- Email: [email protected]
Endovascular Stenting of Portal Vein for Graft Rescue after a Pancreas Transplant Venous Graft Thrombosis: A Case Report
Accepted Manuscript Endovascular Stenting of Portal Vein for Graft Rescue after a Pancreas Transplant Venous Graft Thrombosis: A Case Report Ossama M. Reslan, MD, Jordan M. Kirsch, DO, Hitesh Kaul, MD, Stalin Campos, MD, Radi Zaki, MD, Paul S. Brady, MD, Kamran Khanmoradi, MD PII:
S0890-5096(17)30438-7
DOI:
10.1016/j.avsg.2016.11.021
Reference:
AVSG 3229
To appear in:
Annals of Vascular Surgery
Received Date: 24 July 2016 Accepted Date: 30 November 2016
Please cite this article as: Reslan OM, Kirsch JM, Kaul H, Campos S, Zaki R, Brady PS, Khanmoradi K, Endovascular Stenting of Portal Vein for Graft Rescue after a Pancreas Transplant Venous Graft Thrombosis: A Case Report, Annals of Vascular Surgery (2017), doi: 10.1016/j.avsg.2016.11.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Endovascular Stenting of Portal Vein for Graft Rescue after a Pancreas Transplant
2
Venous Graft Thrombosis: A Case Report
3 4
Ossama M. Reslan, MD1
5
Jordan M. Kirsch, DO2
6
Hitesh Kaul, MD1
7
Stalin Campos, MD1
8
Radi Zaki, MD1
9
Paul S. Brady, MD3
10
Kamran Khanmoradi, MD1
Department of Transplantation, Einstein Medical Center, Philadelphia, PA 2
Department of Surgery, Wellspan York Hospital, PA
12 3
Division of Interventional Radiology, Department of Radiology, Einstein Medical Center, Philadelphia, PA
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Correspondence: Ossama M Reslan, MD Department of Surgery
Einstein Medical Center 5501 Old York Road, Klein 510 Philadelphia, PA19141 [email protected]
ACCEPTED MANUSCRIPT
Abstract
36
Venous thrombosis of pancreas transplant allografts often leads to graft loss. Its worrisome
37
complication and difficult to treat, forming the most common nonimmunological cause of
38
graft loss. Multiple risk factors have been implicated in the development of venous
39
thrombosis of pancreas transplant. Color Doppler ultrasonography (CDUS) enables early
40
diagnosis of venous thrombosis, thus increasing the possibility of graft-rescue treatments.
41
Endovascular management of pancreatic transplant vascular complications are scant and in
42
the form of case reports. We report a case of early detection of pancreatic graft venous
43
thrombosis that was treated successfully by catheter-directed thrombolysis (CDT)
44
mechanical thrombectomy, percutaneous angioplasty (PTA) and stenting of portal vein
45
(PV).
46
Introduction
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35
Pancreas graft thrombosis remains a serious surgical complication with incidence
48
reported as high as 10% to 20%1. Both arterial and venous thrombosis of graft vessels
49
occurs after pancreas transplantation, but venous thrombosis predominates in an
50
approximately 2:1 ratio2. Pancreatic venous graft thrombosis (PVGT) is an especially
51
worrisome complication because of the increased risk of hemorrhagic pancreatitis, organ
52
necrosis, infection, and thrombus propagation. Contributing factors to PVGT include
53
diabetes, organ preservation and procurement, and grafting technical aspects3. The
54
transplanted pancreas appears to be particularly susceptible to thrombosis because of its
55
inherently low microcirculatory flow and blood supply based on collateral circulation3.
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47
56
Clinical symptoms of pancreas graft thrombosis include sudden onset of otherwise
57
unexplained hyperglycemia, graft tenderness and enlargement, dark, massive hematuria
58
and markedly decreased or absent urinary amylase on a spot urinary amylase check of
59
bladder-drained grafts3.
ACCEPTED MANUSCRIPT
Imaging techniques have an important role in the diagnosis of pancreas transplant
61
complications. Color Doppler ultrasonography (CDUS), currently the first line technique in
62
postoperative pancreas graft monitoring, enables early diagnosis of PVGT, thus increasing
63
the possibility of graft-rescue treatments. Graft-rescue treatments include anticoagulation,
64
surgical thrombectomy, and endovascular treatment.
RI PT
60
We present a case of a PVGT developed after a simultaneous pancreas-kidney (SPK)
66
transplantation treated successfully by catheter-directed thrombolysis (CDT) mechanical
67
thrombectomy, percutaneous angioplasty (PTA) and stenting of portal vein (PV).
SC
65
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68 69 70 71
CASE REPORT
The patient is a 31-year-old male with a history of type I diabetes mellitus since age 10
73
and end stage renal disease on hemodialysis. He underwent SPK transplantation of an
74
organ from a young 18-year-old donor with no significant past medical history who became
75
brain dead due to car accident. Midline incision was performed and both organs were
76
transplanted intraperitoneally. The pancreaticoduedenal graft was implanted in the right iliac
77
fossa, and the exocrine drainage was performed by a side to side duodenoenterostomy.
78
The superior mesenteric artery and splenic artery were anastomosed to the recipient right
79
external iliac artery using an arterial Y-graft derived from the donor iliac bifurcation (Fig. 1).
80
The donor PV was anastomosed to the recipient’s right external iliac vein (EIV), no venous
81
extension was used (Fig. 2). The cold and warm ischemic times were around 11 hours and
82
22 minutes, respectively. Patient received Anti-thymocyte globulin (rabbit ATG) for induction
83
and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and
84
prednisone. There were no intraoperative complications.
AC C
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72
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The patient’s initial course was uneventful with immediate active pancreatic and renal
86
function. Two days after the surgery, the serum amylase level and blood sugar were
87
increased abruptly. Doppler ultrasound (DUS) revealed a non-occlusive thrombus within the
88
splenic vein (SV) towards the distal body and tail and close to the head of the pancreas
89
involving PV (Fig. 3). Immediately on the same day, the patient was started on systemic
90
anticoagulation therapy with heparin (UFH). However, repeated DUS showed propagation
91
of thrombus through portal and splenic veins.
SC
RI PT
85
Percutaneous transcatheter intervention was attempted one day after diagnosis of
93
thrombosis. CDT was performed under local anesthesia in the angiography room. Venous
94
access was achieved via the right femoral vein using a micropuncture kit under real-time
95
ultrasound (US) guidance and a 6F catheter sheath was inserted. The portal outflow venous
96
drainage for the pancreas transplant was selected by a glidewire and glide catheter. The
97
catheter was advanced to the SV and a venogram from the catheter was performed which
98
demonstrated nonocclusive thrombus involving PV near anastomosis, confluence with
99
superior mesenteric vein (SMV) and SV, and distal part of the SV (Fig. 4). CDT and
100
mechanical thrombectomy was performed using 4mg recombinant tissue type plasminogen
101
activator and AngioJet Ultra Thrombectomy System (Boston Scientific, Marlborough, MA),
102
respectively. However, completion venography demonstrated residual thrombus and
103
stenosis of the PV near the anastomosis with EIV. Percutaneous angioplasty (PTA) and
104
stenting of portal vein using vascular self-expanding 10x40mm Zilver stent (Cook® Medical,
105
Bloomington, IN) (Fig. 5). Completion venography revealed good graft vein patency and
106
excellent flow. Catheters were removed, and the patient was systemically anticoagulated
107
with heparin to a goal of PTT from 60 to 80 sec.
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92
108
During the hospital stay, the patient had developed lower gastrointestinal bleeding
109
probably from duodenoenterostomy that was treated conservatively. The heparin was
ACCEPTED MANUSCRIPT
110
stopped and patient started on plavix and aspirin. Insulin-free status was achieved 8 days
111
after the intervention. Follow-up CDUS after one year showed excellent flow, patent stent
112
and no residual clot within the vein (Fig. 6). Patient remained insulin free during this period.
114
RI PT
113
Discussion
Thrombosis of the pancreas graft can cause early graft loss in pancreas
116
transplantation. PVGT occur in approximately 5 % of pancreas transplants4. Venous graft
117
thrombosis is an especially worrisome complication and usually occurs within the first week
118
after transplantation4.
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115
It is very difficult to determine which risk factor is potentially implicated in the
120
pathogenesis of graft thrombosis due to the variety of etiologic factors that have been
121
described. Factors described in literature in detail which include hemodynamic instability,
122
traumatic head injury, vasopressor administration of the donor; excessive intraoperative
123
manipulation during procurement; excessive amounts of flush volume or perfusion pressure;
124
and total cold and warm ischemic time5. In the present case, donor cause of death was
125
head injury, and cold ischemic time (CIT) was 10 hrs. and 34 mins. Reduced preservation
126
time may help to reduce reperfusion injury and edema of the pancreas allograft, but CIT has
127
not been shown to affect graft survival in large studies5.
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128
PVGT clinical signs and symptoms are nonspecific. PVGT is often suspected because
129
of abnormal findings such as increased serum amylase levels, increased serum glucose
130
levels or increased insulin requirements, abdominal pain and lower extremity edema, and in
131
patient with bladder drainage decreased urine amylase levels, dark hematuria, tissue
132
fragments in the urine are the most commonly seen 3.
133
Immediate diagnosis is imperative because the risks associated with failure to promptly
134
diagnose and rescue or surgically excise the thrombosed graft are grave and include
ACCEPTED MANUSCRIPT
thrombus propagation and pulmonary embolus, hemorrhagic pancreatitis, infection, organ
136
necrosis, and death. CDUS currently is the first line technique in postoperative pancreas
137
graft monitoring, enables early diagnosis of PVGT, thus increasing the possibility of graft-
138
rescue treatments. Foshager et al. demonstrated that elevated pancreatic transplant arterial
139
resistance (RI ≥1.00), and absence of venous flow, in combination, are highly sensitive and
140
specific for the diagnosis of PVGT6. Our patient’s serum amylase level and blood sugar
141
were increased abruptly, and DUS revealed decreased flow within the splenic vein (SV)
142
towards the distal body and tail and close to the head of the pancreas associated with
143
arterial RI >1.
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135
Prophylaxis for pancreas thrombosis with low-dose aspirin is recommended for all
145
pancreas recipients, unless there is a history of allergy or severe thrombocytopenia2. The
146
use of systemic anticoagulation has been controversial. Sollinger suggested that the use of
147
systemic anticoagulation does not reduce the incidence of PVGT, but may enhance
148
postoperative bleeding, which may compress the splenic or portal vein or the splenoportal
149
confluence, thereby increasing the risk of vascular graft thrombosis7. Systemic
150
anticoagulation is well accepted when splenic vein thrombosis is documented by CDUS8.
151
The exact protocol of anticoagulation is not well established along with the duration of
152
treatment, but a 3-month period seems reasonable by several centers9. Our patient started
153
on systemic anticoagulation when portal and splenic veins thrombosis was documented by
154
CDUS but lower gastrointestinal bleeding was developed. Systemic anticoagulation was
155
stopped and patient was started on aspirin and plavix.
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156
The management of PVGT is controversial. Although there are no consensus
157
guidelines about the best therapeutic option, it is clear that for graft salvage, treatment must
158
be performed promptly. Endovascular management of venous thrombosis has been widely
159
used successfully for dialysis grafts and extremity thrombosis for years. Use of similar
ACCEPTED MANUSCRIPT
techniques in the salvage of a pancreas transplant due to venous thrombosis seems
161
reasonable given the higher morbidity of surgical alternatives. Fridell et al. reported their
162
experience with surgical thrombectomy which was performed in six grafts with graft rescue
163
in five cases10. CDT and mechanical thrombectomy, have been reported in small series of
164
patients with PVGT11,12. Stokland et al. reported a group of 6 symptomatic patients with
165
pancreas vein thrombosis treated with endovascular pharmacomechanical techniques
166
achieved 50 % graft survival with 100 % patient survival12. This is the only study to date that
167
used metal stents in two patients to treat anastomotic stenoses or kinks after endovascular
168
intervention9. Recently published study reported a group of 17 patients with PVGT treated
169
successfully with endovascular pharmacomechanical techniques that resulted in patient and
170
pancreas graft survival rates at 12 months of 94 and 76 %, respectively13. Our patient’s was
171
treated, in addition to CDT and mechanical thrombectomy, with PTA and stenting of PV
172
because completion venography demonstrated residual thrombus caused by possible
173
anastomotic stenosis or kinking.
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In conclusion, early percutaneous endovascular interventions for pancreas transplant
175
venous thrombosis allows graft salvage and appears to be an effective therapy to remove
176
the thrombus and is associated with a low complication rate.
178 179 180 181 182 183 184
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1. Schenker P, Vonend O, Ertas N, Wunsch A, Schaeffer M, Rump LC, Viebahn R. Incidence of pancreas graft thrombosis using low-molecular-weight heparin. Clin Transplant. 2009 ;23(3):407-14. 2. Farney AC, Rogers J, Stratta RJ. Pancreas graft thrombosis: causes, prevention, diagnosis, and intervention. Curr Opin Organ Transplant. 2012; 17(1):87-92. 3. Troppmann C. Complications after pancreas transplantation. Curr Opin Organ Transplant. 2010 ;15(1):112-8. 4. Sutherland DE, Gruessner R, Gillingham K, Moudry-Munns K, Dunn D, Brayman K, Morel P, Najarian JS. A single institution's experience with solitary pancreas transplantation: a multivariate analysis of factors leading to improved outcome. Clin Transpl. 1991:141-52. 5. Troppmann C, Gruessner AC, Benedetti E, Papalois BE, Dunn DL, Najarian JS, Sutherland DE, Gruessner RW. Vascular graft thrombosis after pancreatic transplantation: univariate and multivariate operative and nonoperative risk factor analysis. J Am Coll Surg. 1996 ;182(4):285-316. 6. Foshager MC, Hedlund LJ, Troppmann C, Benedetti E, Gruessner RW. Venous thrombosis of pancreatic transplants: diagnosis by duplex sonography. AJR Am J Roentgenol. 1997 ;169(5):1269-73. 7. SOLLINGER HW. Pancreatic transplantation and vascular graft thrombosis (Editorial). J Am Coll Surg 1996: 182:362. 8. Kuo PC, Wong J, Schweitzer EJ, Johnson LB, Lim JW, Bartlett ST. Outcome after splenic vein thrombosis in the pancreas allograft. Transplantation. 1997 ;64(6):9335. 9. Delis S, Dervenis C, Bramis J, Burke GW, Miller J, Ciancio G. Vascular complications of pancreas transplantation. Pancreas. 2004 ;28(4):413-20. 10. Fridell JA, Mangus RS, Mull AB, Taber TE, Sanders CE, Slisher RC, Goble ML, Powelson JA. Early reexploration for suspected thrombosis after pancreas transplantation. Transplantation. 2011 ;91(8):902-7. 11. Yoshimatsu R, Yamagami T, Terayama K, Matsumoto T, Miura H, Nishimura T, Okamoto M, Ushigome H, Nobori S, Yoshimura N. Percutaneous transcatheter thrombolysis for graft thrombosis after pancreas transplantation. Pancreas. 2009 ;38(5):597-9. 12. Stockland AH, Willingham DL, Paz-Fumagalli R, Grewal HP, McKinney JM, Hughes CB, Walser EM. Pancreas transplant venous thrombosis: role of endovascular interventions for graft salvage. Cardiovasc Intervent Radiol. 2009 ;32(2):279-83. 13. Barrufet M, Burrel M, Angeles García-Criado M, Montañà X, Real MI, Ferrer J, Fernández-Cruz L, Gilabert R. Pancreas transplants venous graft thrombosis: endovascular thrombolysis for graft rescue. Cardiovasc Intervent Radiol. 2014 ;37(5):1226-34.
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References
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Fig. 1. Schematic diagram of donor pancreas with Y-graft derived from then donor iliac
228
bifurcation.
229
Fig. 2. Schematic diagram of simultaneous pancreas-kidney (SPK) transplantation
231
technique.
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232
Fig. 3. (A) Grayscale Doppler US demonstrating nonocclusive thrombus involving the entire
234
splenic vein (SV) almost to the confluence with portal vein (PV). (B) Color Doppler US
235
demonstrating progression of nonocclusive thrombus to involve the portal vein (PV) near
236
anastomosis with external iliac vein and confluence with superior mesenteric vein (SMV)
237
and splenic vein (SV).
238
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239
Fig. 4. Venogram of the venous drainage of pancreatic graft shows nonocclusive thrombus
240
involving portal vein (PV), confluence with superior mesenteric vein (SMV) and splenic vein
241
(SV), and distal part of the SV.
242
Fig. 5. Self-expanding metal stent placement near the venous anastomosis, the splenic vein
244
and superior mesenteric/ portal components of the pancreas transplant venous drainage
245
have excellent flow and no residual clot.
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246
Fig. 6. Follow-up Color Doppler US after one year of catheter-directed thrombolysis (CDT)
248
and stenting of portal vein shows excellent flow, patent stent and no residual clot within the
249
vein.
251
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S0890-5096(17)30438-7
DOI:
10.1016/j.avsg.2016.11.021
Reference:
AVSG 3229
To appear in:
Annals of Vascular Surgery
Received Date: 24 July 2016 Accepted Date: 30 November 2016
Please cite this article as: Reslan OM, Kirsch JM, Kaul H, Campos S, Zaki R, Brady PS, Khanmoradi K, Endovascular Stenting of Portal Vein for Graft Rescue after a Pancreas Transplant Venous Graft Thrombosis: A Case Report, Annals of Vascular Surgery (2017), doi: 10.1016/j.avsg.2016.11.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Endovascular Stenting of Portal Vein for Graft Rescue after a Pancreas Transplant
2
Venous Graft Thrombosis: A Case Report
3 4
Ossama M. Reslan, MD1
5
Jordan M. Kirsch, DO2
6
Hitesh Kaul, MD1
7
Stalin Campos, MD1
8
Radi Zaki, MD1
9
Paul S. Brady, MD3
10
Kamran Khanmoradi, MD1
Department of Transplantation, Einstein Medical Center, Philadelphia, PA 2
Department of Surgery, Wellspan York Hospital, PA
12 3
Division of Interventional Radiology, Department of Radiology, Einstein Medical Center, Philadelphia, PA
14
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Correspondence: Ossama M Reslan, MD Department of Surgery
Einstein Medical Center 5501 Old York Road, Klein 510 Philadelphia, PA19141 [email protected]
ACCEPTED MANUSCRIPT
Abstract
36
Venous thrombosis of pancreas transplant allografts often leads to graft loss. Its worrisome
37
complication and difficult to treat, forming the most common nonimmunological cause of
38
graft loss. Multiple risk factors have been implicated in the development of venous
39
thrombosis of pancreas transplant. Color Doppler ultrasonography (CDUS) enables early
40
diagnosis of venous thrombosis, thus increasing the possibility of graft-rescue treatments.
41
Endovascular management of pancreatic transplant vascular complications are scant and in
42
the form of case reports. We report a case of early detection of pancreatic graft venous
43
thrombosis that was treated successfully by catheter-directed thrombolysis (CDT)
44
mechanical thrombectomy, percutaneous angioplasty (PTA) and stenting of portal vein
45
(PV).
46
Introduction
M AN U
SC
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35
Pancreas graft thrombosis remains a serious surgical complication with incidence
48
reported as high as 10% to 20%1. Both arterial and venous thrombosis of graft vessels
49
occurs after pancreas transplantation, but venous thrombosis predominates in an
50
approximately 2:1 ratio2. Pancreatic venous graft thrombosis (PVGT) is an especially
51
worrisome complication because of the increased risk of hemorrhagic pancreatitis, organ
52
necrosis, infection, and thrombus propagation. Contributing factors to PVGT include
53
diabetes, organ preservation and procurement, and grafting technical aspects3. The
54
transplanted pancreas appears to be particularly susceptible to thrombosis because of its
55
inherently low microcirculatory flow and blood supply based on collateral circulation3.
AC C
EP
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47
56
Clinical symptoms of pancreas graft thrombosis include sudden onset of otherwise
57
unexplained hyperglycemia, graft tenderness and enlargement, dark, massive hematuria
58
and markedly decreased or absent urinary amylase on a spot urinary amylase check of
59
bladder-drained grafts3.
ACCEPTED MANUSCRIPT
Imaging techniques have an important role in the diagnosis of pancreas transplant
61
complications. Color Doppler ultrasonography (CDUS), currently the first line technique in
62
postoperative pancreas graft monitoring, enables early diagnosis of PVGT, thus increasing
63
the possibility of graft-rescue treatments. Graft-rescue treatments include anticoagulation,
64
surgical thrombectomy, and endovascular treatment.
RI PT
60
We present a case of a PVGT developed after a simultaneous pancreas-kidney (SPK)
66
transplantation treated successfully by catheter-directed thrombolysis (CDT) mechanical
67
thrombectomy, percutaneous angioplasty (PTA) and stenting of portal vein (PV).
SC
65
M AN U
68 69 70 71
CASE REPORT
The patient is a 31-year-old male with a history of type I diabetes mellitus since age 10
73
and end stage renal disease on hemodialysis. He underwent SPK transplantation of an
74
organ from a young 18-year-old donor with no significant past medical history who became
75
brain dead due to car accident. Midline incision was performed and both organs were
76
transplanted intraperitoneally. The pancreaticoduedenal graft was implanted in the right iliac
77
fossa, and the exocrine drainage was performed by a side to side duodenoenterostomy.
78
The superior mesenteric artery and splenic artery were anastomosed to the recipient right
79
external iliac artery using an arterial Y-graft derived from the donor iliac bifurcation (Fig. 1).
80
The donor PV was anastomosed to the recipient’s right external iliac vein (EIV), no venous
81
extension was used (Fig. 2). The cold and warm ischemic times were around 11 hours and
82
22 minutes, respectively. Patient received Anti-thymocyte globulin (rabbit ATG) for induction
83
and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and
84
prednisone. There were no intraoperative complications.
AC C
EP
TE D
72
ACCEPTED MANUSCRIPT
The patient’s initial course was uneventful with immediate active pancreatic and renal
86
function. Two days after the surgery, the serum amylase level and blood sugar were
87
increased abruptly. Doppler ultrasound (DUS) revealed a non-occlusive thrombus within the
88
splenic vein (SV) towards the distal body and tail and close to the head of the pancreas
89
involving PV (Fig. 3). Immediately on the same day, the patient was started on systemic
90
anticoagulation therapy with heparin (UFH). However, repeated DUS showed propagation
91
of thrombus through portal and splenic veins.
SC
RI PT
85
Percutaneous transcatheter intervention was attempted one day after diagnosis of
93
thrombosis. CDT was performed under local anesthesia in the angiography room. Venous
94
access was achieved via the right femoral vein using a micropuncture kit under real-time
95
ultrasound (US) guidance and a 6F catheter sheath was inserted. The portal outflow venous
96
drainage for the pancreas transplant was selected by a glidewire and glide catheter. The
97
catheter was advanced to the SV and a venogram from the catheter was performed which
98
demonstrated nonocclusive thrombus involving PV near anastomosis, confluence with
99
superior mesenteric vein (SMV) and SV, and distal part of the SV (Fig. 4). CDT and
100
mechanical thrombectomy was performed using 4mg recombinant tissue type plasminogen
101
activator and AngioJet Ultra Thrombectomy System (Boston Scientific, Marlborough, MA),
102
respectively. However, completion venography demonstrated residual thrombus and
103
stenosis of the PV near the anastomosis with EIV. Percutaneous angioplasty (PTA) and
104
stenting of portal vein using vascular self-expanding 10x40mm Zilver stent (Cook® Medical,
105
Bloomington, IN) (Fig. 5). Completion venography revealed good graft vein patency and
106
excellent flow. Catheters were removed, and the patient was systemically anticoagulated
107
with heparin to a goal of PTT from 60 to 80 sec.
AC C
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M AN U
92
108
During the hospital stay, the patient had developed lower gastrointestinal bleeding
109
probably from duodenoenterostomy that was treated conservatively. The heparin was
ACCEPTED MANUSCRIPT
110
stopped and patient started on plavix and aspirin. Insulin-free status was achieved 8 days
111
after the intervention. Follow-up CDUS after one year showed excellent flow, patent stent
112
and no residual clot within the vein (Fig. 6). Patient remained insulin free during this period.
114
RI PT
113
Discussion
Thrombosis of the pancreas graft can cause early graft loss in pancreas
116
transplantation. PVGT occur in approximately 5 % of pancreas transplants4. Venous graft
117
thrombosis is an especially worrisome complication and usually occurs within the first week
118
after transplantation4.
M AN U
SC
115
It is very difficult to determine which risk factor is potentially implicated in the
120
pathogenesis of graft thrombosis due to the variety of etiologic factors that have been
121
described. Factors described in literature in detail which include hemodynamic instability,
122
traumatic head injury, vasopressor administration of the donor; excessive intraoperative
123
manipulation during procurement; excessive amounts of flush volume or perfusion pressure;
124
and total cold and warm ischemic time5. In the present case, donor cause of death was
125
head injury, and cold ischemic time (CIT) was 10 hrs. and 34 mins. Reduced preservation
126
time may help to reduce reperfusion injury and edema of the pancreas allograft, but CIT has
127
not been shown to affect graft survival in large studies5.
AC C
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119
128
PVGT clinical signs and symptoms are nonspecific. PVGT is often suspected because
129
of abnormal findings such as increased serum amylase levels, increased serum glucose
130
levels or increased insulin requirements, abdominal pain and lower extremity edema, and in
131
patient with bladder drainage decreased urine amylase levels, dark hematuria, tissue
132
fragments in the urine are the most commonly seen 3.
133
Immediate diagnosis is imperative because the risks associated with failure to promptly
134
diagnose and rescue or surgically excise the thrombosed graft are grave and include
ACCEPTED MANUSCRIPT
thrombus propagation and pulmonary embolus, hemorrhagic pancreatitis, infection, organ
136
necrosis, and death. CDUS currently is the first line technique in postoperative pancreas
137
graft monitoring, enables early diagnosis of PVGT, thus increasing the possibility of graft-
138
rescue treatments. Foshager et al. demonstrated that elevated pancreatic transplant arterial
139
resistance (RI ≥1.00), and absence of venous flow, in combination, are highly sensitive and
140
specific for the diagnosis of PVGT6. Our patient’s serum amylase level and blood sugar
141
were increased abruptly, and DUS revealed decreased flow within the splenic vein (SV)
142
towards the distal body and tail and close to the head of the pancreas associated with
143
arterial RI >1.
M AN U
SC
RI PT
135
Prophylaxis for pancreas thrombosis with low-dose aspirin is recommended for all
145
pancreas recipients, unless there is a history of allergy or severe thrombocytopenia2. The
146
use of systemic anticoagulation has been controversial. Sollinger suggested that the use of
147
systemic anticoagulation does not reduce the incidence of PVGT, but may enhance
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postoperative bleeding, which may compress the splenic or portal vein or the splenoportal
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confluence, thereby increasing the risk of vascular graft thrombosis7. Systemic
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anticoagulation is well accepted when splenic vein thrombosis is documented by CDUS8.
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The exact protocol of anticoagulation is not well established along with the duration of
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treatment, but a 3-month period seems reasonable by several centers9. Our patient started
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on systemic anticoagulation when portal and splenic veins thrombosis was documented by
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CDUS but lower gastrointestinal bleeding was developed. Systemic anticoagulation was
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stopped and patient was started on aspirin and plavix.
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The management of PVGT is controversial. Although there are no consensus
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guidelines about the best therapeutic option, it is clear that for graft salvage, treatment must
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be performed promptly. Endovascular management of venous thrombosis has been widely
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used successfully for dialysis grafts and extremity thrombosis for years. Use of similar
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techniques in the salvage of a pancreas transplant due to venous thrombosis seems
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reasonable given the higher morbidity of surgical alternatives. Fridell et al. reported their
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experience with surgical thrombectomy which was performed in six grafts with graft rescue
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in five cases10. CDT and mechanical thrombectomy, have been reported in small series of
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patients with PVGT11,12. Stokland et al. reported a group of 6 symptomatic patients with
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pancreas vein thrombosis treated with endovascular pharmacomechanical techniques
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achieved 50 % graft survival with 100 % patient survival12. This is the only study to date that
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used metal stents in two patients to treat anastomotic stenoses or kinks after endovascular
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intervention9. Recently published study reported a group of 17 patients with PVGT treated
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successfully with endovascular pharmacomechanical techniques that resulted in patient and
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pancreas graft survival rates at 12 months of 94 and 76 %, respectively13. Our patient’s was
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treated, in addition to CDT and mechanical thrombectomy, with PTA and stenting of PV
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because completion venography demonstrated residual thrombus caused by possible
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anastomotic stenosis or kinking.
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In conclusion, early percutaneous endovascular interventions for pancreas transplant
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venous thrombosis allows graft salvage and appears to be an effective therapy to remove
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the thrombus and is associated with a low complication rate.
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1. Schenker P, Vonend O, Ertas N, Wunsch A, Schaeffer M, Rump LC, Viebahn R. Incidence of pancreas graft thrombosis using low-molecular-weight heparin. Clin Transplant. 2009 ;23(3):407-14. 2. Farney AC, Rogers J, Stratta RJ. Pancreas graft thrombosis: causes, prevention, diagnosis, and intervention. Curr Opin Organ Transplant. 2012; 17(1):87-92. 3. Troppmann C. Complications after pancreas transplantation. Curr Opin Organ Transplant. 2010 ;15(1):112-8. 4. Sutherland DE, Gruessner R, Gillingham K, Moudry-Munns K, Dunn D, Brayman K, Morel P, Najarian JS. A single institution's experience with solitary pancreas transplantation: a multivariate analysis of factors leading to improved outcome. Clin Transpl. 1991:141-52. 5. Troppmann C, Gruessner AC, Benedetti E, Papalois BE, Dunn DL, Najarian JS, Sutherland DE, Gruessner RW. Vascular graft thrombosis after pancreatic transplantation: univariate and multivariate operative and nonoperative risk factor analysis. J Am Coll Surg. 1996 ;182(4):285-316. 6. Foshager MC, Hedlund LJ, Troppmann C, Benedetti E, Gruessner RW. Venous thrombosis of pancreatic transplants: diagnosis by duplex sonography. AJR Am J Roentgenol. 1997 ;169(5):1269-73. 7. SOLLINGER HW. Pancreatic transplantation and vascular graft thrombosis (Editorial). J Am Coll Surg 1996: 182:362. 8. Kuo PC, Wong J, Schweitzer EJ, Johnson LB, Lim JW, Bartlett ST. Outcome after splenic vein thrombosis in the pancreas allograft. Transplantation. 1997 ;64(6):9335. 9. Delis S, Dervenis C, Bramis J, Burke GW, Miller J, Ciancio G. Vascular complications of pancreas transplantation. Pancreas. 2004 ;28(4):413-20. 10. Fridell JA, Mangus RS, Mull AB, Taber TE, Sanders CE, Slisher RC, Goble ML, Powelson JA. Early reexploration for suspected thrombosis after pancreas transplantation. Transplantation. 2011 ;91(8):902-7. 11. Yoshimatsu R, Yamagami T, Terayama K, Matsumoto T, Miura H, Nishimura T, Okamoto M, Ushigome H, Nobori S, Yoshimura N. Percutaneous transcatheter thrombolysis for graft thrombosis after pancreas transplantation. Pancreas. 2009 ;38(5):597-9. 12. Stockland AH, Willingham DL, Paz-Fumagalli R, Grewal HP, McKinney JM, Hughes CB, Walser EM. Pancreas transplant venous thrombosis: role of endovascular interventions for graft salvage. Cardiovasc Intervent Radiol. 2009 ;32(2):279-83. 13. Barrufet M, Burrel M, Angeles García-Criado M, Montañà X, Real MI, Ferrer J, Fernández-Cruz L, Gilabert R. Pancreas transplants venous graft thrombosis: endovascular thrombolysis for graft rescue. Cardiovasc Intervent Radiol. 2014 ;37(5):1226-34.
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Fig. 1. Schematic diagram of donor pancreas with Y-graft derived from then donor iliac
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bifurcation.
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Fig. 2. Schematic diagram of simultaneous pancreas-kidney (SPK) transplantation
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technique.
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Fig. 3. (A) Grayscale Doppler US demonstrating nonocclusive thrombus involving the entire
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splenic vein (SV) almost to the confluence with portal vein (PV). (B) Color Doppler US
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demonstrating progression of nonocclusive thrombus to involve the portal vein (PV) near
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anastomosis with external iliac vein and confluence with superior mesenteric vein (SMV)
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and splenic vein (SV).
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Fig. 4. Venogram of the venous drainage of pancreatic graft shows nonocclusive thrombus
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involving portal vein (PV), confluence with superior mesenteric vein (SMV) and splenic vein
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(SV), and distal part of the SV.
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Fig. 5. Self-expanding metal stent placement near the venous anastomosis, the splenic vein
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and superior mesenteric/ portal components of the pancreas transplant venous drainage
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have excellent flow and no residual clot.
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Fig. 6. Follow-up Color Doppler US after one year of catheter-directed thrombolysis (CDT)
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and stenting of portal vein shows excellent flow, patent stent and no residual clot within the
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vein.
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