Principles Of Medicolegal Aspects Of Organ Donation And Organ Transplantation Notes

Organ Transplantation

Principles Of Transplantation

Principles Of Transplantation Introduction:

For end-stage renal or liver disease, transplantation is the best answer as of today. Over 25,000 transplantations are performed annually for different conditions and more than 100,000 patients are awaiting an organ for kidney, liver, or other organs.

Read And Learn More: Surgery of Urology Notes

The acceptance of an organ depends often on the beliefs and decisions related to the country, race, and religion. In certain countries, living donor transplantation, even though risky, is the only realistic organ donation method, greatly limiting the potential for transplantation of organs from cadaver.

Surgical advances have permitted successful transplantation of lungs, pancreas, and intestines from living donors.

Because of the limited supply, use of living donors may be the only means to achieve timely kidney or liver transplantation as it is happening in IndiFirst let us study the principles and pathophysiology of organ transplant.

Pathophysiology of Organ Transplant

Generally the word “immunity” is used in the context of infections. “Immunity” implies defense against infections.

Immunity is of two types, namely:

1. Innate immunity
2. Adaptive or acquired immunity

Innate immunity:

Important components of innate immunity are:

• Phagocytic neutrophils
• Natural killer cells (NK cells)
• Circulating plasma proteins mainly complements.

Adaptive immunity: Adaptive immunity is normally quiescent but is pressed into action by the presence of suitable stimulus such as microbes. Components of adaptive immunity are lymphocytes and their products. Adaptive immunity may be

• Humoral immunity—mediated by antibodies which are synthesised by B-lymphocytes (B cells). They offer protection against extracellular microbes.
• Cell mediated immunity—mediated by T-lymphocytes (T cells). T cells may be CD4 T cells which indirectly facilitate killing of microbes by macrophages or CD8 T cells which directly kill microbes. CD8 T cells are also called cytotoxic T cells.

Major Histocompatibility Complex (MHC):

The MHC complex is also known as human leucocyte antigen (HLA) complex. It consists of a cluster of genes located on chromosome 6. MHC gene products are displayed on the cell surface to the notice of circulating T cells. Such MHC gene products fall into two categories.

1. Class 1 MHC molecules—which display peptides synthesised within the cytoplasm of the respective cell. Class 1 MHC molecules are present in all cells.
2. Class 2 MHC molecules—which display antigens synthesised outside the cell. Class 2 MHC molecules are mainly expressed in antigen processing cells (APCs) or dendritic cells.

Role of MHC in Organ Transplant:

Following an allograft, the host cells recognise the foreign nature of the graft by two mechanisms.

1. Direct recognition—the T cells recognise the foreign class 1 MHC because of immunologic cross reaction. Subsequently cytotoxic T cells are activated which kill the graft cells.
2. Indirect recognition—the host APCs present the antigens in the graft (transplant) in class 2 MHThis activates T cells which secrete cytokines, induce inflammation and damage the graft.

Towards Improving Graft Survival:

• ABO blood group antigens are expressed in all cells and are not just by RBCs. ABO incompatibility results in hyperacute rejection of graft. Hence, it is recommended to ensure ABO compatibility.
• Better HLA matching improves transplant outcomes. This is particularly relevant in live donor kidney transplant. However, HLA matching is not done in heart, lung and liver transplants as the urgency of transplant requirement overweighs the benefits of
• HLA matching. Also in these situations other factors such as size of the graft assume more practical significance.

Graft Rejection:

Based on the timing and mediators of rejection, graft rejection may be classified as follows:

1. Hyperacute rejection:

• Occurs within minutes to days following transplant
• Mediated by preformed antibodies
• Untreatable but preventable
• Cross-matching prevents hyperacute rejection
• Methods of cross-matching include—lymphocytotoxic assay, flow cytometric technique, beadbased screening assays, panel-reactive antibody assay.

2. Acute rejection:

• Occurs in weeks to months following transplant
• Mediated by T cells to a great extent and B cells to a lesser extent.
• Accordingly they are termed T cell-mediated rejection (TCMR) or antibody mediated rejection (ABMR).
• Immune suppression helps to overcome acute rejection

3. Chronic rejection:

• Most common cause of long-term allograft loss
• Occurs over months to years following transplant
• Involves both T cells and B cells
• Examples for chronic graft rejection—interstitial fibrosis, tubular atrophy and chronic allograft nephropathy in renal transplant, vanishing bile duct syndrome in liver transplant and bronchiolitis obliterans in lung transplant.

Liver Transplantation

Liver Transplantation Introduction:

Liver transplantation is a lifesaving procedure for patients who have chronic end-stage liver disease and acute liver failure (ALF) when there are no alternative treatment options. In 1963, Dr Thomas Starzl performed the first three human liver transplantations at the University of Colorado but patient suffered from biliary atresia, had coagulopathy and did not survive surgery. Introduction to cyclosporine for immunosuppression in solid organ transplantation revolutionised the liver transplantation surgery.

Indications for Liver Transplant:

1. Fulminant hepatic failure: It is acute onset of liver failure in the absence of pre-existing liver disease. Here coagulopathy sets in within 8 weeks of onset of jaundice. Causes are acetaminophen overdose and hepatitis B infection in AsiIf left untreated, patients most often succumb to coma due to cerebral oedema.
2. Hepatitis C: Chronic hepatitis C is the commonest indication for liver transplant in the West. However, hepatitis C recurs even after liver transplantation because the virus persists in the extrahepatic tissues. Pre-transplant and post-transplant treatment with interferon and ribavirin can potentially improve the outcome in these patients.
3. Hepatitis B
4. Primary biliary cirrhosis
5. Primary sclerosing cholangitis
6. Alcoholic liver disease
7. Nonalcoholic steatohepatitis (NASH)
8. Biliary atresia—it is the commonest indication for liver transplant in the paediatric age group.
9. Hepatocellular carcinoma: Theoretically liver transplant should offer the best chance of cure in HCC but there is always the risk of recurrence of HCC following transplant. Many transplant centres follow “Milan criteria” to decide the feasibility of liver transplant in HCC, which says that liver transplant can be considered in HCC when there is a single nodule of <5 cm or there are fewer than 3 nodules, the largest of which is measuring <3 cm. Those who follow the “Milan criteria” believe that the recurrence of HCC is very low if the criteria are strictly adhered to.

Contraindications for Liver Transplant:

1. Systemic infections other than liver infections
2. Pulmonary manifestations of chronic liver disease
3. Inability to abstain from alcohol when liver transplantation is being contemplated for alcoholic liver disease.
4. Lack of commitment to immunosuppressive drugs
5. Metastatic HCC
6. Following are not contraindications for liver transplantation:
   • Failure of other organs in addition to liver, e.g. amyloidosis—here combined liver and kidney transplants can be undertaken.
   • HIV infection
   • Portal vein thrombosis

Donor Criteria for Liver Transplantation:

Donors for liver transplant can be deceased donors or live donors. The outcomes are better with deceased donors, but the limitation is shortage of such donors. The ideal donor should be young and otherwise healthy. The donor factors associated with increased risk are older age, a fatty infiltration and use of split liver from these donors. Two categories of donors who are increasingly considered although not ideal are:

• Older donors: If liver from older donors are used for hepatitis C recipients, there is an increased risk of development of cirrhosis in the transplanted liver.
• Donor after cardiac death: These are donors who do not meet brain death criteria but become donors once life support is taken off. Liver from such donors can be considered for transplant with cut off time of 30 minutes.

Model for End-stage Liver Disease (MELD Score):

Candidates needing liver transplants far outnumber the available donors. Therefore, candidates needing liver transplants are listed in the transplant register in organ transplant programs. The order in which candidates are placed in the waiting list for liver transplant is determined by MELD formulated formula that incorporates three components, namely—creatinine, bilirubin, and INR. These components provide an objective assessment of the severity of liver disease.

MELD score = [0.957 × Ln creatinine (mg/dl)] + [0.378 × Ln bilirubin (mg/dl)] + [1.120 × Ln INR]

In the waiting list, candidates with higher MELD score come first. MELD score is nowadays preferred to Child-Pugh’s score for being more objective.

Types of Liver Transplantation:

1. Conventional liver transplant: This is performed to replace the diseased liver with a healthy liver from a deceased donor.
2. Expanded criteria donor (ECD): A diseased donor over the age of 60 with mild liver abnormalities. The term “expanded” is used because an expansion of the donor pool is considered to increase transplantation. With an ECD liver, the waiting time may be shorter— not done in India.
3. Living donor liver transplantation (LDLT): A procedure in which a healthy, living person donates a portion of his or her liver to another person. Finding a living donor match shortens waiting time, increases long-term transplant success and gives the flexibility of scheduling the date of surgery.
4. Split liver transplant: A deceased donor liver is split into two functioning units, which are used for transplantation to a child (left lobe) and an adult (right lobe).
5. Combined organ transplant: A person may receive more than one organ during the same transplant procedure such as liver and kidney or liver and heart. This may be recommended for patients who are experiencing multiple organ failure.

Technical Aspects of Liver Transplantation:

More often the donor in liver transplant is decease However, with severe shortage of donors, live donor liver transplants are becoming common. The donor liver transplant is placed in its native position in the abdomen of recipient after removing the diseased liver. Hence, the term “Orthotopic liver transplant” is use(This may be compared with kidney transplant where the transplanted kidney is placed in the iliac fossa, thereby deriving the term heterotopic transplant.) Sometimes, the donor liver is split and the left liver is used for a paediatric recipient and the right liver is used for an adult recipient. Such a liver transplant is termed “split liver transplant”. A few operative steps in the back table where the donor live is prepared for transplantation

Immunosuppression after Liver Transplantation:

Chronic rejection is uncommon following liver transplantation. The need for immunosuppression decreases over time. Combination of calcineurin inhibitors (tacrolimus, cyclosporin), steroids (methylprednisolone) and antiproliferative agents (mycophenolate mofetil) are use

In the context of liver transplantation sirolimus deserves a special mention:

• It has antineoplastic activity and, hence, is an attractive option in HCC.
• It delays wound healing.
• It is associated with hepatic artery thrombosis.

Complications of Liver Transplantation:

1. Primary non-function—these patients need retransplant.
2. Hepatic artery thrombosis—these patients need early thrombectomy or retransplant.
3. Portal vein thrombosis
4. Bile duct leak and stricture
5. Other complications—bleeding, coagulopathy

Future Trends:

Hepatocyte transplantation: In chronic liver diseases due to specific enzyme deficiencies like Crigler-Najjar syndrome, hepatocytes or stem cell transplant seems logical. With only a few cells needed to restore functioning of liver, this concept makes sense as it avoids the morbidity and mortality of a major surgical procedure.

Renal Transplantation

Preparation for Transplantation. The recipient is prepared by haemodialysis. It also enhances the chances of success of a transplant.

Donors: Two Sources

1. Cadaver kidney is obtained from ‘brain dead’ patients who are still living with mechanical ventilatory support. Consent should be taken from patient’s relatives.
2. Living
   Living related
   Living non-related

Criteria of an Ideal Donor:

1. Less than 60 years of age
2. No previous renal disease
3. No diabetes
4. No hypertension
5. Adequate renal perfusion 50 ml/hour urine output is necessary.
6. No systemic infections such as hepatitis B, C, HIV infection.
7. No malignancy

Living Related Donors:

• An identical twin is ideal
• Father or mother
• Son or daughter
• Brother or sister

Tests Done Before Transplantation:

• Blood group ABO compatibility
• Biochemical investigations
• Complete blood picture
• Renal function tests
• Rule out: Diabetes, hypertension, hepatitis B infection, hepatitis C infection, HIV.
• Bilateral renal angiography to study vascular pattern. Tissue typing.

Operation Technique:

Donor Operation:

1. Living-related donor: Donor nephrectomy with preservation of as much length of the artery, vein and ureter.

2. Cadaver donor: The donor kidney is perfused with icy perfusion fluid and removed along with vena cava and aorta, and packed in plastic bags surrounded by ice in an insulated box. It can be stored like this for 72 hours.

Perfusion fluid: It has high concentration of potassium (80 mmol/l) and high osmolarity (400 mOsm/kg). This is used during transplant anastomosis.

Recipient operation: Kidney is transplanted in the right iliac fossa by anastomosing renal artery to internal iliac artery and renal vein to external iliac vein. Ureter is implanted in the bladder.

Postoperative Management:

1. Immunosuppression: Cyclosporin A is given alone or in combination with low doses of azathioprine and steroids.

2. Fluid balance: Aim to maintain urinary output at the rate of 20 ml/hour. Even an anephric patient needs 500 ml of fluid/day to replace insensible loss. CVP is ideal for management of fluids in the postoperative period.

3. Postoperative oliguria: Monitoring of renal function—serum creatinine should drop by 50% in 48 hours post-transplant period.

Renal Transplantation Causes:

1. Acute tubular necrosis (ATN): Minimal ATN is common due to short ischaemic time. Hence, oliguria phase may be a few hours.
2. Rejection: More likely on the 5th day. Twice weekly DTPA (diethyl triamine penta-acetic acid) isotope renography and gamma camera scan of the kidney confirms perfusion of the kidney when oliguria is present. Percutaneous needle biopsy can confirm the rejection.

Treatment of Rejection:

1. Acute rejection: Within 3 months, this responds to high doses of intravenous steroids. 90 mg methylprednisolone IV/day × 3 days.
2. Chronic rejection involves the vascular element. It does not respond to steroids.

Surgical Complications:

1. Haemorrhage manifests as oliguria, hypotension. Wound should be re-explored and bleeding vessels should be ligated.
2. Renal artery thrombosis results in nonfunctioning of the transplanted kidney. It can be diagnosed by ultrasonogram and isotope studies. This is treated by nephrectomy.
3. Renal artery stenosis can develop later. It should be treated by an angioplasty.
4. Lymphocoele can develop due to perivascular dissection and increased flow of lymph. Such lymphocoele can lead to ureteric obstruction. Small collection needs to be observed, large ones need drainage.
5. Ureteric obstruction or urinary leakage due to disruption of ureteroneocystostomy can be due to ischaemia or necrosis of the distal ureter. During donor nephrocystostomy, care should be taken not to remove too much of periureteric tissues and avoid too much dissection in the renal hilum to prevent ureteric ischaemia.

Small Bowel Transplant

Small Bowel Transplant Introduction:

• The small bowel is rich in lymphoid tissue and the large mucosal surface area with major histocompatibility antigens. This definitely evokes a fight between graft and host.
• Small bowel is colonised by a multitude of bacteria and other micro-organisms. This is one of the reasons for failure.
• Intestinal transplantation is an established treatment modality for patients with intestinal failure. Any patient who cannot meet >50% of their calorie needs via the enteric route is considered to have intestinal failure and they require intestinal transplantation.

Common Causes for Intestinal Failure Indications:

• Common cause in adults: Massive resection of intestine for SMA/SMV thrombosis, Crohn‘s disease, radiation injury or traumAfter massive small intestine resection, one has to do intestinal transplantation within fifteen days and if it is not possible for any reason, then wait for at least four to six weeks, allow for the infection/inflammation to settle before performing intestinal transplantation.
• Common cause in children: Necrotizing enterocolitis, long segment intestinal atresia, midgut volvulus.
• Uncommon causes in children: Gastroschisis, motility disorders, microvillous inclusion disease, tufting enteropathy. Even though these children have full length of intestine, it is not functional and will not allow them to eat normal food and grow.

Small Bowel Transplant Contraindications:

Lack of central venous access, presence of active infection, aggressive malignancy, multisystem organ failure, cerebral oedema, and HIV are contraindications for intestinal transplantation.

Managing Patients with Intestinal Failure:

• It is ideal to maintain continuity of the intestine, use the remaining length to its maximum capacity. If the colon along with ileocecal valve is intact, one may attempt at rehabilitating the intestine, allow it to adapt. Successful intestinal rehabilitation is more often successful in children compared to adults.
• Most of these patients need total parenteral nutrition to survive and meet their calorie requirement.

Managing Total Parenteral Nutrition (TPN):

• Placing of lines: Tunneled lines (Hickman’s line) placed in the neck or upper extremity are preferred for long-term TPN. These lines carry less risk of infection and it can be used for home TPN.
• The calorie requirements are calculated based on standard formulFor weight reduction, 20 to 25 cal/ kg/day for weight maintenance 25 to 30 kcal/kg/ day and for weight gaining 30 to 35 kcal/kg/day. Of these calories 60% must be met with carbohydrates, 30% with fat and 10% with proteins. Limiting lipids to less than 2 gm/kg/day, and will help protect liver from cholestasis. Giving lipids three days a week will also help achieve this goal. For long-term TPN one has to pay attention to micro-nutrients as well and have replace vitamins and selenium, manganese, chromium, iodine on regular basis. Iron stores are most often enough for a few months and iron injections will be needed only when TPN is continued for more than six months.
• Giving these calories in limited volume is a challenge in children, but in adults it is usually not a problem. Long-term TPN must be managed by dedicated physician along with dietician. Giving dextrose, amino acids and lipids separately will not give rise to acid–base balance problems in the short term, but in the long run patients will develop acidosis and other deficiencies. It is best to custom prepare the TPN for those who need long-term TPN.

Managing Central Line Infections:

• When there is suspected central line related infection, tendency is to remove the line and give appropriate antibiotics.
• In patients with short gut and those who are dependent on TPN the central venous accesses are precious and one has to make attempts to save them. Repeated access to these central access will lead to stenosis/ thrombosis of the veins and we loose those venous accesses. Hence we usually treat them for the infection while we retain the lines.
• Remove them only when it is absolutely necessary or when they have repeated fungal infections.

Pretransplant Evaluation of the Recipient:

The team includes transplant surgeon, gastroenterologist, social worker, nutritionist, psychologist and financial co-ordinator, infectious disease specialist, cardiologist and pulmonologist.

Small Bowel Transplant Investigations:

• Ultrasound of liver and central veins
• Serology tests: CMV, EBV, HIV, HBsAg, anti-HCV
• Blood group, HLA typing
• Hypercoagulable status and liver biopsy—if indicated
• Cardiopulmonary evaluation

Donor Selection:

• A haemodynamically stable, heart beating brain dead donor with no intestinal pathology is preferred.
• CMV-positive donors are accepted for CMV-positive recipients.

The Donor Procurement:

• It is similar to the procurement of the liver. A long midline incision from suprasternal notch to pubic symphysis is made and the concerned teams assess their concerned organs. Intestine is assessed for any injury. The contents are milked either into the stomach or large intestine without creating any serosal tears. SMA and portal veins are dissected and looped at their origin using vessel loops.
• Organs are preserved in university of Wisconsin solution or HTK (custodial) solution. Cold ischaemia time is kept to minimum by co-ordinating timing of the donor operation with the recipient’s surgery team. Acceptable cold ischaemia time for small intestine is less than 12 hours.

Types and Operative Procedure:

Three primary procedures:

1. Isolated transplantation of the small intestine (with or without the portion of the right colon with the ileocaecal valve).
2. Combined transplantation of the intestine and liver as separate grafts.
3. Multivisceral transplantation (MVT), which is the simultaneous transplantation of a composite graft including the liver, stomach, duodenum, pancreas, and small intestine.

Small Bowel Transplant Details:

1. Isolated intestinal transplantation is performed for patients with isolated intestinal failure. If they have liver failure also then they would require multivisceral transplant (combined liver, intestine along with pancreas in one cluster).

• The incision is carefully planned keeping in mind the previous surgery, stoma and the need to create new stomThe arterial flow is usually provided from infra-renal aorta (via a conduit) and venous outflow to the portal vein.
• In patients with mesenteric vein thrombus, it is provided to inferior vena cavThe portal outflow is preferred because it provides growth factors to liver for optimal hepatocyte function.
• Intestine continuity is maintained by enteroenterostomy performed in side to side fashion (there may be size discrepancy) in four layers.
• Ileostomy, feeding jejunostomy and venting gastrostomy may also be performed if neede Stoma (ileostomy) is used to perform biopsy in the early postoperative period to monitor for possible rejection.
• The abdominal wall closure may be difficult in some patients due to multiple past surgeries, recurrent infection, scar tissue formation and contracted abdominal cavity. In some cases, temporary mesh may be useIn some cases, plastic surgery procedures like flaps may be needed to obtain closure. Some surgeons have used abdominal wall transplantation (from same cad donor) based on inferior epigastric vessels (donor) connected to (rec) femoral or iliac vessels.

Living donor small intestinal transplantation:

• It is a way of increasing the donor pool where there is very long waiting time for recipients. A segment of terminal ileum (200 cm for adults and 150 cm for children) is harvested about 20 to 30 cm proximal to ileocaecal valve.
• The donor is left with >60% of the intestine.

2. Combined transplantation of the intestine and liver:

• It is indicated when patients have cholestatic jaundice also secondary to TPN and require combined liver and small bowel transplantation.
• When combined liver and small bowel transplantation is carried out, the two grafts are transplanted en bloc.
• The donor aorta is fashioned into a conduit including the superior mesenteric and coeliac arteries and anastomosed to the recipient aorta.
• The portal vein anastomosis is similar to that in liver transplantation.

3. Multivisceral transplantation (MVT):

• Multivisceral, also called ‘cluster’ transplants may be necessary in the case of large desmoid tumors.

Immunosuppression:

• Intestinal transplantation is more successful now because of better immunosuppression available.
• Most centers use induction with steroids, antithymocyte globulin or OKT3. Long-term maintenance is achieved with tacrolimus, mycofenolate with or without steroids.

Postoperative Care:

Intestine output is monitored carefully. Excessive stoma output may be associated with rejection or CMV infection. They are monitored with intestinal biopsy and blood test respectively. While intestinal motility comes to normal and the anastomosis heal, the patients are given TPN. It may take a few weeks to couple of months for the intestinal function to come back to normal.

Small Bowel Transplant Complications:

Technical complications: Encountered are bleeding, thrombosis and anastomotic leaks. These require re-exploration. They are sources of morbidity and mortality. Bleeding is easy to control. If there is thrombosis (incidence <10%) of the graft vessel, it is difficult to salvage it and we may have to take out the transplanted organ.

Rejection:

1. Acute cellular rejection: Acute cellular rejection usually occurs within the first year posttransplantation but can occur at any time. Clinically, it can present as diarrhoea, unexplained fever, abdominal pain and/or cramping.
2. Chronic rejection: Clinically, these patients may have chronic diarrhoea despite adequate treatment. Patients have an obliterative arteriopathy.

Infection:

1. Bacterial: Bacterial infections can manifest as intra-abdominal infection, opportunistic infections, surgical site infections, pneumoni Pathogenic organisms are: Escherichia coli, Klebsiella, Enterobacter, Enterococci, and commonly, polymicrobial infections.
2. Viral: Cytomegalovirus (CMV) is a common pathogen post-intestinal transplantation, which often affects the allograft. Treatment with ganciclovir and/or CMV immunoglobulin and rarely, reduction in immunosuppression are methods that are used to minimise graft loss.
3. EBV (Epstein-Barr virus) also presents a unique challenge to intestinal transplant recipients because of the higher rates of post-transplantation lymphoproliferative disorder (PTLD) when compared with other solid organ transplant recipients.

GVHD: Graft-versus-host disease (GVHD) occurs when donor lymphoid cells begin to target recipient tissues, most notably the epithelial cells in the skin and intestine. It is relatively uncommon.

Small Bowel Transplant Other complications: Postoperative haemorrhage, biliary (if liver is also used) thrombosis of vessels resulting in graft loss, bowel anastomosis leak and wound infections.

Islet Cell Transplantation

Islet Cell Transplantation Introduction:

• Type 1 diabetes mellitus, also known as juvenile-onset or insulin-dependent diabetes, is a chronic polygenic autoimmune disorder that has a strong hereditary basis in the human leucocyte antigen system. It results from destruction of pancreatic beta cells in the islets of Langerhans. Beta cells constitute 28–75% of pancreatic islets.
• Percutaneous islet cell transplantation is a minimally invasive cellular replacement therapy. It avoids risk of hypoglycaemia which is one of the major problems of exogenous insulin.

Islet Cell Transplantation Indications:

• Type 1 diabetes mellitus (DM) with disease presence for at least 5 years, absence of endogenous C-peptide secretion.
• Islet cell transplantation may be performed alone, in combination with renal transplantation, or following kidney transplantation. Example: Diabetic patients with imminent or established end-stage renal disease

Islet Cell Transplantation Contraindications:

• Age less than 18 years or greater than 70 years
• DM duration less than 5 years
• Residual C-peptide secretion (i.e. stimulated C-peptide level: 0.5 ng/dL).
• Proliferative diabetic retinopathy, portal hypertension.
• Active infection (including hepatitis C, hepatitis B, HIV and tuberculosis).

Islet Cell Preparation:

• After cold perfusion of the abdominal organs, the pancreas, spleen and duodenum is removed en bloThe portal vein is transected at the duodenal border and the common bile duct is transected close to the pancreatic border.
• The organ is packed in a triple-barrier bag with cold preservation solution and stored at 4°C for transportation. The maximum cold ischaemia time is 12 hours.
• The most commonly used preservation solution is University of Wisconsin solution.
• Obtaining islet cells: The initial step is infusion of collagenase through the main pancreatic duct; the collagenase is delivered with pressure monitoring aimed at duct distension with minimum leakage of the enzyme. Collagenase cannot digest thick interlobar fibrous tissue. This is achieved by the Ricordi chamber. The chamber includes five or six stainless steel balls, which provide mechanical fracture of the fibrous tissue. Thus, it provides effective digestion, dilution and collection of the digested tissue. The purity of the final cell suspension is analysed and the cells are washed and placed in culture media for 12–72 hours in an incubator at 22°– 37°The isolated islets are then transplante

Technique of Transplantation:

• The portal venous system is used for islet cell transplantation.
• With ultrasound (US) and/or fluoroscopic guidance, a branch of portal vein is punctured with a 20–22- gauge needle via a percutaneous transhepatic approach.
• The percutaneous access is dilated to accept a 5–6 F catheter or vascular sheath, which is advanced into the main portal vein.
• Confirm the catheter placement using ultrasound.
• Systemic anticoagulation with heparin should be initiated—5000 units is routinely administere

Islet Cell Infusion:

• At least 10,000 islet equivalents per kilogram of body weight.
• An islet equivalent refers to an islet measuring at least 150 µm in diameter. In general, harvested islet cells are infused by using gravity flow or direct syringe injection.
• Other sites of injecting islet cells

Peri- and Post-procedural Imaging, DM Management and Immunosuppression:

It includes a combination of a T cell-depleting agent and interleukin-2 monoclonal antibody receptor blocker (daclizumab) for induction and maintenance with a combination of a calcineurin inhibitor (tacrolimus) and a mammalian target of rapamycin inhibitor (sirolimus).

Complications of Islet Cell Transplantation:

• Bleeding—either intraperitoneal or liver subcapsular is the most common procedure-related complication. Fortunately, effective hepatic parenchymal tract embolisation significantly reduces bleeding.
• Partial portal vein thrombosis is another complication. It is because of activation of coagulation system by transplanted cells.
• Other complications of islet cell transplantation include transient liver enzyme elevation, abdominal pain, focal hepatic steatosis and severe hypoglycaemia.

Drugs used for Maintenance Therapy after Transplantation:

• Steroids: Prednisolone is commonly useSide effects are hypertension, Cushing’s syndrome, diabetes, cataract, muscle wasting.
• Antiproliferating agents: Azathioprine is the drug use It inhibits both humoral and cell mediated immunity. Bone marrow suppression and toxic hepatitis are side effects.
• T cell directed immunosuppressants: Cyclosporine, Tacrolimus and Sirolimus are a few drugs. Cyclosporine inhibits formation of mature CD4 and CD8 T cells in the thymus. It does not cause myelosuppression. Side effects are nephrotoxicity, hypertension, hyperkalaemia, hirsutism, etIt is used in a dose of 4 mg/kg in 500 ml saline, IV and later oral therapy with 12 mg/kg daily. After a few weeks tapered to 5 mg/kg/day. Tacrolimus: Used in liver transplant and in acute rejection of the kidney. Effects are similar to cyclosporine. Side effects are also similar to cyclosporin but without hirsutism and gingival hypertrophy.

Medicolegal Aspects Of Organ Donation

Transplantation of Human Organs Act (THOA) 1994: It regulates the removal, storage, and transplantation of human organs for therapeutic purposes and prevents the commercial trade of human organs. The organs that can be donated as per the act are the kidneys, cornea, liver, heart, lungs, pancreas, ear drum, and ear bones.

There are three types of live organ donations as per the act:

1. Relatives by blood
2. Spouse
3. Out of affection.

Applications of unrelated transplants are scrutinized by state authorization committees. Registration of hospitals conducting transplantation should be done with these committees.

Cadaver organ donation: Organs can be donated if brainstem death has occurred, which is certified twice by a panel of doctors over a period of at least 6 hours.

The panel should include:

1. Registered medical practitioner in-charge of the hospital in which the brainstem death has occurred.
2. Registered medical practitioner nominated from the panel of names approved by the appropriate authority.
3. Neurologist/neurosurgeon nominated from the panel of names approved by the appropriate authority.
4. Registered medical practitioner treating the deceased person.

Beating heart donor: This method is used for cadaveric organ transplantation. After the declaration of death, the person is connected to artificial life-sustaining methods. This will better preserve the organs, which can then be successfully transplanted to the recipient.

Punishments for commercial dealings involving human organs: 10 years of imprisonment and a fine of 20 lakh rupees.

Doctor: 3 years suspension (temporary erasure) from the medical register by a regulatory body (NMC) with permanent erasure for a subsequent offense

Organ Transplantation Multiple Choice Questions

Question 1. Which of the following is not a component of innate immunity?

1. Phagocytic neutrophils
2. Natural killer cells
3. Complements
4. Mast cells

Answer: 3. Complements

Question 2. Which of the following is a cytotoxic T cell?

1. CD8
2. CD4
3. CD6
4. CD2

Answer: 1. CD8

Question 3. Which of the following are included under MELD score in liver transplantation?

1. Creatinine, bilirubin, albumin
2. Creatinine, bilirubin, INR
3. Creatinine, bilirubin, bleeding time
4. Creatinine, bilirubin, ammonia

Answer: 2. Creatinine, bilirubin, INR

Question 4. Tacrolimus is a:

1. Calcineurin inhibitor
2. Steroids
3. Antiproliferative agents
4. Antibacterial agent

Answer: 1. Calcineurin inhibitor

Question 5. Following intestinal transplantation, which is the common intestinal pathogen causing infection?

1. Shigella
2. Cytomegalovirus
3. Streptococci
4. Meningococci

Answer: 2. Cytomegalovirus