Resectable disease

The therapeutic approach to resectable distal cholangiocarcinoma (stage 0, IA, IB, IIA, IIB) is similar to that of pancreatic head ductal adenocarcinoma. The operation of choice is a potentially curative pancreaticoduodenectomy with regional lymphadenectomy. Pancreatic resection with synchronous portal vein resection, resection of the common bile duct at the porta hepatis, and liver resection should be performed in selected cases.

Although recent advances of cross sectional imaging allow detailed evaluation of the common bile duct, pancreas, and liver, the accuracy of radiologic staging is not 100%. When there is a good chance the tumor can be completely removed, surgery is undertaken, and the surgical exploration still plays the key role for the finally assessment of resectability. Sometimes an unexpected locally advanced or a metastatic disease is found. In this case, the surgeon may continue the operation as a palliative procedure to relieve or prevent symptoms.

However, the anatomy of the tumor is not the whole story. Other patient-related factors are equally as important to the decision-making process. Foremost among these include comorbidities and functional status. Comorbidities refer to other diseases that the patient may suffer from, such as heart disease or diabetes. Functional status refers to nutritional status, the ability to go through a major surgery, and to function independently after the operation. So assessment of resectability requires a complex evaluation of tumor anatomy, age, comorbidities, functional status and the results of a blood test (Ca 19.9) to determine the risk-benefit profile of surgery. 

The goal of pancreaticoduodenectomy is a complete tumor clearance, without leaving behind cancer residual. This concept is known as R0 surgery (without residual disease). Furthermore, regional lymphadenectomy is always performed. The role of extended lymph node dissection is controversial and does not seem to be beneficial. After resection, intraoperative frozen rection of the common bile duct and pancreatic pancreatic resection margins is performed to rule out microscopic disease residual (R1) in the pancreatic remnant. Extension of the resection to the superior tract of the bile duct, up to the porta hepatis; or to the pancreatic body up to total pancreatectomy with splenectomy may be necessary when the resection margins are positive for tumor cells.

The resection specimen is examined by the Pathologist. Histological examination confirms the diagnosis and assigns the pathologic tumor stage (according to the TNM system, AJCC, www.cancerstaging.org). Although not formally part of the TNM system, other histologic features are of paramount importance. The grade of the cancer (how abnormal the cells look under the microscope) is listed on a scale from G1 to G4, with G1 cancers looking the most like normal cells and having the best outlook. As seen, another important factor is the tumor clearance, whether or not all of the tumor is removed. This is listed on a scale from R0 (where all visible and microscopic tumor was removed) to R2 (where some visible tumor could not be removed). Furthermore, lymph nodes are analyzed to look for cancer involvement (lymph node status).

Patients are given chemotherapy or chemo-radiotheraphy after the cancer has been surgically removed to try to eliminate any cancer cells that have been left behind. This type of treatment is called adjuvant treatment, and lowers the chance that the cancer will recur. 

Locally advanced disease

Distal cholangiocarcinoma is defined locally advanced (stage III) when has spread to the portal vein and the hepatic artery, or when has spread to the superior mesenteric artery.

When cross-sectional imaging reveals a locally advanced distal cholangiocarcinoma, it is necessary to obtain a pathologic diagnosis (usually cytologic). This ban be obtained through a fine needle aspiration biopsy. For this test, a thin needle is inserted through the skin and into the tumor. Ultrasonography is used to look at the position of the needle and make sure that it is in the tumor. Biopsies can be also performed using endoscopic ultrasound, placing the needle directly through the wall of the stomach or through the duodenum into the tumor. In either case, small tissue samples can be removed through the needle. If an ERCP is performed, brushing biopsied can be obtained. Tissue samples are then examined under a microscope. The abnormal cells are found and examined by the Pathologist, who decides on a diagnosis. 

If the neoplasm has caused symptoms, a palliative treatment may be necessary to relieve them:

• A plastic or metal stent can be placed endoscopically to relieve the jaundice caused by blocked common bile duct. Alternatively, a percutaneous biliary drainage may be placed. For more information click here. 
• If necessary, surgery can reroute the flow of bile from the common bile duct directly into the small intestine, bypassing the obstructed area (bypass operation). The stomach connection to the duodenum can be rerouted at this time as well to relieve or prevent duodenal obstruction. Furthermore, intraoperative biopsies may be performed. 

The first-line treatment of locally advanced distal cholangiocarcinoma is medical therapy. Chemotherapy involves the use of medications to kill cancer cells, and may be given intravenously or by mouth. These drugs are usually given in cycles, with alternating periods of treatment and recovery, and may be given alone or in conjunction with radiation therapy (chemo-radiotherapy). The Oncology team chooses the best treatment plan for any given patient. Once the treatment schedule has been completed, re-staging is performed. This involves a detailed clinical examination, the measurement of serum Ca 19.9, and cross-sectional imaging (CT-scan or PET-CT). The results are discussed within our multidisciplinary team. Outcomes after first-line medical treatment for locally advanced distal cholangiocarcinoma include:  

• Disease regression (down-staging). This means that the disease has become resectable, at least on the basis of cross-sectional imaging. The Surgeon may decide for surgical exploration, if it is likely the neoplasm can be completely removed surgically. 
• Stable disease. This means that no new tumors have developed, and that the neoplasm has not spread to any new regions of the body (in other words, the neoplasm is not getting better or worse). In such a situation, the management is tailored to the single patient, after multidisciplinary discussion. Additional chemotherapy or chemo-radiotherapy may be advised.
• Disease progression. This means that the tumor has progressed locally (has grown in size) or has spread to other organs of the body (has metastasized). The most common metastatic site is the liver. In such a situation, second-line chemotherapy may be indicated, as well as the inclusion into experimental clinical trials.

Metastatic disease