Parissa Tabrizian1, Kiumars Ranjbar Tabar2, Ron Shapiro1, Kishore R. Iyer1, and Sander Florman1
1 Icahn School of Medicine at Mount Sinai, New York, NY, USA
2 Allegheny Health Network, Pittsburgh, PA, USA
Liver transplantation
Background
Orthotopic liver transplantation (OLT) is the treatment of choice for selected patients with end‐stage liver disease and acute liver failure.
The first human OLT was performed by Dr. Thomas Starzl in 1963.
With the development of surgical techniques and the introduction of newer and more effective immunosuppressive medications, survival has now reached 70–80% at 5 years.
Organ allocation has also evolved over time, with the current system based upon the model for end‐stage liver disease (MELD) score (see Chapter 39), prioritizing patients based upon the severity of their disease and likelihood of death without transplantation.
Non‐cholestatic cirrhosis is the most common diagnosis of patients on the waiting list for liver transplantation.
Indications and contraindications
With improvement in medical and surgical techniques, conditions prohibiting transplantation have decreased over time, and most contraindications have become relative rather than absolute.
Assessment of overall health and performance status
Severe malnutrition or morbid obesity
Associated with poor outcome, technical challenges
Other organ failure
Consideration for multiorgan transplantation
Complex previous upper abdominal surgery
Not technically feasible
Poor functional status
Associated with poor outcome
Poor medical compliance
Unlikely to comply with immunosuppression
Absolute contraindications
Severe cardiopulmonary disease
Heart/lung disease that would prevent a successful operation
Irreversible cerebral injury
Elevated intracranial pressure unresponsive to treatment
Sepsis/active infection
Severe uncontrolled systemic infection
HIV/AIDS
Untreated AIDS, unresponsive to treatment
Extrahepatic malignancy
Disease‐free period of <2 years depending on the type of malignancy
Vascular
Anatomic variations, extensive portal and mesenteric vein thrombosis leading to technical difficulties
Active chronic alcohol and drug usage
Required abstinence for a minimum of 6 months
Psychosocial issues
Severe disorder, lack of social support
Techniques
Whole liver recipient procedure
Step 1: total hepatectomy via bilateral subcostal incisions with or without midline extension to the xiphoid process.
Step 2: assessing the need for veno‐venous bypass. This involves the extracorporeal circulation of blood from the venous system below the caval clamps (inferior mesenteric and femoral veins) and return to the central veins (axillary or internal jugular veins). This procedure is, however, associated with major complications (up to 30%) including lymphocele, hematomas, coagulopathies, plexus injury, and fatal pulmonary emboli. Relative indications of the use of veno‐venous bypass are pulmonary hypertension, poor left ventricular function, fulminant hepatic failure, renal failure, severe portal hypertension, and massive bleeding during the hepatectomy.
Step 3: implantation and caval techniques:
Standard technique with caval replacement (Figure 40.1): requiring anastomosis of supra‐ and infrahepatic cava.
Piggyback technique (Figure 40.2): this technique avoids caval cross clamping and preserves the retrohepatic native IVC. It helps maintain IVC flow during the anhepatic phase, therefore preserving venous return to the heart and minimizing effects related to full clamping. Potential additional advantages that have been described with this technique are reduction of renal dysfunction, reduced warm ischemia time, and less bleeding.
Step 4: portal reconstruction: end–end anastomosis or graft to native superior mesenteric vein (retrogastric/retrocolic).
Step 5: arterial reconstruction: end–end anastomosis or arterial graft to native aorta (retrogastric/retrocolic).
Step 6: biliary reconstruction: duct‐to‐duct with/without T‐tube or Roux‐en‐Y hepaticojejunostomy.
Special considerations and technique
Pre‐existing portal vein thrombosis: partial vein thrombectomy or donor iliac vein grafts from the superior mesenteric vein (tunneled retrogastric/retrocolic).
Hepatic artery dissection or inadequate flow: donor interposition graft to native aorta (retrogastric/retrocolic).
Pre‐existing transjugular intrahepatic portosystemic shunt (TIPS): incision of the pericardium and intrapericardial control of the suprahepatic cava may be necessary to remove TIPS that extends into the heart.
Partial liver recipient procedure
This includes reduced size, split, and living donor liver transplantation.
The piggyback technique is mandatory.
The actual splitting can be performed ex vivo or in situ in a manner analogous to living donor liver transplantation, at the discretion of the surgeon performing the procedure.
Immunosuppression
Tacrolimus (FK506), a calcineurin inhibitor (CNI) is used as the first line drug in OLT.
Corticosteroids have been the mainstay for induction of immunosuppression.
Antimetabolites such as mycophenolate mofetil (MMF) are used in combination with steroids and CNIs to reduce CNI‐related renal insufficiency and to prevent rejection.
Complications
Early complications
Hemorrhage
Primary non‐function
Early graft dysfunction
Acute cellular rejection
Hepatic artery or portal or hepatic vein thrombosis
Biliary stricture or leak
Infections (bacterial, viral, fungal)
Late complications
Recurrence of disease (HCV, HBV, NASH, autoimmune disease)
Two, 5, and 10 year survival in patients undergoing transplantation is 94%, 79%, and 60%, respectively.
Graft survival at 2, 5, and 10 years is 87%, 75%, and 59%, respectively.
Recurrence of disease is an important determinant of survival as some conditions do not recur after transplant, while others may recur.
Kidney transplantation
Background
The first successful kidney transplant was with a living donor between identical twin brothers in 1954.
With the development of 6‐mercaptopurine, followed by azathioprine in the early 1960s, and implementing the use corticosteroids, the medical community has witnessed great advances in patient and graft survival rates in kidney transplantation.
As knowledge of the immune system evolved, the first polyclonal antilymphocyte globulin was used in 1967, ciclosporine was introduced in 1980s, followed by the introduction of MMF and tacrolimus in 1990s in kidney transplantation.
Kidney transplantation, depending on the source of the donor organ, is classified as deceased donor/cadaveric or living donor transplantation.
Living donors are genetically related (living related) or non‐related (living unrelated), depending on whether a biologic relationship exists between the donor and recipient.
Currently, there are over 120 000 people waiting for a life‐saving organ transplant in the USA, among whom about 100 000 are on the kidney transplant waiting list.
Indications and contraindications
Kidney transplantation is definitive treatment for eligible patients with end‐stage renal disease (ESRD) (creatinine clearance <20 mL/min) regardless of the primary cause.
Indications
Contraindications
Chronic glomerulonephritis
Chronic illness with life expectancy of less than 1 year
Systemic arterial hypertension
AIDS untreated or unresponsive to treatment
Fabry’s disease
Sepsis
Hyperoxaluria
Advanced cardiovascular disease
Diabetes mellitus
Poor respiratory status
Unknown renal insufficiency
Cancer (active/unresolved)
Obstructive and toxic uropathy
Psychosocial
Alport’s syndrome
Polycystic kidney disease
Nephrotic syndrome
Chronic obstructive pyelonephritis
Lupus nephritis
Focal segmental glomerulosclerosis
Technique
Regardless of the donor type, the kidney transplant operation is the same.
The standard kidney transplant procedure with heterotopic pelvic approach has been widely accepted for its multiple advantages and is considered the standard (Table 40.1).
Internal iliac should not be used except in specific situations
Ureteral anastomosis
Extravesicular implantation at the anterolateral surface of the bladder is the method of choice
Double J stenting prevents major urinary complications
Utero‐ureteral anastomosis is an alternative to a very short or poorly vascularized transplant ureter
Kidneys from donor <15 kg
En bloc transplantation including aorta and IVC
The ureters are implanted either separately or after partial anastomosis using an extravesical technique
Special considerations
If the iliac arteries do not allow clamping, endarterectomy or vascular prosthesis should be considered
If the iliac vein/vena cava is thrombosed, the native renal vein or SMV can be used
Complications
Early complications
Late complications
Acute rejection/acute renal failure
Ureteral stenosis
Infection
Reflux and acute pyelonephritis
Hemorrhage
Kidney stones
Incisional hernia
Renal artery stenosis
Urinary fistula
AVF and pseudoaneurysms
Arterial thrombosis
Lymphocele
Venous thrombosis
Chronic allograft dysfunction
Delayed graft function
Recurrent disease
Malignancy
Immunosuppression
Immunosuppressive drugs are started in the operative room with thymoglobulin (2 mg/kg) and methylprednisolone (500 mg) to suppress the immune system from rejecting the donor kidney.
Thymoglobulin (2 mg/kg) is given on postop day 1 and 2 to complete a total dose of 6 mg/kg. Steroids are tapered and withdrawn after 3 days. In high risk patients the steroid is tapered and maintained for at least 1 year. Note that a number of transplant programs utilize non‐depleting antibody induction in the form of basiliximab 20 mg IV intraoperatively and on postop day 4.
Tacrolimus and MMF are started on postop day 1.
Graft survival
One year survival (living donor): 99%.
Three year survival (living donor): 91%.
One year survival (deceased donor): 88%.
Three year survival (deceased donor): 77%.
Pancreas transplantation
Background
Since the first pancreas transplant performed in 1967, there have been over 1200 pancreas transplants performed annually in the USA.
In most cases, pancreas transplantation is performed in the setting of type 1 diabetes and ESRD.
The three main types of pancreas transplantation are:
Simultaneous pancreas–kidney (SPK) transplantation (Figure 40.3), where the pancreas and kidney are transplanted from the same deceased donor. Performed in two‐thirds of cases.
Pancreas after kidney (PAK) transplantation, where the deceased donor pancreas transplant is performed after a living or deceased donor kidney transplant.
Significant improvements in surgical techniques, organ preservation, and anti‐rejection protocols have made pancreas transplantation an effective therapy for some diabetic patients, and serves to enhance their quality of life and long‐term survival.
Indications and contraindications
In the majority of, cases, pancreas transplantation is performed in individuals with type 1 diabetes with ESRD and associated complications, such as uremia, retinopathy, progressive neuropathy, and hypoglycemic unawareness.
Living donor pancreas transplantation represents only 0.5% of pancreas transplants performed. Long‐term benefits to the recipient must be balanced against both short and long term risks to donors/recipients before this procedure can be advocated.
Acceptance criteria for pancreas transplantation at Mount Sinai Medical Center
Patient on insulin with C peptide value ≤2 ng/mL.
Patient on insulin with a C peptide ≥2 ng/mL and a BMI less than or equal to the Organ Procurement Transplantation Network (OPTN) maximum allowable BMI (currently 28).
Insulin requirement 0.5 U/kg/day if on dialysis and 0.7 U/kg/day if not on dialysis.
Pancreas transplant alone indicated for documented frequent and life‐threatening hypoglycemic unawareness and preserved renal function (Cr clearance >70).
Contraindications
Absolute contraindications to pancreatic transplant include untreated infection at the time of transplant, chronic illness with life expectancy of less than 1 year, and active substance abuse.
Relative contraindications are those which require careful evaluation and possible therapy prior to transplant. These include cirrhosis of the liver (clinical or pathologic diagnosis) and HIV infection (unless the individual is on appropriate medications, has an undetectable viral load, does not have AIDS‐related complications, and has a CD4 >200).
Other contraindications include advanced COPD, severe coronary artery disease, severe congestive heart failure with ejection fraction <20%, and active or recent malignancy (other than superficial skin cancers).
The candidacy and waiting time for clearance will be discussed on a case‐by‐case basis for the following conditions: proven habitual medical non‐compliance, uncontrolled psychiatric condition, active systemic lupus requiring more than 10 mg/day prednisone, lack of cognitive capacity to make informed decisions, understand procedure, and sign the consent, obesity (where the benefits of transplantation do not outweigh the risks of the procedure), severe peripheral vascular disease, and severe cerebrovascular disease.
Guidelines for acceptance of deceased donor pancreas at Mount Sinai Medical Center
Donor age <50 years.
Donor BMI <30.
There should be no history of active alcohol abuse.
Total cold ischemia time should be less than 24 hours.
Preservation of intact pancreato‐duodenal arterial arcade, splenic artery, and superior mesenteric artery.
Pancreas donor grading system
Usable: absence of edema, nodularity, and fatty infiltrate.
Usable in most cases: mild disease, fat infiltrate <20%, mild nodularity but soft, mild edema.
Not usable: any of the following factors – fat infiltrate >20%, firm, significant nodularity, significant edema.
Techniques of exocrine and venous drainage (Tables 40.3 and 40.4)
Immunosuppression
Pancreas transplant (SPK/PTA) immunosuppression starts with induction protocol of methylprednisolone (10 mg/kg) and thymoglobulin (2 mg/kg; total dose 6 mg/kg) intra‐operatively. Methylprednisolone will be switched to prednisone postoperatively and tapered for at least a year in the majority of cases.
Intravenous immunoglobulin (IVIg) is indicated for patients with either positive CDC or positive T‐cell/B‐cell flow cytometry cross match as well as patients with donor‐specific anti‐HLA antibodies. IVIg is given at 1000 mg/kg starting 2 hours before transplantation, 500 mg/kg on postop day 1, and 500 mg/kg on postop day 2.
The most common regimen used for maintenance immunosuppression includes tacrolimus and MMF as triple therapy in conjunction with prednisone. Steroids may be discontinued after a year in selected patients with a low risk of rejection and stable graft function.
Table 40.2Advantages and disadvantages of the different types of pancreas transplant.
Category
Advantage
Disadvantage
Simultaneous kidney‐pancreas transplant (SPK)
Rejection can be monitored by transplant kidney function Immunosuppresion already needed for kidney transplant Better quality of life
Longer waiting list than pancreas transplant with living donor kidney transplant Increased risk of surgery than kidney transplant alone
Pancreas transplant alone (PTA)
Better quality of life
Rejection should be monitored Life‐long immunosuppression Risk of peri‐operative morbidity
Pancreas after kidney transplant (PAK)
Better quality of life Immunosuppression already started for previous kidney transplant
Rejection should be monitored Risk of peri‐operative morbidity
Simultaneous deceased donor pancreas and living donor kidney
Shorter waiting time Immunosuppression already needed for kidney transplant
Rejection should be monitored Increased risk of surgery than kidney transplant alone
Islet cell transplant
No need for surgery
Lower success rate (insulin independence) Multiple injections may be needed
Graft portal vein anastomosed to the recipient inferior vena cava or external iliac vein
Easier technique Lower rate of graft thrombosis due to high flow systemic system
Not physiologic Hyperinsulinemia Long‐term dyslipidemia
Portal drainage
Graft portal vein anastomosed to the recipient superior mesenteric vein
Physiologic
More difficult technique Higher rate of graft thrombosis due to low flow portal system
Complications
Early complications
Late complications
Thrombosis
Urinary tract infections/hematuria
Hemorrhage
Sterile cystitis, urethritis, balanitis
Reperfusion pancreatitis
Metabolic acidosis
Peripancreatic abscess
Reflux pancreatitis
GI bleeding or hematuria
Arterial stenosis (Y graft or native iliac)
Leak (bladder or bowel)
Rejection related
Complication of biopsy
Arterial fistulae
Outcomes
Procedure
1 year survival
5 year survival
SPK
86%
74%
PAK
79%
62%
PTA
74%
51%
Small bowel and multivisceral transplantation
Background
The first case of human bowel transplantation was reported in 1967. The first multivisceral transplantation performed in the USA was in 1987.
Small bowel transplantation (SBT) is one of the most technically challenging procedures and the least commonly performed solid organ transplantation procedure worldwide.
SBT can be done as an isolated procedure (47%), combined small bowel/liver (27%), or small bowel/liver combined with other organs, including stomach, pancreas, or kidney (multivisceral transplantation).
Current survival rates of intestinal transplantation have improved significantly and are similar to other organ transplants.
Indications in adults
Intestinal transplant (Figure 40.4) is a therapeutic option for patients with intestinal failure, defined as the inability to maintain sufficient electrolyte nutrient and fluid balance for >1 month without TPN.
Indications for transplantation include intestinal failure and one of the life‐threatening complications of parenteral nutrition. These include loss of venous access (thrombosis of two or more central venous access sites), recurrent life‐threatening catheter‐associated bloodstream infections, frequent episodes of severe dehydration despite TPN and IV fluid supplementation, and the development of intestinal failure‐associated liver disease.
Intestinal failure Catheter‐related infections Poor venous access Moderate hepatic dysfunction Severe fluid and electrolyte imbalance that cannot be managed with TPN
Intestinal failure Irreversible hepatic failure or coagulopathy
Thrombosis Anatomic Following extensive surgical resection of abdominal organs for aggressive tumor or severe abdominal trauma
Venous outflow
Portal vein (into IVC or portal vein)
Suprahepatic IVC (hepatic piggyback anastomosis)
Suprahepatic IVC (hepatic piggyback anastomosis)
Arterial inflow
Superior mesenteric artery
Celiac and superior mesenteric artery
Celiac and superior mesentenric artery
Biliary reconstruction
No need
Roux‐en‐Y hepatico‐jejunostomy (no need if graft includes pancreas)
No need (Roux‐en‐Y if graft does not include liver)
Proximal GI tract
Jejuno‐jenunostomy
Jejuno‐jenunostomy
Esophago‐ or gastro‐gastrostomy
Distal GI tract
Ileocolostomy with various type of stoma (loop, Mikulicz, Bishop–Koop)
Ileocolostomy with various type of stoma (loop, Mikulicz, Bishop–Koop)
Ileocolostomy with various type of stoma (loop, Mikulicz, Bishop–Koop)
Immunosuppression
SBT induction immunosuppression starts in the operating room with high dose methylprednisolone (20 mg/kg), and prednisone will be continued at least for a year in a tapering fashion.
Thymoglobulin (2 mg/kg) is also infused as an induction agent in the operating room and will be repeated for two more doses to achieve a total amount of 6 mg/kg.
Maintenance immunosuppression begins on postop day 1, with tacrolimus for life.
Complications
Early complications of SBT are mostly surgical. Anastomosis leak with intra‐abdominal infection, graft vessel thrombosis, and bleeding are not uncommon and necessitate surgical exploration.
Intermediate to late complications include rejection, bacterial and viral infection (EBV, CMV, adenovirus), GVHD, and post‐transplant lymphoproliferative disorder.
Rejection is the most common cause of graft loss and requires immediate biopsy when suspicion arises and treatment.
Post‐transplant lymphoproliferative disorder can manifest between 2 weeks and 6 months after transplantation. Depending on the clinical status, treatment can range from reducing/discontinuing immunosuppression to chemoradiotherapy.
Outcomes
One year survival after isolated intestinal transplantation is 79%.
Reading list
Fishbein TM. Intestinal transplantation. N Engl J Med 2009; 361:998–1008.
Kidney Disease: Improving Global Outcomes (KIDGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant Recipients. Am J Transplant 2009; 9:S131–55.
Martin P, et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology 2014; 59:1144.
Robertson RP, et al. Pancreas and islet transplantation in diabetes mellitus. Diabetes Care 2006; 29:935.
Images
Figure 40.1 Standard liver transplantation technique with caval replacement.
Figure 40.2 Piggyback technique in liver transplantation.
