Pleural mesothelioma is the most common type of asbestos-related cancer that develops in the cells that form the outer lining of the lungs and inner lining of the chest cavities. Clinical trials offer access to new treatments such as immunotherapy. All types of mesothelioma are named after the location where they are formed.
Common Symptoms of Pleural Mesothelioma
Pain in the lower back or rib area Night sweats or fever Shortness of breath Chest pain or painful breathing Lumps under the skin on the chest Unexplained weight loss and fatigue Persistent dry or raspy cough Coughing up blood Difficulty Swallowing Swelling of the face or arms.
Patients rarely mention weight loss and fatigue during their initial doctor visit. These symptoms may show if the cancer is advanced. Some patients develop swelling of the face or arms, back pain or nerve pain.
Advances in the Treatment of Malignant Pleural Mesothelioma: Part 1
There is a great deal of historical interest in both this disease and the surgical treatment of it at this institution that’s not going to work. okay! Dr. Marin, do you use a pointer so as many people in this audience know malignant pleural mesothelioma is a disease of the lining of the chest.
It is best known for its association with asbestos and that discovery was made at Mount Sinai by dr. Salik. Approximately 3,000 cases annually seen in the United States most those are men only about 20% of patients presenting with mesothelioma are women.
These pictures here is the normal chest the real test in early stage means of figlio mo we see a disease of the parietal pleura as you recall from Medical School the lining of the chest wall, sometimes a diaphragmatic surface, as well as the pericardial surface but this, is still pleural based disease in this picture.
At least in more advanced stages, it progresses to involve the visceral pleura or the lining of the lung itself and as it advances even into the fissures can invade the diaphragm and even trap the lung and invade the chest wall.
This is a locally invasive disease. It’s a little different than many of the solid cancers we treat. In it’s propensity to metastasize is actually fairly low we rarely see this to the extent that when we’re evaluating these patients preoperatively. If we see other lesions on a PET CT.
They are more likely to be other cancers and/or benign than metastatic disease 30 years ago this was a uniformly fatal disease you can see here the median survival for patients treated with surgery in this series from 1976 with 6 months so people who were diagnosed with disease were told to get their affairs in order and prepare to die.
Pleural Mesothelioma Treatment: Came a long way
We’ve come a long way and that’s one of the major pieces. I want you to take home from this talk that advances in the techniques of surgery in particular, as well as radiation therapy and new forms of chemotherapy. Particularly doublet chemotherapy with pemetrexed and platinum have enabled long term survival in this disease. So, where do we stand currently this is at this point a few years old in 2010. I looked at every series in the literature published on mesothelioma 131 studies from 1982 rather to 2010.
Some of those earlier studies were not included including series describing palliative treatment representing thoracentesis Florrick’s or pleura desus chemotherapy and surgery-based trials. This is not to look at but more to show you the sheer size of the number of series published these were all studies that included at least 30 patients, many of these were retrospective but there were prospective studies as well.
Some Statistics of Pleural Mesothelioma
This is a graph depicting the median survival reported and new studies these little squares show the median survival reported in palliative care studies not surprisingly from 1982 through the 2000s. the natural history of this disease has not changed the median survival is generally 6 to 10 months.
These are all studies including 30 or more patients involved in chemotherapy and there are a variety of agents used and I recognize this is not a meta-analysis and this is subject to the bias of reported literature, but the survival is constant over the decades. these green tribe these green triangles represent all studies including 30 or more patients involving surgery based multi-modality therapy.
If you use your imagination you may see a trend towards improvement now malignant pleural mesothelioma is a little bit like lung cancer in the sense that there are two major histologists in lung cancer. We talk about non-small-cell lung cancer the more common type and it’s more aggressive and more morbid counterpart small cell lung cancer.
These are two different diseases most researchers would not combine the two and mesothelioma has a counterpart in the form of epithelial histology that’s the more favorable histology and the more commonly seen histology versus non epithelial histology. These diseases behave so differently and I will show you slides depicting that that they really should be described separately.
There are many series that have done that these purple Pentagon’s represent the chemotherapy trials that describe data for patients with epithelial or the more favorable cell type and these represent the surgical series that did the same this is a study by deeper oat up in Toronto. It’s a bit of an outlier this is actually a select subset but generally speaking there is some hint that patients with epithelial histology may benefit from surgical therapy.
Pleural Mesothelioma treatment: Time Travel
As I mentioned 30 years ago everyone died and many still carry a nihilistic attitude towards malignant pleural mesothelioma and argue that surgery is simply useless, so this is we shouldn’t even be discussing surgery for this disease. I looked at all series by some notable people and reported the and looked at the five-year survival reported in this series and we see the range is 9 to 27%.
In surgery-based treatment, this includes two types of surgery surgical techniques that I will describe to put that in the context of diseases with which most of the people in this audience are more familiar. it kind of resembles pancreatic cancer and there are many similarities from a tumor biology perspective and a multi-modality therapy perspective. But the point is pleural mesothelioma is on the map. There are survivors and I believe much of that may be attributable to surgery-based therapy, but this is a controversial subject.
How do we improve survival in this very challenging disease? First is to refine the treatment. If you knock everyone off like, then that series that chart published in 1776, people aren’t going to survive the disease. But the second part of that is to refine patient selection and I’ll discuss both.
The goal of surgery in Middle and malignant pleural mesothelioma is to optimize site or reduction. We talked about this is a term coined by Dave Sugar baker macroscopic complete resection this is different than the R0 resection most people in this room are used to describing and attaining. we don’t get microscopically negative margins when we resect this disease.
I mean this (Pleural Mesothelioma) is a disease of the pleural lining it’s essentially carcinomatosis by definition but this grocery section disease no visible disease can be obtained with two different techniques, one is cleric t’me decortication that’s removal of the lining of the lung the parietal and visceral pleura sometimes the line the pericardium sometimes the diaphragm depending on extensive disease and then there’s the extra pleural pneumonectomy, that’s the same but includes removal of the entire lung.
Generally, with EPP or extra pleural pneumonectomy, the pericardium and diaphragm are taken as well. Over the years many surgeons and others have worked towards refining that technique and reducing the perioperative mortality and morbidity.
The first extra pleural pneumonectomy was developed, performed and the technique was developed and described at Mount Sinai by dr. Seurat. Seaview hospital just for a little tangent and historical note was a tuberculosis sanitarium located where else but in Staten Island. it’s currently a historical landmark.
This was a technique used to treat tuberculosis it’s since closed by the way I’m sure you’ve noticed we don’t usually treat TB with surgery but as dr. Aziz described Seurat was a sign eye surgeon.
Fast Forwarding the Pleural Mesothelioma treatment process
Fast-forward approximately 34 years a little more actually, in 1976 Eric Butchart of England was the first person to describe the use of extra pleural pneumonectomy in the treatment of mesothelioma, and he single-handedly turned the entire country of England against surgery for mesothelioma and this viewpoint persists to today. In this series of 29 patients.
He had a 31% perioperative mortality. Can you imagine consenting your patients and telling them there’s a one in three chance that they won’t make it out of the hospital.
That’s where this graph I showed earlier comes from and a big part of not only why there’s a nihilistic attitude towards this disease in England but also why the technique was abandoned for at least a decade. Many people have worked in the subsequent decades to improve that technique as well as another that I will describe.
Cleric demean decortication you should know that these three series were all published in the same journal. This is another tangent but there’s only one first author that was worthy of having his picture taken and put and just knowing the players there’s a reason for that.
The technique for extra plural pneumonectomy antler ectomy decortication is somewhat similar other than the whole removal of lung thing but starts with an extended posterolateral thoracotomy. Some of you may have seen before we remove the sixth rib and we start dissecting the extra pleural space when it’s clean and the whole extra pleural dissection has been completed this is a left-sided resection.
One of the reasons I went into Pleural Mesothelioma surgery:
You can see the distal arch and the descending aorta it’s beautiful anatomy a little bloody but beautiful. On the right side anteriorly as the lung is retracted posterior, you can see the cava the trachea the pericardium residents who have scrubbed through these cases. I think really enjoy seeing this Anatomy, this is one of the reasons I went into surgery.
In general, is the anatomy of the chest obviously drastic in particular posterior lis when the lungs retracted anteriorly on the right side, you see the sympathetic and they get kind of stunned. we’ll say with this operation many of our residents and fellows have seen the Basel II gia that results from this epidural or no epidural many of them are hypotensive for a few days postoperatively.
This I call the gentleman’s technique of dissecting the diaphragmatic pleura or even the diaphragm itself. The diaphragmatic pleura off the diaphragm or the diaphragm itself off the perineum. This is the Cobb and in Boston this is how I learned how to do it. You stick your paw in there and you rip the diaphragm off the chest wall basically and that’s only if the diaphragm is involved with disease dr. Flores and I both believe that is behooves the patient to preserve the diaphragm if possible they do seem to breathe better postoperatively.
This is this is tumor this is a fairly low volume disease on the lung itself but the next part of the operation, if you’re going to proceed withthe cleric to meet decortication, is internal decortication or the visceral pleura ectomy and it’s a little bit like peeling the skin off of a tomato. it’s not really a plane that’s supposed to exist. It’s a little messy tomato. Looks like dog meat underneath but you can remove bulky disease well into the fissures and this is something dr. Flores taught me where I trained.
Being Honest as a Pleural Mesothelioma doctor
I’ll be honest when disease involved the fissures we just took the lung out, but I have since refined my technique based on dr. Flores is teaching and I’ve been able to remove bulky disease with pleura ectomy as well and there’s the specimen.
It’s kind of hard to stage that the pathologists can’t stand it. I don’t know what’s up what’s down but if we are going to proceed with extra coral pneumonectomy, that is if tumor involves the lung parenchyma itself the pericardium is going to go we enter the pericardium anteriorly.
We take the right pulmonary artery has taken inch repair cardio Lee the left is taken extra pericardial II that’s because the left int repair cardio. PA is very short, and the veins are taken into pair cardio Lee, and here they are divided as branches and here we’ve removed the pericardium as well as the diaphragm.
This requires reconstruction because there is no lung to keep the liver from herniating into the chest this is what it looks like in real life this is the extra pleural pneumonectomy specimen a little easier to stage and I’ll allude to that later when I describe my data.
We now have the pericardium and this is removed intact we have the diaphragmatic surface including the tendon and you can see where it abutted the aorta it’s really beautiful anatomy ugly disease beautiful anatomy to reconstruct the diaphragm I use two sheets of a 2 millimeter gore-tex and it’s not shown here but I actually use a TA stapler to staple them together and that gives a little flexibility so that’s not to put on tension this is the surface set of butts.
The heart looks a little like a kidney mean and here it is in sight too I use interrupted stitches. This is actually the endo fascial suture device that Carter Thompson pull the stitches through with that and I learned this from dr. Sugar baker tie them down over gore-tex buttons, so they don’t pull through about two interfaces below the exposed rib.
Here we have the patch in place and here we are sewing in the pericardial patch. I use interrupted stitches again and then we fenestrated it to prevent tamponade and here both patches in place the reconstruction complete and then we cover that bronchial stump.
If the diaphragm is removed, you can bring up a pedicle of momentum to cover that otherwise some thymic fat or whatever you can find to help buttress that the remainder of this talk is going to be discussing refining patient selection.
I admit not everyone needs surgery not everyone should have surgery but figuring out who those people are who benefit from surgery has been the subject of my research and going forward what I’d like to help delineate.
Summarizing the Advancement in Pleural Mesothelioma Treatment: Part 1
In summary, Pleural Mesothelioma has come a long way from no long-term survivors to 15%. Approximately 15% five-year survival with surgery-based therapy surgical macroscopic resection can be accomplished with less morbid surgery with cleric time decortication and many of us have turned toward doing this operation preferentially when feasible. Pleura ectomy decortication even in bulky disease further impact on improving survival in this disease. it is going to depend on advances in individualizing therapy and individualizing treatment.