Figure 3. US shows stones (arrows) in the intrahepatic ducts.
圖 3. 超音波顯示肝內膽管內有結石（箭頭）。

Figure 4. CT shows stones (arrows) in the intrahepatic ducts.
圖 4. CT 顯示肝內膽管內有結石（箭頭）。
biliary tract with contrast enhancement, ruptured biliary trees with biloma formation, biliary tree abruption, associated liver abscess, and hyper-enhanced walls of the biliary trees, which are indicative of acute suppurative cholangitis. The presence of calculi within the biliary tress, calculated by Hounsfield units, is a direct diagnostic sign of intrahepatic stones $(43,44)$$(43,44)$(43,44)(43,44).
膽道攝影增強、膽管破裂伴隨膽汁瘤形成、膽管早期剝離、合併肝膿瘍、膽管壁強化，這些皆提示急性化膿性膽管炎。膽管內結石（以亨斯菲爾德單位計算）是肝內結石的直接診斷指標 $(43,44)$$(43,44)$(43,44)(43,44) 。

MRI is a non-invasive imaging technique that can be used to survey the hepatobiliary system without exposing patients to radiation. While MRI does not allow for therapeutic intervention, it can provide detailed
MRI 是一種非侵入性影像技術，可用於檢查肝膽系統，且無需病患接受放射線照射。雖然 MRI 無法進行治療幹預，但它可以提供詳細的

Figure 5. Filling defects in the intrahepatic ducts by magnetic resonance cholangiopancreatography.
圖 5. 磁振造影胰膽管攝影顯示的肝內管道充盈缺損。

Figure 6. Percutaneous transhepatic cholangiography.
圖 6.經皮肝穿刺膽管攝影。
cholangiographic studies without the need for invasive procedures (Figure 5). In an MRI scan, dilatation or stricture in the extra- or intra-hepatic bile ducts, acute tapering of the peripheral biliary trees with arrowhead signs, and complete biliary obstruction with missing duct signs can provide clues that may suggest the presence of intrahepatic stones (45). However, in addition to stones, tumors or blood clots can also present filling defects in the biliary trees to reach an equivocal diagnosis.
無需侵入性操作即可進行膽道攝影檢查（圖 5）。 MRI 掃描中，肝內外膽管擴張或狹窄、週邊膽管系統急劇變細（箭頭徵）以及膽管完全阻塞（膽管徵缺失）等情況，可能提示肝內結石的存在（45）。然而，除結石外，腫瘤或血塊也可能導致膽管系統充盈缺損，從而得出不明確的診斷。

Cholangiography can be performed via the oral route (endoscopic retrograde cholangiography), percutaneous route (percutaneous transhepatic cholangiography) (Figure 6), or via T-tube postoperatively. Antibiotics are usually given and some
膽管攝影可經由經口途徑（內視鏡逆行性膽管攝影）、經皮途徑（經皮肝穿刺膽管攝影）（圖 6）或術後經 T 管進行。通常給予抗生素，有些
complications, such as cholangitis, hemorrhage, or hollow organ perforation may occur. In addition to diagnosis, these procedures can also provide therapeutic intervention.
可能會發生併發症，例如膽管炎、出血或空腔器官穿孔。除了診斷外，這些手術還可以提供治療介入。

To treat acute cholangitis, penicillin/beta-lactamase inhibitor, third generation cephalosporin, or carbapenem are commonly prescribed to cover Gramnegative bacteria (46). Antimicrobial agents are usually given for 7 to 14 days, and sometimes antifungal agents are required in cases of hospital-acquired infection or when biliary prostheses are in place (47). Bile culture is crucial in guiding the choice of antimicrobial agents, as blood culture may not always yield pathogens.
治療急性膽管炎時，常用青黴素/β-內醯胺酶抑制劑、第三代頭孢菌素或卡巴培南類抗生素來治療革蘭氏陰性菌(46)。抗菌藥物通常持續7至14天，有時在醫院內感染或置入膽道假體的情況下也需要使用抗真菌藥物(47)。膽汁培養對於指導抗菌藥物的選擇至關重要，因為血液培養並非總是能找到病原體。

For liver fluke infestation, oral triclabendazole is given in one or two doses. A short course of corticosteroids is sometimes prescribed for severe symptoms. Albendazole ( 400 mg once), mebendazole ( 100 mg twice for 3 days or 500 mg once), or ivermectin ( 150 $-200\mathrm{mcg}/\mathrm{kg}$$-200\mathrm{mcg}/\mathrm{kg}$-200mcg//kg-200 \mathrm{mcg} / \mathrm{kg} once) are recommended for treating ascariasis (48).
對於肝吸蟲感染，可口服一至兩次三氯苯達唑。有時，對於嚴重症狀，會開立短期皮質類固醇療程。建議使用阿苯達唑（400 毫克，一次）、甲苯達唑（100 毫克，兩次，連服 3 天，或 500 毫克，一次）或伊維菌素（150 毫克，一次）治療蛔蟲病 (48)。

Early biliary drainage within 48 hours of diagnosis has been shown to reduce the incidence of organ failure, hospital stay, and mortality (49). In fact, the European Society of Gastrointestinal Endoscopy (ESGE) recommends biliary decompression within 12 hours in cases of septic shock (50).
診斷後 48 小時內進行早期膽道引流已被證實可降低器官衰竭的發生率、住院時間和死亡率(49)。事實上，歐洲胃腸內視鏡學會(ESGE)建議，對於敗血症休克病例，應在 12 小時內進行膽道減壓(50)。

Agents for stone lysis or anti-inflammation
溶石劑或抗發炎劑
Ursodeoxycholate is a promising therapy for cholelithiasis, as it can decrease the level of secretory phospholipase A2, a pronucleating protein, and increase biliary flow (19). It has been shown to induce resolution of intrahepatic stones with high cholesterol content. $(51,52)$$(51,52)$(51,52)(51,52). Fibrates, on the other hand, can upregulate multidrug resistance 3 P-glycoprotein to decrease phospholipid secretion into bile, leading to lower levels of transaminase, alkaline phosphatase,
熊去氧膽酸是一種很有前景的膽結石治療方法，因為它可以降低分泌型磷脂酶 A2（一種促核蛋白）的水平，並增加膽汁流量(19)。研究表明，它能夠誘導高膽固醇肝內結石的溶解。 $(51,52)$$(51,52)$(51,52)(51,52) 。另一方面，貝特類藥物可以上調多重抗藥性 3P-糖蛋白，從而減少磷脂分泌到膽汁中，從而降低轉氨酶、鹼性磷酸酶和膽汁酸的水平。
and r-GT after administration (53). Selective cyclo-oxygenase-2 inhibitors and prostaglandin E-receptor antagonists can reduce the inflammatory response in intrahepatic stones, which is caused by the stimulatory effects of prostaglandin E on cell proliferation, apoptosis, and angiogenesis (54). Monoclonal antibodies such as gefitinib are monoclonal antibodies that can inhibit biliary hyperplasia, mucin 3 expression, and beta-glucuroniadse activity $(55,56)$$(55,56)$(55,56)(55,56). Inchinkoto, a herbal medicine, can stimulate bile secretion to reduce stone formation, and geniposide can decrease intestinal inflammation by lowering fecal short-chain fatty acids to impair stone formation and biliary hyperplasia (19, 57, 58). Furthermore, the transcription factor nuclear factor kappa B (NF- $\kappa \mathrm{B}$$\kappa \mathrm{B}$kappaB\kappa \mathrm{B} ) and the protein kinase C (PKC) can reduce lipopolysaccharide expression of the bacteria to decrease beta-glucuronidase activity (59). However, it is important to note that compared to procedural stone removal, the effect of stone lysis or anti-inflammation by the pharmacological agents may be less efficient and impractical.
和 r-GT（53）。選擇性環氧合酶-2 抑制劑和前列腺素 E 受體拮抗劑可以減輕肝內結石的發炎反應，這種發炎反應是由前列腺素 E 刺激細胞增殖、凋亡和血管生成引起的（54）。吉非替尼等單株抗體是一種可以抑制膽道增生、黏蛋白 3 表現和β-葡萄醣醛酸酶活性的單株抗體 $(55,56)$$(55,56)$(55,56)(55,56) 。草藥 Inchinkoto 可以刺激膽汁分泌，減少結石形成，梔子苷可以透過降低糞便短鏈脂肪酸來減輕腸道炎症，從而抑制結石形成和膽道增生（19,57,58）。此外，轉錄因子核因子κB (NF- $\kappa \mathrm{B}$$\kappa \mathrm{B}$kappaB\kappa \mathrm{B} ) 和蛋白激酶 C (PKC) 可以降低細菌的脂多醣表達，進而降低β-葡萄醣醛酸酶活性 (59)。然而，值得注意的是，與手術取石相比，藥物溶石或抗發炎治療的效果可能較低且不切實際。

Compared to percutaneous endoscopy, peroral endoscopy for stone retrieval offers several advantages. First, it has a lower complication rate for procedures such as hemorrhage, intra-abdominal abscess, hollow organ perforation, pneumothorax or hemothorax, liver laceration, disruption of the cutaneo-biliary tract, and waiting time for the tract maturation (6). In 1987, peroral cholangioscopic lithotomy with a mother-baby endoscope system was introduced, which allowed for direct visualization of the biliary trees. However, this method has the shortcomings of a poor visual field and a small working channel for therapeutic devices (6). To overcome these limitations, a small-diameter gastroscopy (Olympus, GIF-N180) with a flexible ureteroscope (Olympus Medical, Tokyo, Japan) inserted into the biliary trees via the working channel was designed. However, it is limited by the two-operator system and poor manipulativeness (60, 61). In 2015, a digital version of a single-operator peroral
與經皮內視鏡檢查相比，經口內視鏡檢查取石具有多項優勢。首先，它在出血、腹腔膿腫、空腔器官穿孔、氣胸或血胸、肝撕裂、皮膽道中斷以及等待管道成熟的時間等手術併發症發生率較低 (6)。 1987 年，引進了使用母嬰內視鏡系統的經口膽道鏡取石術，可以直接觀察膽道系統。然而，這種方法的缺點是視野較差、治療設備的工作通道較小 (6)。為了克服這些局限性，設計了一種小直徑胃鏡（Olympus，GIF-N180），帶有一根柔性輸尿管鏡（Olympus Medical，日本東京），可透過工作通道插入膽道系統。然而，它受到雙操作員系統和較差的可操作性的限制（60，61）。 2015 年，出現了單人口述的數位版本
cholangiopancreatoscope (SpyGlassTM, Bostyon Scientific Corp, Natick, MA, USA) adapted on a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP) was introduced, and lithotomy can be facilitated by laser lithotripsy or electrohydraulic lithotripsy (EHL) (62). Nevertheless, SpyGlass requires further studies to clarify its value for intrahepatic stones, and the longer peroral route relative to the percutaneous route demands more skillful steering.
十二指腸鏡上改裝的胰膽管鏡（SpyGlassTM，美國麻薩諸塞州納蒂克市波士頓科學公司）已在內視鏡逆行胰膽管造影術（ERCP）中投入使用，並可透過雷射碎石術或液態電碎石術（EHL）輔助取石(62)。然而，SpyGlass 仍需進一步研究以明確其對肝內結石的價值，而且與經皮入路相比，經口入路的路徑更長，需要更熟練的操作技巧。

Percutaneous transhepatic cholangioscopic lithotomy (PTCSL) was introduced by Nimura in 1981 (63). To prevent infection, systemic antibiotics are given 30-60 minutes prior to percutaneous transhepatic biliary drainage (PTBD), and vitamin K is administered if coagulopathy or prolonged prothrombin time is found. The patient is kept in a supine or left oblique position, without general anesthesia. Immediately before PTBD, 50 mg of intravenous meperidine and local lidocaine are given. Under US-guidance, an 18-gauge needle is used to puncture the post-obstructed dilated bile duct. A 7F PTBD drainage tube is inserted through a 0.035 -inch guide wire, which is introduced into the bile duct through the puncture needle under fluoroscopic guidance. One to two weeks after PTBD, the fistula tract is dilated step by step by changing the drainage tube to $16-18\mathrm{F}$$16-18\mathrm{F}$16-18F16-18 \mathrm{~F} size after 2 to 3 sessions. A cholangioscope can then be inserted through the PTBD fistula to remove the stones (Figure 7). Sometimes laser lithotripsy or EHL can be used to fragment large or hard stones (5, 64-68). Extracorporeal shockwave lithotripsy (ESWL) has also been attempted, but with a lower stone clearance rate and higher complication rate (69). Isolated intrahepatic stones in left hepatic lobe can be completely removed by hepatectomy, but PTCSL has been reported to achieve complete stone clearance without sacrificing liver mass (70). However, the presence of biliary stricture is related to incomplete lithotomy and stone recurrence(5). To address this issue, dilatation of the
經皮肝穿刺膽管鏡取石術（PTCSL）由 Nimura 於 1981 年提出（63）。為預防感染，經皮肝穿刺膽道引流術（PTBD）前 30～60 分鐘給予全身性抗生素，如發現凝血功能障礙或凝血酶原時間延長，則給予維生素 K。患者取仰臥或左斜位，不予全身麻醉。 PTBD 前即刻靜脈注射 50mg 哌替啶，局部使用利多卡因。在超音波引導下，使用 18G 穿刺針穿刺阻塞後擴張的膽管。經 0.035 吋導絲插入 7F PTBD 引流管，在透視引導下經由穿刺針插入膽管。 PTBD 術後 1 至 2 週，經 2 至 3 次療程後更換引流管至 $16-18\mathrm{F}$$16-18\mathrm{F}$16-18F16-18 \mathrm{~F} 尺寸，逐步擴張瘻管。然後，可透過 PTBD 瘻管插入膽道鏡取出結石（圖 7）。有時可使用雷射碎石術或 EHL 碎石大塊或堅硬的結石 (5, 64-68)。體外震波碎石術 (ESWL) 也曾嘗試過，但其結石清除率較低，且併發症發生率較高 (69)。左肝葉孤立的肝內結石可透過肝切除術完全清除，但據報道，PTCSL 可在不犧牲肝臟質量的情況下完全清除結石 (70)。然而，膽道狹窄的存在與取石不完全和結石復發有關 (5)。為了解決這個問題，擴張膽道
strictured biliary trees can be attempted by passing a large size catheter, placing a metallic stent, or balloon dilatation across the strictured sites $(5,71)$$(5,71)$(5,71)(5,71). Compared to hepatectomy, PTCSL can conserve more liver volume. However, biliary cast syndrome, characterized by casts or debris in the intra- and extra-hepatic bile ducts, can occur in $3-25\mathrm{\%}$$3-25\mathrm{\%}$3-25%3-25 \% of transplanted livers, presenting with cholangitis and jaundice (72).
可以透過插入大號導管、放置金屬支架或球囊擴張狹窄部位來嘗試疏通膽管系統 $(5,71)$$(5,71)$(5,71)(5,71) 。與肝切除術相比，PTCSL 可以保留更多肝臟體積。然而，移植肝臟可能發生膽管管型綜合徵，其特徵是肝內外膽管中存在管型或碎片 $3-25\mathrm{\%}$$3-25\mathrm{\%}$3-25%3-25 \% ，並伴隨膽管炎和黃疸(72)。

The definite management for intrahepatic stones is resecting the involved segment with exploration lithotomy, which can be performed by laparoscopic or open surgery (72). Surgery is most indicated in cases with concurrent cholangiocarcinoma, unilobar distribution of stones, atrophy or fibrosis of the involved liver segments, or multiple strictures of the intrahepatic ducts, as it has the lowest rates of residual stones and stone recurrence. Post-operative cholangioscopy (POC) can be complementary to surgery to achieve complete stone clearance and conserve more liver reserve (73, 74). Compared to open surgery, laparoscopic hepatectomy has the advantages of less blood loss, quicker recovery of intestinal peristalsis, shorter hospital stay, and lower complication rates, such as wound infection, biliary leakage, or injury of the vessels (75). The rate of complete stone clearance can be improved by utilizing the 3-dimensional reconstruction technique (76). In some cases, hepaticojejunostomy,
肝內結石的確診治療是切除受累肝段並進行探查取石術，手術方式可採用腹腔鏡或開放性手術（72）。手術最適用於合併膽管癌、結石單葉分佈、受累肝段萎縮或纖維化、或肝內膽管多發性狹窄的患者，因為手術的殘留結石率和復發率最低。術後膽道鏡檢查（POC）可作為手術的補充，以達到徹底清除結石的目的，並保留更多的肝臟儲備（73, 74）。與開放性手術相比，腹腔鏡肝切除術有出血量少、腸道蠕動恢復更快、住院時間更短、傷口感染、膽漏、血管損傷等併發症發生率更低（75）等優點。利用三維重建技術（76）可提高結石的徹底清除率。在某些情況下，肝管空腸吻合術，

Figure 7. A cholangioscope was inserted through the PTBD fistula.
圖 7. 透過 PTBD 瘻管插入膽管鏡。