Michael J. Levy, M.D., a gastroenterologist at Mayo Clinic's campus in Rochester, Minnesota, discusses the use of EUS-guided pancreatic antitumoral therapy for the treatment of pancreatic masses.
Dr. Levy addresses the safety, status, efficacy, and potential advantages and disadvantages associated with options available for local pancreatic ablation, including chemotherapy, alcohol injection and radiofrequency ablation.
Hello. I'm Mike Lee. Be a gastro neurologist at Mayo Clinic, specializing in pancreatic ability. Area disease. My areas of clinical expertise include pancreatic disorders, endoscopic ultrasound, endoscopic, retrograde, Colangelo Pan create, ah, graffiti and tumor ablation. Today I'll be sharing the latest information on US guided pancreatic anti to world therapy, their various options available to us for local pancreatic ablation. And they include chemotherapy, alcohol injection and radio frequency ablation. Thus far, the experience has been primarily limited to treatment of pancreatic ductal, adenocarcinoma, neuroendocrine tumors, functioning and nonfunctioning, and secondary metastases for non pancreatic primaries to the pancreas. I'm gonna start off by discussing chemotherapy, and this pertains to intradermal injection of chemotherapy under US guidance. A za little background. You know that there's an estimated 57,000 plus patients who will be newly diagnosed with pancreatic ductal adenocarcinoma in the United States this year. It represents the fourth leading cause of cancer related mortality. Unfortunately, there have been few major advances in therapy or outcomes at the time of presentation. 50% of patients already have metastatic disease, and only approximately 20% of patients have locally advanced pancreatic Carson No most. That's considered respectable and unfortunately, the overall five year survival is quite poor. It's approximately 5% although it has increased recently and his approaching 10% the question is. Can introduce general therapy. Is it a key to improving outcomes? Systemic therapy? More than 90 chemotherapeutic agents have been evaluated thus far, and unfortunately, they provide minimal improvement in terms of respectability, rate and survival. This limited efficacy is often the result of the underlying tumor biology, those restrictions that are necessary to limit the damage to normal tissues and the fact that drug delivery inside the tumor is limited due to tumor related dismal pleasure and inflammation. The goal, therefore, is to use the U. S guided intro to Meral therapy to overcome some of these limitations. The goal is to increase intra to Meral drug concentration to decrease the systemic toxicity. In doing so, we hope to increase the advocacy of systemic chemo radiotherapy and ultimately increase the success of down, staging, increase and improve the quality of life, increase the survival duration to decrease disease recurrence, and to improve the curate e just want to give a little bit of background information with some of the work we've done. here. This is one paper in which we evaluated injection of Jim side of being for locally advanced and metastatic pancreatic carcinoma. I should stay for these patients. Not only had the U. S guided therapy, they also had standard therapy. Aziz. Well, our primary aim was to evaluate the toxicity for us guided fine needle injection which inside of being and secondary endpoints, including down staging that led to our recession and overall survival. Six months, 12 months and five year 36 patients were enrolled. 33 patients had un respectable disease, three patients were respectable or two were deemed to pour on operative candidate to undergo resection, and one patient refused resection even though he waas respectable. Okay, For these patients, 92% were stage three or stage four disease. Remembering the Stage four disease is defined by m one or distant disease and it is a part of the study we injected typically 2.5 mL of Jim side of being which equated to a dose of 95 mg and we did so usually with three needle passes. There were no great three or four emperors events in this trial. You're going to see a video here in which the needle is now located within the tumor and as the inside of Venus injected, it results in a hyper ochoa, or bright white cloud, that infiltrates the tumor itself. We also evaluated the extent and pattern of spread we would regard. This is ideal spread because here's the tumor prior to therapy and after therapy, you can see that this hyper a code bright cloud fills the entire boundary off the pancreas. If you compare that to this patient who had suboptimal spread here again is the needle. As Jim Side of Venus injected, you'll see that very little of the gym side of being actually stays within the tumor. And this was important because the pattern and extent of spread did correlate with outcomes. So this is an example of post therapy and which your sub optimal spread of this hyper co. A cloud representing the gym side of being in terms of overall survival. The six months survival was 78% 12 month was 44% and five year was 3%. Four patients were able to downstage to Aro reception, and one patient remains alive. More than 10 years after therapy. Unfortunately, this gentleman who was disease free at 42 months died of an alternate cause, which was severe C. Difficile infection. So this study and a few others published else were suggests the safety and feasibility of the U. S. Guided anti to world therapy for pancreatic Dr Landau carcinoma. It offers promise in terms of tumor down staging and impact on survival nevertheless is still regarded as investigational and is not part of routine clinical care. At any center, ongoing work is underway and hopefully it will be sometime in the future. We now want to turn our attention to the intradermal injection of alcohol. There are a number of studies here and elsewhere that have evaluated alcohol injection for this role, and it appears to be quite efficacious. This was a small study that we published more than 10 years ago. Certainly the experience has grown since then, but I think it does nicely represent our current experiences. Well, so surgery was not performed in this study because six patients would have required pancreatic or do it in ectomy, and the patient and or surgeon felt so that was not in their best interest by patients had co morbidity is one patient had a recent incomplete resection. One patient had multiple prior surgeries and a frozen abdomen, and one patient had inter operative bleeding. During attempted resection. You could see these patients had an array of neurologic and simple adrenal manifestations, and the average duration of disease was 6.4 years, and their blood sugar, NATO was 26. C T and endoscopic ultrasound demonstrated that the masses mawr 12 to 14 millimeters in size, located predominantly in the pancreatic. It most were enhancing and a few were calcified. So we treated patients typically with one treatment session, occasionally requiring too and seldom three separate treatment sessions, using usually a 22 gauge needle, a mean of 3.2 needle injections per mass procession and injected 95 to 99% alcohol and a mean volume of less than one millimeter. The care of this patient nicely highlights that are experienced. This was a 72 year old female with the thyroid cancer COPD in the left atrial mix Oma. She had hypoglycemia, conduced manifestations for approximately 20 years. However, insulin Oma was just recently diagnosed and she was deemed a poor operative candidate C T. Here nicely shows the pancreatic mass, which is hyper Coke or enhancing on C T and magnified views will show the mass again because with the 17 by 15 millimeter insulin oma located in the pancreatic head, it was enhancing and was calcified. The EU s video outlines the insulin oma, and in a moment you'll see the needle pass into the Mass and much as our experience, which inside of being the alcohol, gives a hyper coke or bright white appearance as it's injected. While surgery is still the standard of care, broad experience here and at other centers indicates the safety and efficacy of the U. S. Guided anti to Meral therapy of ethanol for insulin. Omagh's. This is a clinically available alternative, and most of us believe it should be more often considered over major resection, particularly in elderly patients and all those with co morbidity ease. Three. Use of alcohol is not as fully a blade of is we would like for certain tumor types, and that's led to the exploration of other methods and technologies, including radio frequency ablation. There was an original device that's no longer on the market but I'd like to talk about it for a moment. All our devices used electromagnetic energy involves thermal injury and coagulation necrosis again, The care of this patient highlights some of the limitations of the original device. This is a 69 year old female. We had a resected rectal Molyneaux in 2012, along with Task. This is that was respected in 2015 and a pancreatic mass was identified on surveillance imaging. Image ing here shows the mass within the pancreas and us demonstrates the mass as well. You will now see the needle be advanced into the mass, and this are if a probe involved 0.35 inch guide wire of sorts that would be advanced through the needle and perform the inflation. The floppy nous and the tendency for the needle to become bent and the guide wire often lead to some of the poor outcomes. Just Eisley shows off laparoscopy the needle and the R F A device in the same here. Here's the needle and the R F. A device being extended through the needle you can see in this patient. While the math was originally of this size There was then this degree of injury because of the R F A probe. It was unclear whether this represented needle tracks eating and or inflammation Follow up. Scanning revealed it was just inflammation. But I'll highlight some of the problems with this probe that it would injure not only the mass itself, but intervening issues that led to the development off the new and current design, which has overcome the limitations thus far. This is a nice bro. That's 19 gaijin caliber. The entire device is the R F A probe. It's not simply a needle with the probe that extends through it, and this part of the needle is the ablation zone. It has an internal cooling mechanism. So what that allows is it limits the injury to the area of interest and does not allow longitudinal spread through the needle path, which did occur with the prior design. And there are three separate sizes so we can tailor therapy to the specific tumor. This patient was a 17 year old female who had multiple comb or abilities. She had an enlarging nonfunctioning, learned the consumer that was starting to attach the main pancreatic duck. This shows on C, T and M R I. The Enhancing Mass same lesion under in the Scott the culture sound. And it did have tiny cystic components and or necrosis. Here's the R F A probe on Flora Skopje and the R F. A probe under us This hyper coed cloud of sorts is the effect. After ablation, this special responded very nicely. There is no evidence of enhancement on C. T and, on contrast, enhanced the U. S. You can see this complete loss of blood flow as compared to prior to therapy. The clinical efficacy of this device is approximately 85%. Based on a broad literature bars has been approximately 95 or 85 to 95%. An inverse of that rate is 5 to 33%. In the literature, most have been minor, and mayo are. Rate is approximately 5 to 10%. All have been minor, except one patient did have a severe complication. She had market societies and developing infection. Afterwards, it's no longer an indication it's a contra indication of therapy in our center. So we talked about various options for local ablation of pancreatic masses, chemotherapy, alcohol and radio frequency ablation a regard. Chemotherapy. The experience thus far has shown its safety. It's still investigation will do toe uncertain advocacy, and the role is still purely investigational. Alcohol is safe. It is clinically used. It is somewhat effective. It depends a little bit on the on the treatment goals and the type of lesion and pathology that your trading and radio frequency ablation is safe. Rare major complications. It is used clinically, and it appears to be the most effective treatment modality in this setting. At this point, I would say that pancreatic ductal adenocarcinoma should not be treated clinically. It's purely investigational because we do not impact the overall course and outcomes thus far. But there is a clear role for neuroendocrine tumors, functioning, nonfunctioning and secondary metastases to the pancreas. What are some of the realized Their potential advantages of using us for guidance. It allows real time control and monitoring of the blade of dose and settings. There is potential prediction of the A blade of zone. It is tolerated by elderly in patients with co morbidity ease and has a lower morbidity and mortality hospitalization rates and cost relative to surgery. Some of the disadvantages of the fact that the techniques have not been standardized, they do vary from center to center, which probably impacts the outcomes. And there's an uneven a blade of a zone. There's a limited ability to treat when the masses in proximity to large blood vessels and or ducks. And there's a heat sink effect that occurs when the lesion is vascular and are located proximate toe, large blood vessels. We continue to refine current and emerging US guided anti to moral therapies to optimize their safety and efficacy. And in doing so, we believe it important to deliver care and a multi disciplinary manner in order to enhance clinical care and outcomes. Thank you.