Katoh, Y Kawaharada, H Shimada, H Takamatsu, H Miyake, T Todani, Committee for Registration of the Japanese Study Group on Pancreaticobiliary Maljunction
雑誌名: J Hepatobiliary Pancreat Surg. 2003;10(5):345-51. doi: 10.1007/s00534-002-0741-7.
Abstract/Text Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a union of the pancreatic and biliary duct that is located outside the duodenal wall. The Japanese Study Group on Pancreaticobiliary Maljunction and the Committee for Registration enrolled and analyzed 1627 patients with PBM who had been diagnosed and treated from January 1, 1990 to December 31, 1999 at 141 hospitals throughout the country. There were 1239 patients with dilatation of the bile duct (group A) and 388 patients without dilatation (group B). The average age was 24 years in group A and 47 years in group B; the age was significantly higher in group B. The type of confluence between the terminal choledochus and the pancreatic duct has been classified into three types (type a, right-angle type; type b, acute-angle type; and type c, complex type). In group A, type a accounted for 57.9% and was significantly more frequent compared with the other types (type b, 32.4%; type c, 5.6%). In group B, type b accounted for 60.8%, being significantly more frequent compared with the other types (type a, 29.4%; type c, 7.2%). Subjective symptoms, preoperative complications (e.g., liver dysfunction and acute pancreatitis), pancreatic stone, and pancreatic duct morphological abnormality were significantly more frequent in group A. However, the amylase levels in the bile and gallbladder were significantly higher in group B, and the presence of gallstone and morphological abnormality of the gallbladder was significantly more frequent in group B. The occurrence rate of cancer in the biliary tract was 10.6% in group A and 37.9% in group B, being significantly higher in group B. In group A, cancer of the extrahepatic bile duct was seen in 33.6% and cancer of the gallbladder was seen in 64.9%, but gallbladder cancer was present significantly more frequently in the patients with diffuse or cylindrical dilatation, and bile duct cancer was present significantly more frequently in the patients with cystic dilatation. In group B, 93.2% of the patients had gallbladder cancer, and bile duct cancer was found in as few as 6.8%. Against this background Japanese surgeons regard cholecystectomy, resection of the extrahepatic bile duct, and hepaticojejunostomy as standard operations for PBM with dilatation of the bile duct. However, opinion on whether or not the bile duct should be removed in the treatment of PBM without dilatation of the bile duct has been divided among Japanese surgeons. A randomized controlled trial is necessary.

PMID 14598134  J Hepatobiliary Pancreat Surg. 2003;10(5):345-51. doi: ・・・
著者: Yi-Lei Deng, Nan-Sheng Cheng, Yi-Xin Lin, Rong-Xing Zhou, Chen Yang, Yan-Wen Jin, Xian-Ze Xiong
雑誌名: Hepatobiliary Pancreat Dis Int. 2011 Dec;10(6):570-80.
Abstract/Text BACKGROUND: Reports on the relationship between pancreaticobiliary maljunction (PBM) and gallbladder carcinoma (GBC) are conflicting. The frequency of PBM in GBC patients and the clinical features of GBC patients with PBM vary in different studies.
DATA SOURCES: English-language articles describing the association between PBM and GBC were searched in the PubMed and Web of Science databases. Nine case-control studies fulfilled the inclusion criteria and addressed the relevant clinical questions of this analysis. Data were extracted independently by two reviewers using a predefined spreadsheet.
RESULTS: The incidence of PBM was higher in GBC patients than in controls (10.60% vs 1.76%, OR: 7.41, 95% CI: 5.03 to 10.87, P<0.00001). The proportion of female patients with PBM was 1.96-fold higher than in GBC patients without PBM (80.5% vs 62.9%, OR: 1.96, 95% CI: 1.09 to 3.52, P=0.12). GBC patients with PBM were 10 years younger than those without PBM (SMD: -9.90, 95% CI: -11.70 to -8.10, P<0.00001). And a difference in the incidence of associated gallstone was found between GBC patients with and without PBM (10.8% vs 54.3%, OR: 0.09, 95% CI: 0.05 to 0.17, P<0.00001). Among the GBC patients with PBM, associated congenital dilatation of the common bile duct was present with a higher incidence ranging from 52.2% to 85.7%, and 70.0%-85.7% of them belonged to the P-C type of PBM (the main pancreatic duct enters the common bile duct). No substantial heterogeneity was found and no evidence of publication bias was observed.
CONCLUSIONS: PBM is a high-risk factor for developing GBC, especially the P-C type of PBM without congenital dilatation of the common bile duct. To prevent GBC, laparoscopic cholecystectomy is highly recommended for PBM patients without congenital dilatation of the common bile duct, especially relatively young female patients without gallstones.

PMID 22146619  Hepatobiliary Pancreat Dis Int. 2011 Dec;10(6):570-80.
著者: M Sugiyama, Y Atomi, T Yamato
雑誌名: Gut. 2000 Feb;46(2):250-4.
Abstract/Text BACKGROUND: Differential diagnosis is often difficult for small (AIM: To assess the diagnostic accuracy of endoscopic ultrasonography (EUS) for polypoid lesions in a surgical and follow up series.
METHODS: A total of 194 patients with small polypoid lesions underwent both ultrasonography and EUS. A tiny echogenic spot or an aggregation of echogenic spots and multiple microcysts or a comet tail artefact indicated cholesterol polyp and adenomyomatosis respectively. Other lesions were diagnosed as neoplastic (adenoma or adenocarcinoma). In the 58 patients who underwent surgery, the histological diagnoses were cholesterol polyp (n = 36), adenomyomatosis (n = 7), adenoma (n = 4), and adenocarcinoma (n = 11). Of the remaining 136 patients with an EUS diagnosis of non-neoplastic lesions, 125 were followed up with ultrasonography alone or with EUS for 1-8.7 years (mean 2.6 years).
RESULTS: In the surgical series, EUS (97%) differentiated polypoid lesions more precisely than ultrasonography (76%). During follow up, the lesions remained unchanged in size in 109 (87%) of the 125 patients with non-neoplastic lesions diagnosed by EUS. No neoplastic lesions developed in these patients. Ultrasonography had shown lesions to be neoplastic in 13% of the follow up series.
CONCLUSIONS: EUS is highly accurate for differentially diagnosing polypoid gall bladder lesions. It is recommended when ultrasonography cannot rule out neoplastic lesions. Non-neoplastic lesions diagnosed by EUS may be followed and observed with ultrasonography.

PMID 10644321  Gut. 2000 Feb;46(2):250-4.
著者: Kiyoaki Ouchi, Junichi Mikuni, Yoichiro Kakugawa, Organizing Committee, The 30th Annual Congress of the Japanese Society of Biliary Surgery
雑誌名: J Hepatobiliary Pancreat Surg. 2002;9(2):256-60. doi: 10.1007/s005340200028.
Abstract/Text BACKGROUND/PURPOSE: The long-term effects of initial laparoscopic cholecystectomy on the prognosis of patients with GBC remain unknown because of the limited numbers of patients reported from single institutions. This study was designed to determine the long-term prognosis of patients with gallbladder carcinoma (GBC) who had undergone laparoscopic cholecystectomy (LC), and to clarify the role of LC for the treatment of GBC and the benefit of aggressive additional excision.
METHODS: The clinical courses and outcomes of 498 patients with laparoscopically removed GBC registered in a nationwide survey were examined. Written questionnaires sent to members of the Japanese Society of Biliary Surgery included questions on Preoperative diagnosis, timing and methods to obtain final diagnosis, depth of invasion, second surgical procedure, prognosis of patients, and type of recurrence, if any.
RESULTS: The 5-year survival rates of patients after LC according to the depth of invasion were as follows: 99% in those with pT1a (limited to the mucosa), 95% in those with pT1b (muscularis), 70% in those with pT2 (subserosa), 20% in those with pT3 (serosa), and 0% in those with pT4 (serosa with invasion to adjacent organs). Perforation of the gallbladder during LC was found in 20% of the patients. Patients with gallbladders perforated during LC showed a significantly lower survival rate than did those without perforated gallbladders ( P < 0.01). Additional excision during or after LC was carried out in 48% of the patients, and the frequency of additional excision increased in accordance with the depth of invasion. Compared with patients who underwent LC only, additional excision resulted in better survival in patients with pT2 or pT3 tumors ( P = 0.051 and P < 0.05, respectively), but this difference was not found in patients with pT1 or pT4 tumors.
CONCLUSIONS: LC is not likely to worsen the survival rate of patients with GBC compared with the survival rate of patients undergoing a standard open radical procedure, as long as additional excision is conducted for patients with laparoscopically removed pT2 or pT3 GBCs. Special attention should be paid to prevention of bile spillage during LC.

PMID 12140616  J Hepatobiliary Pancreat Surg. 2002;9(2):256-60. doi: 1・・・
著者: Masato Nagino, Junichi Kamiya, Hideki Nishio, Tomoki Ebata, Toshiyuki Arai, Yuji Nimura
雑誌名: Ann Surg. 2006 Mar;243(3):364-72. doi: 10.1097/01.sla.0000201482.11876.14.
Abstract/Text OBJECTIVE: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer.
SUMMARY BACKGROUND DATA: Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases.
METHODS: This study involved 240 consecutive patients with biliary cancer (150 cholangiocarcinomas and 90 gallbladder cancers) who underwent PVE before an extended hepatectomy (right or left trisectionectomy or right hepatectomy). All PVEs were performed by the "ipsilateral approach" 2 to 3 weeks before surgery. Hepatic volume and function changes after PVE were analyzed, and the outcome also was reviewed.
RESULTS: There were no procedure-related complications requiring blood transfusion or interventions. Of the 240 patients, 47 (19.6%) did not undergo subsequent hepatectomy. The incidence of unresectability was higher in gallbladder cancer than in cholangiocarcinoma (32.2% versus 12.0%, P < 0.005). The remaining 193 patients (132 cholangiocarcinomas and 61 gallbladder cancers) underwent hepatectomy with resection of the caudate lobe and extrahepatic bile duct (n = 187), pancreatoduodenectomy (n = 42), and/or portal vein resection (n = 63). Seventeen (8.8%) patients died of postoperative complications: mortality was higher in gallbladder cancer than in cholangiocarcinoma (18.0% versus 4.5%, P < 0.05); and it was also higher in patients whose indocyanine green clearance (KICG) of the future liver remnant after PVE was <0.05 than those whose index was >or=0.05 (28.6% versus 5.5%, P < 0.001). The 3- and 5-year survival after hepatectomy was 41.7% and 26.8% in cholangiocarcinoma and 25.3% and 17.1% in gallbladder cancer, respectively (P = 0.011). In 136 other patients with cholangiocarcinoma who underwent a less than 50% resection of the liver without PVE, a mortality of 3.7% and a 5-year survival of 27.6% were observed, which was similar to the 132 patients with cholangiocarcinoma who underwent extended hepatectomy after PVE.
CONCLUSIONS: PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

PMID 16495702  Ann Surg. 2006 Mar;243(3):364-72. doi: 10.1097/01.sla.0・・・

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