A comprehensive presentation on Pancreatic transplantation types

1. SUBJECT SEMINAR :
PANCREAS TRANSPLANT
CHAIRPERSON:
Dr. UDAYKUMAR K V
ASSOCIATE PROFESSOR
DEPT OF GENERAL SURGERY
KMCRI, HUBLI
PRESENTED BY:
Dr. ARHAM
POST GRADUATE STUDENT
DEPT OF GENERAL SURGERY
KMCRI, HUBLI

2. TOPICS
• Anatomy
• Physiology

3. EMBRYOLOGY
• The liver and pancreas arise as dorsal and a ventral outpouching of
the duodenum
• The dorsal pouch is the rudiment of the pancreatic duct from which
the neck, body and tail of the pancreas develops.
• The ventral pouch arises from the duodenum at a lower level and is
the rudiment of the bile passages from which a pancreatic duct arises
to form the head and the uncinate process.

5. ANATOMY
• The pancreas is both an exocrine and an endocrine gland.
• It is an elongated structure that lies on the posterior abdominal wall
behind the stomach and behind the peritoneum.
• It may be divided into a head, a neck, a body, and a tail

6. • The head is disc shaped and lies within the concavity of the C-shaped
duodenum.
• A portion of the head inferiorly is termed the uncinate process and is
intimately related to the SMV and SMA.
• The neck is narrow and connects the head to the body; it lies in front
of the beginning of the portal vein.

7. • The body passes upward and to the left across the midline, and the
tail extends to the hilus of the spleen in the splenicorenal ligament.
• Posteriorly, the pancreas is r lated to the IVC, aorta, left renal vein and
kidney, and spleen.
• The portion lateral to the portal vein averages 56.4% of the total
weight.

8. • The pancreatic capsule is loosely attached to the surface of the
pancreas and is contiguous with the anterior layer of the mesocolon
such that it can be dissected in continuity if necessary.
• The mesenteric attachments to the pancreas tend to be contiguous

12. • PANCREATIC DUCTS
• The duct of Wirsung, beginning in the distal tail as a confluence of
small ductules, runs through the body to the head, where it usually
passes downward and backward in close juxtaposition to the CBD.
• The sphincter of Oddi has been thoroughly studied and consists of a
unique r of smooth muscle fibers distinguishable from the a cent
smooth muscle of the duodenal wall.

13. • The papilla of Vater at the termination of the CBD is a small, nipple-
like structure that protrudes into the duodenal lumen and is marked
by a longitudinal fold of duodenal mucosa.
• The duct of Wirsung runs downward and parallel to the CBD for
approximately 2 cm and joins it within the sphincter segment in 70%
to 85% of patients; it enters the duodenum independently in 10% to
13% of patients and is replaced by the duct of Santorini in 2% of
patients.

16. RELATIONS OF SURGICAL IMPORTANCE
• The head of the pancreas lies within the concavity of the duodenum
in front of the 2nd lumbar vertebra; the body lies in front of the 1st
lumbar vertebra and the upwardly sloping tail is at the level of the
12th thoracic vertebra.
• The common bile duct passes through the head of the pancreas and
the portal vein is incompletely surrounded by the neck, head and
uncinate process On its anterior, right lateral and posterior aspects.

17. • The stomach and spleen are separated from the anterior surface of
the body of the pancreas by the lesser sac.
• The tail of the pancreas projects a variable distance into the
lienorenal ligament and may come into contact with the hilum of the
spleen where it can be damaged during splenectomy.

18. • The retroperitoneal position of the pancreas contributes to the severe
epigastric pain radiating to the back in patients with acute pancreatitis.
In acute pancreatitis, collections of fluid with a high amylase content may form
in the lesser sac or in the retroperitoneal tissue behind the lesser sac. These
fluid collections are pseudopancreatic cysts which have no epithelial lining.
• The main pancreatic duct courses the length of the gland and hes
close to the upper surface of the gland. It joins the common bile duct
at the ampulla of Vater (see p. 89) and passes through the duodenal
wall. The duct of Santonni usually empties into the duodenum 2-3 cm
proximal to the ampulla.

19. ARTERIAL SUPPLY
• The arterial supply consists of a vertically directed system of arteries (from the
gastroduodenal and superior mesenteric arteries) around the head of the
pancreas and a horizontally directed system (from the splenic or coeliac arteries),
around the body and tail of the pancreas.
There is a rich anastomosis between the two systems.
• The anastomoses between the coeliac artery and the superior mesenteric artery
form an important collateral pathway if either of these vessels is occluded.
• The dorsal pancreatic artery, which arises from the coeliac artery or one of its
branches, may replace the middle colic artery and form part of the marginal
artery.

20. • In the operation of subtotal pancreatectomy, either the superior or
inferior pancreaticoduodenal artery may be divided.
division of both arteries causes necrosis of the duodenum.
• When the main pancreatic duct has to be drained, it may be opened
anteriorly to within 15 mm of the duodenum without serious
haemorrhage or duodenal ischaemia occurring.
• If the incision extends closer to the duodenal wall the anterior superior
pancreaticoduodenal artery will be damaged.

21. • Occasionally the hepatic artery arises from the superior mesenteric
artery in which case a pancreaticoduodenectomy might endanger the
blood supply to the liver.

23. VENOUS DRAINAGE
• Most of the veins draining the pancreas are tributaries of the splenic
vein. Other veins empty into the superior mesenteric and portal veins.
• In performing a pancreaticoduodenectomy for a carcinoma of the
ampulla of Vater, a plane of dissection has to be developed between
the neck of the pancreas and the portal vein. This has to be done
strictly anterior to the portal vein because veins draining the head of
the pancreas enter the right side of the portal vein and dissection to
the right of the portal vein will, therefore, result in tearing of the vein.

25. LYMPHATIC DRAINAGE
This is to the root of the superior mesenteric artery and then to the
coeliac nodes.
NERVE SUPPLY
• The sympathetic nerve supply is from the splanchnic nerves and the
parasympathetic supply is from the vagus.

26. • Afferent pain fibres are carried by the sympathetic nervous system
but bilateral sympathectomy is not effective in alleviating pain of
chronic pancreatitis or pancreatic carcinoma because intercostal
nerves and retroperitoneal tissue also become involved.
• Motor fibres are carried by both sympathetic and parasympathetic
systems.

27. PHYSIOLOGY
• The pancreas is composed of two major types of tissues
(1) the acini, which secrete digestive juices into the duodenum
(2) the islets of Langerhans, which secrete insulin and glucagon directly into the
blood.
• DIGESTIVE JUICE
• The pancreatic digestive enzymes are secreted by pancreatic acini,
and large volumes of sodium bicarbonate solution are secreted by the
small ductules and larger ducts leading from the acini.

28. • The combined product of enzymes and sodium bicarbonate then
flows through a long pancreatic duct that normally joins the hepatic
duct immediately before it empties into the duodenum through the
papilla of Vater, surrounded by the sphincter of Oddi.
• Pancreatic juice is secreted most abundantly in response to the
presence of chyme in the upper portions of the small intestine, and
the characteristics of the pancreatic juice are determined to some
extent by the types of food in the chyme.

29. • PANCREATIC DIGESTIVE ENZYMES
• Pancreatic secretion contains multiple enzymes for digesting all of the
three major types of food: proteins, carbohydrates, and fats.
• t also contains large quantities of bicarbonate ions, which play an
important role in neutralizing the acidity of the chyme emptied from
the stomach into the duodenum.

30. • The most important of the pancreatic enzymes for digesting proteins
are trypsin, chymotrypsin, and carboxypolypeptidase.
• Trypsin and chymotrypsin split whole and partially digested proteins
into peptides of various sizes but do not cause release of individual
amino acids.
• Carboxypolypeptidase splits some peptides into individual amino
acids, thus completing digestion of some proteins all the way to the
amino acid state.

31. • The pancreatic enzyme for digesting carbohydrates is pancreatic
amylase, which hydrolyzes starches, glycogen, and most other
carbohydrates (except cellulose) to form mostly disaccharides and a
few trisaccharides.
• The main enzymes for fat digestion are (1) pancreatic lipase, which is
capable of hydrolyzing neutral fat into fatty acids and monoglycerides;
(2) cholesterol esterase, which causes hydrolysis of cholesterol esters;
and (3) phospholipase, which splits fatty acids from phospholipids.

32. • When first synthesized in the pancreatic cells, the proteolytic digestive
enzymes are in their enzymatically inactive forms trypsinogen,
chymotrypsinogen, and procarboxypolypeptidase.
• They become activated only after they are secreted into the intestinal
tract.
• Trypsinogen is activated by an enzyme called enterokinase, which is
secreted by the intestinal mucosa when chyme comes in contact with
the mucosa.

33. • Chymotrypsinogen is activated by trypsin to form chymotrypsin, and
procarboxypolypeptidase is activated in a similar manner.
• Secretion of Trypsin Inhibitor Prevents Digestion of the Pancreas.
• It is important that the proteolytic enzymes of the pancreatic juice
not become activated until after they have been secreted into the
intestine because the trypsin and the other enzymes would digest the
pancreas.

34. • The same cells that secrete p teolytic enzymes into the acini of the pancreas
simultaneously secrete another substance called trypsin inhibitor.
• This substance, which is formed in the cytoplasm of the glandular cells,
prevents activation of trypsin both inside the secretory cells and in the acini
and ducts of the pancreas.
• In addition, because it is trypsin that activates the other pancreatic
proteolytic enzymes, trypsin inhibitor prevents activation of the other
enzymes as well.

35. • When the pancreas becomes severely damaged or when a duct
becomes blocked, large quantities of pancreatic secretion sometimes
become pooled in the damaged areas of the pancreas.
• Under these conditions, the effect of trypsin inhibitor is often overwhelmed,
in which case the pancreatic secretions rapidly become activated and can
literally digest the entire pancreas within a few hours, giving rise acute
pancreatitis.

36. • SECRETION OF BICARBONATE IONS
• The other two important components of pancreatic juice, bicarbonate
ions and water, are secreted mainly by the epithelial cells of the
ductules and ducts that lead from the acini.
• When the pancreas is stimulated to secrete copious quantities of
pancreatic juice, the bicarbonate ion concentration can rise to as high
as 145 mEq/L, a value about five times that of bicarbonate ions in the
plasma.

37. • This high concentration provides a large quantity of alkali in the
pancreatic juice that serves to neutralize the hydrochloric acid
emptied into the duodenum from the stomach.
• The basic steps in the cellular mechanism for secreting sodium
bicarbonate solution into the pancreatic ductules and ducts

38. 1. Carbon dioxide diffuses to the interior of the cell from the blood and, under the
influence of carbonic anhydrase, combines with water to form carbonic acid (H2 CO
3 ).
The carbonic acid dissociates into bicarbonate ions and hydrogen ions (HCO 3 and H +).
• Additional bicarbonate ions enter the cell through the basolateral membrane by co-
transport with sodium ions (Na + ).
• The bicarbonate ions are then exchanged for chloride ions (Cl − ) by secondary active
transport through the luminal border of the cell into the lumen of the duct.
• The chloride that enters the cell is recycled back into the lumen by special chloride
channels.

39. 2. The hydrogen ions formed by dissociation of carbonic acid inside the cell are
exchanged for sodium ions through the basolateral membrane of the cell by
secondary active transport.
• Sodium ions also enter the cell by co-transport with bicarbonate across the
basolateral membrane.
• Sodium ions are then transported across the luminal border into the pancreatic
duct lumen.
• The negative voltage of the lumen also pulls the positively charged sodium ions
across the tight junctions between the cells.

40. • 3. The overall movement of sodium and bicarbonate ions from the
blood into the duct lumen creates an osmotic pressure gradient that
causes osmosis of water also into the pancreatic duct, thus forming
an almost completely isosmotic bicarbonate solution.

42. • REGULATION OF PANCREATIC SECRETION
• Basic Stimuli That Cause Pancreatic Secretion
• Three basic stimuli are important in causing pancreatic secretion:
1. Acetylcholine, which is released from the p pathetic vagus nerve endings and from
other cholinergic nerves in the enteric nervous system
2. Cholecystokinin, which is secreted by the duodenal and upper jejunal mucosa
when food enters the small intestine
3. Secretin, which is also secreted by the duodenal and jejunal mucosa when highly
acidic food enters the small intestine

43. • The first two of these stimuli, acetylcholine and cholecystokinin,
stimulate the acinar cells of the pancreas, causing production of large
quantities of pancreatic digestive enzymes but relatively small
quantities of water and electrolytes to go with the enzymes.
• Without the water, most of the enzymes remain temporarily stored in
the acini and ducts until more fluid secretion comes along to wash
them into the duodenum.

44. • Secretin, in contrast to the first two basic stimuli, stimulates secretion of
large quantities of water solution of sodium bicarbonate by the pancreatic
ductal epithelium.
• Multiplicative Effects of Different Stimuli.
• When all the different stimuli of pancreatic secretion occur at once, the
total secretion is far greater than the sum of the secretions caused by each
one separately.
• Therefore, the various stimuli are said to “multiply,” or “potentiate,” one another.
Thus, pancreatic secretion normally results from the combined effects of the
multiple basic stimuli, not from one alone.

45. • Phases of Pancreatic Secretion
• three phases: the cephalic phase, the gastric phase, and the intestinal
phase.
• Cephalic phase
• During the cephalic phase of pancreatic secretion, the same nervous
signals from the brain that cause secretion in the stomach also cause
acetylcholine release by the vagal nerve endings in the pancreas.

46. • This signaling causes moderate amounts of enzymes to be secreted
into the pancreatic acini, accounting for about 20 percent of the total
secretion of pancreatic enzymes after a meal.
• Gastric Phase
• During the gastric phase, the nervous stimulation of enzyme secretion
continues, accounting for another 5 to 10 percent of pancreatic
enzymes secreted after a meal.

47. • Intestinal phase
• After chyme leaves the stomach and enters the small intestine,
pancreatic secretion becomes copious, mainly in response to the
hormone secretin.

48. ENDOCRINE FUNCTION
• The human pancreas has 1 to 2 million islets of Langerhans.
• Each islet is only about 0.3 millimeter in diameter and is organized
around small capillaries, into which its cells secrete their hormones.
• The islets contain three major types of cells—alpha, beta, and delta
cells—that are distinguished from one another by their morphological
and staining characteristics.

50. • The beta cells, constituting about 60 percent of all the cells of the
islets, lie mainly in the middle of each islet and secrete insulin and
amylin, a hormone that is often secreted in parallel with insulin,
although its function is not well understood.
• The alpha cells, about 25 percent of the total, secrete glucagon, and
the delta cells, about 10 percent of the total, secrete somatostatin.

51. • In addition, at least one other type of cell, the PP cell, is present in
small numbers in the islets and secretes a hormone of uncertain
function called pancreatic polypeptide.
• The close interrelations among these cell types in the islets of
Langerhans allow cell-to-cell communication and direct control of
secretion of some of the hormones by the other hormones.
• insulin inhibits glucagon secretion, amylin inhibits insulin secretion, and
somatostatin inhibits the secretion of both insulin and glucagon.

53. INTRODUCTION
• Current World Health Organization estimates are that about 9% of the
global population have diabetes; approximately 10% of this
population has type 1 diabetes
• The aims of pancreas transplantation are to
• restore normoglycaemia,
• freedom from insulin therapy,
• to limit the progression of complications associated with diabetes.

54. • Pancreas transplantation is most commonly (but not exclusively)
performed in individuals with type 1 diabetes with end-stage renal
disease.
• Current data indicate that more than 42 000 pancreas transplants
have been performed worldwide, with the majority having been in
the USA.

55. HISTORY
• Kelly, Lillehei and colleagues performed the frst successful pancreas
transplant in a human at the University of Minnesota, USA, in 1966.
• Initial results were poor, with high mortality associated with sepsis,
rejection and other complications, but over the subsequent 30 years
there was a steady increase in the numbers of pancreas transplants
and an improvement in outcomes.

56. • Important factors in this improvement were changes in surgical
techniques and the introduction of the immunosuppressive agent
ciclosporin in the mid-1980s: this reduced both the need for steroids
and the incidence of rejection.
• The introduction of tacrolimus and mycophenolate mofetil as
maintenance immunosuppression and the use of T-cell-depleting
agents such as rabbit antithymocyte globulin (ATG) and alemtuzumab
in the 1990s and 2000s resulted in further reductions in cellular
rejection rates and improved graft survival.

57. TYPES OF SOLID ORGAN PANCREAS
TRANSPLANT
1. Simultaneous pancreas–kidney transplant (SPK)
• Both organs come from the same deceased donor.
• This is the commonest type of pancreas transplant and is indicated in patients
with chronic renal failure (on or close to requiring dialysis) secondary to
diabetes.
2. Pancreas transplant alone (PTA)
• Primarily for patients with type 1 diabetes who have repeated episodes of
hypoglycaemia associated with unawareness (i.e. patients develop
hypoglycaemic coma without warning).

58. 3. Pancreas-after-kidney transplant (PAK)
• Deceased donor pancreas transplantation is performed after a previous
kidney transplant, from either a living or deceased donor.
4. Simultaneous deceased donor pancreas and live donor kidney
transplant
• This option may shorten waiting times but is logistically very challenging and
rarely performed.

59. • Transplantation of the islets of Langerhans (islet cell transplant) is
an alternative to pancreas transplant alone for patients with
hypoglycaemic unawareness.
• ISLET CELL TRANSPLANT
• After pancreas retrieval, islets are isolated, prepared and delivered into the
portal vein (PV) of the recipient, usually via a percutaneous transhepatic
radiologically guided procedure.
• Immunosuppression is required for islet transplantation and the associated
long-term risks need to be balanced with the treatment benefits.

60. INDICATION
• The indications for pancreas transplant can be split into those for
patients with concomitant renal failure and those without.
• SPK is the most frequently performed procedure for patients with
type 1 diabetes and renal failure due to diabetic nephropathy.
• There is a small population of patients with type 1 diabetes with renal
failure due to primary renal disease or non-diabetic causes and they
are also included in this group.

61. • SPK indications as defned by the NHS Blood and Transplant Pancreatic
Advisory Group (NHSBT PAG) include
• type 1 diabetes with end-stage renal failure requiring dialysis or dialysis
predicted within 6 months (glomerular fltration rate [GFR] <20 mL/min).
• Patients with type 1 diabetes without renal failure but with life-
threatening hypoglycaemic unawareness are potential candidates of
solid organ PTA or islet transplantation.

62. • Patients with type 2 diabetes can also be considered for SPK, although
after careful selection.
• Suitable candidates are non-morbidly obese patients, typically with
insulin requirements of less than <1 unit/kg body weight in 24 hours
(to exclude patients with insulin resistance). When selected in this
way, the results of SPK in these patients are similar to those in
patients with type 1 diabetes.

63. PATIENT SELECTION
• Once the indication for pancreas transplantation is satisfed the patient needs a
comprehensive assessment of cardiovascular and surgical fitness.
• If cardiac assessment demonstrates occult ischaemic heart disease (IHD) then
angiography and revascularisation via angioplasty or bypass surgery may be needed
prior to wait-listing.
• Patients with diabetic nephropathy usually have other manifestations of secondary
diabetic complications, including sensory neuropathy, retinopathy, , peripheral
vascular disease, and autonomic neuropathy leading to postural hypotension.
• These complications should be sought and discussed prior to listing as they can have an
impact on whether a pancreas transplant is appropriate and may alter the surgical strategy.

65. ORGAN DONATION AND PRESERVATION
• Organ retrieval
• Pancreas organ retrieval is standardised in the UK and is carried out
by dedicated abdominal organ retrieval teams.
• Donation after brain death (DBD) donors constitute 75% of all
pancreas donors with donation after circulatory death (DCD) donors
making up 25%.
• The pancreas can be retrieved either alone or en bloc with the liver.

66. • If the liver and pancreas are retrieved en bloc the retrieval surgeon
separates the organs, ensuring that there is 10 mm of PV and an
adequate length of splenic artery (SA) and superior mesenteric artery
(SMA) for reconstruction.
• The bifurcation of the iliac vessels is sent with the pancreas to
facilitate a vascular Y-graft construction, creating a single arterial
infow.

68. • Only around 50% of pancreases that are retrieved with the intention
of transplantation are actually transplanted. This is because
• The condition of the pancreas is frequently suboptimal owing to fatty
infltration or fbrosis, features that are associated with a poorer outcome.
• Also, injury to the pancreas during retrieval is much more common than in
other organs: it is easily damaged and the consequences of even a relatively
minor parenchymal injury can be severe, with postoperative leakage of
exocrine secretions

69. • Acceptance criteria for pancreases varies between centres and is
usually related to donor age, BMI, alcohol intake and lifestyle factors.
• ORGAN PRESERVATION
• Static cold storage (SCS) has remained the gold standard preservation
method for the pancreas graft since the frst transplantation was
performed in 1966.

70. • Hypothermic preservation is based on the principle that cooling an organ
reduces the metabolic rate and the demand for adenosine triphosphate (ATP).
• The pancreas is extremely sensitive to both warm and cold ischaemia, which
has a signifcant impact on preservation.
• Once retrieved from the donor, the pancreas is inspected for any damage and
for adequacy of perfusion and then submerged in preservation solution
within an organ bag and placed in an icebox for transport to the transplant
centre.

71. • Unlike other organs the pancreas is not flushed following retrieval in
order to minimise endothelial damage and (supposedly) to reduce the
risk of early graft pancreatitis and thrombosis.
• Early pancreas transplants sufered from a signifcant thrombosis rate of
up to 25%.
• For this reason, in 1986 Belzer and Southard set out to redefne the
needs of pancreas preservation by developing a new preservation
solution.

72. • This new solution – University of Wisconsin (UW) solution – was first
successfully applied in experimental pancreas transplantation;
• The colloid constituent, hydroxyethyl starch (HES), was particularly important
in the pancreas, especially in suboptimal organs and those with longer cold
ischaemia times. Translation to clinical use of the UW solution led to a
signifcant improvement in the results of pancreas transplantation and a
marked reduction in pancreatitis and thrombosis of the grafts.

73. • There have been studies in experimental pancreas preservation using
hypothermic machine perfusion
- In these studies the organ is continuously pumped with a cooled solution.
• Normothermic machine perfusion of pancreases has been performed
on animal and discarded human organs but led to organ injury,
possibly because of high concentrations of autolytic enzymes
(amylase and lipase).

74. • Normothermic regional perfusion is a technique in which, following
cessation of circulation in a DCD organ donor, the donor blood is
warmed, oxygenated and then pumped back around the abdominal
organs.

76. SURGICAL TECHNIQUES
• Preparation for transplant
• Once the organ has been inspected and is deemed suitable for transplant
it needs to be prepared for implantation.
• This is a crucial step and meticulous attention to detail and a systematic
approach are vital to minimise bleeding and complications after
reperfusion.
• The pancreas is retrieved with the spleen attached, a length of duodenum
and the cut ends of the SMA, SA and PV.

77. • The splenic vessels are ligated and the spleen removed; the duodenum
is shortened, stapled and the staple lines buried with a suture.
• Excess fat and omentum are removed, and the cut end of the inferior
mesenteric vein ligated.
• An arterial ‘Y-graft’ is usually fashioned between the SMA and SA of
the pancreas using donor iliac vessels, so that the end of the common
iliac artery (CIA) can be used for a single arterial anastomosis.

79. • TRANSPLANTATION PROCEDURE
• Pancreas transplant can be performed as an intraperitoneal or
extraperitoneal procedure and the exocrine drainage of the pancreas
can be managed by connection to the small intestine or urinary
bladder.
• The majority of surgeons favour an intraperitoneal approach as the
peritoneal cavity has an excellent capacity for containing and
reabsorbing fuid generated as a result of reperfusion pancreatitis.

81. • The steps of the surgical procedure are as follows.
• A midline laparotomy is performed and the retroperitoneum is exposed.
• The inferior vena cava (IVC) and CIA are dissected and controlled.
• In the enteric drainage procedure (donor duodenum anastomosed to
recipient jejunum) the organ is positioned with the head of the pancreas
towards the liver and the tail towards the pelvis.

82. • However, for bladder drainage (donor duodenum anastomosed to recipient
urinary bladder) the organ is positioned with the head facing towards the
pelvis and tail towards the liver.
• A side-biting vascular clamp is used to partially occlude the IVC and the PV is
anastomosed end to side to the IVC.
• Whether performing a single arterial anastomosis or separate SMA and SA
anastomoses, the right CIA is most frequently used.
• Heparin is administered prior to clamping the CIA and the arterial anastomosis is
performed.

83. • The organ is reperfused and haemostasis is ensured before
performing the duodenal anastomosis (this renders the organ less
mobile and more difcult to access).
• For enteric drainage, the jejunum is identifed as close as convenient
to the duodenojejunal fexure and anastomosed side to side to the
duodenum in two layers.

84. • This can be performed by passing the duodenum through a window in
the colonic mesentery, using a Roux-en-Y technique or with the two
sections of bowel lying adjacent underneath the colon.

85. • The Roux-en-Y technique creates a blind-ending loop of bowel; if
severe complications develop and the pancreas needs to be removed,
then separation from the main enteric flow is straightforward and the
need for a defunctioning stoma is avoided.
• In the bladder drainage technique, the anastomosis to the bladder is
also performed in two layers and a urinary catheter is kept in place for
7–10 days to reduce the chance of anastomotic leak.

87. • Enteric conversion
• Bladder drainage of the exocrine secretions is associated with complications
that may require conversion to enteric drainage.
• Enteric conversion is performed in patients to eliminate these complications
of bladder drainage
• It is usually delayed until 1 year post transplant but can be performed
sooner if indicated.

88. • A lower midline laparotomy is performed and the urinary bladder is
flled and the transplant duodenum is identifed.
• The transplant duodenum is disconnected from the bladder and the
bladder is closed in two layers.
• An adjacent section of small bowel is identifed and a longitudinal
enterotomy is performed on the antimesenteric border; the
anastomosis to the duodenum is completed in two layers.

89. • Surgical drains are placed adjacent to the anastomoses and a urinary
catheter is usually kept in place for 14 days.

90. POSTOPERATIVE MANAGEMENT
• ANTICOAGULATION
• To minimise the risk of graft thrombosis in the early postoperative
period anticoagulation is indicated for all patients.
• Intravenous un fractionated heparin, dextran or epoprostenol are
examples of preparations used
• Monitoring of their efect can be achieved by measuring prothrombin
time (PT) and/or thromboelastography (TEG).

91. • Patients usually require 24–48 hours of high-dependency care (high-
dependency unit or intensive care unit) and close blood glucose
monitoring is essential.
• Insulin secreted by the transplant pancreas drains directly into the IVC
and straight into the systemic circulation without passing through the
liver, thereby avoiding frst-pass metabolism.
This is unlike normal physiology where insulin drains via the portal vein through
the liver.

92. • As a result of high systemic insulin levels the patient may require
intravenous glucose supplementation to maintain blood glucose
levels.
• If blood glucose levels rise above 144mg/dL, then cross-sectional
imaging with arterial phase contrast is usually performed to assess for
thrombosis.

93. • The presence of a small volume of thrombus in the distal ligated end
of the SMA is considered normal.
• However, thrombus propagating from the stump into the SMA, SA
thrombus or PV thrombus should be treated with full anticoagulation.
• The indication for surgery is limited to complete thrombosis of the
arterial inflow or PV; thrombectomy usually fails, resulting in graft
pancreatectomy.

94. • COMPLICATIONS:
• Intraoperative complications such as bleeding following reperfusion
can lead to the need for blood transfusion and inotropic support.
• Reperfusion pancreatitis (a manifestation of ischaemia–reperfusion-
related injury) can result in an amylase-rich transudate around the
pancreas and in the abdominal cavity. Drainage may be necessary to
aid recovery.

95. • Thrombosis afects up to 8% of patients and this may result in early graft
loss or β-cell dysfunction.
• Anastomotic leaks, particularly from the duodenum, are rare but difcult
to manage; they can be controlled with direct drainage, such as a Foley
catheter within the duodenum.
• Bladder-drained pancreases can cause cystitis from pancreatic enzyme
secretion and electrolyte disturbance, acidosis and dehydration from
the loss of bicarbonate.

96. • Up to 50% of patients with bladder-drained pancreas transplants
require enteric conversion (where the transplant duodenum is
surgically detached from the bladder and reconnected to the small
bowel) within the frst year following transplant.
• Late complications of pancreas transplantation include
pseudoaneurysm formation, which may result from fungal infection or
a vascular anastomosis, and highlights the importance of culturing the
preservation fuid at the time of transplant and treating any cultured
microorganisms.

98. IMMUNOSUPPRESSION AND FOLLOW-UP
LONG TERM MONITORING
• Blood glucose monitoring is reassuring for the patient but, once glucose levels
are raised as a result of graft rejection, it is usually too late to reverse.
• Haemoglobin A1c (HbA1c) levels are an independent predictor of long-term graft
function and oral glucose tolerance testing can also be used to assess organ
dysfunction and aid management.
• Fasting C-peptide and insulin levels can also give an idea of pancreatic function.

99. • Cellular rejection is difcult to diagnose owing to the absence of a biomarker
• In patients who have undergone SPK, serum creatinine can be used as a
surrogate marker and renal biopsy performed, although discordant
rejection of kidney and pancreas is a well-recognised event.
• In PTA, the exocrine secretions can be managed by anastomosis with the
urinary bladder, which means that urinary amylase can be measured
sequentially and used as a biomarker of pancreatic function and a surrogate
for rejection.
• A reduction in levels of urinary amylase may indicate rejection

100. • Computed tomography angiography may show peripancreatic
infammation, which would be consistent with rejection and be an
indication for rescue therapy.
OUTCOMES
There are no randomised controlled trials that compare the outcome of
SPK transplantation with kidney transplantation alone, so best practice
has mostly been determined from registry analyses and single-centre
experiences.

101. • Adjusted 10-year patient survival rates were 67% for SPK recipients,
65% for LD kidney recipients and 46% for deceased donor kidney
recipients.
• In the UK, 1- and 5-year pancreas graft survival for patients undergoing
their frst SPK is 90% and 81%, respectively.
• PTA has the poorest long-term survival because of high rates of early
thrombosis and cellular rejection but provides exogenous insulin
production to treat the complications detailed above.

102. • For pancreas alone transplants the outcomes are still inferior with 1-
and 5-year pancreas graft survival of 82% and 54%, respectively.
IMMUNOSUPRESSION
• Immunosuppression is split into induction (immediate post
transplant) and maintenance (long term) therapy.

103. • Induction therapies include non-depleting antilymphocyte antibodies that
cause T-cell inactivation, such as basiliximab, which blocks the interleukin-
2 receptor and inhibits T-cell expansion.
• T-cell-depleting antibodies have largely replaced non-depleting therapies
as a more effective way of suppressing lymphocytes.
• These include polyclonal ATG and the monoclonal antibody alemtuzumab (Sanof).
• Alemtuzumab is easier to administer and is associated with lower rates of
viral infection than ATG, so is preferred by some transplant units.

104. • Maintenance immunosuppression has evolved from triple therapy
with ciclosporin, azathioprine and steroid to current practice with
tacrolimus and mycophenolate mofetil.
• Steroid-free regimes are aimed at minimising insulin resistance and
wound infection.

105. • Comparison of ciclosporin with tacrolimus in combination with
mycophenolate mofetil (MMF) and steroid, plus induction with ATG,
in the EUROSPK 001 trial showed a reduction in the rates of severe
rejection, with lower rates of pancreas graft loss at 3 years in the
tacrolimus combination group.

107. FUTURE WORK
• The major limiting factor in pancreas transplantation is greater
morbidity compared with kidney transplantation alone.
• This is largely a function of the immediate reperfusion pancreatitis
that is a common sequel to implantation.
• A second limitation is the very poor utilisation of donor organs: in the
UK, only 25% of organs that are ofered are actually transplanted.

108. • The development of novel preservation methods, such as machine
perfusion, has been successful in other organs, but there has been no
such advance in pancreas transplantation – this is largely a function of
the relatively small numbers of patients undergoing this procedure.
• New methods of graft surveillance to detect rejection or other
complications at a much earlier stage are also needed.
• If it were possible to reduce the morbidity and improve the survival of
pancreas transplants to the same level as kidney transplants, the
indications for this procedure would expand, possibly allowing
patients to beneft before developing kidney failure.

109. THANK YOU