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Point/Counterpoint: Is intraoperative drain placement essential during pancreatectomy?
Yes, placing drains is essential.
It’s important to look at the evidence in the literature, starting with a randomized controlled trial of 179 patients from 2001 that showed no reduction in death or complication rate associated with use of surgical intraperitoneal closed suction drainage (Ann. Surg. 2001;234:487-94). Interestingly, even though this study showed there was no benefit to using drains, they address the use of closed suction drainage. The investigators were not claiming all drains are unnecessary.
Why drain placement? The argument for drains includes evacuation of blood, pancreatic juice, bile, and chyle. In addition, assessing drainage can act as a warning sign for anastomotic leak or hemorrhage, so patients can potentially avoid additional interventions.
A study from University of Tokyo researchers found three drains were more effective than one. In addition, the investigators argued against early removal, pointing out that the risk for infection associated with drains only increased after day 10. The researchers were not only in favor of drains but in favor of multiple drains (World J Surg. 2016;40:1226-35).
A multicenter, randomized prospective trial conducted in the United States compared 68 patients with drains to 69 others without during pancreaticoduodenectomy. They reported an increase in the frequency and severity of complications when drains were omitted, including the number of grade 2 or greater complications. Furthermore, the safety monitoring board stopped the study early because mortality among patients in the drain group was 3%, compared with 12% in the no-drain group. (Ann. Surg. 2014:259:605-12).
Another set of researchers in Germany conducted a prospective, randomized study that favored omission of drains. However, a closer look at demographics shows that about one-fourth of participants had chronic pancreatitis, which is associated with a low risk of fistula (Ann Surg. 2016;263:440-9). In addition, they found no significant difference in fistula rates between patients who underwent pancreaticojejunostomy or pancreaticoduodenectomy. Interestingly, the authors noted that surgeons were reluctant to omit drains in many situations, even in a clinical trial context.
Furthermore, a systematic review of nine studies with nearly 3,000 patients suggests it is still necessary to place abdominal drains during pancreatic resection, researchers at the Medical College of Xi’an Jiaotong University in China reported (World J Gastroenterol. 2015;21:5719-34). The authors cited a significant increase in morbidity among patients in whom drains were omitted (odds ratio, 2.39).
Perhaps the cleverest way to address this controversy with drains during pancreatic resection comes from researchers at the University of Pennsylvania. They looked at surgical risk factors to gain a more nuanced view. They used the Fistula Risk Score (FRS) to stratify patients and re-examined the outcomes of the multicenter U.S. study I cited earlier that was stopped early because of differences in mortality rates. The University of Pennsylvania research found that FRS correlated well with outcomes, suggesting its use as a mitigation strategy in patients at moderate to high risk for developing clinically relevant postoperative pancreatic fistula (J Gastrointest Surg. 2015;19:21-30). In other words, they suggest routine prophylactic drainage for patients at moderate to high risk but also suggest that there may be no need for prophylactic drainage for negligible to low risk patients.
I would like to conclude that drains appear essential in many cases, including for moderate to higher risk patients. We need to tailor our practices as surgeons regarding placement of drains during pancreatectomy or pancreaticoduodenectomy. Our goal remains to create opportunities for prolonged survival and better quality of life for our patients.
Dr. Dervenis is head of the Department of Surgical Oncology at the Metropolitan Hospital in Athens, Greece. He is also chair of the hepato-pancreato-biliary surgical unit. He reported no disclosures.
No, drain placement is not always necessary.
Drain placement is not essential during all pancreatectomies. The practice is so historically entrenched in our specialty that I need you to check your dogma at the door and take a look at the data with an open mind.
There are many, many retrospective studies that examine drainage versus no drainage. All of these studies have shown the same thing: There is no difference in many outcomes, including mortality. There may be a difference in terms of complicated, postoperative fistulae, which are difficult to manage in patients who have drains.
Another prospective randomized trial from Germany compared the reintervention rate, an endpoint I like, among 439 patients (Ann Surg. 2016;264:528-37). There was no statistically significant difference between the drain or no drain groups, further suggesting that drains are not essential in all cases.
We also need to take a closer look at the study Dr. Dervenis cited (Ann Surg. 2014:259:605-12). It’s true this trial was stopped early because of a higher mortality rate of 12% in the no drain group, but the difference was not statistically significant (P = .097). There was no difference in the fistula rate.
When you look at these data, there are a couple of conclusions you can reach. One conclusion is that a trial of 130 people designed for 750 found something uniquely different that had never been reported in any retrospective series, including one by the study’s senior author that demonstrated drains are essential (HPB [Oxford]. 2011;13:503-10). Another conclusion is that drains are not needed, and there is a very good chance this is a false positive finding. Look at the reasons the 10 participants died. I’m not sure a drain would have helped some of the patients without them, and some of the patients who had drains still died.
A study looking at practice at my institution, MSKCC, shows that drains are still used about half the time, indicating they are not essential. (Ann. Surg. 2013 Dec;258[6]:1051-8). Drains were more commonly used for pancreaticoduodenectomy and when the surgeon thought there might be a problem, such as a soft gland, difficult time in the OR, or a small pancreatic duct.
If you look at these data, this pans out in every retrospective study I’ve seen comparing drain versus no drain – the patients with drains tend to have higher morbidity. Among the 1,122 resection patients in the MSKCC study, those without operative drains had significantly lower rates of grade 3 complications and overall morbidity and fewer readmissions and lower rates of grade 3 or higher pancreatic fistula. Mortality and reintervention rates were no different.
I also looked at our most recent data, between 2010 and 2015. Now we are using intraoperative drains even less often. They are not considered essential at this point.
There are multiple retrospective and well-designed prospective, randomized trials that show no benefit to routine drainage following pancreatectomy. Acceptance of randomized clinical data is slow, particularly when it flies in the face of what you were taught by your mentors over the past 40 or 50 years. I encourage you to look at these data carefully and utilize them in your practice.
Dr. Allen is associate director for clinical programs at David M. Rubenstein Center for Pancreatic Cancer Research and the Murray F. Brennan chair in surgery at Memorial Sloan-Kettering Cancer Center in New York City. He reported no disclosures.
Yes, placing drains is essential.
It’s important to look at the evidence in the literature, starting with a randomized controlled trial of 179 patients from 2001 that showed no reduction in death or complication rate associated with use of surgical intraperitoneal closed suction drainage (Ann. Surg. 2001;234:487-94). Interestingly, even though this study showed there was no benefit to using drains, they address the use of closed suction drainage. The investigators were not claiming all drains are unnecessary.
Why drain placement? The argument for drains includes evacuation of blood, pancreatic juice, bile, and chyle. In addition, assessing drainage can act as a warning sign for anastomotic leak or hemorrhage, so patients can potentially avoid additional interventions.
A study from University of Tokyo researchers found three drains were more effective than one. In addition, the investigators argued against early removal, pointing out that the risk for infection associated with drains only increased after day 10. The researchers were not only in favor of drains but in favor of multiple drains (World J Surg. 2016;40:1226-35).
A multicenter, randomized prospective trial conducted in the United States compared 68 patients with drains to 69 others without during pancreaticoduodenectomy. They reported an increase in the frequency and severity of complications when drains were omitted, including the number of grade 2 or greater complications. Furthermore, the safety monitoring board stopped the study early because mortality among patients in the drain group was 3%, compared with 12% in the no-drain group. (Ann. Surg. 2014:259:605-12).
Another set of researchers in Germany conducted a prospective, randomized study that favored omission of drains. However, a closer look at demographics shows that about one-fourth of participants had chronic pancreatitis, which is associated with a low risk of fistula (Ann Surg. 2016;263:440-9). In addition, they found no significant difference in fistula rates between patients who underwent pancreaticojejunostomy or pancreaticoduodenectomy. Interestingly, the authors noted that surgeons were reluctant to omit drains in many situations, even in a clinical trial context.
Furthermore, a systematic review of nine studies with nearly 3,000 patients suggests it is still necessary to place abdominal drains during pancreatic resection, researchers at the Medical College of Xi’an Jiaotong University in China reported (World J Gastroenterol. 2015;21:5719-34). The authors cited a significant increase in morbidity among patients in whom drains were omitted (odds ratio, 2.39).
Perhaps the cleverest way to address this controversy with drains during pancreatic resection comes from researchers at the University of Pennsylvania. They looked at surgical risk factors to gain a more nuanced view. They used the Fistula Risk Score (FRS) to stratify patients and re-examined the outcomes of the multicenter U.S. study I cited earlier that was stopped early because of differences in mortality rates. The University of Pennsylvania research found that FRS correlated well with outcomes, suggesting its use as a mitigation strategy in patients at moderate to high risk for developing clinically relevant postoperative pancreatic fistula (J Gastrointest Surg. 2015;19:21-30). In other words, they suggest routine prophylactic drainage for patients at moderate to high risk but also suggest that there may be no need for prophylactic drainage for negligible to low risk patients.
I would like to conclude that drains appear essential in many cases, including for moderate to higher risk patients. We need to tailor our practices as surgeons regarding placement of drains during pancreatectomy or pancreaticoduodenectomy. Our goal remains to create opportunities for prolonged survival and better quality of life for our patients.
Dr. Dervenis is head of the Department of Surgical Oncology at the Metropolitan Hospital in Athens, Greece. He is also chair of the hepato-pancreato-biliary surgical unit. He reported no disclosures.
No, drain placement is not always necessary.
Drain placement is not essential during all pancreatectomies. The practice is so historically entrenched in our specialty that I need you to check your dogma at the door and take a look at the data with an open mind.
There are many, many retrospective studies that examine drainage versus no drainage. All of these studies have shown the same thing: There is no difference in many outcomes, including mortality. There may be a difference in terms of complicated, postoperative fistulae, which are difficult to manage in patients who have drains.
Another prospective randomized trial from Germany compared the reintervention rate, an endpoint I like, among 439 patients (Ann Surg. 2016;264:528-37). There was no statistically significant difference between the drain or no drain groups, further suggesting that drains are not essential in all cases.
We also need to take a closer look at the study Dr. Dervenis cited (Ann Surg. 2014:259:605-12). It’s true this trial was stopped early because of a higher mortality rate of 12% in the no drain group, but the difference was not statistically significant (P = .097). There was no difference in the fistula rate.
When you look at these data, there are a couple of conclusions you can reach. One conclusion is that a trial of 130 people designed for 750 found something uniquely different that had never been reported in any retrospective series, including one by the study’s senior author that demonstrated drains are essential (HPB [Oxford]. 2011;13:503-10). Another conclusion is that drains are not needed, and there is a very good chance this is a false positive finding. Look at the reasons the 10 participants died. I’m not sure a drain would have helped some of the patients without them, and some of the patients who had drains still died.
A study looking at practice at my institution, MSKCC, shows that drains are still used about half the time, indicating they are not essential. (Ann. Surg. 2013 Dec;258[6]:1051-8). Drains were more commonly used for pancreaticoduodenectomy and when the surgeon thought there might be a problem, such as a soft gland, difficult time in the OR, or a small pancreatic duct.
If you look at these data, this pans out in every retrospective study I’ve seen comparing drain versus no drain – the patients with drains tend to have higher morbidity. Among the 1,122 resection patients in the MSKCC study, those without operative drains had significantly lower rates of grade 3 complications and overall morbidity and fewer readmissions and lower rates of grade 3 or higher pancreatic fistula. Mortality and reintervention rates were no different.
I also looked at our most recent data, between 2010 and 2015. Now we are using intraoperative drains even less often. They are not considered essential at this point.
There are multiple retrospective and well-designed prospective, randomized trials that show no benefit to routine drainage following pancreatectomy. Acceptance of randomized clinical data is slow, particularly when it flies in the face of what you were taught by your mentors over the past 40 or 50 years. I encourage you to look at these data carefully and utilize them in your practice.
Dr. Allen is associate director for clinical programs at David M. Rubenstein Center for Pancreatic Cancer Research and the Murray F. Brennan chair in surgery at Memorial Sloan-Kettering Cancer Center in New York City. He reported no disclosures.
Yes, placing drains is essential.
It’s important to look at the evidence in the literature, starting with a randomized controlled trial of 179 patients from 2001 that showed no reduction in death or complication rate associated with use of surgical intraperitoneal closed suction drainage (Ann. Surg. 2001;234:487-94). Interestingly, even though this study showed there was no benefit to using drains, they address the use of closed suction drainage. The investigators were not claiming all drains are unnecessary.
Why drain placement? The argument for drains includes evacuation of blood, pancreatic juice, bile, and chyle. In addition, assessing drainage can act as a warning sign for anastomotic leak or hemorrhage, so patients can potentially avoid additional interventions.
A study from University of Tokyo researchers found three drains were more effective than one. In addition, the investigators argued against early removal, pointing out that the risk for infection associated with drains only increased after day 10. The researchers were not only in favor of drains but in favor of multiple drains (World J Surg. 2016;40:1226-35).
A multicenter, randomized prospective trial conducted in the United States compared 68 patients with drains to 69 others without during pancreaticoduodenectomy. They reported an increase in the frequency and severity of complications when drains were omitted, including the number of grade 2 or greater complications. Furthermore, the safety monitoring board stopped the study early because mortality among patients in the drain group was 3%, compared with 12% in the no-drain group. (Ann. Surg. 2014:259:605-12).
Another set of researchers in Germany conducted a prospective, randomized study that favored omission of drains. However, a closer look at demographics shows that about one-fourth of participants had chronic pancreatitis, which is associated with a low risk of fistula (Ann Surg. 2016;263:440-9). In addition, they found no significant difference in fistula rates between patients who underwent pancreaticojejunostomy or pancreaticoduodenectomy. Interestingly, the authors noted that surgeons were reluctant to omit drains in many situations, even in a clinical trial context.
Furthermore, a systematic review of nine studies with nearly 3,000 patients suggests it is still necessary to place abdominal drains during pancreatic resection, researchers at the Medical College of Xi’an Jiaotong University in China reported (World J Gastroenterol. 2015;21:5719-34). The authors cited a significant increase in morbidity among patients in whom drains were omitted (odds ratio, 2.39).
Perhaps the cleverest way to address this controversy with drains during pancreatic resection comes from researchers at the University of Pennsylvania. They looked at surgical risk factors to gain a more nuanced view. They used the Fistula Risk Score (FRS) to stratify patients and re-examined the outcomes of the multicenter U.S. study I cited earlier that was stopped early because of differences in mortality rates. The University of Pennsylvania research found that FRS correlated well with outcomes, suggesting its use as a mitigation strategy in patients at moderate to high risk for developing clinically relevant postoperative pancreatic fistula (J Gastrointest Surg. 2015;19:21-30). In other words, they suggest routine prophylactic drainage for patients at moderate to high risk but also suggest that there may be no need for prophylactic drainage for negligible to low risk patients.
I would like to conclude that drains appear essential in many cases, including for moderate to higher risk patients. We need to tailor our practices as surgeons regarding placement of drains during pancreatectomy or pancreaticoduodenectomy. Our goal remains to create opportunities for prolonged survival and better quality of life for our patients.
Dr. Dervenis is head of the Department of Surgical Oncology at the Metropolitan Hospital in Athens, Greece. He is also chair of the hepato-pancreato-biliary surgical unit. He reported no disclosures.
No, drain placement is not always necessary.
Drain placement is not essential during all pancreatectomies. The practice is so historically entrenched in our specialty that I need you to check your dogma at the door and take a look at the data with an open mind.
There are many, many retrospective studies that examine drainage versus no drainage. All of these studies have shown the same thing: There is no difference in many outcomes, including mortality. There may be a difference in terms of complicated, postoperative fistulae, which are difficult to manage in patients who have drains.
Another prospective randomized trial from Germany compared the reintervention rate, an endpoint I like, among 439 patients (Ann Surg. 2016;264:528-37). There was no statistically significant difference between the drain or no drain groups, further suggesting that drains are not essential in all cases.
We also need to take a closer look at the study Dr. Dervenis cited (Ann Surg. 2014:259:605-12). It’s true this trial was stopped early because of a higher mortality rate of 12% in the no drain group, but the difference was not statistically significant (P = .097). There was no difference in the fistula rate.
When you look at these data, there are a couple of conclusions you can reach. One conclusion is that a trial of 130 people designed for 750 found something uniquely different that had never been reported in any retrospective series, including one by the study’s senior author that demonstrated drains are essential (HPB [Oxford]. 2011;13:503-10). Another conclusion is that drains are not needed, and there is a very good chance this is a false positive finding. Look at the reasons the 10 participants died. I’m not sure a drain would have helped some of the patients without them, and some of the patients who had drains still died.
A study looking at practice at my institution, MSKCC, shows that drains are still used about half the time, indicating they are not essential. (Ann. Surg. 2013 Dec;258[6]:1051-8). Drains were more commonly used for pancreaticoduodenectomy and when the surgeon thought there might be a problem, such as a soft gland, difficult time in the OR, or a small pancreatic duct.
If you look at these data, this pans out in every retrospective study I’ve seen comparing drain versus no drain – the patients with drains tend to have higher morbidity. Among the 1,122 resection patients in the MSKCC study, those without operative drains had significantly lower rates of grade 3 complications and overall morbidity and fewer readmissions and lower rates of grade 3 or higher pancreatic fistula. Mortality and reintervention rates were no different.
I also looked at our most recent data, between 2010 and 2015. Now we are using intraoperative drains even less often. They are not considered essential at this point.
There are multiple retrospective and well-designed prospective, randomized trials that show no benefit to routine drainage following pancreatectomy. Acceptance of randomized clinical data is slow, particularly when it flies in the face of what you were taught by your mentors over the past 40 or 50 years. I encourage you to look at these data carefully and utilize them in your practice.
Dr. Allen is associate director for clinical programs at David M. Rubenstein Center for Pancreatic Cancer Research and the Murray F. Brennan chair in surgery at Memorial Sloan-Kettering Cancer Center in New York City. He reported no disclosures.
Point/Counterpoint: Should all suspected mucinous cystic neoplasms be resected?
Dr. Pawlik is a pretty clever guy and a strong adversary. Mucinous cystic neoplasm is literally the only topic in hepato-pancreato-biliary surgery he has not written about – yet.1
But I will argue that all suspected mucinous cystic neoplasms (MCNs) should be surgically removed. Reasons include: the natural history of a benign MCN in a typical 45-year-old remains unknown, clinical features are not always reliable, and it’s difficult to distinguish benign from malignant neoplasms without surgery.
Although many MCNs are benign when resected, all have malignant potential.
The prevalence of cancer at time of diagnosis with an MCN is fairly low, about 15%. This means most of these cysts are benign when resected. However, discrimination between benign and malignant is difficult without surgery, and the degree of epithelial dysplasia at time of resection ranges from mild to severe with invasive carcinoma.
When cancer is present, patients tend to do poorly. In one study where 44 out of 344 patients developed invasive cancer, the group with cancer had a 3-year overall survival rate of 59%.2
In addition, aspiration of cyst fluid is often of limited utility. It is poor at distinguishing whether a cyst is benign or malignant. For example, in a series of 55 patients with MCNs that underwent fine-needle aspiration of cyst epithelium, 71% of assays were nondiagnostic.3 So this diagnostic test is very insensitive and may miss at least half of cancers – another point in favor of surgical resection for all MCNs.
It is true that evidence in the literature associates certain clinical factors with a higher risk for malignancy in suspected MCNs. These include male gender, larger cysts, and location in the pancreatic head or neck or larger cyst diameter and presence of nodules.2,4 However, use of clinical features is not perfect.
In another study, of 163 resected MCNs, those with invasive cancer were often – but not always – larger than 4 cm with nodules.5 These same series revealed that those with invasive cancer were often, but again not always, larger than 4 cm.
We see this in our practice as well – that a large cyst or presence of nodules is not a foolproof indicator of malignancy. We had a 38-year-old woman with a large cyst and nodules who did not have cancer. In contrast, a 45-year-old woman at our institution presented with small cysts and no cancer on fine-needle aspiration. However, final pathology in her case revealed high-grade dysplasia.
Also, we only know what happens to cysts that have been resected. We know nothing about duration or other best practices for following patients who do not undergo surgery. For this reason, we really don’t know what these tumors will do if left alone.
Surgery is curative and carries a pretty low risk. Following resection, these patients do well. We’re talking about curative operations.
Dr. Katz is an Associate Professor, Department of Surgical Oncology, Division of Surgery at the University of Texas MD Anderson Cancer Center in Houston. He is also Chief of the Pancreas Surgery Service at MD Anderson. Dr. Katz noted he was asked to provide the pro side of the argument, and he may not necessarily uphold these positions in his own practice. Dr. Katz had no relevant financial disclosures.
References:
1. Dr. Pawlik’s list of selected publications: http://pathology.jhu.edu/liver/pawlik.cfm.
2. JAMA Surg. 2017;152:19-25.
3. Cancer. 2017;125:169-77.
4. Pancreas. 2011;40:67-71.
5. Ann Surg. 2008;247:571-9.
Some mucinous cystic neoplasms can be safely followed.
Data in the literature suggest some of these suspected mucinous cystic neoplasms can be followed; surgery may not be indicated solely because “as surgeons we tend to take all masses out” and because operative complications occur. Therefore, resection is not a benign procedure.
Dr. Katz, you were done before you got started. The evidence shows that some of the MCNs can be followed rather than resected.
Most of the published studies focus on IPMN, but I think the topic of MCNs is becoming increasingly important; they follow IPMNs as the second most common type of cystic neoplasms. So we’re going to be finding more small MCNs. In this debate, we are not talking about an 8-cm MCN, but rather what do we do when we see a 2- to 3-cm MCN. Do these patients all need to undergo resection?
What Dr. Katz is concerned about is that we are going to miss a cancer. We should operate on all patients because – at least as Dr. Katz’s argues – the surgery can always be done without complications.
However, even at the very, very experienced centers, morbidity was 30%-50%, and a pancreatic fistula developed for 1 in 10 patients. So it’s not a benign procedure.1
As surgeons, we tend to take every mass out. Although operative mortality is low, it is still in a measurable range, 1%-2%, and that is even at expert centers. Many of these small cysts are being found at smaller and community hospitals, and undue morbidity and mortality may weigh more heavily in these settings.2
Rather than “being a hammer and seeing everything as a nail,” we need a more rational approach. For example, we should identify a subgroup that will the most benefit from resection.
Investigators from Memorial Sloan Kettering Cancer Center reported that certain clinical factors identify patients at higher risk for mortality, such as nodules.3 Patients with invasive cancer almost all had nodules. And all patients with invasive cancer without nodules had a tumor larger than 4 cm.
Maybe using both presence of nodules and size is the right approach to identifying underling malignancy in suspected MCNs. Again, size is important, as is male gender, presence of solid nodules, and duct dilatation.4
We are arguing whether all MCNs should be resected. I’m positing that many 2-cm to 3-cm MCNs can be followed. There is only a small chance they will grow over time, and it’s unlikely they are harboring a malignancy.
Dr. Pawlik is Chair of Surgery at the Ohio State Wexner Medical Center in Columbus. He is also the Urban Meyer III and Shelley Meyer Chair for Cancer Research at Ohio State. He has no disclosures.
References
1. HPB (Oxford). 2007;9:8-15.
2. Diagnosis and Management of Cystic Lesions of the Pancreas. Diagnostic and Therapeutic Endoscopy Volume 2011 (2011), Article ID 478913.
3. JAMA Surg. 2017;152:19-25.
4. Ann Surg. 2006;244:572-82.
This Point/Counterpoint feature is based on comments Dr. Katz and Dr. Pawlik made during a debate at AHPBA 2017, the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
Dr. Pawlik is a pretty clever guy and a strong adversary. Mucinous cystic neoplasm is literally the only topic in hepato-pancreato-biliary surgery he has not written about – yet.1
But I will argue that all suspected mucinous cystic neoplasms (MCNs) should be surgically removed. Reasons include: the natural history of a benign MCN in a typical 45-year-old remains unknown, clinical features are not always reliable, and it’s difficult to distinguish benign from malignant neoplasms without surgery.
Although many MCNs are benign when resected, all have malignant potential.
The prevalence of cancer at time of diagnosis with an MCN is fairly low, about 15%. This means most of these cysts are benign when resected. However, discrimination between benign and malignant is difficult without surgery, and the degree of epithelial dysplasia at time of resection ranges from mild to severe with invasive carcinoma.
When cancer is present, patients tend to do poorly. In one study where 44 out of 344 patients developed invasive cancer, the group with cancer had a 3-year overall survival rate of 59%.2
In addition, aspiration of cyst fluid is often of limited utility. It is poor at distinguishing whether a cyst is benign or malignant. For example, in a series of 55 patients with MCNs that underwent fine-needle aspiration of cyst epithelium, 71% of assays were nondiagnostic.3 So this diagnostic test is very insensitive and may miss at least half of cancers – another point in favor of surgical resection for all MCNs.
It is true that evidence in the literature associates certain clinical factors with a higher risk for malignancy in suspected MCNs. These include male gender, larger cysts, and location in the pancreatic head or neck or larger cyst diameter and presence of nodules.2,4 However, use of clinical features is not perfect.
In another study, of 163 resected MCNs, those with invasive cancer were often – but not always – larger than 4 cm with nodules.5 These same series revealed that those with invasive cancer were often, but again not always, larger than 4 cm.
We see this in our practice as well – that a large cyst or presence of nodules is not a foolproof indicator of malignancy. We had a 38-year-old woman with a large cyst and nodules who did not have cancer. In contrast, a 45-year-old woman at our institution presented with small cysts and no cancer on fine-needle aspiration. However, final pathology in her case revealed high-grade dysplasia.
Also, we only know what happens to cysts that have been resected. We know nothing about duration or other best practices for following patients who do not undergo surgery. For this reason, we really don’t know what these tumors will do if left alone.
Surgery is curative and carries a pretty low risk. Following resection, these patients do well. We’re talking about curative operations.
Dr. Katz is an Associate Professor, Department of Surgical Oncology, Division of Surgery at the University of Texas MD Anderson Cancer Center in Houston. He is also Chief of the Pancreas Surgery Service at MD Anderson. Dr. Katz noted he was asked to provide the pro side of the argument, and he may not necessarily uphold these positions in his own practice. Dr. Katz had no relevant financial disclosures.
References:
1. Dr. Pawlik’s list of selected publications: http://pathology.jhu.edu/liver/pawlik.cfm.
2. JAMA Surg. 2017;152:19-25.
3. Cancer. 2017;125:169-77.
4. Pancreas. 2011;40:67-71.
5. Ann Surg. 2008;247:571-9.
Some mucinous cystic neoplasms can be safely followed.
Data in the literature suggest some of these suspected mucinous cystic neoplasms can be followed; surgery may not be indicated solely because “as surgeons we tend to take all masses out” and because operative complications occur. Therefore, resection is not a benign procedure.
Dr. Katz, you were done before you got started. The evidence shows that some of the MCNs can be followed rather than resected.
Most of the published studies focus on IPMN, but I think the topic of MCNs is becoming increasingly important; they follow IPMNs as the second most common type of cystic neoplasms. So we’re going to be finding more small MCNs. In this debate, we are not talking about an 8-cm MCN, but rather what do we do when we see a 2- to 3-cm MCN. Do these patients all need to undergo resection?
What Dr. Katz is concerned about is that we are going to miss a cancer. We should operate on all patients because – at least as Dr. Katz’s argues – the surgery can always be done without complications.
However, even at the very, very experienced centers, morbidity was 30%-50%, and a pancreatic fistula developed for 1 in 10 patients. So it’s not a benign procedure.1
As surgeons, we tend to take every mass out. Although operative mortality is low, it is still in a measurable range, 1%-2%, and that is even at expert centers. Many of these small cysts are being found at smaller and community hospitals, and undue morbidity and mortality may weigh more heavily in these settings.2
Rather than “being a hammer and seeing everything as a nail,” we need a more rational approach. For example, we should identify a subgroup that will the most benefit from resection.
Investigators from Memorial Sloan Kettering Cancer Center reported that certain clinical factors identify patients at higher risk for mortality, such as nodules.3 Patients with invasive cancer almost all had nodules. And all patients with invasive cancer without nodules had a tumor larger than 4 cm.
Maybe using both presence of nodules and size is the right approach to identifying underling malignancy in suspected MCNs. Again, size is important, as is male gender, presence of solid nodules, and duct dilatation.4
We are arguing whether all MCNs should be resected. I’m positing that many 2-cm to 3-cm MCNs can be followed. There is only a small chance they will grow over time, and it’s unlikely they are harboring a malignancy.
Dr. Pawlik is Chair of Surgery at the Ohio State Wexner Medical Center in Columbus. He is also the Urban Meyer III and Shelley Meyer Chair for Cancer Research at Ohio State. He has no disclosures.
References
1. HPB (Oxford). 2007;9:8-15.
2. Diagnosis and Management of Cystic Lesions of the Pancreas. Diagnostic and Therapeutic Endoscopy Volume 2011 (2011), Article ID 478913.
3. JAMA Surg. 2017;152:19-25.
4. Ann Surg. 2006;244:572-82.
This Point/Counterpoint feature is based on comments Dr. Katz and Dr. Pawlik made during a debate at AHPBA 2017, the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
Dr. Pawlik is a pretty clever guy and a strong adversary. Mucinous cystic neoplasm is literally the only topic in hepato-pancreato-biliary surgery he has not written about – yet.1
But I will argue that all suspected mucinous cystic neoplasms (MCNs) should be surgically removed. Reasons include: the natural history of a benign MCN in a typical 45-year-old remains unknown, clinical features are not always reliable, and it’s difficult to distinguish benign from malignant neoplasms without surgery.
Although many MCNs are benign when resected, all have malignant potential.
The prevalence of cancer at time of diagnosis with an MCN is fairly low, about 15%. This means most of these cysts are benign when resected. However, discrimination between benign and malignant is difficult without surgery, and the degree of epithelial dysplasia at time of resection ranges from mild to severe with invasive carcinoma.
When cancer is present, patients tend to do poorly. In one study where 44 out of 344 patients developed invasive cancer, the group with cancer had a 3-year overall survival rate of 59%.2
In addition, aspiration of cyst fluid is often of limited utility. It is poor at distinguishing whether a cyst is benign or malignant. For example, in a series of 55 patients with MCNs that underwent fine-needle aspiration of cyst epithelium, 71% of assays were nondiagnostic.3 So this diagnostic test is very insensitive and may miss at least half of cancers – another point in favor of surgical resection for all MCNs.
It is true that evidence in the literature associates certain clinical factors with a higher risk for malignancy in suspected MCNs. These include male gender, larger cysts, and location in the pancreatic head or neck or larger cyst diameter and presence of nodules.2,4 However, use of clinical features is not perfect.
In another study, of 163 resected MCNs, those with invasive cancer were often – but not always – larger than 4 cm with nodules.5 These same series revealed that those with invasive cancer were often, but again not always, larger than 4 cm.
We see this in our practice as well – that a large cyst or presence of nodules is not a foolproof indicator of malignancy. We had a 38-year-old woman with a large cyst and nodules who did not have cancer. In contrast, a 45-year-old woman at our institution presented with small cysts and no cancer on fine-needle aspiration. However, final pathology in her case revealed high-grade dysplasia.
Also, we only know what happens to cysts that have been resected. We know nothing about duration or other best practices for following patients who do not undergo surgery. For this reason, we really don’t know what these tumors will do if left alone.
Surgery is curative and carries a pretty low risk. Following resection, these patients do well. We’re talking about curative operations.
Dr. Katz is an Associate Professor, Department of Surgical Oncology, Division of Surgery at the University of Texas MD Anderson Cancer Center in Houston. He is also Chief of the Pancreas Surgery Service at MD Anderson. Dr. Katz noted he was asked to provide the pro side of the argument, and he may not necessarily uphold these positions in his own practice. Dr. Katz had no relevant financial disclosures.
References:
1. Dr. Pawlik’s list of selected publications: http://pathology.jhu.edu/liver/pawlik.cfm.
2. JAMA Surg. 2017;152:19-25.
3. Cancer. 2017;125:169-77.
4. Pancreas. 2011;40:67-71.
5. Ann Surg. 2008;247:571-9.
Some mucinous cystic neoplasms can be safely followed.
Data in the literature suggest some of these suspected mucinous cystic neoplasms can be followed; surgery may not be indicated solely because “as surgeons we tend to take all masses out” and because operative complications occur. Therefore, resection is not a benign procedure.
Dr. Katz, you were done before you got started. The evidence shows that some of the MCNs can be followed rather than resected.
Most of the published studies focus on IPMN, but I think the topic of MCNs is becoming increasingly important; they follow IPMNs as the second most common type of cystic neoplasms. So we’re going to be finding more small MCNs. In this debate, we are not talking about an 8-cm MCN, but rather what do we do when we see a 2- to 3-cm MCN. Do these patients all need to undergo resection?
What Dr. Katz is concerned about is that we are going to miss a cancer. We should operate on all patients because – at least as Dr. Katz’s argues – the surgery can always be done without complications.
However, even at the very, very experienced centers, morbidity was 30%-50%, and a pancreatic fistula developed for 1 in 10 patients. So it’s not a benign procedure.1
As surgeons, we tend to take every mass out. Although operative mortality is low, it is still in a measurable range, 1%-2%, and that is even at expert centers. Many of these small cysts are being found at smaller and community hospitals, and undue morbidity and mortality may weigh more heavily in these settings.2
Rather than “being a hammer and seeing everything as a nail,” we need a more rational approach. For example, we should identify a subgroup that will the most benefit from resection.
Investigators from Memorial Sloan Kettering Cancer Center reported that certain clinical factors identify patients at higher risk for mortality, such as nodules.3 Patients with invasive cancer almost all had nodules. And all patients with invasive cancer without nodules had a tumor larger than 4 cm.
Maybe using both presence of nodules and size is the right approach to identifying underling malignancy in suspected MCNs. Again, size is important, as is male gender, presence of solid nodules, and duct dilatation.4
We are arguing whether all MCNs should be resected. I’m positing that many 2-cm to 3-cm MCNs can be followed. There is only a small chance they will grow over time, and it’s unlikely they are harboring a malignancy.
Dr. Pawlik is Chair of Surgery at the Ohio State Wexner Medical Center in Columbus. He is also the Urban Meyer III and Shelley Meyer Chair for Cancer Research at Ohio State. He has no disclosures.
References
1. HPB (Oxford). 2007;9:8-15.
2. Diagnosis and Management of Cystic Lesions of the Pancreas. Diagnostic and Therapeutic Endoscopy Volume 2011 (2011), Article ID 478913.
3. JAMA Surg. 2017;152:19-25.
4. Ann Surg. 2006;244:572-82.
This Point/Counterpoint feature is based on comments Dr. Katz and Dr. Pawlik made during a debate at AHPBA 2017, the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
Three-strategy combo reduces pancreatoduodenectomy fistula risk
MIAMI BEACH – Pancreaticojejunostomy reconstruction, use of stents, and avoidance of prophylactic octreotide, especially in combination, could reduce the fistula rate associated with pancreatoduodenectomy.
Failure of the anastomosis is “of greatest concern” to surgeons performing a pancreatoduodenectomy, said Brett L. Ecker, MD, a surgical resident at the University of Pennsylvania, Philadelphia.
“There is no shortage of high-quality data to help guide the use of [fistula reduction] strategies,” he added. However, “the utility of these strategies in patients most vulnerable to fistula … has rarely been particularly explored.”
Dr. Ecker and his colleagues conducted a study with 62 surgeons at 17 institutions to compare various fistula mitigation strategies in this higher-risk population. They assessed surgical reconstruction, dunking, tissue patches, intraperitoneal drains, stents, prophylactic octreotide, and use of tissue sealants.
“Ultimately, we want to know the best way to deal with this high-stakes situation, and whether outcomes might be optimized by bundling these proactive strategies,” Dr. Ecker explained.
“We found the combination of externalized stents and PJ [pancreaticojejunostomy] reconstruction with the omission of prophylactic octreotide was associated with significant improvements in fistula that exceeded the benefit of any individual mitigation approach or any other combination of strategies,” he said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“The mitigation of risk in real-life practice is often the result of multiple moving parts,” Dr. Ecker said. “The best outcomes [may result from] the synergistic effects of multiple strategies.”
Of the approximately 10% of patients with a Fistula Risk Score of 7-10, 152 ended up with clinically relevant postoperative pancreatic fistula (CR-POPF). “An FRS score of 7 or higher is associated with worse outcomes, including a fistula rate approaching 30%,” Dr. Ecker said. Grade B or C fistula based on International Study Group on Pancreatic Surgery criteria were considered clinically relevant. All patients had surgery from 2003 to 2016 in the retrospective, multinational study.
“This represents the only series of high-risk cases where current international standards were used to define both the risk and the outcome,” he noted.
“Almost all [of the 522] patients had a soft gland and a small duct, a median of 2 mm,” Dr. Ecker added. “High-risk pathology was common, in 86%.”
Surgeons contributing to the series were at high-volume centers and had performed more than 200 Whipple procedures in their careers. “Both institutional and surgeon volume were associated with improved fistula outcomes,” Dr. Ecker said. “We found that intraperitoneal drains were not associated with improved fistula outcomes, but that is limited by the fact that drains were rarely omitted in these cases.”
Four strategies compared
The investigators compared the outcomes of four fistula strategies among the patients considered high risk prior to surgery. When they combined pancreaticogastrostomy, prophylactic octreotide, and no stent, the CR-POPF rate was 47%. “This was associated with an alarming fistula rate approaching 50%,” Dr. Ecker said.
When surgeons combined pancreaticojejunostomy, octreotide, and no stent, the CR-POPF rate declined to 34%. Furthermore, pancreaticojejunostomy without octreotide or a stent yielded a 26% CR-POPF rate.
Ultimately, the most effective strategy to avoid clinically relevant fistula was pancreaticojejunostomy with an external stent and no octreotide.
“The use of PJ reconstruction with an external stent and omission of octreotide was associated with a fistula rate of about 13%, which was a greater than 50% risk reduction from the overall cohort,” Dr. Ecker said.
The researchers also performed propensity score matching to reduce bias associated with surgeon or patient factors. They matched 167 participants in the study with 155 controls. Dr. Ecker said, “Still, we observed that patients managed this way had significantly lower fistula rates.”
“This is an excellent paper and an important topic,” said study discussant Michael L. Kendrick, MD, a general surgeon at the Mayo Clinic in Rochester, Minn.
“At our institution, we’ve used the same Fistula Risk Score and found it very helpful for a mitigation strategy in a separate protocol, and we found that reduced our leak rates as well,” Dr. Kendrick noted.
Dr. Ecker and Dr. Kendrick had no relevant disclosures.
MIAMI BEACH – Pancreaticojejunostomy reconstruction, use of stents, and avoidance of prophylactic octreotide, especially in combination, could reduce the fistula rate associated with pancreatoduodenectomy.
Failure of the anastomosis is “of greatest concern” to surgeons performing a pancreatoduodenectomy, said Brett L. Ecker, MD, a surgical resident at the University of Pennsylvania, Philadelphia.
“There is no shortage of high-quality data to help guide the use of [fistula reduction] strategies,” he added. However, “the utility of these strategies in patients most vulnerable to fistula … has rarely been particularly explored.”
Dr. Ecker and his colleagues conducted a study with 62 surgeons at 17 institutions to compare various fistula mitigation strategies in this higher-risk population. They assessed surgical reconstruction, dunking, tissue patches, intraperitoneal drains, stents, prophylactic octreotide, and use of tissue sealants.
“Ultimately, we want to know the best way to deal with this high-stakes situation, and whether outcomes might be optimized by bundling these proactive strategies,” Dr. Ecker explained.
“We found the combination of externalized stents and PJ [pancreaticojejunostomy] reconstruction with the omission of prophylactic octreotide was associated with significant improvements in fistula that exceeded the benefit of any individual mitigation approach or any other combination of strategies,” he said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“The mitigation of risk in real-life practice is often the result of multiple moving parts,” Dr. Ecker said. “The best outcomes [may result from] the synergistic effects of multiple strategies.”
Of the approximately 10% of patients with a Fistula Risk Score of 7-10, 152 ended up with clinically relevant postoperative pancreatic fistula (CR-POPF). “An FRS score of 7 or higher is associated with worse outcomes, including a fistula rate approaching 30%,” Dr. Ecker said. Grade B or C fistula based on International Study Group on Pancreatic Surgery criteria were considered clinically relevant. All patients had surgery from 2003 to 2016 in the retrospective, multinational study.
“This represents the only series of high-risk cases where current international standards were used to define both the risk and the outcome,” he noted.
“Almost all [of the 522] patients had a soft gland and a small duct, a median of 2 mm,” Dr. Ecker added. “High-risk pathology was common, in 86%.”
Surgeons contributing to the series were at high-volume centers and had performed more than 200 Whipple procedures in their careers. “Both institutional and surgeon volume were associated with improved fistula outcomes,” Dr. Ecker said. “We found that intraperitoneal drains were not associated with improved fistula outcomes, but that is limited by the fact that drains were rarely omitted in these cases.”
Four strategies compared
The investigators compared the outcomes of four fistula strategies among the patients considered high risk prior to surgery. When they combined pancreaticogastrostomy, prophylactic octreotide, and no stent, the CR-POPF rate was 47%. “This was associated with an alarming fistula rate approaching 50%,” Dr. Ecker said.
When surgeons combined pancreaticojejunostomy, octreotide, and no stent, the CR-POPF rate declined to 34%. Furthermore, pancreaticojejunostomy without octreotide or a stent yielded a 26% CR-POPF rate.
Ultimately, the most effective strategy to avoid clinically relevant fistula was pancreaticojejunostomy with an external stent and no octreotide.
“The use of PJ reconstruction with an external stent and omission of octreotide was associated with a fistula rate of about 13%, which was a greater than 50% risk reduction from the overall cohort,” Dr. Ecker said.
The researchers also performed propensity score matching to reduce bias associated with surgeon or patient factors. They matched 167 participants in the study with 155 controls. Dr. Ecker said, “Still, we observed that patients managed this way had significantly lower fistula rates.”
“This is an excellent paper and an important topic,” said study discussant Michael L. Kendrick, MD, a general surgeon at the Mayo Clinic in Rochester, Minn.
“At our institution, we’ve used the same Fistula Risk Score and found it very helpful for a mitigation strategy in a separate protocol, and we found that reduced our leak rates as well,” Dr. Kendrick noted.
Dr. Ecker and Dr. Kendrick had no relevant disclosures.
MIAMI BEACH – Pancreaticojejunostomy reconstruction, use of stents, and avoidance of prophylactic octreotide, especially in combination, could reduce the fistula rate associated with pancreatoduodenectomy.
Failure of the anastomosis is “of greatest concern” to surgeons performing a pancreatoduodenectomy, said Brett L. Ecker, MD, a surgical resident at the University of Pennsylvania, Philadelphia.
“There is no shortage of high-quality data to help guide the use of [fistula reduction] strategies,” he added. However, “the utility of these strategies in patients most vulnerable to fistula … has rarely been particularly explored.”
Dr. Ecker and his colleagues conducted a study with 62 surgeons at 17 institutions to compare various fistula mitigation strategies in this higher-risk population. They assessed surgical reconstruction, dunking, tissue patches, intraperitoneal drains, stents, prophylactic octreotide, and use of tissue sealants.
“Ultimately, we want to know the best way to deal with this high-stakes situation, and whether outcomes might be optimized by bundling these proactive strategies,” Dr. Ecker explained.
“We found the combination of externalized stents and PJ [pancreaticojejunostomy] reconstruction with the omission of prophylactic octreotide was associated with significant improvements in fistula that exceeded the benefit of any individual mitigation approach or any other combination of strategies,” he said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“The mitigation of risk in real-life practice is often the result of multiple moving parts,” Dr. Ecker said. “The best outcomes [may result from] the synergistic effects of multiple strategies.”
Of the approximately 10% of patients with a Fistula Risk Score of 7-10, 152 ended up with clinically relevant postoperative pancreatic fistula (CR-POPF). “An FRS score of 7 or higher is associated with worse outcomes, including a fistula rate approaching 30%,” Dr. Ecker said. Grade B or C fistula based on International Study Group on Pancreatic Surgery criteria were considered clinically relevant. All patients had surgery from 2003 to 2016 in the retrospective, multinational study.
“This represents the only series of high-risk cases where current international standards were used to define both the risk and the outcome,” he noted.
“Almost all [of the 522] patients had a soft gland and a small duct, a median of 2 mm,” Dr. Ecker added. “High-risk pathology was common, in 86%.”
Surgeons contributing to the series were at high-volume centers and had performed more than 200 Whipple procedures in their careers. “Both institutional and surgeon volume were associated with improved fistula outcomes,” Dr. Ecker said. “We found that intraperitoneal drains were not associated with improved fistula outcomes, but that is limited by the fact that drains were rarely omitted in these cases.”
Four strategies compared
The investigators compared the outcomes of four fistula strategies among the patients considered high risk prior to surgery. When they combined pancreaticogastrostomy, prophylactic octreotide, and no stent, the CR-POPF rate was 47%. “This was associated with an alarming fistula rate approaching 50%,” Dr. Ecker said.
When surgeons combined pancreaticojejunostomy, octreotide, and no stent, the CR-POPF rate declined to 34%. Furthermore, pancreaticojejunostomy without octreotide or a stent yielded a 26% CR-POPF rate.
Ultimately, the most effective strategy to avoid clinically relevant fistula was pancreaticojejunostomy with an external stent and no octreotide.
“The use of PJ reconstruction with an external stent and omission of octreotide was associated with a fistula rate of about 13%, which was a greater than 50% risk reduction from the overall cohort,” Dr. Ecker said.
The researchers also performed propensity score matching to reduce bias associated with surgeon or patient factors. They matched 167 participants in the study with 155 controls. Dr. Ecker said, “Still, we observed that patients managed this way had significantly lower fistula rates.”
“This is an excellent paper and an important topic,” said study discussant Michael L. Kendrick, MD, a general surgeon at the Mayo Clinic in Rochester, Minn.
“At our institution, we’ve used the same Fistula Risk Score and found it very helpful for a mitigation strategy in a separate protocol, and we found that reduced our leak rates as well,” Dr. Kendrick noted.
Dr. Ecker and Dr. Kendrick had no relevant disclosures.
AT AHPBA 2017
Key clinical point: Reconstruction, use of stents, and avoidance of octreotide, especially in combination, could reduce the fistula rate associated with pancreatoduodenectomy.
Major finding: The incidence of fistula decreased from 33% to 13% by combining the three strategies.
Data source: Multicenter retrospective study from 2003 to 2016 with 522 patients undergoing pancreatoduodenectomy.
Disclosures: Dr. Ecker and Dr. Kendrick had no relevant disclosures.
Debulking called reasonable for unresectable liver cancer
MIAMI BEACH – Cytoreductive debulking surgery for neuroendocrine liver metastases provides a lower but “reasonable” long-term survival, compared with curative intent surgery, according to results of a study presented at the annual meeting of the Americas Hepatico-Pancreato-Biliary Association.
Liver debulking for patients with grossly unresectable disease is therefore an option that may extend survival, the study researchers said.
“Surgical resection offers the best chance for long-term survival but may not be technically feasible for all our patients,” said Fabio Bagante, MD, a resident at the University of Verona (Italy). “Debulking neuroendocrine liver metastases has been proposed as an alternative.”
Dr. Bagante and coinvestigators compared outcomes between 180 patients who had debulking surgery (defined as an R2 outcome) and 449 who underwent curative intent resection (R0 or R1). Patients had surgery between 1990 and 2015 at eight institutions, and the primary outcome was overall survival. The mean follow-up was 51 months; during that time, 174 patients died.
The 5-year overall survival was 72% in the debulking group and 89% in the curative intent group. The 10-year overall survival was 41% in the debulking group and 77% among the curative intent surgery patients.
“Debulking operations for neuroendocrine liver metastases provide lower but reasonable long-term survival, compared with patients who underwent curative intent,” Dr. Bagante said.
“Nearly 3 in 10 patients underwent debulking surgery,” Dr. Bagante said. “It was more common among the elderly, males with symptomatic disease, and patients with greater liver involvement.”
Patients in the liver-debulking groups were also significantly more likely to have high–tumor grade disease, 35%, versus 13% of the curative intent resection group (P less than .001). They were also more likely to have metastatic disease, with an N1 rate of 73% versus 52% (P less than .001).
“Great work. Thanks for presenting this topic. It’s quite a debated topic,” said study discussant Aaron Lee, DO, of the department of general surgery at Cleveland Clinic Florida in Weston. “I looked at your data on asymptomatic patients who had a 5-year survival of 60%; U.K. data show [the] same survival without any intervention.” He asked Dr. Bagante to comment on operating on patients without any symptoms.
“Regarding the role of symptoms as a predictor of survival, there are many papers in the literature debating what are the true predictors of survival,” Dr. Bagante noted. “We don’t think [symptoms have an] impact; our data do not demonstrate that. We think the biologic behavior of the disease, the impact of the progression of the disease, and the grade of the tumor, [indicated by] Ki-67, could have more of a role.”
MIAMI BEACH – Cytoreductive debulking surgery for neuroendocrine liver metastases provides a lower but “reasonable” long-term survival, compared with curative intent surgery, according to results of a study presented at the annual meeting of the Americas Hepatico-Pancreato-Biliary Association.
Liver debulking for patients with grossly unresectable disease is therefore an option that may extend survival, the study researchers said.
“Surgical resection offers the best chance for long-term survival but may not be technically feasible for all our patients,” said Fabio Bagante, MD, a resident at the University of Verona (Italy). “Debulking neuroendocrine liver metastases has been proposed as an alternative.”
Dr. Bagante and coinvestigators compared outcomes between 180 patients who had debulking surgery (defined as an R2 outcome) and 449 who underwent curative intent resection (R0 or R1). Patients had surgery between 1990 and 2015 at eight institutions, and the primary outcome was overall survival. The mean follow-up was 51 months; during that time, 174 patients died.
The 5-year overall survival was 72% in the debulking group and 89% in the curative intent group. The 10-year overall survival was 41% in the debulking group and 77% among the curative intent surgery patients.
“Debulking operations for neuroendocrine liver metastases provide lower but reasonable long-term survival, compared with patients who underwent curative intent,” Dr. Bagante said.
“Nearly 3 in 10 patients underwent debulking surgery,” Dr. Bagante said. “It was more common among the elderly, males with symptomatic disease, and patients with greater liver involvement.”
Patients in the liver-debulking groups were also significantly more likely to have high–tumor grade disease, 35%, versus 13% of the curative intent resection group (P less than .001). They were also more likely to have metastatic disease, with an N1 rate of 73% versus 52% (P less than .001).
“Great work. Thanks for presenting this topic. It’s quite a debated topic,” said study discussant Aaron Lee, DO, of the department of general surgery at Cleveland Clinic Florida in Weston. “I looked at your data on asymptomatic patients who had a 5-year survival of 60%; U.K. data show [the] same survival without any intervention.” He asked Dr. Bagante to comment on operating on patients without any symptoms.
“Regarding the role of symptoms as a predictor of survival, there are many papers in the literature debating what are the true predictors of survival,” Dr. Bagante noted. “We don’t think [symptoms have an] impact; our data do not demonstrate that. We think the biologic behavior of the disease, the impact of the progression of the disease, and the grade of the tumor, [indicated by] Ki-67, could have more of a role.”
MIAMI BEACH – Cytoreductive debulking surgery for neuroendocrine liver metastases provides a lower but “reasonable” long-term survival, compared with curative intent surgery, according to results of a study presented at the annual meeting of the Americas Hepatico-Pancreato-Biliary Association.
Liver debulking for patients with grossly unresectable disease is therefore an option that may extend survival, the study researchers said.
“Surgical resection offers the best chance for long-term survival but may not be technically feasible for all our patients,” said Fabio Bagante, MD, a resident at the University of Verona (Italy). “Debulking neuroendocrine liver metastases has been proposed as an alternative.”
Dr. Bagante and coinvestigators compared outcomes between 180 patients who had debulking surgery (defined as an R2 outcome) and 449 who underwent curative intent resection (R0 or R1). Patients had surgery between 1990 and 2015 at eight institutions, and the primary outcome was overall survival. The mean follow-up was 51 months; during that time, 174 patients died.
The 5-year overall survival was 72% in the debulking group and 89% in the curative intent group. The 10-year overall survival was 41% in the debulking group and 77% among the curative intent surgery patients.
“Debulking operations for neuroendocrine liver metastases provide lower but reasonable long-term survival, compared with patients who underwent curative intent,” Dr. Bagante said.
“Nearly 3 in 10 patients underwent debulking surgery,” Dr. Bagante said. “It was more common among the elderly, males with symptomatic disease, and patients with greater liver involvement.”
Patients in the liver-debulking groups were also significantly more likely to have high–tumor grade disease, 35%, versus 13% of the curative intent resection group (P less than .001). They were also more likely to have metastatic disease, with an N1 rate of 73% versus 52% (P less than .001).
“Great work. Thanks for presenting this topic. It’s quite a debated topic,” said study discussant Aaron Lee, DO, of the department of general surgery at Cleveland Clinic Florida in Weston. “I looked at your data on asymptomatic patients who had a 5-year survival of 60%; U.K. data show [the] same survival without any intervention.” He asked Dr. Bagante to comment on operating on patients without any symptoms.
“Regarding the role of symptoms as a predictor of survival, there are many papers in the literature debating what are the true predictors of survival,” Dr. Bagante noted. “We don’t think [symptoms have an] impact; our data do not demonstrate that. We think the biologic behavior of the disease, the impact of the progression of the disease, and the grade of the tumor, [indicated by] Ki-67, could have more of a role.”
AT AHPBA 2017
Key clinical point:
Major finding: The 10-year overall survival was 77% in the curative intent surgery group, compared with 41% among the debulking patients.
Data source: A retrospective database study of 629 people with neuroendocrine liver metastases.
Disclosures: Dr. Bagante and Dr. Lee had no relevant financial disclosures.
Neoadjuvant chemoradiation may give transplant the edge over resection in biliary cancer
MIAMI BEACH – Survival for patients with hilar cholangiocarcinoma was similar between those who underwent transplantation and those who underwent resection, but neoadjuvant therapy may give transplant strategy the edge, findings of a study and meta-analysis suggest.
“Neoadjuvant chemoradiation therapy is clearly a factor that affects patient survival, and may be the only reason the patients who received transplantation had better overall survival than [did those who had] resection,” Michele Gage, MD, a general surgeon at Johns Hopkins Medicine in Baltimore, said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“We found survival in the group that received neoadjuvant chemoradiation therapy and transplant had a statistically significantly better outcome compared to a control group of resection,” Dr. Gage said. More importantly, patients who received a transplant without neoadjuvant therapy had a statistically significant worse outcome than patients who got resection alone.”
The investigators noted that patient selection for neoadjuvant therapy might also be a factor contributing to superior overall survival. In a multicenter study of 147 patients undergoing liver transplantation for hilar cholangiocarcinoma, a subgroup of patients who met the selection criteria of the Mayo Clinic protocol but had not undergone neoadjuvant therapy had a 59% 5-year survival rate (PLoS One. 2016:11:e0156127).
Study discussant Maria B. Majella Doyle, MD, a general surgeon at Washington University in St. Louis, agreed that patient selection for transplantation is a likely factor.
Dr. Doyle then asked Dr. Gage how she accounts for the heterogeneity among studies performed over a 20-year period.
“That is why we did subgroup analysis of neoadjuvant versus no neoadjuvant therapy,” Dr. Gage replied.
In the future, an intent-to-treat analysis might be more accurate, Dr. Majella Doyle said, because more patients are placed on a liver transplant list than typically have the procedure.
Dr. Gage noted that 28%-48% of patients started on neoadjuvant therapy in the two studies that offered both neoadjuvant therapy and a transplant in the meta-analysis never made it to transplantation. When they were included, overall survival dropped to approximately 35% in one study and 44% in the other.
In the primary meta-analysis (before the subanalysis looking at neoadjuvant therapy), 398 patients underwent resection and another 200 underwent liver transplantation between 1996 and 2106. Patient demographics were similar between groups, including more men than women, except the average age in the resection group was older, Dr. Gage said.
Overall survival favored the transplant group at each time point: 78% versus 70% with resection at 1 year; 56% versus 42% at 3 years; and 46% versus 29% at 5 years. The odds ratios, respectively, were 1.27, 1.49 and 1.83, but the findings were not statistically significant at a 95% confidence interval.
Margin involvement was 9% in the transplant patients versus 32% in the resection patients, Dr. Gage said. The best chance of cure is R0 resection, but half of patients with hilar cholangiocarcinoma, the most common cancer of the biliary tract, are unresectable, she added.
Six of the nine studies in the meta-analysis reported margin status. Of the 344 patients in these studies, 79% achieved R0 status overall.
“The goal of treatment is R0 resection,” Dr. Gage said in response to a question about when neoadjuvant therapy is warranted. “In the patients who are resectable, I think the correct answer would be to proceed with resection. However, for those patients who are borderline resectable, it would be reasonable to consider neoadjuvant therapy.”
“One of the major things that is undervalued is neoadjuvant therapy allows better patient selection,” said session moderator Eric Jensen, MD, FACS, of University of Minnesota Health in Minneapolis. “When you say an obviously resectable tumor, when you look at the data – we’re wrong 30% of the time. So I’m in favor of neoadjuvant therapy for everybody, but that is just my bias.”
The small number of studies is a limitation of the study, Dr. Gage said. Also, all the studies were nonrandomized and retrospective, and some research spanned many years, which could introduce bias because of changes in practice over time, she added.
Based on their findings, the investigators proposed that future studies explore routine administration of neoadjuvant therapy prior to resection.
Dr. Gage and Dr. Majella Doyle had no relevant financial disclosures.
MIAMI BEACH – Survival for patients with hilar cholangiocarcinoma was similar between those who underwent transplantation and those who underwent resection, but neoadjuvant therapy may give transplant strategy the edge, findings of a study and meta-analysis suggest.
“Neoadjuvant chemoradiation therapy is clearly a factor that affects patient survival, and may be the only reason the patients who received transplantation had better overall survival than [did those who had] resection,” Michele Gage, MD, a general surgeon at Johns Hopkins Medicine in Baltimore, said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“We found survival in the group that received neoadjuvant chemoradiation therapy and transplant had a statistically significantly better outcome compared to a control group of resection,” Dr. Gage said. More importantly, patients who received a transplant without neoadjuvant therapy had a statistically significant worse outcome than patients who got resection alone.”
The investigators noted that patient selection for neoadjuvant therapy might also be a factor contributing to superior overall survival. In a multicenter study of 147 patients undergoing liver transplantation for hilar cholangiocarcinoma, a subgroup of patients who met the selection criteria of the Mayo Clinic protocol but had not undergone neoadjuvant therapy had a 59% 5-year survival rate (PLoS One. 2016:11:e0156127).
Study discussant Maria B. Majella Doyle, MD, a general surgeon at Washington University in St. Louis, agreed that patient selection for transplantation is a likely factor.
Dr. Doyle then asked Dr. Gage how she accounts for the heterogeneity among studies performed over a 20-year period.
“That is why we did subgroup analysis of neoadjuvant versus no neoadjuvant therapy,” Dr. Gage replied.
In the future, an intent-to-treat analysis might be more accurate, Dr. Majella Doyle said, because more patients are placed on a liver transplant list than typically have the procedure.
Dr. Gage noted that 28%-48% of patients started on neoadjuvant therapy in the two studies that offered both neoadjuvant therapy and a transplant in the meta-analysis never made it to transplantation. When they were included, overall survival dropped to approximately 35% in one study and 44% in the other.
In the primary meta-analysis (before the subanalysis looking at neoadjuvant therapy), 398 patients underwent resection and another 200 underwent liver transplantation between 1996 and 2106. Patient demographics were similar between groups, including more men than women, except the average age in the resection group was older, Dr. Gage said.
Overall survival favored the transplant group at each time point: 78% versus 70% with resection at 1 year; 56% versus 42% at 3 years; and 46% versus 29% at 5 years. The odds ratios, respectively, were 1.27, 1.49 and 1.83, but the findings were not statistically significant at a 95% confidence interval.
Margin involvement was 9% in the transplant patients versus 32% in the resection patients, Dr. Gage said. The best chance of cure is R0 resection, but half of patients with hilar cholangiocarcinoma, the most common cancer of the biliary tract, are unresectable, she added.
Six of the nine studies in the meta-analysis reported margin status. Of the 344 patients in these studies, 79% achieved R0 status overall.
“The goal of treatment is R0 resection,” Dr. Gage said in response to a question about when neoadjuvant therapy is warranted. “In the patients who are resectable, I think the correct answer would be to proceed with resection. However, for those patients who are borderline resectable, it would be reasonable to consider neoadjuvant therapy.”
“One of the major things that is undervalued is neoadjuvant therapy allows better patient selection,” said session moderator Eric Jensen, MD, FACS, of University of Minnesota Health in Minneapolis. “When you say an obviously resectable tumor, when you look at the data – we’re wrong 30% of the time. So I’m in favor of neoadjuvant therapy for everybody, but that is just my bias.”
The small number of studies is a limitation of the study, Dr. Gage said. Also, all the studies were nonrandomized and retrospective, and some research spanned many years, which could introduce bias because of changes in practice over time, she added.
Based on their findings, the investigators proposed that future studies explore routine administration of neoadjuvant therapy prior to resection.
Dr. Gage and Dr. Majella Doyle had no relevant financial disclosures.
MIAMI BEACH – Survival for patients with hilar cholangiocarcinoma was similar between those who underwent transplantation and those who underwent resection, but neoadjuvant therapy may give transplant strategy the edge, findings of a study and meta-analysis suggest.
“Neoadjuvant chemoradiation therapy is clearly a factor that affects patient survival, and may be the only reason the patients who received transplantation had better overall survival than [did those who had] resection,” Michele Gage, MD, a general surgeon at Johns Hopkins Medicine in Baltimore, said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
“We found survival in the group that received neoadjuvant chemoradiation therapy and transplant had a statistically significantly better outcome compared to a control group of resection,” Dr. Gage said. More importantly, patients who received a transplant without neoadjuvant therapy had a statistically significant worse outcome than patients who got resection alone.”
The investigators noted that patient selection for neoadjuvant therapy might also be a factor contributing to superior overall survival. In a multicenter study of 147 patients undergoing liver transplantation for hilar cholangiocarcinoma, a subgroup of patients who met the selection criteria of the Mayo Clinic protocol but had not undergone neoadjuvant therapy had a 59% 5-year survival rate (PLoS One. 2016:11:e0156127).
Study discussant Maria B. Majella Doyle, MD, a general surgeon at Washington University in St. Louis, agreed that patient selection for transplantation is a likely factor.
Dr. Doyle then asked Dr. Gage how she accounts for the heterogeneity among studies performed over a 20-year period.
“That is why we did subgroup analysis of neoadjuvant versus no neoadjuvant therapy,” Dr. Gage replied.
In the future, an intent-to-treat analysis might be more accurate, Dr. Majella Doyle said, because more patients are placed on a liver transplant list than typically have the procedure.
Dr. Gage noted that 28%-48% of patients started on neoadjuvant therapy in the two studies that offered both neoadjuvant therapy and a transplant in the meta-analysis never made it to transplantation. When they were included, overall survival dropped to approximately 35% in one study and 44% in the other.
In the primary meta-analysis (before the subanalysis looking at neoadjuvant therapy), 398 patients underwent resection and another 200 underwent liver transplantation between 1996 and 2106. Patient demographics were similar between groups, including more men than women, except the average age in the resection group was older, Dr. Gage said.
Overall survival favored the transplant group at each time point: 78% versus 70% with resection at 1 year; 56% versus 42% at 3 years; and 46% versus 29% at 5 years. The odds ratios, respectively, were 1.27, 1.49 and 1.83, but the findings were not statistically significant at a 95% confidence interval.
Margin involvement was 9% in the transplant patients versus 32% in the resection patients, Dr. Gage said. The best chance of cure is R0 resection, but half of patients with hilar cholangiocarcinoma, the most common cancer of the biliary tract, are unresectable, she added.
Six of the nine studies in the meta-analysis reported margin status. Of the 344 patients in these studies, 79% achieved R0 status overall.
“The goal of treatment is R0 resection,” Dr. Gage said in response to a question about when neoadjuvant therapy is warranted. “In the patients who are resectable, I think the correct answer would be to proceed with resection. However, for those patients who are borderline resectable, it would be reasonable to consider neoadjuvant therapy.”
“One of the major things that is undervalued is neoadjuvant therapy allows better patient selection,” said session moderator Eric Jensen, MD, FACS, of University of Minnesota Health in Minneapolis. “When you say an obviously resectable tumor, when you look at the data – we’re wrong 30% of the time. So I’m in favor of neoadjuvant therapy for everybody, but that is just my bias.”
The small number of studies is a limitation of the study, Dr. Gage said. Also, all the studies were nonrandomized and retrospective, and some research spanned many years, which could introduce bias because of changes in practice over time, she added.
Based on their findings, the investigators proposed that future studies explore routine administration of neoadjuvant therapy prior to resection.
Dr. Gage and Dr. Majella Doyle had no relevant financial disclosures.
AT AHPBA 2017
BRCA2 mutations linked to greater risk for pancreatic cancer
MIAMI BEACH – Although population-wide screening for pancreatic cancer is considered unfeasible and costly, new evidence suggests a benefit to screening a select population: people who test positive for BRCA2 genetic mutations.
Cross-sectional imaging of 117 people with BRCA2 mutations revealed pancreatic abnormalities in 10 patients, including a patient with pancreatic cancer whose only symptom was unexplained weight loss.
Pancreatic cancer is not as common as are some other malignancies, with an incidence estimated between 1% and 3%. However, it is a particularly deadly form of cancer, with only 7.7% of people living to 5 years after diagnosis, according to data from the National Cancer Institute.
A relatively low incidence is a good thing, but it also limits widespread screening. “There is a low predictive value of screening the population at large, and it is not considered cost effective,” said Eugene P. Ceppa, MD, a general surgeon at IU Health University Hospital, Indianapolis. However, patients at high risk for pancreatic adenocarcinoma might be worth targeting for screening, he added.
“This represents a 21% increase in the chance of pancreatic cancer in these patients,” Dr. Ceppa said.
Buoyed by these and other findings, Dr. Ceppa and his colleagues launched a study of their own. “Our hypothesis is that screening all BRCA2s would identify more patients with pancreatic cancer,” he said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
Dr. Ceppa and coinvestigators reviewed electronic medical records at their institution from 2005 to 2015. They identified 204 BRCA mutation carriers, and after excluding 87 BRCA1 positive patients, further assessed the 117 with documented BRCA2 mutations. A total 47 people (40%) of this group had undergone cross-sectional imaging. The images were initially reviewed, and then re-reviewed for the study, by radiologists with specific expertise in pancreatology.
The cross-sectional imaging revealed pancreatic abnormalities in 10 people, including 1 patient with a pancreatic ductal adenocarcinoma located in the head of the pancreas. Another nine patients had intraductal papillary mucinous neoplasms (IPMNs). There were no significant demographic or clinical differences between the groups of patients with and without the imaging abnormalities, Dr. Ceppa said.
The investigators also compared the patients with BRCA2 mutations against a historical cohort representing the general population. They found 21% of patients with BRCA2 had a defined pancreatic abnormality, compared with 8% in the general population. The difference was statistically significant (P = .007).
Interestingly, the same comparison also revealed a rate of IPMN of 19%, versus 1%, respectively (P less than .001). “BRCA2 mutation carriers have significantly higher incidence of IPMN than the general population,” Dr. Ceppa said.
The study results support a high-risk screening protocol in asymptomatic BRCA patients regardless of family history, he said. In fact, a high-risk screening protocol implemented at his institution in 2013 led to a 14% detection rate of pancreatic cancer among BRCA2-positive patients, compared with a 3% rate in the general population.
“Your most significant finding might be the more IPMN patients – but how do we follow them, and will it be cost effective?” asked invited discussant Matthew J. Weiss, MD, of Johns Hopkins Medicine in Baltimore.
One of the most notable impacts of instituting the high-risk screening protocol has been an increase in patient referrals from other specialists at Dr. Ceppa’s institution. “I’ve looked at every single breast surgeon in our department, and I know how each of them are referring,” he explained.
Following initial screening of BRCA2 mutation patients, Dr. Ceppa repeats screening at 6 months, 1 year, and then annually. “However, some insurers may balk at our recommendations for frequency of screening,” he noted.
Dr. Ceppa and Dr. Weiss had no relevant financial disclosures.
MIAMI BEACH – Although population-wide screening for pancreatic cancer is considered unfeasible and costly, new evidence suggests a benefit to screening a select population: people who test positive for BRCA2 genetic mutations.
Cross-sectional imaging of 117 people with BRCA2 mutations revealed pancreatic abnormalities in 10 patients, including a patient with pancreatic cancer whose only symptom was unexplained weight loss.
Pancreatic cancer is not as common as are some other malignancies, with an incidence estimated between 1% and 3%. However, it is a particularly deadly form of cancer, with only 7.7% of people living to 5 years after diagnosis, according to data from the National Cancer Institute.
A relatively low incidence is a good thing, but it also limits widespread screening. “There is a low predictive value of screening the population at large, and it is not considered cost effective,” said Eugene P. Ceppa, MD, a general surgeon at IU Health University Hospital, Indianapolis. However, patients at high risk for pancreatic adenocarcinoma might be worth targeting for screening, he added.
“This represents a 21% increase in the chance of pancreatic cancer in these patients,” Dr. Ceppa said.
Buoyed by these and other findings, Dr. Ceppa and his colleagues launched a study of their own. “Our hypothesis is that screening all BRCA2s would identify more patients with pancreatic cancer,” he said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
Dr. Ceppa and coinvestigators reviewed electronic medical records at their institution from 2005 to 2015. They identified 204 BRCA mutation carriers, and after excluding 87 BRCA1 positive patients, further assessed the 117 with documented BRCA2 mutations. A total 47 people (40%) of this group had undergone cross-sectional imaging. The images were initially reviewed, and then re-reviewed for the study, by radiologists with specific expertise in pancreatology.
The cross-sectional imaging revealed pancreatic abnormalities in 10 people, including 1 patient with a pancreatic ductal adenocarcinoma located in the head of the pancreas. Another nine patients had intraductal papillary mucinous neoplasms (IPMNs). There were no significant demographic or clinical differences between the groups of patients with and without the imaging abnormalities, Dr. Ceppa said.
The investigators also compared the patients with BRCA2 mutations against a historical cohort representing the general population. They found 21% of patients with BRCA2 had a defined pancreatic abnormality, compared with 8% in the general population. The difference was statistically significant (P = .007).
Interestingly, the same comparison also revealed a rate of IPMN of 19%, versus 1%, respectively (P less than .001). “BRCA2 mutation carriers have significantly higher incidence of IPMN than the general population,” Dr. Ceppa said.
The study results support a high-risk screening protocol in asymptomatic BRCA patients regardless of family history, he said. In fact, a high-risk screening protocol implemented at his institution in 2013 led to a 14% detection rate of pancreatic cancer among BRCA2-positive patients, compared with a 3% rate in the general population.
“Your most significant finding might be the more IPMN patients – but how do we follow them, and will it be cost effective?” asked invited discussant Matthew J. Weiss, MD, of Johns Hopkins Medicine in Baltimore.
One of the most notable impacts of instituting the high-risk screening protocol has been an increase in patient referrals from other specialists at Dr. Ceppa’s institution. “I’ve looked at every single breast surgeon in our department, and I know how each of them are referring,” he explained.
Following initial screening of BRCA2 mutation patients, Dr. Ceppa repeats screening at 6 months, 1 year, and then annually. “However, some insurers may balk at our recommendations for frequency of screening,” he noted.
Dr. Ceppa and Dr. Weiss had no relevant financial disclosures.
MIAMI BEACH – Although population-wide screening for pancreatic cancer is considered unfeasible and costly, new evidence suggests a benefit to screening a select population: people who test positive for BRCA2 genetic mutations.
Cross-sectional imaging of 117 people with BRCA2 mutations revealed pancreatic abnormalities in 10 patients, including a patient with pancreatic cancer whose only symptom was unexplained weight loss.
Pancreatic cancer is not as common as are some other malignancies, with an incidence estimated between 1% and 3%. However, it is a particularly deadly form of cancer, with only 7.7% of people living to 5 years after diagnosis, according to data from the National Cancer Institute.
A relatively low incidence is a good thing, but it also limits widespread screening. “There is a low predictive value of screening the population at large, and it is not considered cost effective,” said Eugene P. Ceppa, MD, a general surgeon at IU Health University Hospital, Indianapolis. However, patients at high risk for pancreatic adenocarcinoma might be worth targeting for screening, he added.
“This represents a 21% increase in the chance of pancreatic cancer in these patients,” Dr. Ceppa said.
Buoyed by these and other findings, Dr. Ceppa and his colleagues launched a study of their own. “Our hypothesis is that screening all BRCA2s would identify more patients with pancreatic cancer,” he said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
Dr. Ceppa and coinvestigators reviewed electronic medical records at their institution from 2005 to 2015. They identified 204 BRCA mutation carriers, and after excluding 87 BRCA1 positive patients, further assessed the 117 with documented BRCA2 mutations. A total 47 people (40%) of this group had undergone cross-sectional imaging. The images were initially reviewed, and then re-reviewed for the study, by radiologists with specific expertise in pancreatology.
The cross-sectional imaging revealed pancreatic abnormalities in 10 people, including 1 patient with a pancreatic ductal adenocarcinoma located in the head of the pancreas. Another nine patients had intraductal papillary mucinous neoplasms (IPMNs). There were no significant demographic or clinical differences between the groups of patients with and without the imaging abnormalities, Dr. Ceppa said.
The investigators also compared the patients with BRCA2 mutations against a historical cohort representing the general population. They found 21% of patients with BRCA2 had a defined pancreatic abnormality, compared with 8% in the general population. The difference was statistically significant (P = .007).
Interestingly, the same comparison also revealed a rate of IPMN of 19%, versus 1%, respectively (P less than .001). “BRCA2 mutation carriers have significantly higher incidence of IPMN than the general population,” Dr. Ceppa said.
The study results support a high-risk screening protocol in asymptomatic BRCA patients regardless of family history, he said. In fact, a high-risk screening protocol implemented at his institution in 2013 led to a 14% detection rate of pancreatic cancer among BRCA2-positive patients, compared with a 3% rate in the general population.
“Your most significant finding might be the more IPMN patients – but how do we follow them, and will it be cost effective?” asked invited discussant Matthew J. Weiss, MD, of Johns Hopkins Medicine in Baltimore.
One of the most notable impacts of instituting the high-risk screening protocol has been an increase in patient referrals from other specialists at Dr. Ceppa’s institution. “I’ve looked at every single breast surgeon in our department, and I know how each of them are referring,” he explained.
Following initial screening of BRCA2 mutation patients, Dr. Ceppa repeats screening at 6 months, 1 year, and then annually. “However, some insurers may balk at our recommendations for frequency of screening,” he noted.
Dr. Ceppa and Dr. Weiss had no relevant financial disclosures.
Key clinical point: Although general population screening for pancreatic cancer is considered costly, with a low predictive value, targeting screening to patients with BRCA2 mutations could detect more cases of this deadly disease.
Major finding: People with BRCA2 mutations had a significantly greater incidence of intraductal papillary mucinous neoplasms, 19%, versus 1% in the general population (P less than .001).
Data source: Retrospective study of electronic medical records of 117 patients with BRCA2 mutations at a single academic institution.
Disclosures: Dr. Ceppa and Dr. Weiss had no relevant financial disclosures.