BACKGROUND: The bile duct is a thin tube, about four to five inches long, that reaches from the liver to the small intestine. The major function of the bile duct is to move a fluid called bile from the liver and gallbladder to the small intestine, where it helps digest the fats in foods. Bile duct cancer or cholangiocarcinoma is a cancerous (malignant) growth in one of the ducts.  (SOURCE: www.ncbi.nlm.nih.gov, www.cancer.org)

Bile duct cancer is extremely rare, only two out of every 100,000 people are diagnosed with this disease, and most patients are over the age of 65. Both men and women can contract bile duct cancer. Based on its location, bile duct cancer is divided into three groups: Intrahepatic, Perihilar (also called hilar), and Distal. Intrahepatic bile duct cancers develop in the smaller bile duct branches inside the liver, Perihilar in the hilum, where the hepatic ducts have joined and are just leaving the liver, and Distal bile duct cancers are found further down the bile duct, closer to the small intestine. (SOURCE:   http://www.cancer.org)
 
TREATMENT: The goal is to treat the cancer and the blockage it causes. Endoscopic therapy with stent placement can temporarily relieve blockages in the biliary ducts and relieve jaundice in patients. Laser therapy combined with light-activated chemotherapy medications is another treatment option for those with blockages of the bile duct. When possible, surgery to remove the tumor is the treatment of choice, and may result in a cure. Traditionally, the disease is treated with resection, surgically removing the tumor, but in many cases the cancer tends to continue to spread around the bile duct. In the past, patients with non-resectable bile duct cancer had little chance of survival.  (SOURCE: www.ncbi.nlm.nih.gov/pubmedhealth)
A TRANSPLANT FOR CANCER CURE: According to a study published in the American Journal of Gastroenterology, treatment of nonresectable bile duct cancer with photodynamic therapy results in improved patient survival. With this approach, a photosensitizing agent (an agent that makes cells sensitive to light) is applied to cancer cells. A laser light with a specific wave length can then be used to destroy the cells. The precancerous and cancerous cells bind to the drug, allowing doctors to target them. Then, carefully, a flexible fiber thread goes down through the intestines into the bile ducts and exposes the cells to a laser which destroys them. Over the subsequent days and weeks, the tumor cells die and the bile ducts are opened. Because the treatment is given from the center of the tumor, the laser cannot penetrate through the entire mass, so some tumor cells remain. Unlike radiation, patients can repeat the photodynamic therapy treatments as often as needed. (Source: American Journal of Gastroenterology, Jefferson University Hospitals)

Dr. David Loren, an Associate Director of Medical Endoscopy and an Assistant Professor of Medicine at Thomas Jefferson University Hospital, talks about a cutting-edge therapy to improve the lives of patients battling a hard-to-treat condition.
What is bile duct cancer?
Dr. Loren:  The liver makes bile. It’s a fluid that the liver makes to help digest your food. The bile normally travels down the ducts, these tubes are called the bile ducts, and it travels down through these ducts and ultimately in to the intestine, where it mixes with the food to help the food digest. Sometimes cancer can arise in these bile ducts and that causes blockage in the bile ducts. That in itself causes a host of problems.
What kind of problems could patients have?
Dr. Loren: Patients can have jaundice, which is where their eyes turn yellow their skin may turn yellow and their urine turns dark. They can have problems with infections in the bile ducts because the bile can’t get out and sometimes they can have liver failure.
How common of a cancer is this?
Dr. Loren: It’s an uncommon cancer. About three thousand cases in the United States annually.
Any indication of what may cause it?
Dr. Loren: We really don’t know what causes bile duct cancer. There is an inflammatory condition of the bile ducts called primary sclerosis cholangitis, and that’s an inflammation of the bile ducts. Those patients have a much higher risk.  There are certain genetic syndromes that have a slightly increased risk of bile duct cancer but we don’t know a definitive direct cause.
What’s the prognosis for a person with bile duct cancer?
Dr. Loren: Unfortunately the prognosis is generally poor. Patients who are diagnosed about only a third of them are ultimately candidates to have an attempted curative resection. This means two thirds of patients at the time of their diagnosis don’t have an option for cure. The lifespan for those who don’t have an option for cure is generally measured in months.
Why would it be so difficult for more patients to have surgery to be able to remove the cancer?
Dr. Loren: The cancer has a few features that make it hard to diagnose early. The first of which is, there is no obvious sign with the early development of cancer. There are a lot of structures where they are located, not just the liver and the ducts. There are adjacent structures and very important blood vessels and these tumors often involve these blood vessels or they may involve multiple segments in the liver. When they do that, it precludes surgery and it prevents people from having a cure because cure can only be achieved by removing the tumor surgically.
What are the options then for patients with this type of cancer?
Dr. Loren: Chemotherapy and radiation have traditionally been offered to these patients. The benefit to them is modest, at best maybe a few months of improvement and survival. We have used direct therapies, notably photo dynamic therapy, which is a laser therapy in the bile ducts where we actually destroy the tumor in the bile duct. That offers the best prognosis amongst all of these therapies for patients who are not surgical candidates.
How does PDT work?
Dr. Loren: PDT happens in two steps. A patient comes in and has an intravenous medication administered. That medicine although it travels throughout the body, it gets concentrated in the cancer cells. The job of that medicine is to make the cancer cells very sensitive to the laser light. We use a very specific wave length of laser and at another session two days later following the administration that the laser is advanced in to the bile ducts and then the laser is used to destroy the cancer.
Is this the kind of treatment that can cure the cancer?
Dr. Loren: Unfortunately it cannot cure the cancer. The problems that people run in to from cholangiocarcinoma to the infectious issues, the liver failure issues these have traditionally been the reasons that people die from the disease. In fact, jaundice and the high Billie Ruben, the abnormal blood test that accompanies that and the jaundice precludes people from being able to get even chemotherapy. Improving upon that by opening up the bile ducts letting the bile flow out resolving infection is really key to prolonging life. That’s how photo dynamic therapy helps improve patients. It keeps those bile ducts open longer; it kills some of the tumor. Sometimes we see tumors even shrink but it’s not a cure.
Does it improve quality of life?
Dr. Loren: It improves quality of life. In fact, in all the studies that have been done, the quality of life has uniformly improved across all measures for patients having PDT.
Is it safe to say that it buys patients time? Is there any indication how much time that might be for the average patient?
Dr. Loren: The data are that the photo dynamic therapy improves survival depending upon the study incrementally meaning above other therapies an additional nine to sixteen months. I tell patients on average that they can expect to have an additional year of life with improved quality of live. That’s very important. These are patients who’ve been told that they have a cancer that has no cure. They have a cancer that can’t even be treated with chemotherapy or radiation with any significant affect and that their lifespan is going to be short. To be able to offer them an additional year of life is a tremendous thing for these individuals. These patients have one treatment every three months; they don’t have to come to the doctor every day. In fact, I only see patients one time in between treatments. So their quality of life and the interruption in their life is actually quite good.
Is it used in other forms of cancer?
Dr. Loren: It is.
Is it more commonly used in other forms of cancer?
Dr. Loren: Traditionally it had been very commonly used for early esophageal cancers. There have been newer technologies that have replaced photo dynamic therapy in that application. Those technologies and their application in the bile ducts have not really come to fruition and so it still remains the only treatment directed at the bile duct with data behind it. PDT is also used for cancers of the lung in order to open up blocked lung passageways. Then there are a number of investigators who are trying it in a few other cancers.
Is this becoming more widely used for bile duct cancers or is there just a handful of centers doing it now?
Dr. Loren:  There are a handful of centers that are doing it now and really not very many. The barriers are many. First of all insurance companies can be a major barrier and I’ve had to fight with insurers really for hours and hours writing appeals. However, we’ve had all of our patients be covered. We’ve had to go to an independent committee from the state that has reviewed and forced the insurers and required them to pay for the patients. Medicare does cover this however. For Medicare recipients it’s not a problem. The other barrier is the procedure is long, it requires specialized tools, the laser is a very expensive device and it requires an expertise.  Biliary endoscopy meaning doing endoscopy in the bile ducts that is limited to academic centers.
What should people know about PDT?
Dr. Loren: You might want to know that the most common side effect of photo dynamic therapy is light sensitivity. The medicine itself makes the patients sensitive to light. After the injection of the medicine it’s important that the patient stay out of direct sunlight for a period of time until that medication can wear off. Then they can be re-introduced to the sun over time.
Tell me about the laser.
Dr. Loren: During the procedure what happens is we use a scope that’s introduced through the mouth and goes down to the small intestine and then goes up into the bile ducts. We use an actual scope that goes up in to the bile ducts. Through that scope we deliver the laser, so we see exactly where we need to deliver the laser. The laser is up right where the cancer is and then we treat that site with the laser. The patient is asleep; they’re protected from the sunlight because we need to be careful about that in the other monitors carefully monitored. Each site that we treat is a twelve and a half minute laser treatment. We may treat one, two or three sites in any session depending upon where the blockage is.
Can this be repeated?
Dr. Loren: There’s no maximum therapy. We continue to treat every three months and we continue as long as the patient is willing to participate. We’ve had patients alive, in excess of going through the therapies that have lived in excess of two years. There have been reports of individuals longer than five years.

FOR MORE INFORMATION, PLEASE CONTACT:

Joan Digneo
Thomas Jefferson University
joan.digneo@jefferson.edu