Chapter One - INCIDENCE OF GALLSTONE DISEASE

10% of American population might have gallstones, and we do diagnose one million gallstone patients each year. Among the million, we do over half a million cholecystectomies in the United States. Actually, at any given time 20 million Americans might have gallstones. Among these patients around 80% have gallstones that are cholesterol in nature. This is important for our topic because for biliary lithotripsy we're going to select patients with cholesterol gallstones. And our selection criteria according to the FDA is a little bit restricted. We will follow the guidelines: single stone, 5 millimeters to 20 millimeters single stone, functioning gallbladder. In United States, in the world, gold standard for the gallstone treatment is the lap. cholecystectomy.

Chapter Two - HISTORY

There was an era before the lap. Cholecystectomy in which we worked. At that time gallstone lithotripsy was led by Germans, French people and, still, despite the lap. cholecystectomy, the European countries. In selected European countries, still gallstone lithotripsy is an alternative to lap. cholecystectomy. And I understand we have various surgeons in the room. This modality has absolutely revolutionized, or created some kind of revolution for surgeons and changed, I think, the training part of the surgery and many parts of the surgical approach and, obviously, is a very acceptable modality. This system, piezoelectric, electrohydraulic, or otherwise, has been used for gallstones in Western countries since '85. Germany is the leading country in this regard. In France, Japan, and Belgium, extra corporeal shock wave lithotripsy is a non surgical modality just complementary to surgical option.

Chapter Three - THE DRY SPARK GAP LITHOTRIPTER

This dry machine, is operator friendly. The patient is on the dry machine, lies down, and we put the right upper quadrant to the right spot. There is an x-ray capability, an ultrasound capability. In biliary lithotripsy, we use the ultrasound to find the stone. And by the ultrasound there is a shield (I will show it to you) it has 6 lights on it (red lights) and carries the image to the ceiling like a NASA space system. There are two sensors there. Through those sensors the image goes to the computer. This is a pretty interesting technology and works for our patients benefit. There is our area spark gap under it and there's a column (water column). Patient's right upper quadrant gallbladder is going to come to that point and then we will catch it (which I will show you step by step) by the ultrasound image. Let's go step by step.

Chapter Four - COUPLING

This is one important step, which maybe in the learning curve sometimes we didn't, some of us, pay enough attention to. This coupling is very important to give the patient less pain and the most effective lithotripsy. Putting mineral oil at the patient's right upper quadrants should couple area properly and lead to less pain and less damage in the skin, and possibly more effective lithotripsy.

Chapter Five - LOCALIZATION

More close up, this is the shock wave lithotripsy. You see the shock wave, our spark gap is there, and there is an ellipsoid deflector, water column, and the patient's gallbladder, and the ultrasound image goes to our computer.
The steps are, again, the physician locates the stone with a hand-held ultrasound probe, and the physician uses a little light pen to indicate the stone, and the computer system triangulates the stone location, what we call F2 point. You really have to keep this F2 point in your mind, and that F2 point is very important. The patients even move a little bit during the procedure. Take your time. After every 400 to 500 shock waves, be sure the F2 point is in the proper place and relocate the patient. An operator moves the table to the place. Again, a little bit close up. This is our ultrasound probe with the 6 red lights which is going to carry your image to the sensor, and we are looking at the patient's gallstone. This is the gallbladder. The wall appears to be pretty normal. It's not inflamed. It's not thick, There is fluid around it. It's an ideal gallbladder for the lithotripsy. It has a single stone possibly around 16 millimeters or 18 millimeters.
We put the cursor there, this is a pen. The cursor in the ultrasound machine and then we connect by that system, as I already mentioned. We carry that image to our computer monitor. Now, this patient on the table is not in the target point. We have to put this patient a little bit down and to the left side and to the foot side. There is a machine that we previously worked with in which we did the labor manual., we pushed the patient. Now, whatever the target point is, you can push the button and automatically the table comes to your target point as you see here. Everything is in the zero point: the patient, gallstone is in the proper target, you can start to pulverize. This is, again, a computer triangulation and this is your stone at 2 point. Now, when everything is ready it looks like that. I hope every time is going to be this ideal. Single stone, probe, and our shock wave lithotripsy system.

Chapter Six - PROCEDURE

Then we start action. When the action is started, a spark gap gets discharged by the spark gap electrode and this extra corporeal shock wave lithotripsy, like Dr. Zabbo also mentioned in the physics presentation a few minutes ago, is going to go by this ellipsoidal deflector to the F2 point. This is actually what you'd like to do ideally, and you have to spend some time, especially when in the learning curve, to keep this point every time available for you because we're going to use roughly 1,500 to 2,000 shock waves. If you start to shock wave the patient after you find this point all the way down 2,000 you might make a mistake, so that's the reason I'm really reemphasizing that this point should be in your focus every time. Please take your time. You may use the 300, 500, or you might use some other number for yourself and then look again at the computer: this at the 2 point is still there. If the patient moves a little bit, it might be difficult.
One other thing is very important. Our maximum effective F2 point is plus and minus 2-centimeters in the system, so even at 2 point, you might be around 1-centimeters out. You're still in pretty good shape but don't do this thing out of the 2-centimeters.

Chapter Seven - PATIENT SELECTION

Now, what criteria do you use when you have this patient? I think the FDA completely copied from this system because this is the most experienced group in the world. Gustav Paumgartner's group in Germany. And this is Gustav Paumgartner's chapter in our alphabet text book Sleisenger and Fordtran's Gatrointestinal and Liver Disease, and I would strongly recommend that any people interested in gallstone lithotripsy should read this chapter a few times. It gives all that you need with all the details, with all the previous experience. According to the selection criteria from this 1998 textbook (we're going to use the same thing) we're going to have symptomatic gallstones with pain, biliary pain, not the irritable bowel syndrome pain, which we can discuss later on ¾ that's a very important point to select the patients in the right way. And the gallbladder should be functioning.

Chapter Eight - FUNCTION TESTING

Many years ago in Germany (still they do it and in other places they do it), you can check by oral cholecystogram. After the oral cholecystogram is done, the dye gets in the gallbladder, and you can do two things: 1.) Give the patient high protein, high calorie American breakfast diet, or 2.) you can give IV cholecystokinen. You see that the gallbladder is functioning, that it contracts. We did so many years.
Now, a little bit more civilized, but more expensive way, can be done, which we will do in our protocol: HIDA-scan. When you give the HIDA-scan, radio opaque material goes to the gallstone, gallbladder. Feel the gallbladder, and after the gallbladder takes the HIDA, give the IV cholecystokinen and check gallbladder contraction, you can say 50%, 60% ¾ you need to see at least 50% contraction. At this time in the market we don't have pure cholecystokinen. It's very expensive. I don't think it's necessary, but Kinevac is available (5 micrograms). We use IV with very little side-effects.

Chapter Nine - STONE COMPOSITION AND NUMBER

And the stones should be non-calcified. There are some others that use a similar machine for calcified gallstones with some kind of 50% success rate. Stones number? It should be one, according to our criteria. One stone between 5 to 20 millimeter in size (FDA approval is 4mm to 20mm). So what we do, we put the gallstones, really, under a microscope. And like I said at the beginning, the percentage we're going to select is going to be about 10 to 15%, not every gallstone for FDA protocol. Previously our group, Mountain Center Group, all around the world they used this machine for multiple stones, which we can discuss later on. At this time we are not allowed to do that but when you do that your success rate is less than 80%. I will show you some numbers.

Chaper Ten - CASES

Now, after the selection, if the patient has no bleeding problem, no systemic diseases, is not crazy, is not psychotic, has no substance abuses, and after all this exclusion criteria used, we have the stone around 8 to 9 millimeter and a functioning gallbladder. Second patient, this is a different patient, a little bit larger stone. By ultrasound you see the shadowing. Single stone, our focus in our FDA approved protocol.
Now, when you have that type of stone in ideal conditions as you see here, single stone, after one day stones are pulverized. This is the particles, possibly around 2, 3 millimeter, floating in the gallbladder, and then after 6 weeks with also the oxycholic acids complementary conjunction, patients are stone free. This patient is stone free.

Chapter Eleven - EFFICACY

Now, every time we look at the subject there are some pros and cons and there are some number differences in the success. This is the shock wave lithotripters, every investigator used different way. This is our Medstone lithotripsy, US trial, which I will go a little bit more into. Some of them use piezoelectric, electrohydraulic, and electromagnetic. You can use the years of the studies done, number of the patients, and stone-free gallbladder percentage-wise after 6 months to 12 months. 6 months altogether possibly around 65 to 70%, even might go down to 47%, and after 12 months this might go up to 80.
Now, let me focus this 51% a little bit and a little bit of history on that. I was one of the investigators. I was a little younger at that time and I was pretty enthusiastic. I stayed with my patient and I really did every patient personally along with my other collaborators. Radiologist was together with us, later on radiology technician. I will show my results. From my single center we had results up to 90% stone free gallbladder (with single stone). But some other centers, the number was around 30%, even 28% at one center. So what happened when you put all that center experience together, is some of the centers have only three patients, some centers have around 40 patients at a given time in the study. We had one more than 50 patients. So when you put all this together this comes to 51%. I was in the FDA panel and the FDA told us, all right, this doesn't look very promising, all the numbers are little, all numbers are small. Your results are not very attractive. Do more studies and we might approve this thing. Now, the FDA approved this thing because some of the Americans went to Europe, most likely for that reason (might be minor reason) to have this non surgical modality in Germany or France and even in Canada. There is one center in Canada leading the centers. If it's done casually, as shown in my study published in Gastroenterology in 1992, with the same machine you're going to use, if you have a single stone, again, if you really select the patient properly, if you stay with the patient, locate the F2 point properly, your patient might leave the table after the procedure around 59% stone-free. This is a pretty impressive number. And after 6 months this number goes to 75%, and after 12 months 89 to 90% for single stones. But if you have multiple stones as shown in yellow bars, stone-free gallbladder immediately after procedure is 33%; later on it's 50%, doesn't go up to more than 65%. But overall if you put all the patients with stones, multiple or single stones, overall success rate at the end of the trial months was 77% in our hand at that time with the same machine.

Chapter Twelve - COMPLICATIONS

Now, what are the complications? Like every action might come with a reaction. As shown here, again, from my study (but these numbers really did not change too much in any study you look) ¾ around 50% of the patients might have biliary pain. This pain is expected pain because we pulverize stones into multiple little fragments. You pulverize and you expect that fragments pass from cystic duct and pass from the papilla, and during this passage, the patient is going to have the pain. And most of the time (a majority of the time) this pain is acceptable pain. It might be controlled with Tylenol type minor analgesics, but some of the time there are 19% (might go up to 20%) in our hand that might go up to 10 to 20%, might have severe pain, patient might need Demerol, Motrin, that type of stronger analgesics or morphine type of medications.
Patients, around 25%, one-fourth, are going to have transient hematuria because even when you select very carefully your shock waves, the right kidney is going to be in your track off and on, and so that's the reason hematuria is going to be seen but within a few days, like Dr. Zabbo already mentioned, even in renal stones, it clears.
Cystic duct obstruction is one of the hurdles. Some of the fragments, if it fragments larger than 4 or 5 millimeters, or if the patient's cystic duct is very tortuous, stone fragments might stick there. This percentage is around 5% overall in the literature, so this patient with the cystic duct occlusion might have cystitis biliary pain because of cystic duct occlusion, and these patients, most of them are going to need a lap. cholecystectomy. That's one of the major reasons why if the surgeon is not the primary investigator on the team, at least one or two surgeons should be co-investigators on the team at this time to prevent further problems related to the cystic duct obstruction.
Biliary pancreatitis is another complication maybe. In our small group we did not have biliary pancreatitis but it doesn't mean anything. Overall if you look at the whole picture, .5 to 1% of the patients do have biliary pancreatitis. As you know, the reason for biliary pancreatitis, like any other pancreatitis, if the stone fragment cannot pass the papilla and is stuck in the papilla, there might be a problem of the pancreatic duct drainage and then patients may develop some kind of obstructive pancreatitis, and that is one of the reasons you have to have invasive or therapeutic endosco-(inaudible) gastroenterologist in the system, this type of cases, although it's 1% or less than 1% occurs, you have to act within 24 hours to release the papilla and release the pancreatic duct drainage, so this is another point when you put the team together.
Usually most of the severe pain comes within 3 to 4 days and biliary pancreatitis overall occurs within 5 to 7 days. If we remember previous studies in that regard, if you have an acute pancreatitis patient we were told it's etiopathic acute pancreatitis. At this time we really don't have any etiopathic acute pancreatitis in my understanding especially after biliary pancreatitis and pancreas disease are understood better. Now, you collect a stool of these patients, all the biliary pancreatitis patients. They do have a stone, 90% of the time. That's across studies published in The New England Journal of Medicine so many years ago, I think that stones mostly passed by stool but some of them might not and usually that occurs within the 5 to 7 days after the procedure.

Chapter Thirteen - TREATMENT ALGORITHM

Now, I'd like to take your attention again. This is the same algorithm published in our alphabet, in our gastroenterology book in Sleisenger. The algorithm hasn't been used in the United States yet. Hopefully, after our study is finished and we get the CPT code and we're going to use the system, we can use this algorithm accordingly. According to this algorithm, like what we do here, we see the gallstones, if they have a biliary colic ¾ let's assume first, if they don't have a biliary colic, we watch this patient. Supposedly. In real life I don't know how it works, but if the patients don't have any symptoms, they don't need any modalities and we will watch these patients. But if they have a pain, any complications, like cystitis and others, those patients might need a cholecystectomy, ideally lap. cholecystectomy. If the patient is in pain but has no complications, no acute cholecystitis, no acute pancreatitis or this type of thing, patients normal function and gallbladder, and if they have a non-calcified stone, small stone less than 5 to 20 millimeters (4 to 20 mm is FDA protocol), might go with the dissolution therapy. It's the long way to do it but it is done in the United States. This option was given to our patients in Europe. In the United States we are a little bit more aggressive and I think we like to do things as soon as possible. The managed care system is pushing us in this regard, also, but nevertheless, this is one of the options patients might have. And the patients with the single stone 5 to 20 millimeters (4 to 20 mm is FDA protocol), acceptable option is extra corporeal shock wave lithotripsy. So I hope in the short run we might go and be able to use this type of algorithm in our patients.

Chapter Fourteen - RECURRENCE

Now, recurrence of gallstones is another problem we have openly discussed. If you have 100 patients using only oral dissolution agents (this is the first paper) if you use oral dissolution agents and achieve a stone-free gallbladder, these patients do re-develop gallstones within five years roughly 50% of the time. This is the stone treated only with dissolution agents. There is no extra corporeal shock wave lithotripsy involved in this study. Now the question comes up: is it different when you use the extra corporeal shock wave lithotripsy, make a stone-free gallbladder and possibly select functioning gallbladder patients? So it's very important to look at that aspect. There are two studies in the literature, published studies. This is a German study. Just recently a Japanese study came in this regard and looks like similar results, and stone recurrence after successful biliary lithotripsy was 7% after one year, and increased to 31% at the end of the 5 years. How can you prevent this one? This is another project but I think oral dissolution agents, or NSAIDS, simple aspirin might be helpful for us to keep the patients gallstone free.

Chapter 15 - CONCLUSION

In summary, treatment of gallstones by lithotripsy is noninvasive. In outpatient procedures we use IV analgesia, ideal is Propofol at this time. Previously they used different aspects. In Germany they still use like our ERCP/Versed/Demerol combination, but at this time, in this stage, we will use with Propofol. This is a 45 to 60-minute procedure and post-procedure recuperation time is very short and the patient might go home after the procedure, if it is done properly. Like I show some numbers from many different countries in our hand, patients might have a stone-free gallbladder 80% of the time at the one year follow-up.