Overview of Pancreas Transplantation
Farhan Asghar1, Hong Zhu2
1Division of Hepatopancreaticobillary Surgery, 2Kunming Medical University, Kunming, Yunnan, China
- *Corresponding Author:
- Hong Zhu
Division of Hepatopancreatic and billary surgery
Second affiliated hospital of Kunming Medical University (KMU)
112 kunrui road , Kunming , Yunnan , China
Tel: + 008618487327303
Fax: + 008613078755609
E-mail: [email protected]
Received November 23rd, 2017 - Accepted March 14th, 2018
According to global report on diabetes by world health organization 1.5 million deaths were directly caused by diabetes in 2012. Pancreas transplantation is the best known treatment for diabetes. Purpose of this review is to give an overview of pancreas transplantation and after a detailed introduction, develop a basic understanding of pancreas transplantation. An overview of the related literature will be assessed and a brief history of pancreas transplantation along with three types of pancreas transplantation (SPKT, PAK, PTA), will be presented. We will elucidate the lectors on how surgical procedure for procurement of pancreatic graft is carried out simultaneously with other organs, in three steps. In the recipient part we describe exocrine drainage of pancreatic graft systemic-bladder technique and systemic enteric technique (surgical procedure with different advantages and disadvantages briefly described in the article). While for endocrine drainage there will be presented two widely used techniques and systemic enteric and portal enteric. Immunosuppression for pancreas transplantation induction and maintenance therapy are recently the most used ones. Corticosteroids and steroid free management are under debate in recent years. In 50 years of transplant history there is no gold standard immunosuppression regimen. Although outcomes of pancreas transplantation improved in last decades, there is a decline in number of transplantation. This review is helpful to make a basic understanding of pancreas transplantation for new surgeons.
Diabetes Mellitus; Pancreas; Transplantation
IQR interquartile range; SPN solid pseudopapillary
According to global report on diabetes by world health
organization 1.5 million deaths were directly caused by
diabetes in 2012 . More than 8% of total health budget is
spent on diabetes . Beside this secondary complications
from diabetes involve a number of micro and macro
vascular complications such are diabetic nephropathy,
neuropathy, and retinopathy [3, 4, 5]. End stage renal
disease is one of the most significant complication from
diabetes . Data received from 54 countries suggested
that at least 80% cases of end-stage renal disease (ERSD)
are because of diabetes , hypertension or a combination
of both hypertension and diabetes . Although after
the discovery of insulin in 1922, prognosis of diabetes
was shifted from lethal to a chronic disease, still it just
delays the progression of secondary complications. Today
pancreas transplantation is the most reliable treatment to
establish normal glucose levels  in patients with type
1 diabetes [9, 10, 11]. Improve quality of life by restoring
endogenous insulin secretion and prevention from
secondary complications [12, 13, 14]. In the end, it also
minimize the risk of hypoglycemia in patients with type 1
Pancreas transplantation was for the first time
performed in December 1966 by William Kelly and
Richard Lilleheiat the university of Minnesota, where
they transplanted pancreas along with kidney to treat
a diabetic uremic female patient and managed to get rid
from exogenous insulin for 6 days and later this transplant
was rejected . In China pancreas transplantation was
performed for the first time on the 22nd of December 1982
With the improvements in immunosuppressive
treatment, surgical technique and preservation of organs,
in the successive 1980’s period, there was a significant
improvement in pancreas transplantation resulting in an
increase in the number of transplants [18, 19].
Methods of Pancreas Transplantation
There are 3 methods of solid organ and pancreas
transplantation. The first and most performed is where
pancreas transplantation is carried out at the same
time with kidney, also known as simultaneous pancreas
and kidney transplantation (SPK). It is a long surgical
procedure. It is treatment of choice for the patients with
type 1 diabetes suffering from end stage renal disease .
Basic reason for SPKT being common is that the patients
are already on immunosuppressive therapy along with
the fact that a minor risk of surgical procedure addition
benefit can be obtained.
Pancreas transplantation after kidney (PAK) is another
way for pancreas transplantation where a pancreatic
allograft is transplanted after kidney transplantation .
This method is highly recommended for diabetic patients
having successful kidney transplant . With this
procedure patient have to go through surgical risk twice.
Pancreas transplantation alone (PTA) is the third
recommended procedure for pancreas transplantation,
where just pancreas transplantation alone is showing
good results . This is the least performed method of
pancreatic transplantation but recently coming with good
results. Pancreatic islet cell transplantation is another
option in practice for the treatment of type one diabetes
Overall percentage of pancreas transplantations
performed is 80% SPK, 15% PAK while PTA are 5% .
Procurement of pancreatic graft is done along with
other multiple intra-abdominal organs transplantation. This
surgery is executed with a unique technique along with liver
en bloc . Performed in three steps, first of all dissection
is done with intact circulation, then organs are cooled in
situ with IV transfusion and heparinized (after that liver
and pancreata are recovered together while intestines
are removed separately) [27, 28]. In the third step organs
are prepared for transplantation on back table surgery
pancreato-duodenal graft is isolated by removing spleen,
(for pancreatic exocrine secretions) and the duodenal
segment shortened. What will follow is the suture and
invagination of duodenal borders , mobilization of portal
vein and vascular Y graft reconstruction. After removal,
pancreata and other vascular grafts must be immersed in
Exocrine drainage of pancreatic graft is always a debate
between transplant surgeons and this lead to a large
number of variations in the expletation of the surgey, all
over the years.
Surgical aspect of recipient: There are two techniques for
the pancreas exocrine secretions named: systemic-bladder
technique and systemic-enteric technique for portal
venous delivery of insulin. Enteric drainage of exocrine
secretions come up with another technique called portalenteric
Bladder drainage of exocrine secretions systemic
bladder technique was very common during 1980s .
With this technique donor duodenum is anastomosed to
viseral dome by using a 2 layered hand sew dn technique
or a circular stapled . This technique is safe, sterile
and easy to perform. There are two major advantages
of this technique. First one is that, bladder-duodenal
anastomosis leakage can be managed by urinary catheter
 and urinary amylase. Second one, that Insulin can
be measured as an important indication for early graft
rejection [33, 34]. On the other hand there are also a
number of complications like reflux pancreatitis, urinary
tract infection and haematuria, all associated with bladder
drainage due to bicarbonates lose .
Enteric Drainage of Exocrine Secretions
With this technique duodenum of donor is anastomosed
with bowel of recipient (proximal jejunum or distal ileum).
Gastric and duodenal drainage are also used [36, 37, 38].
Anastomosis is stapled in a linear fashion , with a
circular device  or hand sewn. A number of urinary
tract complications were reported with bladder drainage
caused by non-physiological drainage of pancreatic
enzymes into the urinary tract . Surgeons report
enteric drainage much safer as compared to bladder
drainage [42, 43].
To manage the endocrine drainage there are two widely
used techniques: systemic enteric and portal enteric
drainage. Portal drainage is mostly used with enteric
exocrine drainage. Donor portal vein and recipient splenic
vein are end to side anastomosed ; distal splenic vein
of donor and portal vein of recipient with bladder drainage
, or draining transplanted pancreas converge directly
in mesenteric vein . Portal venous drainage is said to be
more physiological whereas enteric drainage is associated
with hyperinsulinemia . Different studies showed
same long term and short term outcomes of pancreatic
transplantation with portal venous drainage and enteric
venous drainage [48, 49]. Systemic venous drainage is the
most commonly used technique in America .
Regarding immunosuppression for pancreatic
transplantation, induction  and maintenance therapy
 are most commonly used recently. Anti lymphocyte
serum such as daclizumab (anti CD25 (interleukin-2
receptor) monoclonal antibody) and basiliximab are used
for induction therapy. While prednisone (corticosteroid),
mycophenolate mofetil (anti metabolite), and tacrolimus
(calcineurin inhibitor) are used for maintenance therapy.
SRTR data show that trend for induction therapy
has shifted towards T-cell depleting induction agents,
such as alemtuzumab and thymoglobulin instead of
interleukin-2 receptor antagonist like basiliximab
. Corticosteroids management and steroid free
immunosuppression has been at the center of the debate,
in recent years. As corticosteroids are major cause for
post-transplant,hyperglycemia, hyperlipidemia and
hypertension increase cardiovascular risk in recipient .
UNSO database showed that there is an higher evolving
risk of infectious complications with steroid maintenance
therapy as compared to steroid free therapy . In 2000
mTOR inhibitors were introduced for immunosuppression
of pancreatic transplantation , such as Everolimus and
sirolimus ,both found to be effective and SPKT particularly
to avoid renal complications and an alternative for MMF to
reduce complications caused by MMF such as leucopenia and GI toxicity. Costimulatory blockade agents like
Belatacept are least for immunosuppression of pancreatic
graft recipient. In the 50-year-history of pancreas
transplantation, researchers were unable establish a
gold immunosuppressive regimen standard.
Technical failure is the primary complication for
a graft failure within the first three months after
transplantation, vascular thrombosis account for half of
the pancreatic graft lose  that is: 50%, pancreatitis
20%, infections 18%, fistula 6.5% Bleeding accounts
for 2.4% for total pancreatic graft failure . The risk
factors associated with surgical complications are: age
factor( aging more than 45 for donor or recipient) and
cold ischemia lasting more than 24 hours . Medical
history of recipient also play an important role in survival
of pancreatic graft. About 10-25% pancreatic transplant
with bladder drainage of exocrine secretions need to be
converted to enteric drainage . Enteric drainage(
intestinal leakage) is one of the significant postoperative
complication observed in 5-8% of graft, treated by
removal of pancreatic graft . Even though there are
advancements in immunosuppression and antibiotic
therapy, infections still are the major cause for mortality
and morbidity in pancreas transplantation. An early
detection of infectious agent and etiology of infection can
be helpful to improve graft survival.
Outcomes of pancreas transplantation improved in last
five decades but there was a slight decline in number of
transplants after 2004 [62, 63]. Five year patient survival
rates for all three groups are approximately 90% and for
ten years 70%. Insulin independence for 5 years is 73% in
SPK, 64% in PAK and 53% in PAT. Half life of pancreatic
graft is 10-15 years. Therefore a lot of work is needed
to be done on pancreas transplantation. Increase the
number of transplantation centers should be the urge of
the authorities, as until now pancreas transplantation in
limited to a few centers and only upcoming surgeons are
trained to perform the surgery. Especially in Asia and
developing countries all over the world. As diabetes data
suggest, there is a huge gap to be filled between large
number of patients and lack of surgical skills as well as
scarcity of transplantation centers. Although liver and
kidney transplantation are very common but pancreas
transplantation is limited o to some countries and a few
Pancreas transplantation is the most effective
treatment for diabetes. Better surgical method can
be chosen to minimize the surgical complications
with enteric or bladder drainage. Advancement in
immunosuppression improved life after transplantation.
There is an improved quality of life in uremic diabetic
This study is supported by research grants from
the National Natural Science Foundation of China (NO.
81460132),Yunnan Natural Science Foundation of China
Conflict of interest
Authors report no conflicts of interest.
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