Small intestine transplantation

In 1987, Thomas Starzl et al. performed the first survivable multivisceral transplantation. The first isolated small intestine transplantation was achieved by Goulet et al. in 1989 (Pecora 2013). However, severe rejection reactions regularly led to the loss of the transplanted organ.

Only with the further development of immunosuppressive drugs did rejection reactions improve (Rodeck 2008). The immunosuppressive drug tacrolimus, which is important for small bowel transplantation, came onto the market in the 1990s (Pecora 2013).

Small intestine transplantation (Dtx or ITx) is a relatively young technique that has been slow to develop due to the high immunogenicity of the intestine resulting in high rejection rates (Pascher 2010). Only since the introduction of the immunosuppressant tacrolimus has this high rejection rate been improved (Braun 2011).

The small intestine can be transplanted in isolation or combined with other organs (Braun 2011).

A distinction is made in small bowel transplantation between an

- isolated small intestine transplantation

- combined small intestine transplantation, in which other parts of the digestive tract are also transplanted (Rodeck 2008)

Indication:

• Short bowel syndrome with failure of total parenteral nutrition (Herold 2022). This represents the most common indication (Rosien 2021).
• Development of liver cirrhosis due to cholestatic dysfunction (Müller 2004) on the basis of total parenteral nutrition (Müller 2003).
• permanent intestinal insufficiency
• microvillus atrophy
• motility disorders
• chronic intestinal pseudoobstruction: it is the second most frequent indication with about 20 - 25 % (Rosien 2021)
• constitutional epithelial diseases
• epithelial dysplasia
• M. Hirschsprung
• Intestinal insufficiency complicated by:
  • multiple, severe catheter infections
  • multiple vascular thrombi
  • severe hepatopathy
  • hepatic insufficiency (Rodeck 2008)
• necrotizing enterocolitis
• Volvolus
• M. Crohn's
• autoimmune enteritis
• tumors (von Schweinitz 2009)

Prerequisites:

• Failure of total parenteral nutrition (TPN).
• blood group compatibility and negative cross match (MLC = mixed lymphocyte culture)
• Exclusion of:
  • severe cardiovascular diseases
  • acute infections
  • malignancies (Herold 2022

Small bowel transplantation is required over time in approximately 75% of adults and 50% of children with short bowel syndrome (Rosien 2021).

In total, there are approximately 800 small bowel transplant patients worldwide. Currently, about 100 small bowel transplants are performed worldwide per year. In Germany, however, these have so far been performed only rarely. Reasons for this could be acute rejections and rejection-related complications (Müller 2003).

In children, approximately 40-80 small bowel transplants are performed per year (von Schweinitz 2009).

It is estimated that the incidence of short bowel syndrome is approximately 2 - 5 new cases per 1 million population (Pascher 2010).

In small bowel transplantation, other organs of the digestive tract can be transplanted in addition to the small bowel:

- small intestine only: ITx in 43 %.

- ITx plus liver: ILTx in 30 %

- ITx plus liver, pancreas and other organs such as stomach: multivisceral- MVTx in 24 %

- ITx without liver, plus pancreas and other organs such as stomach: modified multivisceral- mMVTx in 3 % (Herold 2022)

Causes of short bowel syndrome in children may include, in descending order:

• - necrotizing enterocolitis
• - gastroschisis
• - intestinal atresia
• - volvulus
• - pseudoobstruction
• - aganglionosis (Pecora 2013).

Causes in adults:

• - mesenteric ischemia
• - inflammatory diseases
• - actinic enteritis
• - trauma
• - tumors (Pecora 2013)

Histology is the gold standard for the diagnosis of acute cellular rejection.

One differentiates between 4 main parameters for rejection:

- architectural distortion

- epithelial lesion of the crypt

- number of apoptoses per crypt

- Lymphocyte infiltrates in the lamina propria (Pecora 2013).

In the acute phase of an ITx, there may be:

- infection

- sepsis

- thrombosis

- hemorrhage

- Rejection (in the first 90 days).

This is found in 50-75% of patients (Pecora 2013).

- GvHD = Graft- Versus- Host Disease (Acton 2013)

(Herold 2022)

In the late phase of transplantation may occur:

- Chronic rejection (occurs in about 15% of patients [Pecora 2013]).

- infections due to over-immunosuppression (Müller 2003)

- viral infections especially by CMV(cytomegalovirus) and EBV(Eppstein- Barr- virus)

Immunosuppression:

After transplantation, immunosuppression with drugs is carried out throughout the patient's life (Herold 2022). The drugs used are:

- corticosteroids

- tacrolimus

- blocking anti-CD25 antibodies (Rodeck 2008)

Transplantation should be performed within 6 h after explantation, otherwise the risk of lethality increases (Müller 2004). The surgical technique itself is now standardized. Currently, three main surgical techniques exist (Rodeck 2008).

- Isolated small bowel transplantation:

Here, a termino-terminal duodeno- jejunal or else a jejuno- jenal anastomosis is used proximally. Distally, a direct termino-terminal anastomosis to the colon is performed (Rodeck 2008).

- Combined small bowel transplantation:

In this case, an en block transplantation is performed (Rodeck 2008).

Of the 800 patients transplanted to date, about 50% are still alive. Of these, more than 80% are fully rehabilitated, in good general health and free of parenteral nutrition (Müller 2003).

Individual cases with a graft survival of up to 14 years have even been described (Rosien 2021).

In recent years, significant progress has been made in ITx (Müller 2003).

In the meantime, up to 90 % of 1-year patients survive. The 1 - year graft survival is about 80 % (Herold 2022).

However, the complication rate of combined transplantations is incomparably higher. The 1-year patient survival is about 50 % (Müller 2003).

The incidence of acute rejection could be reduced from formerly 85 % to < 25 % by improving immunosuppression (Müller 2003).

In short bowel syndrome, mortality ranges from 15 - 47 % (Braun 2011).

The graft initially absorbs carbohydrates, and later also fats. Therefore, the early establishment of the intestinal mucosa is of great importance (von Schweinitz 2009). Von Schweinitz (2009) considers parenteral nutrition. p. o. is no longer necessary, while Rosien (2021) points out that parenteral nutrition can be terminated after 6 months in up to 80% of cases.

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