Short Bowel Syndrome by Dr. Shahanur Rahman

Definition: Short bowel syndrome (SBS) is a devastating condition in which small intestinal length is inadequate and characterized clinically by inability to absorb adequate enteral nutrition to sustain normal growth and development.

For adult patients SBS has been arbitrarily defined as the presence of less than 200 cm of residual small bowel following massive bowel resection.

For pediatric (neonate) patients SBS can be defined when small bowel length is <25 cm in presence of ileocaecal valve and <40 cm without ileocaecal valve.

In adults, the most common etiologies of SBS are • Acute mesenteric ischemia, • Crohn’s disease,• Radiation enteritis, • Trauma,• Recurrent intestinal obstruction• Malignancy.

75% of cases result from resection of a large amount of small bowel at a single operation (eg. acute mesenteric ischemia).

25% of cases result from the cumulative effects of multiple operations during which small intestine is resected (eg. Crohn’s disease).

Risk factors for development of SBS after massive small bowel resection in adult patients:

• Small bowel length <200 cm• Absence of ileocecal valve• Absence of colon• Diseased remaining bowel (e.g., Crohn’s

disease)• Ileal resection

In pediatric patients, the most common etiologies of SBS are:

• Necrotizing enterocolitis, NEC (35%),• Intestinal atresia (25%).• Gastroschisis (18%).• Midgut volvulus (14%).• Long segment Hirschsprung’s disease (2%).• Meconium ileus.• True congenital short gut.

based on etiology

Acquired Short Gut– • Mesentric vascular

ischaemia/accidents.• Trauma – loss of

intestinal vascularity.• Post-traumatic mesentric

thrombosis.• Regional enteritis.• Proximal ostomy.• Malignancy.

Functional Short Gut –

• Lymphangiectasis. • Pseudo-obstruction.• Radiation enteritis.

Absorption in small intestine

• The jejunum is involved in magnesium absorption.• The absorption of nutrients from the food takes

place in Ileum are: amino acids (the end products of protein digestion), fatty acids (the end products of fat digestion),cholesterol, sodium, potassium alcohol, and fat-soluble vitamins (A, D, E, and K), Vitamin B12. (The terminal ileum is an important part as

this is where vitamin B12 is absorbed into the blood capillaries.)

Clinical Sequale of SBS• Malnutrition- pH of proximal small intestine is reduced inactivation of

digestive enzyme Grossly impaired absorption of all nutrients (malabsorption).

• Diarrhea- Malabsorbed fats in colon fermented by colonic bacteria into

short chain fatty acid diarrhoea.

• Rapid transit- The lowering of intraduodenal pH stimulates peristalsis. This phenomenon seen with proximal and midgut resection.

• Loss of cholecystokinin and secretin- secondary to loss of entero-endocrine cell mass impaired gall bladder motility decreased bile and pancreatic secretion.

1. Malabsorption

• Decreased output of brush border disaccharidases carbohydrate malabsorption.

• Ileal resection – bile salt malabsorption diarrhea, steatorrhea, loss of fat soluble vitamins.

• Malabsorbed fats – in colon – fermented by colonic bacteria into short chain fatty acid –> diarrhoea.

• Decreased bile acid pool which cannot be compensated with increased hepatic synthesis.

2. Bacterial overgrowth• Loss of Ileo-caecal valve – reflux of colonic bacteria into small

bowel.

• Adaptive process – dilated dysfunctional loops bacterial overgrowth.

• Bacterial overgrowth cause of diarrhoea.

• The endotoxins of the bacteria damage mucosa, affect motility, doconjugation of bile salts, aggravate stasis bacterial translocation.

3. Cholelithiasis • decreased bile salt pool.• Poor contractility of GB.

4. Renal stone • Hyperoxaluria , oxalate renal stones.• Metabolism of increased carbohydrate – generates excess oxalate.• Unabsorbed fatty acid binds calcium more than oxalate.

5. D-lactic acidosis• Colonisation of bowel with lactobacilli converts excess carbohydrate to

D-lactate via enzyme D-lactate dehydrogenase.

• Metabolic acidosis altered sensorium coma

• Mx: IV sodium bicarbonate , antibiotic therapy, interruption of enteric feeding.

Adaptation• Crypt cell proliferation: Increased villus height and overall

increase in functioning surface area for nutrient absorption.

• The diameter of the bowel increases significantly.

• Slow down in peristalsis or movement of food through small intestine.

• Intestine lengthens: More if proximal small bowel is resected than distal.

• After resection of jejunum, ileum adopts the morphologic features of jejunum (Ileum adapts more than jejunum).

• Neonates have better adaptation than adults.

• The adaptive process is effective enough to allow full enteral nutrition even 70-80 % small bowel mass has been removed.

• No survival is possible if small intestestine is < 15 cm.

• When ileocaecal valve is present minimum bowel length for survival is 15 cm with TPN support and 30 cm without TPN support.

• When ileocaecal valve is lost, for survival 40 cm of small gut length is compatible with TPN support and 50cm without TPN.

Medical ManagementAcute phase management:

• Replacement of fluid and electrolytes – Ringer lacate is preferred.

• Risk of dehydration, sodium imbalance, metabolic acidosis.

Nutritional support: • After sepsis is cleared – central venous lines are put – TPN

started.• Ongoing losses calculated and added to TPN solution.• TPN given in cycles – so patient has off time from TPN. • This reduces the incidence of cholestasis.• Adequate micronutrients, fat soluble vitamins – added to TPN

solution.

• The use of TPN permits the survival of children who would have otherwise died of the complications of malnutrition.

• In addition, it gives the remaining bowel time to undergo adaptation (mucosal hyperplasia, which results in increased mucosal surface area).

• However, this also is accompanied frequently by bowel dilatation.

• 4 years survival rate for patients on TPN is 70%.

• Complications: ran out of venous access, severe sepsis, liver failure death.

Patient groups for whom parenteral nutrition (TPN) has been used :

• A) Adult patients with SBS secondary to massive small-bowel resection – <60 cm with intact ileocecal valve and colon.

– <120 cm without ileocecal valve or colon .

• B)Neonates with SBS– <15 cm with intact ileocecal valve and colon.

– <40 cm without ileocecal valve or colon .

Enteral Feeding:

• Enteral feeding started as soon as bowel function returns.

• NEC may take 3 weeks to resume normal bowel function.

• Enteral feeding stimulates adaptation and decreases cholestasis.

• Gradual enteral feeding started – as rapid introduction may increase secretory diarrhoea.

• Elemental formulas are started as it has easy absorption and digestion.

• Hypoallergenic formulas – hydrolysed extensively through enzymatic process and have low antigenecity.

• Well tolerated by most children with SBS.

• Infants in comparison to adults tolerate more fat based formulas, while

adults tolerate more carbohydrate based formulas.

• So pediatric formulas have 40-50 % calories as fats.

• Long-chain fatty acids higher calorie density and better stimulators of adaptation but medium-chain are more easily absorbed.

• The carbohydrates are well absorbed except for lactose.

• Ratio of carbohydrate to fat determines the osmotic load presented to the intestine.

• Carbohydrate produce high osmotic load, so formula with modest carbohydrate content is preferred.

• Small children have more difficulty with carbohydrate rich formulas – as they have greater propensity for bacterial overgrowth.

• In older children carbohydrates are converted to short chain fatty acids in colon which are then absorbed providing additional calories.

• Protein absorption is not a problem in SBS.

• But protein is provided in hydrolysed form for easier absorption.

• Feeds are initiated as dilute infusion in a continuous tube feeding.

• Reaching full concentration 0.67 cal/ml for small children and 1 cal / ml for bigger children.

• Once concentration is reached – amount is increased and parenteral fluids are decreased isocalorically every 1-3 days.

• Tolerance estimated – by reducing substance in stools and monitoring volume and consistency of stool.

• As fat absorption is not osmotically significant and protein malabsorption is rarely seen - advancement feeding monitor carbohydrate malabsorption only.

• Vitamin A,D,E,K and heavy metal deficiency such as zinc, calcium, magnesium – should be replaced.

• When short term enteral feeds required or child does not require continuous infusion – N/G feeding preferred.

• Gastrostomy feed – long term feed and continuous drip feed.

• Blockage of the tube is a continuous problem.

• Nowadays infusion pump for bolus feeds.

Control of diarrhoea• Acute phase – gastric hypersecretion – Mx by PPI .

• Medications to slow intestinal transit – Loperamide (dose 1-2 mg TDS).

• If a second agent is required – Codeine (dose of 0.5 – 1 mg / kg / dose TDS/QID) is added.

• Use of anti-motility agents , in children without ileo-caecal valve increases the risk of bacterial overgrowth(pain , fever, diarrhea with foul smelling stool).

• When suspected, stool and gastric aspirate taken for culture. Oral feeding stopped. Anti-motility agents stopped. IV antibiotics , Metronidazole started.

Management of complications• CVP lines has more incidence of sepsis compared to other conditions by

Enteric organisms.

• Regular dressing in aseptic manner, flushing with urokinase and antibiotic solution – antibiotic lock technique.

• Sepsis – gram negative organisms.

• After ileal resection – deficiency of Vit B12. given parenterally every 1-3 months.

• Zn, Ca, Mg – given .• Mg – given parenteral as it causes osmotic diarrhoea.

• Cholelithiasis seen in 10 % of children with SBS Use of ursodeoxy colic acid minimises TPN associated cholestasis.

Medical enhancement of intestinal function

1. Epidermal growth factor (EGF)2. Growth hormone (GH)3. Glucagon-Like Peptide 2 (GLP-2)4. Insulin-like Growth Factor-1 (IGF-1)5. Hepatocyte Growth-Factor (HGF)

1. Epidermal growth factor (EGF)• EGF enhances cellular proliferation, differentiation and

survival. • EGF improves carbohydrate absorption and intestinal

permeability and reduces weight loss. • Possible Mechanisms of action include

a reduction in apoptosis of intestinal cells, increased expression of the anti-apoptotic gene bcl-w, and decreased expression of the pro-apoptotic gene bax .

• Other factors further enhance the adaptive action of EGF such as interleukin-11, bombesin and neurotensin.

• EGF is given orally with foods 100 μg/kg/day for six weeks.

2. Growth hormone (GH)• Receptors of GH have been found throughout

the intestine.• Laboratory studies have shown that GH causes

mucosal hyperplasia and increases the adaptive capacity after small resection.

• enhancement of the villus height and crypt depth, positive nitrogen balance and bowel growth.

• The results in adults are controversial.

3. Glucagon-Like Peptide 2 (GLP-2)• secreted by enteroendocrine L-cells of the

terminal ileum and colon. • Release of GLP-2 is stimulated by food input,• directly or indirectly promotes intestinal

growth and nutrient absorption. • Teleglutide is an analog of GLP-2 with a longer

half-life which encourages villus height and increases crypt depth, improving nutrient absorption, gastric emptying and body weight.

4. Insulin-like Growth Factor-1 (IGF-1)• secreted primarily by hepatocytes, and activated by GH. • mediates growth effects of GH and GLP-2 on the intestine.• may reinforce further growth if given shortly after bowel

resection.• may prevent mucosal atrophy, enhance gut metabolism, and

protect the intestinal barrier against sepsis.

5. Hepatocyte Growth-Factor (HGF)• secreted by mesenchymal cells and carries trophic properties. • enhances small intestine growth and absorptive function

regarding carbohydrates and amino-acids.

Surgical therapy

• The goals of bowel surgery in pediatric short bowel syndrome are :

(1) the small bowel remnant is lengthened to potentially increase the mucosal surface area, slow luminal transit time, and allow improved nutrient absorption; and

(2) the dilated small bowel is tapered so that bowel motility is optimized and the risk for bacterial overgrowth is reduced.

Two main problems of SBS: • the loss in absorptive surface and • dysmotility of the residual bowel.

Surgical procedures categorized into two subgroups:

• I) lengthening of the residual short bowel to provide satisfactory nutrient amount, and

• II) slowing of the intestinal transit .

Small bowel lengthening procedure

A. Bianchi’s procedure,

B. STEP (Serial Sransverse EnteroPlasty) or Kim’s procedure.

C. Kimura procedure.

Patients were divided into two groups depending upon the predominant reason for surgical lengthening

• (a) to increase the enteral caloric intake (decrease/wean TPN requirement) in patients with poor enteral progression/adaptation and had dilated small bowel loops on endoscopy or imaging studies (preferably ≥4 cm in diameter).

• (b) Intractable symptoms of bacterial overgrowth in the setting of SBS not controlled with antibiotics and had dilated small bowel loops. Patients who had anatomical causes of bowel obstruction were corrected at the time of bowel lengthening.

A. Bianchi’s procedure

• In 1980, Bianchi was the first to apply the longitudinal intestinal lengthening and tailoring (LILT) technique.

Based on the principle that • the mesenteric blood supply to the bowel “splits” as it

enters the bowel wall so that the bowel and mesentery can be divided longitudinally while maintaining half of the blood supply to each half of the bowel.

• This technique consists of a construction from a segment of small intestine of two isoperistaltic hemiloops of half the original diameter.

• The two hemiloops are then positioned in a circular manner, and an end-to-end anastomosis is performed between them.

• Subsequently, the new segment is reconnected with the remaining bowel.

Besnefits of Bianchi’s procedure• This allows the doubling of the entire length of

the original segment to be performed.• The reduction of bowel diameter removes the

problems of ineffective peristalsis and stasis.• Increased length of bowel prolongs transit and

intestinal contact time.• Division of the circular muscle fibers –

prolongs transit time.

Disadvantages –• Not recommended in conditions of inflammatory bowel disease, chronic

vascular occlusion.• Segments like duodenum have essentially no mesentry and not suitable

for longitudinal lengthening.

Successful outcome is achieved when the following anatomical conditions are met:

• a) an intestinal diameter > 3 cm; • b) a residual small bowel length > 40cm, • c) a dilated bowel length > 20 cm,• d) presence of ileocaecal valve, • e) presence of colon.

Complications – stenosis due to inadequate vascularity.

B. STEP (Serial Sransverse EnteroPlasty) or Kim’s procedure.

STEP was introduced by Kim et al in 2003.• The STEP procedure is easy to perform, • Does not require any bowel anastomoses, • Could almost double the length of the residual

intestine, • Can be performed either primarily or after a

prior Bianchi procedure.• Carries a low risk of intestinal ischemia, • Can be used repeatedly.

Methods:

• Lengthening of the dilated bowel is performed by serial transverse applications of a GIA stapler sequentially, from alternating and opposite directions, in transverse, partially overlapping fashion to create a zig zag like channel of approximately 2 to 2.5 cm in diameter .

• This required the creation of a mesenteric defect at each staple line.

• The staplers are placed from the 90° and 270° positions (0° being the mesenteric border).

• the STEP procedure has several theoretic advantages over these other methods.

• First, the procedure is quite easy to perform. There are no anastomoses, the bowel is never opened, and the mesentery is never jeopardized.

• Second, the total theoretical increase in length depends on the degree of bowel dilatation and the size of the channel created. With massively dilated segments, one could easily more than double the length of bowel.

• Third, the degree of tapering is customizable. With a Bianchi procedure, the circumference must be reduced by 50%. With the STEP, the channel size and thus the diameter is determined by the surgeon. The bowel after the STEP procedure tends to grow, so that the channel size can be made smaller than the control distal bowel and thus allow even more lengthening and tapering effect.

• Lastly, the STEP procedure can be performed in sequence after a successful Bianchi procedure. Because the blood supply to the bowel after a Bianchi procedure remains perpendicular to the long axis of the bowel, staple lines that remain perpendicular to the long axis of the bowel should not cause ischemia. This would theoretically allow one to first double the length of the bowel with a Bianchi, followed several months later with a STEP, resulting in an increase in bowel length exceeding 2-fold and possibly reaching 3 to 4 fold or greater, depending on the degree of bowel dilatation.

Article on Intestinal Lengthening in Adult Patients with Short Bowel Syndrome. [Accepted: 5 August 2010 / Published online: 24 August 2010]

• This is the first study specifically describing surgical lengthening in adult patients.• Indications were

(a) to increase the enteral caloric intake thereby reduce or wean parenteral nutrition (PN) (b) to decrease bacterial overgrowth.

• Median remnant bowel length prior to surgery, length gained and final bowel length was 60, 20, and 80 cm, respectively.

• Survival was 90% with mean follow-up of 4.1 years (range=1–7.9 years). • Overall, 59% patients achieved enteral autonomy and were off PN. 43% patients

showed significant improvement in enteral caloric intake.

• Conclusions: Bowel lengthening is technically feasible and effectively leads to weaning from PN in more than half of the adult patients. Lengthening procedures may be an underutilized treatment for adults with short bowel syndrome.

C. Kimura procedure

• described by Kimura and Soper.

• based on allowing time for the antimesenteric border of the bowel to “parasitize” a new blood supply from the liver and abdominal wall musculature before dividing it from the mesenteric half and creating a new tube.

Kimura procedure

Surgical techniques to slowing the intestinal transit

• A) Anti-peristaltic segments,• B) Colon interposition,• C) Intestinal valves,• D) Tapering enteroplasty

A) Anti-peristaltic segments:• Surgical reconstruction of the residual small bowel

using antiperistaltic jejunal segments has been recommended for patients with a resected ileum and ICV.

• Method: the technique includes excision of a small segment (10-15cm in length for adults and 3cm for children) of the distal intestine with its mesenteric blood supply rotation over 180 degree of the distal intestine, and an end-to-end anastomosis between the reversed intestinal segment and the proximal jejunum and distally to the remaining colon.

• Clinical improvement seen in 80 % of patients.• A reasonable survival rate of 50% and weaning off total PN.

• Optimal length of anti-peristaltic segment 10 cm in adults and 3-4 cm in children.

• In children the anti-peristaltic segment grows along with the rest of intestine so consistent result cannot be achieved.

• Complications – transient obstructive symptoms. Eosinophilic colitis – with bleeding can occur in the interposed colonic

segment , may necessitate excision.

B) Colon interposition.

• used as an adjuvant method in cases of medical management failure.

• Studies in adults have shown that after interposition, will retard intestinal motility due to inherent slow peristaltic activity of large bowel.

• The technique may be performed iso-or antiperistatically.

• The colon behaves in a similar way to the reversed small intestinal segement Induces retrograde peristalsis by disrupting the myo-electrical activity.

C) Intestinal valves.• The simplest techniques include the installation of sutures or external Teflon around

the circumference of the bowel.

• Another option involves the creation of small intussusceptions by everting a segment of small bowel.

• Intussuscepted nipple valves – purpose is to simulate ileocaecal valve function. To slow intestinal transit, to prevent bacterial back wash into proximal bowel.

• Valve construction at ileocolonic junction – with 8 cm of intestine.

• PTFE valve uses 3 cm of native intestine.

• Problem – obstruction due to construction of too tight a valve.

• No benefit –with loose valve.

• Complication: Erosion of valve into the lumen of the intestine.

D) Tapering enteroplasty.

• another option in the management of PSBS• involves reducing the caliber of the dilated intestinal segment in patients with

PSBS. Usually, this portion exhibits low contraction resulting in stasis, malabsorption and bacterial overgrowth.

• As patients with PSBS have a short residual intestine, excision of the dilated intestine may be not reasonable.

• The reduction could be performed either by excising the antimesenteric portion of the dilated segment or by the folding and placation of the intestine. A drawback to this method is the possible breakdown of the sutures lines with recurrence of dilation and functional obstruction of the bowel.

Intestinal transplantationIndicated • in patients with failure of intestinal improvement after

various surgical techniques,

• in those with no possible feeding tolerance,

• irreversible hepato-intestinal disease,

• recurrent sepsis, and

• failure of central venous sites.

Post-operative immunosuppression is done with tacrolimus, mycofenolate, azathioprine, cyclophosphamide.

No useful marker to see rejection – like creatinine in renal transplant, albumin in liver transplant.

During follow up Stool frequency, volume , consistency, repeated endoscopic mucosal biopsy.

Complications include acute cellular rejection (fever, nausea, vomiting,

abdominal distention), Rejection is common due to gut associated lymphoid tissue.

graft vs. host disease,post-transplant lymphoproliferative disorder, Sepsis is common complication.

Post operative Mortality up to 30%.Most common causes – sepsis and hepatic failure.

1 year survival is 90% and 4 years survival is 60%

Tissue Engineering Small Intestine (TESI)

• In order to build a viable and functional small intestine, the armamentarium of TESI includes sophisticated materials, human pluripotential stem cells, and biopharmaceutical means.

• A number of proteins or nucleic acid, known as biopharmaceuticals, have been used either in clinical trials or in vitro .

• Available biopharmaceuticals products include IGF-I, IGF-II, EGF, TNF-a, etc.