Good morning, my name is Haroon Choudry, I’m on faculty in the Division of Surgical Oncology at the University of Pittsburgh.  The focus of my talk today will be on the management of peritoneal surface malignancies.  The objectives of the talk today will be to provide an introduction to peritoneal surface malignancies, to discuss the concept of an aggressive early approach to local regional management of these tumors, to provide a rationale for the aggressive cytoreductive surgery and hyperthermic chemoperfusion that we provide to these patients, and to provide a clinical update on the management of the peritoneal surface malignancies and then if we have some time we’ll discuss some of the basic science research that we are doing here at UPMC to do with appendiceal pseudomyxoma peritonei.

So there are two major varieties of peritoneal surface malignancies. There is the primary de novo malignancies of the peritoneum, for example mesothelioma and peritoneal serous papillary carcinomas, and then you have the secondary varieties which are metastatic from other sources or other organs and these can include multiple organs like colorectal cancer, appendiceal cancers, ovarian cancers and then others like gastric cancers, sarcomas, breast cancer and other tumors that metastasize to the peritoneum.

In general when patients present with peritoneal surface malignancies they will present with clinical symptoms or signs involving abdominal distention, they can have abdominal pain, they develop ascites, they can have bowel obstructions, anorexia, inanition, infection and death eventually. And as you see in these pictures they present with these large abdominal cavities due to massive accumulation of intraabdominal tumor and ascites.

When it comes to imaging of these peritoneal surface malignancies often CT scans are used and these are some representative CT scans of patients with peritoneal surface malignancies.  And as you can see they develop this massive amount of ascites and tumor within the abdominal cavity, it leads to compression and displacement of organs and eventually leads to organ obstructions or bowel obstructions and eventually leads to death.

So as far as the local regional aggressive therapies that we provide for these malignancies there are two major components to it, there is the actual cytoreductive surgery in which we provide aggressive surgical therapies with the aim of eradicating all the macroscopic disease that’s present inside the abdominal cavity, and I’ll go into more detail in a few minutes.  And then the second component is the hyperthermic intraperitoneal chemoperfusion which is the perfusion of chemotherapy or heated chemotherapy into the abdominal cavity with the aim of eradicating the microscopic disease that’s left behind after the cytoreductive surgery.

These are some representative pictures of our cytoreductive surgery.  If you look over here in this top left picture you’ll see this amount of tumor that’s engulfing the omentum in the abdominal cavity and you can see tumor studding along the small bowel.  This kind of tumor then accumulates all over the abdominal cavity. And then you can see in the other picture some resection of this abdominal mass that’s engulfing the omentum, the small bowel and then some of this thick tumor rind that engulfs the peritoneal lining of the diaphragm and the abdominal cavity.  Similarly tumor tends to engulf or form a thick rind over the liver surfaces and other organ surfaces that have to be cytoreduced.

And this is the type of macroscopic tumor cytoreduction that we are aiming to do in order to get all the bulky tumor out of the abdominal cavity.  Subsequently once the macroscopic disease has been removed the next step is to provide intraperitoneal chemoperfusion, and if you look at the top left picture here what we do during the same operation after the cytoreduction we place catheters into the abdominal cavity and temporarily close the skin over the top of them. And then through this, these catheters we provide heated chemotherapy using a heat exchanger and a roller pump to provide chemotherapy into the abdominal cavity, and this goes on for about 100 minutes and temperatures of around 42 degrees Centigrade.  So just know this chemotherapy is provided during the same operation.

And the aim here basically is after we have done the macroscopic resection and then provided the chemotherapy for microscopic removal of disease the aim here is to remove all disease from the abdominal cavity and this is a representative imaging of a patient with peritoneal surface malignancies a few years down the line showing minimal to no residual disease within the abdominal cavity, and that’s the aim of our surgical procedure.

So the discussion today will focus on three major types of tumors that we common perform cytoreductive surgery and HIPEC in. So if you look at the left side here, mucinous appendiceal carcinomas, they are very rare, there is only about 1500 cases a year in the US, but about more than 50% of the patients present with peritoneal disease only. And then if you look at the third and fourth column here, the third column discusses the – or describes the median survival in the setting of maximal medical therapy, and only palliative surgery, and then the fourth column discusses median or shows median survival after cytoreduction surgery and hyperthermic intraperitoneal chemoperfusion.  And so for mucinous appendiceal carcinomas based on the literature there is anywhere from 20 to 50 months median survival for maximal medical therapy, versus median survivals of 60 to 150 months with 5 year survivals up to 70% for aggressive surgical local regional therapies.  This is based on Level IV data, mostly large retrospective studies and there are no randomized controls for this tumor.

The second cancer I’ll discuss will be colorectal cancers, much more common, about 140,000 cases a year in the US.  About 10 to 40% either present with synchronous or metachronous peritoneal disease. Once again with best systemic therapy and palliative surgery median survival can be anywhere from 5 to 24 months, whereas after cytoreductive surgery and hyperthermic chemoperfusion median survival can be anywhere from 20 to 60 months with 5 year survivals up to 50%. And three is Level I randomized control data to support this.

And finally the one I’ll talk about will be malignant peritoneal mesothelioma, again a rare peritoneal disease with only about 500 peritoneal cases a year in the US, which we often see. All these patients present with peritoneal disease and median survival for best systemic therapy is about 13 months with rare 5 year survivals compared to hyperthermic chemoperfusion with cytoreduction where we see up to 90 month median survivals and 5 year survivals up to 50%.  Once again there is no randomized control data for this, however there are some large retrospective Level IV data to support this approach.

At the University of Pittsburgh we have a large perspective database in which we do keep track of all the patients we treat.  Our prospective database has been running since 2001, and these are the number of patients that we have on our database.  Looking at appendiceal carcinoma we have up to 435 patients in the database and see about 40 patients a year.  Colorectal carcinoma we have about 248 patients on our database and see about 60 patients a year who undergo this treatment. And for malignant peritoneal mesothelioma we have about 95 patients in the database so far.  Other smattering of patients for whom we do provide cytoreductive surgery and hyperthermic chemoperfusion include patients with peritoneal disease in the setting of gastric cancer, sarcomatosis, GIST tumors, sometimes breast cancers and other tumors as well.

So going into more detail, cytoreductive surgery as we discussed earlier the aim here is to eradicate all macroscopic disease and the rationale here include: one is a lot of these patients present with symptoms, pain, bowel obstructions and so the aim here is to treat and overcome some of these symptoms that patients present with.  And then the theory of resetting the clock, especially in patients who have low grade, less aggressive, noninvasive disease if you can take out all the macroscopic disease then you basically are resetting the clock so that they don’t have the compressive or obstructive symptoms from the tumor.

And then there is the Goldie-Coldman model or the hypothesis whereby the larger the tumor bulk the more mutations, the more resistance to chemotherapy, and so by cytoreducing these patients we are reducing the amount of resistance to chemotherapy.  In addition we know that once we have cytoreduced these patients the number of cells going into the proliferative phase goes high and therefore these cells are more susceptible to chemotherapy once again providing a rationale for cytoreductive surgery.  And finally, we know that when we do give local intraperitoneal chemotherapy it is only – it only penetrates tumors up to about 3 mm in depth and so by cytoreducing the bulky tumor we are providing easier access for chemotherapy to actually have an effect locally.

When we are thinking about cytoreductive surgery there are some indexes in the literature which help us quantitate how much disease is present within the abdominal cavity and the two more common ones used are the peritoneal cancer index, which was described by Dr. Sugarbaker and the simplified peritoneal cancer index which is used mostly in Europe.  The basic concept behind these indexes is that you assess the number of segments in the abdominal cavity in which you have disease, and then  you multiple that by the size of the tumor in each one of those segments within the abdominal cavity, and you come up with a number, and that number is a quantitative assessment of the bulk of tumor that’s present in the abdominal cavity.

And so if you look at the two, the one on the left is the peritoneal cancer index by Dr. Sugarbaker, and the one on the right is the SPCI, which came out of the Netherlands.  And you can see there is a tumor size associated with it, and then there is the abdominal cavity is divided into different number of abdominal organ, or abdominal regions.  In the peritoneal cancer index it’s the abdomen is divided into 13 different regions, whereas in the simplified peritoneal cancer index it’s divided into only 7 different regions and so the product score is different in each case.

And the second thing when thinking about cytoreductive surgery, the aim I discussed was to remove all macroscopic disease and based on the literature the optimal cytoreduction is considered when you have resected tumor down to about 2.5 mm in size, and so in the US we use the CC score, which the completeness of cytoreduction and we want a CC score of 0 or 1, in which case the residual tumor size is less than 2.5.  And in the Netherlands and in Europe they use the R score and you want an R score of less than R2A, which is once again less than 2.5 mm.  And that’s considered an adequate cytoreduction so that the hyperthermic chemoperfusion has the best chance of working well.

The second component is the intraperitoneal chemotherapy and we already discuss that the aim here is to basically eradicate all the microscopic disease. And the rationale here is that we have a peritoneal to plasma barrier that separates the peritoneal cavity from the systemic circulation and this barrier prevents excessive drug from the peritoneal cavity from getting into the systemic circulation, so you can give very high doses of chemotherapy into the abdominal cavity and have a large – a very good local toxic effect on cancer cells.  And as we already discussed with the cytoreductive surgery you want more and more cells in the proliferative phase so that this chemotherapy can have a better effect on the cancer cells.     

And why the concept of hyperthermia?  This is also based on some basic science research. The aim here is that tumor cells or tumor tissue is more susceptible to hyperthermic chemotherapy, and the rationale here is that tumor cells are not as well developed, their vascular system is not as well developed and so they are more susceptible to hyperthermia.  In addition in vitro studies have shown that synergy, that heat provides synergy with chemotherapy, especially in certain drugs like Mitomycin C, Cisplatin, Oxaliplatin, which are the more common drugs used. And then hypothermia itself has direct toxic effects, it can anywhere from DNA repair inhibition to denaturing of proteins to induction of heat chuck proteins to induction of apoptosis or angiogenesis, so there is multiple reasons why hypothermia has an additional effect in addition to chemotherapy. 

So this is some of the data for hypothermia that’s been published. This is some in vitro data looking at the percentage of cells that are alive and then the X axis here shows the time that the cells are exposed to temperature.  And there are two major phases here, the early phase of exposure to temperature leads to a initial growth arrest of the cells and then after that the temperature allows an exponential cell death. And as you can see from this graph you want about at least a temperature of 40 degrees C to induce growth arrest and then you want temperatures above that, preferable around 42 degrees C in order to cause adequate cell death. And that’s the aim when we are providing hyperthermic chemoperfusion within the abdominal cavity.

I already showed this picture, the aim is to place catheters into the abdominal cavity and then using a heat exchanger and a roller circuit we provide chemotherapy into the abdominal cavity. And as we just saw we want the temperature around 42 degrees C and it’s usually, the chemotherapy is usually run four about around 10 minutes but it varies depending on institution. 

So going back to our patients what are the general eligibility criteria for this aggressive cytoreductive surgery and hyperthermic chemoperfusion?  In general we want patients not to have extraperitoneal disease obviously because it’s a local regional management.  Patients need to be able to tolerate these procedures so their performance status should be quite good.  And then the aim here is to be able to maximize our cytoreduction so we can get optimal effect and so we want to look at things that may prevent adequate surgery, and the main, main areas that we cannot resect are the small bowel and small bowel mesentery, and the porter region within the abdominal cavity and so those are some of the areas that are harder to, to treat.  At the same time you don’t want parenchymal metastases, so if they are small liver metastases we may still resect those but large liver resections are not performed.  Patients with biliary or urethral or small bowel obstructions they tend to have worse outcomes, so that has to be kept in mind when deciding which patients to operate on.  Patients with bulky lymph node disease tend to have poorer outcomes, so it has to be kept in mind.

And finally as we discussed before, the peritoneal cancer index does tell us to what degree we’ll be able to get an optimal cytoreduction and that depends on the aggressiveness of the tumor and the primary site.  For example for appendiceal you can have a lot – a much more bulky tumor and still be able to get adequate resection whereas in colorectal cancers which are more aggressive you may not be as successful in getting optimal cytoreduction if the PCI is very high.

As far as imaging for these patients you can – the most commonly used is CT imaging although MR imaging is becoming more and more popular.  And that’s because it is a little more sensitive and this study by Dr. Barone and Low published in 1997 shows in the top table here that MRI imaging is more sensitive than CT scan in actually identifying tumors. And then the second table here shows that MRI is also more sensitive in picking up smaller tumors compared to CT imaging. And therefore more and more institutions are shifting towards MR imaging as the modality of choice.

So going back to these peritoneal surface malignancies, each primary or each malignancy tends to have its own prognostic variables but there are ceratin prognostic variables that are common among most of these tumors.  And these are the four more common, most common prognostic variables that we keep in mind when dealing with these, these malignancies.  The completeness of cytoreduction we discussed the adequacy of resection does affect outcome, the tumor burden affects outcome, this histology, certain tumors are less aggressive and less invasive than others and therefore that affects prognosis, and finally lymph node involvement is a prognostic factor. These are some of the more common ones however each primary does have its own additional prognostic variables if you look at the literature.

Just to give you some examples, in terms of completeness of cytoreduction the graph on the left is for appendiceal carcinomatosis and people who have complete cytoreduction depicted by the dark blue line above have a much higher survival or better survival than patients who have incomplete cytoreduction.  Similarly for colorectal cancer people who have a complete cytoreduction are, are more likely or have a higher survival than patients who have an incomplete cytoreduction. 

For burden of disease this is another paper by Dr. Sugarbaker showing patients with a PCI of less than 10 versus a PCI between 10 and 20 and a PCI greater than 20, and as you can see the higher the tumor burden the lower the survival, so it is a significant prognostic factor.

Looking at tumor histology, each cancer has its own subtypes, the graph on the left is for appendiceal cancer and you can see the patients with low grade less aggressive tumors, those with adenomucinosis tend to do much better than patients who have high grade peritoneal carcinomatosis as seen here. And similarly for malignant peritoneal mesothelioma patients with epithelial variety do a lot better than patients with the mixed or sarcomatous variety. Similarly the well differentiated papular variety do even better because they are less aggressive tumors. 

As far as lymph node involvement that’s another prognostic factor, this is a representative graph from Dr. Yan’s paper showing patients with lymph node negative disease do much better than patients with lymph node positive disease. And this can be seen in other tumors as well. 

One of the questions that always comes up when dealing with patients with peritoneal surface malignancies is what about the morbidity associated with these aggressive surgical resections? And there are multiple series, multiple studies showing outcomes or morbidity and mortality outcomes in patients undergoing these procedures.  And in general Grade 3 or Grade 4 morbidity is anywhere from 20 to 50% if you look at the different studies and these morbidities can be either surgical related morbidities or chemotherapy related morbidities.  So in general the morbidities are on the higher side but patients still tend to do well and their outcomes or long term survival is much better.  The degree of morbidity that patients suffer does depend on how aggressive a surgery they undergo, so the PCI score, the blood loss, the operative time, they all play into how much morbidity they develop.  Mortality rate does vary from 2 to 10% depending on what paper you read, and it has been shown that higher, that high volume centers do tend to have less morbidity and less mortality given the complexity of these surgeries.

So that’s that background for cytoreductive surgery and hypothermia, or hyperthermic chemoperfusion, now I just wanted to present some of the clinical update or some of the clinical literature on each of these tumors.   Starting with appendiceal cancers with mucinous carcinomatosis or pseudomyxoma peritonei, as I said before more than 50% of these patients present with peritoneal disease either synchronous or metachronous, and just a brief summary here, if you look at the role of cytoreductive surgery if you look at the natural history of these tumors most patients don’t survive more than 2 years, with best systemic therapy and palliative surgery median survival can be anywhere from 20 to 50 months depending on what subtype of tumor we are talking about.  But with cytoreductive surgery and hyperthermic chemoperfusion the median survival can be anywhere from 60 to 150 months with 5 year survivals and even 10 year survivals up to 70%. 

This table is a little busy but it gives some of the big series that have been published in literature looking at cytoreductive surgery and hyperthermic chemoperfusion for these patients, and all these  – all these studies are retrospective case series so there are no randomized control trials in this disease. And the number of patients you can see on the left here vary anywhere from 50 to 350 out of the Washington Hospital and the second column here shows, or the third column, sorry, shows you the residual disease status, so you can see that most patients up to 80% do get an optimal cytoreduction when undergoing these surgeries.  And the columns on the right show the 5 year survival and medial survival for these patients. It can vary anywhere from 60 all the way up to 150 months with 5 year and even 10 year survivals up to 70% with acceptable morbidity and mortality.

This is looking at the Dutch series, it’s again as I said a retrospective study looking at 103 patients, mostly associated with appendiceal carcinomatosis, these patients underwent cytoreductive surgery and hyperthermic chemoperfusion and as you can see in the graph their median survivals were greater than 96 months showing that these patients do very well in the long term with aggressive surgery.

This is our experience here at Pittsburgh. We looked at our 282 patients undergoing cytoreductive surgery and hyperthermic chemoperfusion for appendiceal carcinomatosis, and as you can see our median survival was 79 months in our patients and our progression free survival was quite good, it was almost between 2 and 3 years, so once again patients tend to do well, their recurrences are later and they can undergo repeat surgeries if needed in order to keep the disease under control.

As far as systemic chemotherapy in appendiceal cancers most of the time if we do give them chemotherapy we use similar chemotherapies as colorectal cancer, there is not a lot of data in the literature for systemic chemotherapy, but these are some of the series that have been published or either completely or in abstract form. And this is using systemic chemotherapy for unresectable disease. And as you can see on the right here the response rate for systemic chemotherapy varies, it’s anywhere from 38% all the way up to 80% where it does depend on what treatment regimen you are using and what subtype of the tumor we are talking about; and median survivals for unresectable disease undergoing systemic chemotherapy again varies in the literature but usually is around 2 years.

There is only one published study on the use of neoadjuvant chemotherapy in appendiceal carcinomatosis.  This was published by Dr. Sugarbaker and it looked at the use of neoadjuvant chemotherapy in resectable disease. So the top table  here looked at the response rates to neoadjuvant chemotherapy and they looked at response rate based on either clinical parameters, basically patient symptoms, imaging parameters, operative findings or pathologic assessment. And their response rates were quite high, around 80% for clinical, 80% for imaging, 50% for operative findings and about 100% for pathologic assessment. 

Then what they did was they compared the patients who underwent neoadjuvant chemotherapy with patients who did not undergo neoadjuvant chemotherapy in resectable disease.  And as you can see in the bottom table here the patients who underwent neoadjuvant chemotherapy, they had, they required less aggressive surgery, so the number of peritoneotomies were less, the number of visceral resections were less, and their grade 3-4 complications were no greater.  Although they did not show an overall survival benefit they did show that patients who had either a complete response or a partial response, they did significantly better in terms of overall survival than those who did not get neoadjuvant chemotherapy.  One thing to keep in mind when assessing response to chemotherapy is that imaging is not very sensitive, it is hard to quantify response to chemotherapy because resist criteria is not very effective, effectively used in these tumors.

So at the University of Pittsburgh our management algorithm for these tumors, if we have low grade appendiceal carcinomatosis, also known as pseudomyxoma peritonei or also known as adenomucinosis, so the low grade variety, we will offer these patients cytoreductive surgery and hyperthermic chemoperfusion upfront. If patients present with high grade disease or the more aggressive carcinomatosis, then usually they will – they will have their initial laparoscopic biopsy and staging and then they’ll undergo a neoadjuvant chemotherapy with Folfox for about 4 to 6 cycles and the subsequently they’ll be restaged and cytoreduced if the are resectable and undergo hyperthermic chemoperfusion at the same time.  They then do go on to receive adjuvant chemotherapy afterwards.

Going on to colorectal carcinomas, with peritoneal carcinomatosis, as we discussed earlier, around 10% of the patients present with synchronous disease and then another up to 30% of patients can present with metachronous disease, and as you can see here natural history, most patients with this kind of disease that has spread to the peritoneum their survival is less than a year, with best systemic therapy you can get the survival up to 24 months but there are no 5 year survivals.  But with hyperthermic chemoperfusion and cytoreduction we have seen median survivals up to 60 months and 5 year survivals of around 20 to 50%. 

Once again this table shows some of the big, bigger studies that have been published. There is one randomized control trial out of the Netherlands which compared patients who underwent systemic chemotherapy versus patients who underwent hyperthermic chemoperfusion and cytoreduction with systemic chemotherapy.  If you look at that trial, the Dutch trial is the top one over here, you can see they did get optimal cytoreduction in up to 80% of patients and they found a significant improvement in medial survival as well as 5 year overall survival in these patients.  Similarly the other studies in the table here also showed improved survival in patients undergoing cytoreductive surgery and hyperthermic chemoperfusion against those getting systemic chemotherapy only. 

So this is the randomized trial I just showed you in the table, this is the Dutch trial comparing systemic chemotherapy versus cytoreductive surgery plus hyperthermic chemoperfusion, they – in their trial their patients had either primary or recurrent colorectal carcinomatosis, they had 87 patients with colorectal carcinoma and 18 patients with appendiceal carcinoma with peritoneal carcinomatosis, 51 patients underwent system chemotherapy only and underwent palliative surgery as needed, and then 54 patients underwent cytoreductive surgery and hyperthermic chemoperfusion with subsequent systemic chemotherapy. And as you can see in the graph here, the medial survival was significantly improved in patients undergoing aggressive local regional therapies. 

Similarly in the same randomized control trial they found that survival was improved in patients who underwent a complete or an optimal cytoreduction, so patients with R-1 resection did better than patients with R2 and who did better than patients with R-2b resection. And similarly patients who had less regions resected, meaning less tumor burden, did better than patients that had a higher tumor burden or needed more abdominal regions resected. 

This is the French retrospective case control study, once again comparing systemic chemotherapy versus cytoreductive surgery and hyperthermic chemoperfusion in patients with either primary or recurrent colorectal carcinoma. The one thing to note, these patients had a much smaller disease burden and when they compared patients undergoing systemic chemotherapy against patients undergoing neoadjuvant chemotherapy plus cytoreductive surgery and hyperthermic chemoperfusion the median survival was significantly improved with aggressive local regional therapies.

We also looked at our experience here at UPMC, comparing systemic chemotherapy to aggressive local regional therapies for primary and recurrent colorectal cancer with peritoneal carcinomatosis, and once again you can see the same theme that with aggressive cytoreductive surgery and hyperthermic chemoperfusion patients have a higher or a longer median survival compared to patients undergoing systemic therapy only.

So once again if you look at our management algorithm here at UPMC these patients undergo a laparoscopic staging and biopsy and then the majority of them first undergo neoadjuvant chemotherapy given the fact that these tumors are usually more aggressive than appendiceal cancers and more invasive. And after having undergone the neoadjuvant therapy they are restaged and then if they are resectable they will undergo cytoreductive surgery and HIPEC. And then following the surgery they will undergo further adjuvant therapy. 

And finally talking about malignant peritoneal mesotheliomas, once as we discussed before all these patients have peritoneal disease since it’s a primary peritoneal malignancy.  Based on looking at the literature if the natural history of this disease patients survival is less than 12 months, with best systemic therapy medial survival is still only around a year, however based on retrospective data patients undergoing cytoreductive surgery and hyperthermic chemoperfusion, median survivals all the way up to 90 months have been described with 5 year survivals of about 30 to 60%.

Looking at the literature that has been published, some of the major series for malignant peritoneal mesothelioma once again a vast majority of patients do undergo an optimal cytoreduction, and then looking at survival, survival as I described before, median survival can be anywhere from 36 months all the way up to 92 months with good 5 year survivals after adequate cytoreduction and intraperitoneal chemoperfusion. 

This is the Italian retrospective review, looking at patients with malignant peritoneal mesothelioma undergoing cytoreductive surgery. They looked at 83 patients and as you can see here their survival, especially in patients who had lymph node negative disease was extremely good compared to those with positive lymph nodes and in general their median survival was 44 months, which is much better than either the natural history or patients just getting systemic chemotherapy. 

This is the retrospective data out of the NIH, once again looking at malignant peritoneal mesothelioma in patients undergoing aggressive local regional therapies and once again they demonstrated a median overall survival of 92 months, especially good in patients undergoing optimal cytoreduction as shown here in the graph. 

The question again comes what about systemic chemotherapy in mesothelioma?  In the literature there are only, there are two randomized trials for systemic chemotherapy, but both of these are in pleural mesotheliomas, there are no randomized control trials in patients with peritoneal mesotheliomas. But the general theme here is all these 3 trials here compared Cisplatin to Cisplatin versus Pemetrexed, also known as Alimta. The second trial by Dr. Van Meerbeeck looked at Cisplatin versus Cisplatin plus Raltitrexed and then the nonrandomized comparison trial in peritoneal mesothelioma compared to Pemetrexed, to Pemetrexed plus Cisplatin.   And as you can see here patients getting double therapy with Cisplatin and Pemetrexed had a higher response rate and better median survivals as well as better progression free survivals.  So systemic therapy does play a role in these patients however better survivals have been seen with aggressive local regional therapies.

So if we look at our management algorithm here at UPMC for well differentiated papillary forms or again the low grade varieties these patients will be offered upfront cytoreductive surgery and hyperthermic chemoperfusion. Whereas patients with more aggressive disease, those with epithelioid varieties, those with mixed or those with sarcomatoid varieties will undergo similar laparoscopic staging and biopsy and then they’ll get neoadjuvant chemotherapy followed by local regional therapies and then followed by adjuvant chemotherapy afterwards. 

So that’s a quick look at the three major peritoneal surface malignancies that we deal with here at UPMC and provide cytoreductive surgery and hyperthermic chemoperfusion. The facilities involved here at UPMC include the Cancer Center here, the David C. Koch Regional Therapy Center and the Hillman Cancer Center and we have a number of faculty on staff that are involved with the treatment of this disease. So thank you very much for this opportunity.