COMMENTARY ON TECHNIQUE/CASE REPORT Commentary on “Better Survival But Changing Causes of Death in Patients With Multiple Endocrine Neoplasia Type 1”
M
ultiple endocrine neoplasia type 1 (MEN-1) is a rare genetic cancer syndrome that requires experience and judgment to balance the risks of disease against the effects of treatment. Over the last 3 decades, no management team has accumulated more experience, nor contributed more to our understanding of this syndrome, than Drs Jeffrey Norton and Robert Jensen. They have carefully studied their patients, and catalogued that experience through more than 5 dozen articles on MEN-1 over 30 years, beginning as colleagues at the National Institutes of Health (where Dr Jensen continues to study these diseases as a gastroenterologist in NIDDK), and continuing a transcontinental collaboration as Dr Norton moved successively to Washington University, UCSF, and now Stanford. Their partnership is a model for consistent interdisciplinary collaboration, each contributing their own expertise to the project while also understanding much of the other’s perspective. When Drs Norton and Jensen address us about MEN-1, we should all listen. This current contribution is predictably nuanced, and brings us up-to-date with their thinking about MEN-1 management.1 Now that the endocrinologic causes of death are rare due to modern management of hyperparathyroidism and peptic ulcer disease, the MEN-1 management focus is on the prevention or delay of death from malignancy. MEN1 is more complex to manage than some other
genetic solid tumor syndromes because we do not have the option for risk reduction through prophylactic surgery. By comparison, MEN-2 (prophylactic thyroidectomy), FAP (prophylactic colectomy), and other syndromes that have a higher penetrance of life-threatening disease can be effectively managed by removal of the target organ without intolerable life changes. The most commonly performed operation to try to prevent or delay death from pancreatic neuroendocrine tumor (pNET) in MEN-1 is to remove all of the demonstrable tumors from the pancreas and duodenum while preserving some pancreatic parenchyma for endocrine function. Though the approach may be customized for various tumor patterns, this is most commonly expressed as a distal pancreatectomy with enucleation of tumors in the proximal pancreas or duodenum. The controversy of the last 2 decades has been to define the timing of this operation. In this update, Drs Norton and Jensen reiterate their evidence and support for intervening when the largest tumor is 2 cm or larger. Given the indolent nature of the disease in many people, and the potential for complicated recovery from the procedure, this is a reasonable trigger for intervention. As new imaging techniques have become available since the early 1980s, this group has investigated each one carefully, and their current recommendation including Ga-DOTATOCPET/CT scan is the best current option for identifying occult metastases. This general strategy—to “reset the clock” on the multiple sites of developing pNET by operation— seems to delay but not completely eliminate, recurrences, reoperations, and deaths from pNET.2 As they have discussed, a currently unresolved issue in MEN-1 patients is the detection and management of thymic NET. These tumors are often aggressive and rarely treatable with good outcome. The removal
of the thymus during parathyroidectomy has been touted as potentially having some effect to decrease the occurrence of these tumors but the data are limited.3,4 The experience in myasthenia gravis suggests that transcervical thymectomy during parathyroidectomy is unlikely to be a complete thymectomy that would best reduce the thymic NET risk. This may be an area for future study or intervention, as, in contrast with the pancreas, complete prophylactic removal of the thymus would not be expected to affect the patient’s quality or duration of remaining life. Drs Norton and Jensen have provided us with a wonderful example of collaborative study, and the value that building and disseminating clinical expertise bring to the rest of the medical community. I am certain that we will learn more from them in the future, as one of their assets has been to never conclude that they have finally reached full understanding of this complex syndrome. Gerard M. Doherty, MD Department of Surgery Boston University Boston, MA E-mail: [email protected]
REFERENCES 1. Norton JA, Krampitz G, Zemek A, et al. Better survival but changing causes of death in patients with MEN-1. Ann Surg. 2015;261;e147–e148. 2. Gauger PG, Doherty GM, Broome JT, et al. Completion pancreatectomy and duodenectomy for recurrent MEN-1 pancreaticoduodenal endocrine neoplasms. Surgery. 2009;146:801–806; discussion 807–808. 3. Powell AC, Alexander HR, Pingpank JF, et al. The utility of routine transcervical thymectomy for multiple endocrine neoplasia 1-related hyperparathyroidism. Surgery. 2008;144:878–883; discussion 883–884. 4. Waldmann J, Lopez CL, Langer P, et al. Surgery for multiple endocrine neoplasia type 1associated primary hyperparathyroidism. Br J Surg. 2010;97:1528–1534.
Disclosure: The author declares no conflict of interest. C 2015 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/15/26106-e0149 DOI: 10.1097/SLA.0000000000001166
Annals of Surgery r Volume 261, Number 6, June 2015
www.annalsofsurgery.com | e149
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
M
ultiple endocrine neoplasia type 1 (MEN-1) is a rare genetic cancer syndrome that requires experience and judgment to balance the risks of disease against the effects of treatment. Over the last 3 decades, no management team has accumulated more experience, nor contributed more to our understanding of this syndrome, than Drs Jeffrey Norton and Robert Jensen. They have carefully studied their patients, and catalogued that experience through more than 5 dozen articles on MEN-1 over 30 years, beginning as colleagues at the National Institutes of Health (where Dr Jensen continues to study these diseases as a gastroenterologist in NIDDK), and continuing a transcontinental collaboration as Dr Norton moved successively to Washington University, UCSF, and now Stanford. Their partnership is a model for consistent interdisciplinary collaboration, each contributing their own expertise to the project while also understanding much of the other’s perspective. When Drs Norton and Jensen address us about MEN-1, we should all listen. This current contribution is predictably nuanced, and brings us up-to-date with their thinking about MEN-1 management.1 Now that the endocrinologic causes of death are rare due to modern management of hyperparathyroidism and peptic ulcer disease, the MEN-1 management focus is on the prevention or delay of death from malignancy. MEN1 is more complex to manage than some other
genetic solid tumor syndromes because we do not have the option for risk reduction through prophylactic surgery. By comparison, MEN-2 (prophylactic thyroidectomy), FAP (prophylactic colectomy), and other syndromes that have a higher penetrance of life-threatening disease can be effectively managed by removal of the target organ without intolerable life changes. The most commonly performed operation to try to prevent or delay death from pancreatic neuroendocrine tumor (pNET) in MEN-1 is to remove all of the demonstrable tumors from the pancreas and duodenum while preserving some pancreatic parenchyma for endocrine function. Though the approach may be customized for various tumor patterns, this is most commonly expressed as a distal pancreatectomy with enucleation of tumors in the proximal pancreas or duodenum. The controversy of the last 2 decades has been to define the timing of this operation. In this update, Drs Norton and Jensen reiterate their evidence and support for intervening when the largest tumor is 2 cm or larger. Given the indolent nature of the disease in many people, and the potential for complicated recovery from the procedure, this is a reasonable trigger for intervention. As new imaging techniques have become available since the early 1980s, this group has investigated each one carefully, and their current recommendation including Ga-DOTATOCPET/CT scan is the best current option for identifying occult metastases. This general strategy—to “reset the clock” on the multiple sites of developing pNET by operation— seems to delay but not completely eliminate, recurrences, reoperations, and deaths from pNET.2 As they have discussed, a currently unresolved issue in MEN-1 patients is the detection and management of thymic NET. These tumors are often aggressive and rarely treatable with good outcome. The removal
of the thymus during parathyroidectomy has been touted as potentially having some effect to decrease the occurrence of these tumors but the data are limited.3,4 The experience in myasthenia gravis suggests that transcervical thymectomy during parathyroidectomy is unlikely to be a complete thymectomy that would best reduce the thymic NET risk. This may be an area for future study or intervention, as, in contrast with the pancreas, complete prophylactic removal of the thymus would not be expected to affect the patient’s quality or duration of remaining life. Drs Norton and Jensen have provided us with a wonderful example of collaborative study, and the value that building and disseminating clinical expertise bring to the rest of the medical community. I am certain that we will learn more from them in the future, as one of their assets has been to never conclude that they have finally reached full understanding of this complex syndrome. Gerard M. Doherty, MD Department of Surgery Boston University Boston, MA E-mail: [email protected]
REFERENCES 1. Norton JA, Krampitz G, Zemek A, et al. Better survival but changing causes of death in patients with MEN-1. Ann Surg. 2015;261;e147–e148. 2. Gauger PG, Doherty GM, Broome JT, et al. Completion pancreatectomy and duodenectomy for recurrent MEN-1 pancreaticoduodenal endocrine neoplasms. Surgery. 2009;146:801–806; discussion 807–808. 3. Powell AC, Alexander HR, Pingpank JF, et al. The utility of routine transcervical thymectomy for multiple endocrine neoplasia 1-related hyperparathyroidism. Surgery. 2008;144:878–883; discussion 883–884. 4. Waldmann J, Lopez CL, Langer P, et al. Surgery for multiple endocrine neoplasia type 1associated primary hyperparathyroidism. Br J Surg. 2010;97:1528–1534.
Disclosure: The author declares no conflict of interest. C 2015 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/15/26106-e0149 DOI: 10.1097/SLA.0000000000001166
Annals of Surgery r Volume 261, Number 6, June 2015
www.annalsofsurgery.com | e149
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
