Cholangiocarcinomas (CCCs) are malignant tumors of the biliary tree that arise from the bile ducts or the liver. Klatskin tumors (KTs) are also referred to as hilar or perihilar cholangiocarcinomas [1]. A large proportion of all cholangiocarcinomas are Klatskin tumors. They are usually undifferentiated and grow rapidly. The majority of occurrences of KTs are sporadic, however, the prevalence is still unknown.

Klatskin tumors are more common in men and are typically reported in older individuals in their 6th decade of life [2]. KTs normally do not produce symptoms until they have progressed to a late stage. This contributes to their poor prognosis. When tumors grow large enough, they may cause obstructive jaundice [3]. KTs are the most commonly reported cause of proximal biliary obstruction, accounting for approximately 80% of such cases [4]. Other signs of disease are non-specific and include abdominal pain, loss of weight, malaise, and fatigue. Cholangitis is less frequently encountered.

KTs are known to metastasize to regional lymph nodes in the abdomen. Metastases can also occur to the head of the pancreas and can spread distally via the systemic or portal circulation.

Certain factors predispose individuals to the development of KTs, the most prominent being primary sclerosing cholangitis (PSC). It is thought to be responsible for up to 40% of KTs. Other risk factors include chronic inflammation of the biliary tree, parasitic infections, namely ascariasis and schistosomiasis, chemical substances exemplified by thorotrast (X-ray contrast) and asbestos, some congenital diseases of the biliary tree, liver cirrhosis, and cholelithiasis [5]. Many patients have comorbidities such as inflammatory bowel disease and viral hepatitis [3] [6].

• Right Upper Quadrant Tenderness

  Physical examination revealed a jaundiced patient with right upper quadrant tenderness but no overt abdominal masses or lymphadenopathy. [consultant360.com]

• Pruritus

  These include jaundice (yellowing of the skin), clay-colored stools (because bile normally darkens the stool, but in this case is not draining into the bowel), bilirubinuria (dark urine), pruritus (itchy skin), weight loss, and abdominal pain. [oncolink.org]

  There have been only a few reports of similar cases in the medical literature. 6-15 Case Report A 41-year-old African American woman presented with new-onset jaundice and pruritus. [acgcasereports.gi.org]

• Testicular Pain

  A 38-year-old man presented with right scrotal enlargement and chronic testicular pain. [ncbi.nlm.nih.gov]

There are various clinical, laboratory and imaging studies that are needed in order to make the diagnosis of Klatskin tumor. Imaging techniques include:

• Ultrasound: This may show evidence of a hyperechoic mass that may cause obstruction at the bifurcation of the common hepatic duct [7]. Endoscopic ultrasound (EUS) is an accurate technique that can be used to facilitate fine needle aspiration (FNA) for cytology [8].
• Computerized tomography (CT): Direct visualization of the tumor via CT scanning is usually not possible, however, biliary tract dilatation, metastases and affected lymph nodes can be seen.
• Magnetic resonance cholangiopancreatography (MRCP): This is the preferred technique, and the gold standard when it comes to diagnosis of KTs, as it is the most accurate in determining the location and extension of the tumor.
• Magnetic resonance imaging (MRI): This reveals similar findings to CT scanning.

• Positron emission (PET): PET scans can be utilized to detect small tumors, as well as distant metastases [9].

Staging of the tumor is necessary for planning treatment, as advanced stages of KT are inoperable. Using the Bismuth-Corlette classification, there are four types of hilar CCCs, of which type IV is the most advanced, involving both hepatic ducts.

The resultant cholestasis from KTs can be detected by measuring the levels of tumor markers such as carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) [10]. Levels of over 100 units per milliliter are a good diagnostic indicator for CCC in patients with PSC [11]. Additionally, liver function tests (LFTs) may show elevated levels of parameters such as alkaline phosphate (ALP) and gamma-glutamyl transpeptidase (GGT).

Surgical resection represents the only potentially curative treatment for hilar cholangicarcinoma. Because of the aggressive nature and the absence of effective adjuvant therapy treatment remains still a challenge. [ncbi.nlm.nih.gov]

The patient's diagnosis, management, and prognosis are discussed. The case highlights the importance of screening for hepato-biliary malignancies in elderly patients with abnormal liver function markers. [ncbi.nlm.nih.gov]

Etiology The etiology of the Klatskin Tumor is not evident based. Multiple pathological conditions, which cause acute or chronic ailments of the biliary tract may have the influence to develop a malignant growth. [cancerwall.com]

Etiology In 90% of cases Klatskin tumors occur sporadically but certain risk factors have been associated with the disease. [orpha.net]

An unusual etiology of biliary hilar obstruction and the potential role of acidic fibroblast growth factor in the development of a biliary neuroma. Am Surgeon. 1999;65:47–51. Zeff R, Pfeffer R, Adams P, Ruoff M. [tropicalgastro.com]

This suggests that imaging studies, although essential in investigations of patient symptoms, might not be helpful in detecting the precise etiology of strictures. [jmedicalcasereports.biomedcentral.com]

Part 1: epidemiology and etiology. J Gastroenterol Hepatol 17: 1049-55 3 Patel T (2001) Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 33: 1353-7. [codes.iarc.fr]

[…] of Cancer Epidemiology and Genetics, National Cancer Institute, EPS 7084, MSC 7234 6120 Executive Blvd., Bethesda, MD 20892 (e-mail: [email protected] ). [academic.oup.com]

Following background chapters on anatomy, epidemiology, and clinicopathologic features, each of the diagnostic imaging techniques is carefully appraised, focusing on new developments in equipment and contrast agents. [books.google.com]

Part 1: epidemiology and etiology. J Gastroenterol Hepatol, 2002, 17(10): 1049–1055 CrossRef PubMed Google Scholar 30. Wu T T, Levy M, Correa A M, Rosen C B, Abraham S C. [oadoi.org]

In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 10th ed. Philadelphia, Pa.: Saunders Elsevier; 2016. . Accessed Feb. 22, 2016. Rizvi S, et al. [mayoclinic.org]

Unlike others on this topic, this text demonstrates how the endoscope incorporates pathophysiology, diagnostic, and treatment modalities into endoscopic practice. [books.google.com]

[…] common in East Asia, due to endemic liver fluke infection More common in older patients (over 75% of patients are older than 65 at initial diagnosis) ( Gastroenterology 2009;136:1134 ) Slightly more common in males than females ( Hepatology 2011;54:173 ) Pathophysiology [pathologyoutlines.com]

[…] without involvement of the secondary intrahepatic ducts Type IIIa - Extends into the right secondary intrahepatic duct Type IIIb - Extends into the left secondary intrahepatic duct Type IV - Involvement of the secondary intrahepatic ducts on both sides Pathophysiology [emedicine.com]

CONCLUSION: The air contrast cholangiography is a safe and effective method, and it appears justified as a routine procedure to prevent or reduce the risk of post-ERCP cholangitis, specially in Klatskin patients (p 0.005). [ncbi.nlm.nih.gov]

Preventive measures For the prevention of neoplastic diseases of the liver and bile ducts, it is necessary to adhere to proper nutrition, not to abuse alcohol and to prevent the infection with parasites. [acikgunluk.net]

Special chapters, such as the Designing Clinical Research in Gastrointestinal Endoscopy, The Prevention of Infection Following Gastrointestinal Endoscopy, Complications of Peptic Ulcer Disease, and Credentialing for Gastrointestinal Endoscopy, help make [books.google.com]

1. Banales JM, Cardinale V, Carpino G, et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016;13(5):261-280.
2. Cannon RM, Brock G, Buell JF. Surgical resection for hilar cholangiocarcinoma: experience improves resectability. HPB (Oxford). 2012;14(2):142–149.
3. Saxena A, Chua TC, Chu FC, Morris DL. Improved outcomes after aggressive surgical resection of hilar cholangiocarcinoma: a critical analysis of recurrence and survival. Am J Surg. 2011;202(3):310-320.
4. Are C, Gonen M, D’Angelica M, et al. Differential diagnosis of proximal biliary obstruction. Surgery. 2006;140(5):756-63.
5. Suarez-Munoz MA, Fernandez-Aguilar JL, Sanchez-Perez B, et al. Risk factors and classifications of hilar cholangiocarcinoma. World J Gastrointest Oncol. 2013;5(7):132–138.
6. Zheng-Rong L, Hai-Bo Y, Xin C, et al. Resection and drainage of hilar cholangiocarcinoma: an 11-year experience of a single center in mainland China. Am Surg. 2011;77(5):627-633.
7. Yeung EY, Mccarthy P, Gompertz RH, Benjamin S, Gibson RN, Dawson P. The ultrasonographic appearances of hilar cholangiocarcinoma (Klatskin tumours). Br J Radiol. 1988;61(731):991-995.
8. Fritscher-Ravens A, Broering DC, Knoefel WT, et al. EUS-guided fine-needle aspiration of suspected hilar cholangiocarcinoma in potentially operable patients with negative brush cytology. Am J Gastroenterol. 2004 Jan;99(1):45-51.
9. Petrowsky H, Wildbrett P, Husarik DB, et al. Impact of Integrated PET and CT on staging and management of glabladder cancer and cholangiocarcinoma. J Hepatol. 2006;45(1):43-50.
10. Berardi R, Mocchegiani F, Pierantoni C, et al. Resected biliary tract cancers: a novel clinical-pathological score correlates with global outcome. Dig Liver Dis. 2013;45(1):70-74.
11. Chalasani N, Baluyut A, Ismail A, et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology. 2000;31(1):7-11.