S P E C I A L C a s e
F E A T U R E
R e p o r t
Percutaneous Autologous Pancreatic Islet Cell Transplantation for Traumatic Pancreatic Injury Avnesh S. Thakor, Bippan S. Sangha, Stephen G. F. Ho, Garth L. Warnock, Mark Meloche, and David M. Liu Department of Radiology (A.S.T., B.S.S., S.G.F.H., D.M.L.) and Department of Surgery (G.L.W., M.M.), University of British Columbia, Vancouver, British Columbia V5Z 4E3, Canada
Context: Traumatic pancreatic injury with pancreatic duct disruption is surgically managed with at least a partial pancreatectomy, often leading to poor blood glucose control and the subsequent development of diabetes mellitus. Autologous -islet cell transplantation may therefore help to preserve pancreatic endocrine function. Case Description: We describe 3 patients with pancreatic duct disruption from traumatic pancreatic injury who were treated with a partial pancreatectomy followed by autologous -islet cell transplantation via a percutaneous transhepatic approach. Immediately after trauma, 2 of the 3 patients had difficulty with glucose control that resolved after autologous -islet cell transplantation. At follow-up, all patients remained normoglycemic. Conclusion: In patients requiring partial pancreatectomy after pancreatic trauma, percutaneous transhepatic autologous -islet cell transplantation should be considered to minimize the risk of development of diabetes mellitus. (J Clin Endocrinol Metab 100: 1230 –1233, 2015)
T
raumatic pancreatic injury is uncommon, accounting for approximately 4% of patients with abdominal injury (1). The extent of pancreatic injury is best characterized using computed tomography (CT) with ductal injury best assessed with endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography. For severe injuries with disruption of the main pancreatic ducts, surgical resection is often indicated to reduce the mortality from pancreatic enzyme leakage (2). Although the effect of partial or complete pancreatectomy has not been specifically investigated in the context of trauma, the effect of partial pancreatectomy for other indications (ie, malignancy and chronic pancreatitis) has shown that up to 36% of patients develop newonset pancreatogenic diabetes within 8 months (3). The aim of both allogenic and autologous -islet cell transplantation is for patients to regulate blood glucose levels, if possible, without the need for insulin or other medications. Because -islet cells possess their own glu-
cose sensor, produce insulin, and release insulin in response to glucose, they can maintain normoglycemia if successfully transplanted (4). However, allogenic transplantation of -islet cells requires patients to receive lifelong immunosuppression. In contrast, in autologous transplantation, -islet cells are harvested from native pancreatic tissue at the time of partial or complete pancreatectomy and then readministered back to the same patient; thus, these patients avoid lifelong immunosuppression (5). The current indications for autologous -islet cell transplantation include complete or partial pancreatectomy for either malignancy or chronic pancreatitis with intractable abdominal pain (6, 7). However, pancreatic trauma requiring pancreatectomy is another indication that is not well recognized. Our experience highlights the success of using a minimally invasive percutaneous approach for autologous pancreatic -islet cell transplantation in patients requiring pancreatectomy for severe traumatic pancreatic injury.
ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2015 by the Endocrine Society Received November 20, 2014. Accepted December 24, 2014. First Published Online January 15, 2015
Abbreviations: CT, computed tomography.
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J Clin Endocrinol Metab, April 2015, 100(4):1230 –1233
doi: 10.1210/jc.2014-4165
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Materials and Methods -Islet cell harvesting and purification After complex pancreatic injury, each patient in this series underwent a partial pancreatectomy to remove damaged pancreatic parenchyma while preserving as much remnant pancreatic tissue as possible. At the time of pancreatectomy, the resected pancreatic tissue was harvested and -islet cells were isolated as described previously (8). None of the patients had active bleeding at the time of islet cell transplantation.
-Islet cell transplantation Under ultrasound guidance, a left portal vein branch was percutaneously accessed with a 15-cm 21-gauge needle, and an 0.018-inch wire was advanced into the portal venous system. A 4-French 25-cm stiffened micropuncture sheath (Cook Medical) was advanced over the wire to establish access. A bolus of 2000 IU of heparin was then administered to the patient to reduce the risk of portal venous thrombosis. Using a 0.035-inch stiff Terumo wire (Terumo Systems) and 5-French DAV catheter (Cook Medical), the main portal vein was cannulated. A portal venogram was performed to confirm main portal and branch vein patency. From the origin of the main portal vein, -islet cells were then transfused over 15 minutes. Portal venous pressures were measured at baseline, during, and after islet cell infusion. On completion of -islet cell transplantation, the catheter was removed, and the tract within the liver parenchyma was embolized with cyanoacrylate glue mixed with lipiodol in a 2:1 ratio to reduce the bleeding risk from the access site. Doppler ultrasonography of the portal vein and liver was performed the next day. From June 3, 2007, to September 30, 2014, 3 patients at our institution underwent autologous percutaneous pancreatic islet cell transplantation via a transhepatic route. The medical records and imaging of these patients were retrospectively reviewed after ethics approval. Time of injury, severity of pancreatic injury, associated injuries, time to surgical management, and time to percutaneous autologous pancreatic islet cell transplantation were collected. Longer term follow-up data were collected where available. All patients had no significant past medial history, and there was no increase in portal venous pressures before, during, or after transplantation. No significant complications were seen from the transplantation procedure.
Figure 1. A, Axial CT scan demonstrates a low attenuation transection through the body of the pancreas (black star). Free fluid in the anterior paranephric space is present. B, Endoscopic retrograde cholangiopancreatography reveals transection of the pancreatic duct (black star).
Case Reports Case 1 An 18-year-old man was stabbed in the abdomen, resulting in transection of the pancreatic body with contusions of the pancreatic tail (Figure 1, A and B). A partial pancreatectomy was performed 232 hours after the injury with 325 000 -islets harvested; 82 hours later, 255 000 purified -islets were transplanted back into the patient. Before pancreatectomy, the patient was normoglycemic with a mean random blood glucose concentration of 6.6 mmol/L (SD, 0.9 mmol/L). After surgical partial pancreatectomy, the patient became hyperglycemic and exhibited difficulties in controlling his random blood glucose concentrations, despite insulin treatment, with a mean value of 12.5 mmol/L (SD, 1.8 mmol/L). After -islet cell transplantation, the patient no longer required insulin and had a random mean blood glucose concentration of 6.1
mmol/L (SD, 1.0 mmol/L). Two months after -islet cell transplantation, the patient remained normoglycemic with a random blood glucose concentration of 5.4 mmol/L. At 6 years followup, the patient was not taking any antidiabetic medication.
Case 2 An 18-year-old man was hit by a train, resulting in multiple injuries including pancreatic transaction (Figure 2, A–C). A partial pancreatectomy was performed 150 hours after the trauma with 262 000 -islets harvested; 41 hours later, 262 000 purified -islets were transplanted back into the patient. Before pancreatectomy, the patient was normoglycemic with a mean random blood glucose concentration of 5.8 mmol/L (SD, 1.6 mmol/L). After pancreatectomy, the patient remained normoglycemic with a mean random blood glucose concentration of
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1232
Thakor et al
Autologous Islet Transplant for Pancreatic Injury
J Clin Endocrinol Metab, April 2015, 100(4):1230 –1233
Discussion
Figure 2. A, Axial CT scan demonstrates linear low attenuation at the pancreatic neck region (black star) in keeping with pancreatic laceration/transection. Peripancreatic and perihepatic free fluid is present. An area of low attenuation in the left renal cortex (white star) and surrounding perinephric fluid and stranding is in keeping with renal injury. B, Axial T2-weighted image demonstrates linear high signal (white star) at the pancreatic head-neck region in keeping with pancreatic laceration/transection. Peripancreatic and perihepatic free fluid is present. C, Coronal magnetic resonance cholangiopancreatography demonstrates a curvilinear fluid signal in the region of the pancreatic head (white arrowhead) corresponding to the common bile duct. The pancreatic duct is not visualized in its expected location (white star).
6.1 mmol/L (SD, 1.0 mmol/L). After islet cell transplantation the blood glucose levels remained within normal limits with a random mean concentration of 5.9 mmol/L (SD, 1.1 mmol/L). At no point did the patient require treatment with insulin. At 32 months follow-up, the patient remained normoglycemic with a random blood glucose concentration of 6.3 mmol/L and did not require any antidiabetic medication.
Case 3 A 25-year-old woman experienced blunt abdominal trauma after a skiing accident with transection of the pancreatic body. Partial pancreatectomy of the body and tail of the pancreas was performed 70 hours later with 260 000 -islets harvested; 43 hours later, 260 000 purified -islets were transplanted back into the patient. Before pancreatectomy, the patient was normoglycemic with a mean random blood glucose concentration of 6.2 mmol/L (SD, 0.7 mmol/L). After pancreatectomy and before islet cell transplantation, her mean random blood glucose level increased to 7.8 mmol/L (SD, 1.9 mmol/L). However, after pancreatectomy and -islet cell transplantation, the patient developed a significant ileus during the postoperative period requiring total parenteral nutrition, which elevated her blood glucose levels such that treatment with insulin was required (mean, 8.6 mmol/L; SD, 3.4 mmol/L). Once an oral diet was established and the total parenteral nutrition was stopped, no further treatment with insulin was required, and her random blood glucose levels were all within normal limits with a mean concentration of 5.8 mmol/L (SD, 1.1 mmol/L). At 2 years follow-up, the patient was not taking any antidiabetic medication.
No study has examined the incidence of pancreatogenic diabetes after pancreatectomy in the setting of trauma. However, pancreatogenic (type 3c) diabetes accounts for up to 10% of the diabetic population in Western countries, with 2% to 3% of patients having undergone surgical pancreatectomy (3, 9, 10). The incidence of newonset pancreatogenic diabetes in nondiabetic patients after partial pancreatectomy has been reported to be as high as 36% with patients who did not develop pancreatogenic diabetes after distal pancreatectomy still having impaired glucose metabolism (3). The goal of islet cell autotransplantation is to salvage as many -islet cells as possible such that endogenous insulin secretion is preserved, thereby preventing or minimizing the magnitude and severity of surgical diabetes. Although pancreatic injury reduces the overall yield of -islet cells (11), autologous islet cell transplantation has durable function and extended insulin-independence rates. This phenomenon is probably due to adverse factors associated with allogenic transplantation including cytokine storms, longer cold ischemia time, donor matching, detrimental side effects from diabetogenic immunosuppression (including poor graft neovascularization) and auto-/alloimmunogenicity (4). In some cases, there can be a delay between the time of islet cell harvesting at pancreatectomy and percutaneous autotransplantation because of the critical clinical status of trauma patients with pancreatic injury and the logistics of trying to coordinate all teams involved in the islet cell transplantation (ie, trauma surgery, hepatobiliary surgery, islet cell team, and interventional radiology). In both Table 1. Clinical Data From Each Patient During Their Hospital Admission
Time from trauma to islet extraction, h Time from extraction to transplant, h Days of hospitalization Pretransplant ALT, U/L Posttransplant day 1 ALT, U/L Posttransplant day 7 ALT, U/L Pretransplant AST, U/L Posttransplant day 1 AST, U/L Posttransplant day 7 AST, U/L
Patient 1
Patient 2
Patient 3
232
150
70
82
41
43
26 26 xa
32 158 336
23 72 37
49
151
46
22 xa
889 1280
39 53
16
163
35
Abbreviations: ALT, alanine aminotransferase (normal range, 5–50 U/L); AST, aspartate aminotransferase (normal range, 4 – 40 U/L). a
Not available, as not performed as routine part of care.
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doi: 10.1210/jc.2014-4165
patients who had islets administered at 41 and 43 hours after harvesting, islet cell recovery was 100%; however, in the patient in whom there was an 82-hour delay, the recovery was only 78%. We therefore advocate for the shortest possible delay between islet cell harvesting and autotransplantation. In this case series, portal venous pressures measured during each islet cell transplantation were always within normal limits. Furthermore, no significant postprocedural complication was detected in any patient, and portal venous patency was confirmed on follow-up ultrasound. None of the patients demonstrated any evidence of pancreatogenic diabetes after their autologous transplant, and all patients were free from any antiglycemic medication, thereby demonstrating the potential utility of this technique in patients with complex pancreatic injuries.
Acknowledgments Address all correspondence and requests for reprints to: David Liu, MD, Clinical Associate Professor, Department of Radiology, Division of Interventional Radiology, Vancouver General Hospital, University of British Columbia, 3350-950 West 10th Avenue, Vancouver, BC V5Z 4E3, Canada. E-mail: david.liu@ vch.ca. Disclosure Summary: The authors have nothing to disclose.
jcem.endojournals.org
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References 1. Lahiri R, Bhattacharya S. Pancreatic trauma. Ann R Coll Surg Engl. 2013;95:241–245. 2. Degiannis E, Levy RD, Velmahos GC, Potokar T, Florizoone MG, Saadia R. Gunshot injuries of the head of the pancreas: conservative approach. World J Surg. 1996;20:68 –71; discussion 72. 3. Shirakawa S, Matsumoto I, Toyama H, et al. Pancreatic volumetric assessment as a predictor of new-onset diabetes following distal pancreatectomy. J Gastrointest Surg. 2012;16:2212–2219. 4. Matsumoto S. Islet cell transplantation for type 1 diabetes. J Diabetes. 2010;2:16 –22. 5. Matsumoto S. Clinical allogeneic and autologous islet cell transplantation: update. Diabetes Metab J. 2011;35:199 –206. 6. Sutherland DE, Gruessner AC, Carlson AM, et al. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation. 2008;86:1799 –1802. 7. Sutherland DE, Radosevich DM, Bellin MD, et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg. 2012;214:409 – 424; discussion 424 – 426. 8. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230 –238. 9. Ewald N, Kaufmann C, Raspe A, Kloer HU, Bretzel RG, Hardt PD. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c). Diabetes Metab Res Rev. 2012;28:338 –342. 10. Cui Y, Andersen DK. Pancreatogenic diabetes: special considerations for management. Pancreatology. 2011;11:279 –294. 11. Andres A, Kin T, O’Gorman D, et al. Impact of adverse pancreatic injury at surgical procurement upon islet isolation outcome. Transplant Int. 2014;27:1135–1142.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 20 May 2015. at 04:20 For personal use only. No other uses without permission. . All rights reserved.
F E A T U R E
R e p o r t
Percutaneous Autologous Pancreatic Islet Cell Transplantation for Traumatic Pancreatic Injury Avnesh S. Thakor, Bippan S. Sangha, Stephen G. F. Ho, Garth L. Warnock, Mark Meloche, and David M. Liu Department of Radiology (A.S.T., B.S.S., S.G.F.H., D.M.L.) and Department of Surgery (G.L.W., M.M.), University of British Columbia, Vancouver, British Columbia V5Z 4E3, Canada
Context: Traumatic pancreatic injury with pancreatic duct disruption is surgically managed with at least a partial pancreatectomy, often leading to poor blood glucose control and the subsequent development of diabetes mellitus. Autologous -islet cell transplantation may therefore help to preserve pancreatic endocrine function. Case Description: We describe 3 patients with pancreatic duct disruption from traumatic pancreatic injury who were treated with a partial pancreatectomy followed by autologous -islet cell transplantation via a percutaneous transhepatic approach. Immediately after trauma, 2 of the 3 patients had difficulty with glucose control that resolved after autologous -islet cell transplantation. At follow-up, all patients remained normoglycemic. Conclusion: In patients requiring partial pancreatectomy after pancreatic trauma, percutaneous transhepatic autologous -islet cell transplantation should be considered to minimize the risk of development of diabetes mellitus. (J Clin Endocrinol Metab 100: 1230 –1233, 2015)
T
raumatic pancreatic injury is uncommon, accounting for approximately 4% of patients with abdominal injury (1). The extent of pancreatic injury is best characterized using computed tomography (CT) with ductal injury best assessed with endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography. For severe injuries with disruption of the main pancreatic ducts, surgical resection is often indicated to reduce the mortality from pancreatic enzyme leakage (2). Although the effect of partial or complete pancreatectomy has not been specifically investigated in the context of trauma, the effect of partial pancreatectomy for other indications (ie, malignancy and chronic pancreatitis) has shown that up to 36% of patients develop newonset pancreatogenic diabetes within 8 months (3). The aim of both allogenic and autologous -islet cell transplantation is for patients to regulate blood glucose levels, if possible, without the need for insulin or other medications. Because -islet cells possess their own glu-
cose sensor, produce insulin, and release insulin in response to glucose, they can maintain normoglycemia if successfully transplanted (4). However, allogenic transplantation of -islet cells requires patients to receive lifelong immunosuppression. In contrast, in autologous transplantation, -islet cells are harvested from native pancreatic tissue at the time of partial or complete pancreatectomy and then readministered back to the same patient; thus, these patients avoid lifelong immunosuppression (5). The current indications for autologous -islet cell transplantation include complete or partial pancreatectomy for either malignancy or chronic pancreatitis with intractable abdominal pain (6, 7). However, pancreatic trauma requiring pancreatectomy is another indication that is not well recognized. Our experience highlights the success of using a minimally invasive percutaneous approach for autologous pancreatic -islet cell transplantation in patients requiring pancreatectomy for severe traumatic pancreatic injury.
ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2015 by the Endocrine Society Received November 20, 2014. Accepted December 24, 2014. First Published Online January 15, 2015
Abbreviations: CT, computed tomography.
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J Clin Endocrinol Metab, April 2015, 100(4):1230 –1233
doi: 10.1210/jc.2014-4165
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doi: 10.1210/jc.2014-4165
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Materials and Methods -Islet cell harvesting and purification After complex pancreatic injury, each patient in this series underwent a partial pancreatectomy to remove damaged pancreatic parenchyma while preserving as much remnant pancreatic tissue as possible. At the time of pancreatectomy, the resected pancreatic tissue was harvested and -islet cells were isolated as described previously (8). None of the patients had active bleeding at the time of islet cell transplantation.
-Islet cell transplantation Under ultrasound guidance, a left portal vein branch was percutaneously accessed with a 15-cm 21-gauge needle, and an 0.018-inch wire was advanced into the portal venous system. A 4-French 25-cm stiffened micropuncture sheath (Cook Medical) was advanced over the wire to establish access. A bolus of 2000 IU of heparin was then administered to the patient to reduce the risk of portal venous thrombosis. Using a 0.035-inch stiff Terumo wire (Terumo Systems) and 5-French DAV catheter (Cook Medical), the main portal vein was cannulated. A portal venogram was performed to confirm main portal and branch vein patency. From the origin of the main portal vein, -islet cells were then transfused over 15 minutes. Portal venous pressures were measured at baseline, during, and after islet cell infusion. On completion of -islet cell transplantation, the catheter was removed, and the tract within the liver parenchyma was embolized with cyanoacrylate glue mixed with lipiodol in a 2:1 ratio to reduce the bleeding risk from the access site. Doppler ultrasonography of the portal vein and liver was performed the next day. From June 3, 2007, to September 30, 2014, 3 patients at our institution underwent autologous percutaneous pancreatic islet cell transplantation via a transhepatic route. The medical records and imaging of these patients were retrospectively reviewed after ethics approval. Time of injury, severity of pancreatic injury, associated injuries, time to surgical management, and time to percutaneous autologous pancreatic islet cell transplantation were collected. Longer term follow-up data were collected where available. All patients had no significant past medial history, and there was no increase in portal venous pressures before, during, or after transplantation. No significant complications were seen from the transplantation procedure.
Figure 1. A, Axial CT scan demonstrates a low attenuation transection through the body of the pancreas (black star). Free fluid in the anterior paranephric space is present. B, Endoscopic retrograde cholangiopancreatography reveals transection of the pancreatic duct (black star).
Case Reports Case 1 An 18-year-old man was stabbed in the abdomen, resulting in transection of the pancreatic body with contusions of the pancreatic tail (Figure 1, A and B). A partial pancreatectomy was performed 232 hours after the injury with 325 000 -islets harvested; 82 hours later, 255 000 purified -islets were transplanted back into the patient. Before pancreatectomy, the patient was normoglycemic with a mean random blood glucose concentration of 6.6 mmol/L (SD, 0.9 mmol/L). After surgical partial pancreatectomy, the patient became hyperglycemic and exhibited difficulties in controlling his random blood glucose concentrations, despite insulin treatment, with a mean value of 12.5 mmol/L (SD, 1.8 mmol/L). After -islet cell transplantation, the patient no longer required insulin and had a random mean blood glucose concentration of 6.1
mmol/L (SD, 1.0 mmol/L). Two months after -islet cell transplantation, the patient remained normoglycemic with a random blood glucose concentration of 5.4 mmol/L. At 6 years followup, the patient was not taking any antidiabetic medication.
Case 2 An 18-year-old man was hit by a train, resulting in multiple injuries including pancreatic transaction (Figure 2, A–C). A partial pancreatectomy was performed 150 hours after the trauma with 262 000 -islets harvested; 41 hours later, 262 000 purified -islets were transplanted back into the patient. Before pancreatectomy, the patient was normoglycemic with a mean random blood glucose concentration of 5.8 mmol/L (SD, 1.6 mmol/L). After pancreatectomy, the patient remained normoglycemic with a mean random blood glucose concentration of
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 20 May 2015. at 04:20 For personal use only. No other uses without permission. . All rights reserved.
1232
Thakor et al
Autologous Islet Transplant for Pancreatic Injury
J Clin Endocrinol Metab, April 2015, 100(4):1230 –1233
Discussion
Figure 2. A, Axial CT scan demonstrates linear low attenuation at the pancreatic neck region (black star) in keeping with pancreatic laceration/transection. Peripancreatic and perihepatic free fluid is present. An area of low attenuation in the left renal cortex (white star) and surrounding perinephric fluid and stranding is in keeping with renal injury. B, Axial T2-weighted image demonstrates linear high signal (white star) at the pancreatic head-neck region in keeping with pancreatic laceration/transection. Peripancreatic and perihepatic free fluid is present. C, Coronal magnetic resonance cholangiopancreatography demonstrates a curvilinear fluid signal in the region of the pancreatic head (white arrowhead) corresponding to the common bile duct. The pancreatic duct is not visualized in its expected location (white star).
6.1 mmol/L (SD, 1.0 mmol/L). After islet cell transplantation the blood glucose levels remained within normal limits with a random mean concentration of 5.9 mmol/L (SD, 1.1 mmol/L). At no point did the patient require treatment with insulin. At 32 months follow-up, the patient remained normoglycemic with a random blood glucose concentration of 6.3 mmol/L and did not require any antidiabetic medication.
Case 3 A 25-year-old woman experienced blunt abdominal trauma after a skiing accident with transection of the pancreatic body. Partial pancreatectomy of the body and tail of the pancreas was performed 70 hours later with 260 000 -islets harvested; 43 hours later, 260 000 purified -islets were transplanted back into the patient. Before pancreatectomy, the patient was normoglycemic with a mean random blood glucose concentration of 6.2 mmol/L (SD, 0.7 mmol/L). After pancreatectomy and before islet cell transplantation, her mean random blood glucose level increased to 7.8 mmol/L (SD, 1.9 mmol/L). However, after pancreatectomy and -islet cell transplantation, the patient developed a significant ileus during the postoperative period requiring total parenteral nutrition, which elevated her blood glucose levels such that treatment with insulin was required (mean, 8.6 mmol/L; SD, 3.4 mmol/L). Once an oral diet was established and the total parenteral nutrition was stopped, no further treatment with insulin was required, and her random blood glucose levels were all within normal limits with a mean concentration of 5.8 mmol/L (SD, 1.1 mmol/L). At 2 years follow-up, the patient was not taking any antidiabetic medication.
No study has examined the incidence of pancreatogenic diabetes after pancreatectomy in the setting of trauma. However, pancreatogenic (type 3c) diabetes accounts for up to 10% of the diabetic population in Western countries, with 2% to 3% of patients having undergone surgical pancreatectomy (3, 9, 10). The incidence of newonset pancreatogenic diabetes in nondiabetic patients after partial pancreatectomy has been reported to be as high as 36% with patients who did not develop pancreatogenic diabetes after distal pancreatectomy still having impaired glucose metabolism (3). The goal of islet cell autotransplantation is to salvage as many -islet cells as possible such that endogenous insulin secretion is preserved, thereby preventing or minimizing the magnitude and severity of surgical diabetes. Although pancreatic injury reduces the overall yield of -islet cells (11), autologous islet cell transplantation has durable function and extended insulin-independence rates. This phenomenon is probably due to adverse factors associated with allogenic transplantation including cytokine storms, longer cold ischemia time, donor matching, detrimental side effects from diabetogenic immunosuppression (including poor graft neovascularization) and auto-/alloimmunogenicity (4). In some cases, there can be a delay between the time of islet cell harvesting at pancreatectomy and percutaneous autotransplantation because of the critical clinical status of trauma patients with pancreatic injury and the logistics of trying to coordinate all teams involved in the islet cell transplantation (ie, trauma surgery, hepatobiliary surgery, islet cell team, and interventional radiology). In both Table 1. Clinical Data From Each Patient During Their Hospital Admission
Time from trauma to islet extraction, h Time from extraction to transplant, h Days of hospitalization Pretransplant ALT, U/L Posttransplant day 1 ALT, U/L Posttransplant day 7 ALT, U/L Pretransplant AST, U/L Posttransplant day 1 AST, U/L Posttransplant day 7 AST, U/L
Patient 1
Patient 2
Patient 3
232
150
70
82
41
43
26 26 xa
32 158 336
23 72 37
49
151
46
22 xa
889 1280
39 53
16
163
35
Abbreviations: ALT, alanine aminotransferase (normal range, 5–50 U/L); AST, aspartate aminotransferase (normal range, 4 – 40 U/L). a
Not available, as not performed as routine part of care.
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doi: 10.1210/jc.2014-4165
patients who had islets administered at 41 and 43 hours after harvesting, islet cell recovery was 100%; however, in the patient in whom there was an 82-hour delay, the recovery was only 78%. We therefore advocate for the shortest possible delay between islet cell harvesting and autotransplantation. In this case series, portal venous pressures measured during each islet cell transplantation were always within normal limits. Furthermore, no significant postprocedural complication was detected in any patient, and portal venous patency was confirmed on follow-up ultrasound. None of the patients demonstrated any evidence of pancreatogenic diabetes after their autologous transplant, and all patients were free from any antiglycemic medication, thereby demonstrating the potential utility of this technique in patients with complex pancreatic injuries.
Acknowledgments Address all correspondence and requests for reprints to: David Liu, MD, Clinical Associate Professor, Department of Radiology, Division of Interventional Radiology, Vancouver General Hospital, University of British Columbia, 3350-950 West 10th Avenue, Vancouver, BC V5Z 4E3, Canada. E-mail: david.liu@ vch.ca. Disclosure Summary: The authors have nothing to disclose.
jcem.endojournals.org
1233
References 1. Lahiri R, Bhattacharya S. Pancreatic trauma. Ann R Coll Surg Engl. 2013;95:241–245. 2. Degiannis E, Levy RD, Velmahos GC, Potokar T, Florizoone MG, Saadia R. Gunshot injuries of the head of the pancreas: conservative approach. World J Surg. 1996;20:68 –71; discussion 72. 3. Shirakawa S, Matsumoto I, Toyama H, et al. Pancreatic volumetric assessment as a predictor of new-onset diabetes following distal pancreatectomy. J Gastrointest Surg. 2012;16:2212–2219. 4. Matsumoto S. Islet cell transplantation for type 1 diabetes. J Diabetes. 2010;2:16 –22. 5. Matsumoto S. Clinical allogeneic and autologous islet cell transplantation: update. Diabetes Metab J. 2011;35:199 –206. 6. Sutherland DE, Gruessner AC, Carlson AM, et al. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation. 2008;86:1799 –1802. 7. Sutherland DE, Radosevich DM, Bellin MD, et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg. 2012;214:409 – 424; discussion 424 – 426. 8. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230 –238. 9. Ewald N, Kaufmann C, Raspe A, Kloer HU, Bretzel RG, Hardt PD. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c). Diabetes Metab Res Rev. 2012;28:338 –342. 10. Cui Y, Andersen DK. Pancreatogenic diabetes: special considerations for management. Pancreatology. 2011;11:279 –294. 11. Andres A, Kin T, O’Gorman D, et al. Impact of adverse pancreatic injury at surgical procurement upon islet isolation outcome. Transplant Int. 2014;27:1135–1142.
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