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Small bowel transplantation 1
Recent advances - Small Bowel
Transplant
Presenter - Dr Kruti Pendyala
Moderator - Dr Arshad K
2
Contents :
- History
- Intestinal failure - Causes, indications of SBT
- Recipient and Donor assessment
- Types of transplants
- Process of organ procurement, surgical procedure
- Advances
3
History -
• Intestine transplantation has become a lifesaving
treatment option for patients with intestinal failure.
• 1967( Lillehei and coworkers) → TPN → increased
cases of PNALD → Cyclosporine immunosuppression
→ 1988, first successful human SBT.
4
Intestinal failure:
• When a patient is unable to maintain satisfactory fluid,
electrolyte or nutritional homeostasis without intravenous
administration
• Intestinal Failure can occur due to:
- inadequate intestinal length (“short bowel syndrome”)
or
- function that prevent adequate nutrient absorption.
5
Causes
• Massive resection of bowel (70%)
• Multiple sequential resections (Crohn’s disease)
• Mesenteric vascular thrombosis
• Midgut volvulus
• Trauma with disruption of mesenteric vessels
• Radiation enteritis
• Tumours
• Necrotising enterocolitis (neonates)
6
Iatrogenic Ischemic Infiltrative Obstructive Functional
Blunt trauma Arterial embolism Desmoid tumours Adhesive Pseudo-obstruction
Penetrating trauma Venous occlusion Amyloidosis Internal hernia IBD
Operative
misadventure
Low flow/shock Malignancy Radiation enteritis Bacterial overgrowth
Adult causes:
7
Paediatric Causes:
Surgical reductions (2) Neuromuscular diseases (3) congenital diseases of the intestinal epithelium
Necrotizing enterocolitis
Intestinal aganglionosis /
Hirschsprung disease
Microvillous atrophy
Intestinal atresia
Chronic intestinal pseudo-
obstruction
Tufting enteropathy
Gastroschisis Intestinal epithelial dysplasia
Midgut volvulus
Indications for small bowel transplant -
- include irreversible intestinal failure and one or more of the following:
- (1) overt or impending liver failure caused by PNALD;
- (2) Limited central venous access;
- (3) multiple episodes of catheter-related infection requiring hospitalization in
any year;
- (4) single episode of fungal line infection;
- (5) frequent and severe episodes of dehydration, despite intravenous (IV) fluid
supplementation and TPN.
- (6) diseases for which no alternative therapy is available (such as complete
splanchnic venous thrombosis and unresectable benign or slow-growing
mesenteric tumors)
Recipient Assessment:
● Routine Labs - CBC , PT/INR, LFT
● Serology - CMV IgG/IgM, EBV antibodies, HBV, HIV, HCV
● Immunologic - HLA typing, HLA antibody
● Venous access
● Liver biopsy - Degree of liver fibrosis (IFALD)
● Cardiovascular and Respiratory,
● Upper and lower gastrointestinal endoscopy
● CT abdomen
● Anaesthetic and psychiatric assessment 9
Donor Evaluation :
- compatible blood type
- ideal donor should have a body weight 50% to 75% that of
the recipient
- cold ischemia time - less than 6hours
- viral serologic testing of the cadaveric donor for Epstein-
Barr virus (EBV) and cytomegalovirus (CMV)
10
• Contain all or part of the donor
jejunoileum.
• The jejunum is stapled past the
ligament of Treitz.
• SMA and SMV are used as the vascular
pedicles at the root of the mesentery.
• SMA can be lengthened to include a
cuff of aorta and the SMV can go up as
far as the portal vein (PV)
Types of transplant
1. ISOLATED INTESTINE GRAFTS
11
12
2. Small intestinal and colon transplant
• Organs included: Small intestine and colon
(+/- pancreas)
• Proximal enteric anastomosis: Duodenum or
proximal jejunum
13
• The jejunum is stapled past the ligament of Treitz
• SMA and SMV are used as the vascular pedicles at the
root of the mesentery
• Indications:
⮚Intestinal failure that cannot be managed on total
parenteral nutrition
⮚Mild to moderate liver dysfunction due to total
parenteral nutrition
14
https://youtu.be/BSQYcrVE1vE?si=WFOixFZAwJbe3OQb
3. Liver and small bowel
transplant
• Organs included: Liver, pancreas,
small intestine and colon
• Extent of resection: Liver, small
intestine and part of colon
• Proximal enteric anastomosis:
Duodenum or proximal jejunum
15
• The duodenum is stapled off distal to
the pylorus, the pancreas is left wholly
intact for biliary drainage, and the
entire jejuno-ileum is mobilized and
controlled
• The vascular pedicles of a common
aorta/celiac/SMA trunk and an intact
donor PV and bile duct
16
• Indications:
⮚Intestinal failure and advanced, irreversible liver
failure due to total parenteral nutrition
⮚Intestinal failure due to a hypercoagulable state
associated with enzyme deficiencies that can be
corrected by a liver graft. Eg: mesenteric vascular
thrombosis secondary to protein C or S deficiency
17
5. Multivisceral transplant
• Organs included: Liver, stomach,
pancreas, small intestine and
colon
• Extent of resection: Liver,
stomach, pancreas, small intestine
and part of colon
• Proximal enteric anastomosis:
Proximal stomach or oesophagus
18
• The stomach is most commonly
included in this allograft type. During
the procurement operation, rather than
dividing at the level of the pylorus, the
esophagus is transected above the GE
junction
• Vascular inflow is the same as
described above for the L-ITx graft
19
• Indications: Intra Abdominal tumors with local
invasion, and require resection of multiple
abdominal organs (evisceration) for surgical cure
20
4. Modified multivisceral
transplant
• Organs included: Stomach,
pancreas, small intestine and
colon
• Extent of resection: Stomach,
pancreas, small intestine and part
of colon
• Proximal enteric anastomosis:
Proximal stomach or oesophagus
21
Process:
• Small bowel transplants can be done using either cadaveric
(brain dead) or living donors
• Combined bowel-liver or multivisceral transplants only from
cadaveric donors
• Donor and recipient operations occur simultaneously; to
minimise cold ischemia time (<6 hours)
• Organs are retrieved en bloc
22
• Arterial inflow:
✔From infrarenal aorta
✔Donor thoracic aorta used as an arterial conduit to
which the donor aortic patch with coeliac artery and
SMA is anastomosed
✔Intestine only grafts: Inflow is from SMA;
anastomosed to the aorta or to the recipient SMA or
using a conduit from donor iliac vessels
23
• Venous outflow:
✔Liver containing graft: Venous outflow is via
hepatic veins and IVC
✔Non-liver containing grafts: Venous outflow is via
the portal vein; draining into the systemic
circulation (IVC) or the portal circulation
24
• Enteric anastomosis
✔ Proximal enteric anastomosis: Oesophago-gastric,
oesophago-jejunal, gastro-gastric, gastro-jejunal or
jejuno-jejunal
✔ Distal stoma or primary distal anastomosis with
covering ileostomy
25
Recepient operation:
• Preoperative mapping with a magnetic resonance
venogram (MRV) is usually performed during the initial
evaluation
• Guides the anesthesiologist during CVC placement
• Central access above the diaphragm is usually necessary
both because of substantial blood loss encountered during
the organectomy in a hostile abdomen and also because
large-bore peripheral IV access is generally not possible in
these patients
26
Advances
27
Indications
• Nowadays, SBT is not indicated for patients who are
dependent on parenteral nutrition, having no complications.
• Indications for STB are thrombosis of two of the six major
venous accesses, episodes of catheter-related infections
(two or more per year, fungemia, shock, or respiratory
failure), liver disease, alterations of growth and development
in children, and refractory electrolyte changes.
28
• Patients with mild liver disease, revealing no signs of portal
hypertension and mild hepatic fibrosis on liver biopsy, may
receive an isolated intestinal graft and do not need a liver
graft transplantation.
• Independent predictors of PNALF were, in descending order,
total bilirubin level, platelet count, and albumin level.
Predicted probabilities of eventual LF to 83% to 84% when
the total bilirubin level was 11.7 mg/dL, platelet count was 168
x 103/μL, and albumin level was 3.0 g/dL.
29
Surgical technique
• In patients with mild portal
hypertension, venous drainage of the
isolated small bowel - into the vena
cava.
• To observe the bowel
endoscopically, ileostomy is
performed in all types of SBTs.
30
• Recent studies - inclusion of the colon does not increase
morbidity, mortality, and bloodstream infections, (8).
• Loss of abdominal flexibility in patients- difficult primary
abdominal wall closure, tissue expanders, staged abdominal
closure with mesh, bioengineered skin equivalents, acellular
dermal matrix, vascularized or nonvascularized rectus muscle
fascia grafts, skin grafts, and vascularized abdominal wall
transplantation from the same donor (12, 13).
31
Donors Preparation
• Donors ideally should be younger than 55 years and under no or
low dose of vasoactive drugs (below 5μg/kg/min of dopamine).
• Cytomegalovirus-seropositive donors are accepted. Ganciclovir
• The mucosa of the small bowel is very sensitive to ischemic injury.
Infection-related mortality rate is higher and the absorptive function
is lower if the intestinal graft is taken from circulatory death donars.
32
• Living donor SBT is a relatively recent type of
transplantation, which is suitable especially for children with
small bowel failure in whom acute decompensated hepatic
failure occurs. To decrease the morbidity and mortality while
waiting on the list, living donors can be used successfully.
• Intestinal grafts contain 150 cm of ileum with or without a
left lateral liver graft depending on the liver function of the
patient.
33
Organ Preservation
• The University of Wisconsin (UW) solution is considered the gold
standard for the preservation of all organs of the abdomen.
• Celsior and HTK, give results similar to those by the UW solution
during ischemic periods up to 8 h in SBT.
• On comparing UW and HTK, results for graft survival, initial function,
endoscopic appearance, and rate of transplant pancreatitis were found
to be similar. HTK gives the advantage of better flushing of the
microvasculature due to its low viscosity (17)
34
35
Postoperative Management and Complications
• Rejection is the main cause of morbidity and mortality.
Rejection negatively correlates with the survival of the graft.
• 50%–75% of recipients experience acute cellular rejection,
most commonly in the first 90 days, while chronic rejection
(CR) occurs in 15% of patients (18)
36
Graft rejection
• The diagnosis of AR is possible by clinical, endoscopic, and
pathological evaluation.
• The gold standard for the diagnosis of AR is pathologic
evaluation by biopsy.
37
• Endoscopic observation and biopsies are performed through
ileostomy. The endoscopic observation should be performed
two to three times in a week in the first three months. Then,
it is performed once a month according to the course of
transplantation.
• Mucosal erythema, edema, shortened and flattened villi,
friability, and ulcerations are endoscopic findings associated
with AR.
38
VENCH
Moderate/severe
rejection
Total VENCH score ≥6 96% sensitivity 39
Immune Monitoring
• Acute rejection, chronic rejection, lymphoproliferative
diseases due to over immune suppression.
• increase in use of measurements of citrulline level in the
blood, cytofluorographic analysis of peripheral immune
cell population, cytokine profiles,
40
• Myeloid dentritic cells (MDC) are potent antigen-presenting
cells and serve as markers for the recipients who are prone to
AR (Biomarkers)
• Laser Doppler monitoring, implantable Doppler - appears to
be the ideal method for monitoring grafts, an early warning
of venous congestion may be detected.
41
42
• Stool Calprotectin testing - >160 mg/kg
• During episodes of intestinal dysfunction, calprotectin levels
significantly increase.
• Recent role of Donor Specific Antibodies(DSAs) - can
develop de novo or are present in recipient - 30% risk of graft
loss <2yrs
43
Immunosuppressive Therapy-
• Anti-lymphocyte antibodies and monoclonal (alemtuzumab,
basiliximab, and daclizumab) or polyclonal (thymoglobulin)
induction therapy (7, 27).
• Tacrolimus - maintenance of immune suppression; in the first
month, levels are kept as 12–15 ng/mL and lowered to 8–12
ng/mL after the first stage
44
• BMMSCs, which show an immunosuppressive activity in
transplantation, are detected for stopping the immunological
refractory cells that attack the transplanted organs.
• They can also urge and carry on the process of
epithelialization of the small intestinal epithelium, enhanced
by cell proliferation and/or inhibition of epithelial cell
apoptosis.
45
Future goal
• In an animal model, small sections of small bowel,
produced by implanting intestine stem cells on
collagen structures, demonstrated improved growth
after placing the graft in continuity with remnant
bowel surgically
46
References
• Kaufman SS, Pehlivanova M, Fennelly EM, Rekhtman YM, Gondolesi GE, Little CA, et al. Predicting liver
failure in parenteral nutrition-dependent short bowel syndrome of infancy. J Pediatr. 2010;156:580–585.
• Kato T, Selvaggi, Gaynor JJ, Takahashi H, Nishida S, Moon J, et al. Inclusion of donor colon and ileocecal valve
in intestinal transplantation. Transplantation. 2008;86:293–297
• Sheth J, Sharif K, Lloyd C, Gupte G, Kelly D, de Ville de Goyet J, et al. Staged abdominal closure after small
bowel or multivisceral transplantation. Pediatr Transplant. 2012;16:36–40.
• Gangemi A, Tzvetanov IG, Beatty E, Oberholzer J, Testa G, Sankary HN, et al. Lessons learned in pediatric
small bowel and liver transplantation from living-related donors. Transplantation. 2009;87:1027–1030.
• 17. Oltean M, Churchill TA. Organ-specific solutions and strategies for the intestinal preservation. Int Rev
Immunol. 2014;33:234–244.
• 18. Mathew JM, Tryphonopoulos P, DeFaria W, Ruiz P, Miller J, Barrett TA, et al. Role of innate and acquired
immune mechanisms in clinical intestinal transplant rejection. Transplantation. 2015;99:1273–1281.
• Chen-Shuan Chung, Chien-Chen Tsai, Kuan-Chih Chen, Cheng-Kuan Lin, Tzong-Hsi Lee, Huang-Wen Tsai, Yun
Chen, Surveillance of Rejection After Intestinal Transplantation Using an Image Enhanced Endoscopy
“VENCH” Scoring System,Transplantation Proceedings,Volume 53, Issue 1,2021,Pages 364-370,ISSN 0041-
1345,https://doi.org/10.1016/j.transproceed.2020.10.002.
47

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Sbt general surgery seminar topicsp.pptx

  • 2. Recent advances - Small Bowel Transplant Presenter - Dr Kruti Pendyala Moderator - Dr Arshad K 2
  • 3. Contents : - History - Intestinal failure - Causes, indications of SBT - Recipient and Donor assessment - Types of transplants - Process of organ procurement, surgical procedure - Advances 3
  • 4. History - • Intestine transplantation has become a lifesaving treatment option for patients with intestinal failure. • 1967( Lillehei and coworkers) → TPN → increased cases of PNALD → Cyclosporine immunosuppression → 1988, first successful human SBT. 4
  • 5. Intestinal failure: • When a patient is unable to maintain satisfactory fluid, electrolyte or nutritional homeostasis without intravenous administration • Intestinal Failure can occur due to: - inadequate intestinal length (“short bowel syndrome”) or - function that prevent adequate nutrient absorption. 5
  • 6. Causes • Massive resection of bowel (70%) • Multiple sequential resections (Crohn’s disease) • Mesenteric vascular thrombosis • Midgut volvulus • Trauma with disruption of mesenteric vessels • Radiation enteritis • Tumours • Necrotising enterocolitis (neonates) 6
  • 7. Iatrogenic Ischemic Infiltrative Obstructive Functional Blunt trauma Arterial embolism Desmoid tumours Adhesive Pseudo-obstruction Penetrating trauma Venous occlusion Amyloidosis Internal hernia IBD Operative misadventure Low flow/shock Malignancy Radiation enteritis Bacterial overgrowth Adult causes: 7 Paediatric Causes: Surgical reductions (2) Neuromuscular diseases (3) congenital diseases of the intestinal epithelium Necrotizing enterocolitis Intestinal aganglionosis / Hirschsprung disease Microvillous atrophy Intestinal atresia Chronic intestinal pseudo- obstruction Tufting enteropathy Gastroschisis Intestinal epithelial dysplasia Midgut volvulus
  • 8. Indications for small bowel transplant - - include irreversible intestinal failure and one or more of the following: - (1) overt or impending liver failure caused by PNALD; - (2) Limited central venous access; - (3) multiple episodes of catheter-related infection requiring hospitalization in any year; - (4) single episode of fungal line infection; - (5) frequent and severe episodes of dehydration, despite intravenous (IV) fluid supplementation and TPN. - (6) diseases for which no alternative therapy is available (such as complete splanchnic venous thrombosis and unresectable benign or slow-growing mesenteric tumors)
  • 9. Recipient Assessment: ● Routine Labs - CBC , PT/INR, LFT ● Serology - CMV IgG/IgM, EBV antibodies, HBV, HIV, HCV ● Immunologic - HLA typing, HLA antibody ● Venous access ● Liver biopsy - Degree of liver fibrosis (IFALD) ● Cardiovascular and Respiratory, ● Upper and lower gastrointestinal endoscopy ● CT abdomen ● Anaesthetic and psychiatric assessment 9
  • 10. Donor Evaluation : - compatible blood type - ideal donor should have a body weight 50% to 75% that of the recipient - cold ischemia time - less than 6hours - viral serologic testing of the cadaveric donor for Epstein- Barr virus (EBV) and cytomegalovirus (CMV) 10
  • 11. • Contain all or part of the donor jejunoileum. • The jejunum is stapled past the ligament of Treitz. • SMA and SMV are used as the vascular pedicles at the root of the mesentery. • SMA can be lengthened to include a cuff of aorta and the SMV can go up as far as the portal vein (PV) Types of transplant 1. ISOLATED INTESTINE GRAFTS 11
  • 12. 12
  • 13. 2. Small intestinal and colon transplant • Organs included: Small intestine and colon (+/- pancreas) • Proximal enteric anastomosis: Duodenum or proximal jejunum 13
  • 14. • The jejunum is stapled past the ligament of Treitz • SMA and SMV are used as the vascular pedicles at the root of the mesentery • Indications: ⮚Intestinal failure that cannot be managed on total parenteral nutrition ⮚Mild to moderate liver dysfunction due to total parenteral nutrition 14 https://youtu.be/BSQYcrVE1vE?si=WFOixFZAwJbe3OQb
  • 15. 3. Liver and small bowel transplant • Organs included: Liver, pancreas, small intestine and colon • Extent of resection: Liver, small intestine and part of colon • Proximal enteric anastomosis: Duodenum or proximal jejunum 15
  • 16. • The duodenum is stapled off distal to the pylorus, the pancreas is left wholly intact for biliary drainage, and the entire jejuno-ileum is mobilized and controlled • The vascular pedicles of a common aorta/celiac/SMA trunk and an intact donor PV and bile duct 16
  • 17. • Indications: ⮚Intestinal failure and advanced, irreversible liver failure due to total parenteral nutrition ⮚Intestinal failure due to a hypercoagulable state associated with enzyme deficiencies that can be corrected by a liver graft. Eg: mesenteric vascular thrombosis secondary to protein C or S deficiency 17
  • 18. 5. Multivisceral transplant • Organs included: Liver, stomach, pancreas, small intestine and colon • Extent of resection: Liver, stomach, pancreas, small intestine and part of colon • Proximal enteric anastomosis: Proximal stomach or oesophagus 18
  • 19. • The stomach is most commonly included in this allograft type. During the procurement operation, rather than dividing at the level of the pylorus, the esophagus is transected above the GE junction • Vascular inflow is the same as described above for the L-ITx graft 19
  • 20. • Indications: Intra Abdominal tumors with local invasion, and require resection of multiple abdominal organs (evisceration) for surgical cure 20
  • 21. 4. Modified multivisceral transplant • Organs included: Stomach, pancreas, small intestine and colon • Extent of resection: Stomach, pancreas, small intestine and part of colon • Proximal enteric anastomosis: Proximal stomach or oesophagus 21
  • 22. Process: • Small bowel transplants can be done using either cadaveric (brain dead) or living donors • Combined bowel-liver or multivisceral transplants only from cadaveric donors • Donor and recipient operations occur simultaneously; to minimise cold ischemia time (<6 hours) • Organs are retrieved en bloc 22
  • 23. • Arterial inflow: ✔From infrarenal aorta ✔Donor thoracic aorta used as an arterial conduit to which the donor aortic patch with coeliac artery and SMA is anastomosed ✔Intestine only grafts: Inflow is from SMA; anastomosed to the aorta or to the recipient SMA or using a conduit from donor iliac vessels 23
  • 24. • Venous outflow: ✔Liver containing graft: Venous outflow is via hepatic veins and IVC ✔Non-liver containing grafts: Venous outflow is via the portal vein; draining into the systemic circulation (IVC) or the portal circulation 24
  • 25. • Enteric anastomosis ✔ Proximal enteric anastomosis: Oesophago-gastric, oesophago-jejunal, gastro-gastric, gastro-jejunal or jejuno-jejunal ✔ Distal stoma or primary distal anastomosis with covering ileostomy 25
  • 26. Recepient operation: • Preoperative mapping with a magnetic resonance venogram (MRV) is usually performed during the initial evaluation • Guides the anesthesiologist during CVC placement • Central access above the diaphragm is usually necessary both because of substantial blood loss encountered during the organectomy in a hostile abdomen and also because large-bore peripheral IV access is generally not possible in these patients 26
  • 28. Indications • Nowadays, SBT is not indicated for patients who are dependent on parenteral nutrition, having no complications. • Indications for STB are thrombosis of two of the six major venous accesses, episodes of catheter-related infections (two or more per year, fungemia, shock, or respiratory failure), liver disease, alterations of growth and development in children, and refractory electrolyte changes. 28
  • 29. • Patients with mild liver disease, revealing no signs of portal hypertension and mild hepatic fibrosis on liver biopsy, may receive an isolated intestinal graft and do not need a liver graft transplantation. • Independent predictors of PNALF were, in descending order, total bilirubin level, platelet count, and albumin level. Predicted probabilities of eventual LF to 83% to 84% when the total bilirubin level was 11.7 mg/dL, platelet count was 168 x 103/μL, and albumin level was 3.0 g/dL. 29
  • 30. Surgical technique • In patients with mild portal hypertension, venous drainage of the isolated small bowel - into the vena cava. • To observe the bowel endoscopically, ileostomy is performed in all types of SBTs. 30
  • 31. • Recent studies - inclusion of the colon does not increase morbidity, mortality, and bloodstream infections, (8). • Loss of abdominal flexibility in patients- difficult primary abdominal wall closure, tissue expanders, staged abdominal closure with mesh, bioengineered skin equivalents, acellular dermal matrix, vascularized or nonvascularized rectus muscle fascia grafts, skin grafts, and vascularized abdominal wall transplantation from the same donor (12, 13). 31
  • 32. Donors Preparation • Donors ideally should be younger than 55 years and under no or low dose of vasoactive drugs (below 5μg/kg/min of dopamine). • Cytomegalovirus-seropositive donors are accepted. Ganciclovir • The mucosa of the small bowel is very sensitive to ischemic injury. Infection-related mortality rate is higher and the absorptive function is lower if the intestinal graft is taken from circulatory death donars. 32
  • 33. • Living donor SBT is a relatively recent type of transplantation, which is suitable especially for children with small bowel failure in whom acute decompensated hepatic failure occurs. To decrease the morbidity and mortality while waiting on the list, living donors can be used successfully. • Intestinal grafts contain 150 cm of ileum with or without a left lateral liver graft depending on the liver function of the patient. 33
  • 34. Organ Preservation • The University of Wisconsin (UW) solution is considered the gold standard for the preservation of all organs of the abdomen. • Celsior and HTK, give results similar to those by the UW solution during ischemic periods up to 8 h in SBT. • On comparing UW and HTK, results for graft survival, initial function, endoscopic appearance, and rate of transplant pancreatitis were found to be similar. HTK gives the advantage of better flushing of the microvasculature due to its low viscosity (17) 34
  • 35. 35
  • 36. Postoperative Management and Complications • Rejection is the main cause of morbidity and mortality. Rejection negatively correlates with the survival of the graft. • 50%–75% of recipients experience acute cellular rejection, most commonly in the first 90 days, while chronic rejection (CR) occurs in 15% of patients (18) 36
  • 37. Graft rejection • The diagnosis of AR is possible by clinical, endoscopic, and pathological evaluation. • The gold standard for the diagnosis of AR is pathologic evaluation by biopsy. 37
  • 38. • Endoscopic observation and biopsies are performed through ileostomy. The endoscopic observation should be performed two to three times in a week in the first three months. Then, it is performed once a month according to the course of transplantation. • Mucosal erythema, edema, shortened and flattened villi, friability, and ulcerations are endoscopic findings associated with AR. 38
  • 40. Immune Monitoring • Acute rejection, chronic rejection, lymphoproliferative diseases due to over immune suppression. • increase in use of measurements of citrulline level in the blood, cytofluorographic analysis of peripheral immune cell population, cytokine profiles, 40
  • 41. • Myeloid dentritic cells (MDC) are potent antigen-presenting cells and serve as markers for the recipients who are prone to AR (Biomarkers) • Laser Doppler monitoring, implantable Doppler - appears to be the ideal method for monitoring grafts, an early warning of venous congestion may be detected. 41
  • 42. 42
  • 43. • Stool Calprotectin testing - >160 mg/kg • During episodes of intestinal dysfunction, calprotectin levels significantly increase. • Recent role of Donor Specific Antibodies(DSAs) - can develop de novo or are present in recipient - 30% risk of graft loss <2yrs 43
  • 44. Immunosuppressive Therapy- • Anti-lymphocyte antibodies and monoclonal (alemtuzumab, basiliximab, and daclizumab) or polyclonal (thymoglobulin) induction therapy (7, 27). • Tacrolimus - maintenance of immune suppression; in the first month, levels are kept as 12–15 ng/mL and lowered to 8–12 ng/mL after the first stage 44
  • 45. • BMMSCs, which show an immunosuppressive activity in transplantation, are detected for stopping the immunological refractory cells that attack the transplanted organs. • They can also urge and carry on the process of epithelialization of the small intestinal epithelium, enhanced by cell proliferation and/or inhibition of epithelial cell apoptosis. 45
  • 46. Future goal • In an animal model, small sections of small bowel, produced by implanting intestine stem cells on collagen structures, demonstrated improved growth after placing the graft in continuity with remnant bowel surgically 46
  • 47. References • Kaufman SS, Pehlivanova M, Fennelly EM, Rekhtman YM, Gondolesi GE, Little CA, et al. Predicting liver failure in parenteral nutrition-dependent short bowel syndrome of infancy. J Pediatr. 2010;156:580–585. • Kato T, Selvaggi, Gaynor JJ, Takahashi H, Nishida S, Moon J, et al. Inclusion of donor colon and ileocecal valve in intestinal transplantation. Transplantation. 2008;86:293–297 • Sheth J, Sharif K, Lloyd C, Gupte G, Kelly D, de Ville de Goyet J, et al. Staged abdominal closure after small bowel or multivisceral transplantation. Pediatr Transplant. 2012;16:36–40. • Gangemi A, Tzvetanov IG, Beatty E, Oberholzer J, Testa G, Sankary HN, et al. Lessons learned in pediatric small bowel and liver transplantation from living-related donors. Transplantation. 2009;87:1027–1030. • 17. Oltean M, Churchill TA. Organ-specific solutions and strategies for the intestinal preservation. Int Rev Immunol. 2014;33:234–244. • 18. Mathew JM, Tryphonopoulos P, DeFaria W, Ruiz P, Miller J, Barrett TA, et al. Role of innate and acquired immune mechanisms in clinical intestinal transplant rejection. Transplantation. 2015;99:1273–1281. • Chen-Shuan Chung, Chien-Chen Tsai, Kuan-Chih Chen, Cheng-Kuan Lin, Tzong-Hsi Lee, Huang-Wen Tsai, Yun Chen, Surveillance of Rejection After Intestinal Transplantation Using an Image Enhanced Endoscopy “VENCH” Scoring System,Transplantation Proceedings,Volume 53, Issue 1,2021,Pages 364-370,ISSN 0041- 1345,https://doi.org/10.1016/j.transproceed.2020.10.002. 47