丹娜法伯專家：膽道惡性腫瘤該如何治療

（丹娜法伯胃腸道中心，Brian Wolpin博士（右側））

膽道惡性腫瘤是在膽道系統中形成的一種惡性腫瘤，其中膽道系統與肝臟、膽囊和小腸相連接，並將膽汁（一種能幫助消化脂肪的液體）送至小腸。雖然該疾病相對少見，但是美國每年約有1.5萬人被診斷為膽道癌。

為了更進一步地了解此種罕見疾病，我們對丹娜法伯/布列根和婦女癌症研究所（DF/BWCC）胰腺與膽管腫瘤中心的聯合主任Brian Wolpin博士進行了採訪。

膽道惡性腫瘤的類型有哪些？

膽道惡性腫瘤通常分為3種：肝內膽管細胞癌（膽管癌）、肝外膽管細胞癌以及膽囊癌。在某種情況下，壺腹癌患者也會和這些類型中的其他亞型歸為一類。壺腹周圍組織位於大膽道和小腸交界處。

通常如何診斷膽管癌？

對於肝內膽管細胞癌來說，通常情況下早期癥狀是不存在的。癥狀出現時，常常是因為肝臟中有較大腫塊，該腫塊會導致上腹部疼痛，或轉移疼痛（腫瘤擴散到其他位置）。如果癌症累及腸胃，患者還會出現體重減輕和提早有飢餓感。

同樣地，擴散的肝內膽管腫瘤還可能導致轉移疼痛或其他局部器官的受累疼痛或體重減輕。

當這些腫瘤出現較早的時候，通常是因為黃疸導致的，因為黃疸會阻塞膽管，同時會使皮膚變成黃色。其他癥狀包括陶土樣大便、醬油尿和瘙癢。

膽囊癌在早期階段常常不易被診斷出來。而且膽囊癌有時還會出現在因感染或膽結石進行膽囊切除術的患者中，但是這些患者常常是因為出現癌症轉移的癥狀才會明確診斷的。膽囊癌這種癌症通常主要擴散至腹腔，因此患者會出現腹痛或體重減輕。如果阻塞膽管，還會出現黃疸。目前還沒有膽囊癌的相關篩查檢測，而且表現出的癥狀都具有相對的非特異性。某些患者在血液檢查后（通常包括肝功能檢測、或肝、膽囊以及膽管等CT掃描）才被診斷出膽囊癌。

最易出現膽囊癌的風險人群是哪類人？

隨著年齡的不斷增加，所有的膽管癌症風險都在增長。肥胖症是所有膽管癌類型的一個風險因素，而且吸煙者、女性以及有膽結石病史的群體常常更容易患膽囊癌。有肝臟感染、尤其是肝炎病毒的群體患肝內膽管癌的風險更大。不太常見的感染（如肝吸蟲），因吃未煮熟的魚而導致的一種寄生蟲感染，而且一種稱作原發性硬化性膽管炎（PSC）的自主免疫炎性疾病還會增加肝內和肝外膽管癌的風險。

膽管癌一般情況下怎麼治療？

如果該疾病確診的較早，通常情況下第一步就是手術治療，其次是放化療。手術可能包括部分肝、膽系或膽囊切除。

在某些病例中如果無法用手術方法去除腫瘤，還常常使用化療或放療的方法。

上述疾病均為複雜的癌症，需要有複雜的治療方法。所以我們需要一個多學科醫療團隊對患者進行專業性地治療。這個多學科團隊由外科醫生、放射科腫瘤學家、臨床腫瘤學家組成，共同參與患者的醫療服務，並且幫助患者提供個性化的診療方案。

膽道癌症研究的基礎是什麼？

目前有許多令人興奮的試驗性藥物正在膽管和膽囊癌症的治療過程中進行檢測。我們已確定了多種基因突變靶點（尤其是肝內膽管癌），這些靶點給患者提供了新的治療方法。在丹娜法伯/布列根和婦女癌症研究所，我們有多項針對特異性靶向突變的臨床試驗，而且

目前的著眼點是觀察每個患者的腫瘤狀況以探求其是否攜帶上述新興藥物治療的基因突變。最常見的靶點選擇包括IDH、NRAS以及FGFR。早期數據還表明免疫療法可能對膽管癌有治療作用，目前我們也在研究這些藥物對上述癌症起作用的機理。

What Is Biliary Cancer?

（Brian Wolpin, MD (right), of Dana-Farber』s Gastrointestinal Cancer Center.）

Biliary cancer is a form of cancer that develops in the bile duct system, which connects the liver, gallbladder, and small intestine, moving bile -a fluid that helps digest fats-to the small intestine. While relatively uncommon, approximately 15,000 people in the United States are diagnosed with this disease each year.

To further understand this rare disease, we spoke with Brian Wolpin, MD, MPH, co-director of the Pancreas and Biliary Tumor Center at Dana-Farber/Brigham and Women』s Cancer Center (DF/BWCC).

Biliary tract cancer is generally categorized into three groups: intrahepatic cholangiocarcinoma (bile duct cancer), extrahepatic cholangiocarcinoma, and gall bladder cancer. In some instances, patients with ampullary carcinoma will also be grouped together with these other subtypes. Periampullary tissue is present at the junction of the large bile duct and the small bowel.

How is biliary cancer usually diagnosed?

For intrahepatic cholangiocarcinoma, early symptoms are often not present. When symptoms develop, it is often because of a large mass in the liver that causes upper abdominal pain, or pain from metastases – the tumor spreading somewhere else. People can also lose weight and become full earlier than normal if the tumor presses on the stomach.

Similarly, extrahepatic biliary tumors that have spread also may cause pain from metastases or compression on other local organs, or weight loss. When these tumors – which occur in the bile duct that drains the liver – are found early, it』s generally because of jaundice, because it obstructs the bile duct and the skin turns yellow. Other symptoms include light-colored stool, dark urine, and itching.

Gall bladder cancer is also not commonly diagnosed at an early stage. It can sometimes be found if a patient has their gall bladder removed for infection or gall stones, but it is also diagnosed because people get symptoms from metastases. This cancer most commonly spreads to the abdominal cavity, so patients may experience abdominal pain or weight loss. Gall bladder cancer can also present with jaundice if the cancer blocks the bile ducts.

As people get older, the risk of all bile duct cancers increases. Obesity is a risk factor for all types of biliary cancers, and smokers, women, and those who have a history of gall stones are more likely to be diagnosed with gall bladder cancer. Infections, particularly hepatitis viruses that affect the liver, put people at a higher risk for intrahepatic bile duct cancer. Less common infections, such as liver flukes, a parasitic infection that can be the result of eating undercooked fish, and an auto-immune inflammatory condition called primary sclerosing cholangitis (PSC), also increase the risk of both intrahepatic and extrahepatic cholangiocarcinoma.

How is the disease generally treated?

If the cancer is caught early, then surgery to remove it is commonly the first step, followed by additional therapy, such as chemotherapy and/or radiation. Surgery may include removing a portion of the liver, the biliary tree, or the gall bladder.

If the tumor cannot be removed surgically, it』s usually treated with chemotherapy, and radiation may also be used in some cases.

These are complicated cancers with complicated management approaches. We recommend patients are treated by a multidisciplinary team, where the surgeon, radiation oncologist, and medical oncologist are all involved in a patient』s care and helping them to make the best treatment decisions.

There are some exciting experimental medications now being tested in the treatment of biliary and gall bladder cancers. We』ve identified several genetic mutations, particularly with intrahepatic cholangiocarcinoma, that are providing patients with new treatment opportunities. At DF/BWCC, we have several clinical trials specifically targeting these mutations, and we now look at each patient』s tumor to see whether it carries a mutation that might be targeted with these emerging medicines. The most common of the alterations that we are targeting include IDH, NRAS, and FGFR. There is also early data to suggest that immunotherapy may have a treatment effect for biliary cancers, and we are currently studying how these drugs may help patients with these cancers.

What』s on the horizon in biliary cancer research?

There are some exciting experimental medications now being tested in the treatment of biliary and gall bladder cancers. We』ve identified several genetic mutations, particularly with intrahepatic cholangiocarcinoma, that are providing patients with new treatment opportunities. At DF/BWCC, we have several clinical trials specifically targeting these mutations, and

we now look at each patient』s tumor to see whether it carries a mutation that might be targeted with these emerging medicines. The most common of the alterations that we are targeting include IDH, NRAS, and FGFR. There is also early data to suggest that immunotherapy may have a treatment effect for biliary cancers, and we are currently studying how these drugs may help patients with these cancers.