Hirschsprung’s disease, polyps, ulcerative colitis, Crohn disease, anorectal malformations

Kacper Kroczek, M.D.

Clinical Ward of General and Oncological Surgery for Children and Adolescents CM UMK, Bydgoszcz

Hirschsprung’s disease Hirschsprung disease

• neurocristopathy • one of the most common causes of intestinal obstruction in newborns • incidence: 1:4400 – 1:7000 live births • male-female ratio: 4:1 (long-segment 1:1) • higher incidence in families of children with HD • 90% diagnosed in newborn period • sporadic occurrence : 80-90%

Etiology

• Genetics: RET mutation, GDNF (glial cell-line derived neurotrophic factor), NTN (neuroturin), END3 (endothelin-3)

• Embryology: neuroenteric cells migration to myenteric and submucosal plexus

- RET proto-oncogene mutation as in multiple endocrine neoplasm (ex. MEN 2B) - neurocristophaty-related tumors - RET penetrance is sex-dependent (more common in males) Pathology

Absence of ganglion cells in the distal intestine is the hallmark of this disease. Gangion cells are absent in both the submucosal (Meisner’s) and intermuscular (Auerbach’s) plexus. • Neural crest-derived neuroblasts first appear in the developing esophagus at 5 weeks, and then migrate down to the in a craniocaudal direction during 5th to 12th weeks of gestation • The earlier the arrest of migration, the longer the aganglionic segment

Marked increase in nerve fibers that extend into the submucosa.

HE and AChE stained, NSE and S-100 reduced amount Adrenergic predominates inhibitory function in the aganglionic segment – increased smooth muscle tone

Immunohistochemistry

A – hypertrophic nerve bundles with AChE stained, Calretinin negative stained Pathology

• typical extent: rectosigmoid region (80%) • TCA – 3-12% of infants • length of transition zone varies • may be cause of bowel dysfunction if we will make a junction in this level • funnel-like transition zone

TCA Clinical presentation

• delayed passage of fecal matter (typically at first 48 hours of life) • • abdominal distension • poor feeding • emesis • important – rectal examination

Clinical Presentation

• 95% full-term infants defecate within their first 24 hours of life • Patients with HD may also present with a history of constipation followed by explosive diarrhea (often indicating the development of enterocolitis) • Rectal examination reveals a tight anus (incorrect diagnosis of anal stenosis) Radiographic studies

• abdominal radiographs - distended loops of intestine and may also reveal paucity of air in the • intraperitoneal air • contrast enema – contraindicated in active enterocolitis!

Radiographic studies

• Intraperitoneal air as a sign of perforation of proximal intestine in HD, perforation is most common in infants with long segment HD • Enema can differentiate other causes of distal intestine obstruction from HD • Enema should contain water-soluble contrast (to avoid barium peritonitis and more effective in relieving obstructing meconium), • Hyperosmolar - electrolytes imbalance • Avoid rectal examination and washouts before enema • Catheter is inserted just inside the anus, initial contrast in instilled slowly in a controlled manner • Post-evacuation image is obtained (after 24h – delayed image) Classic radiographs

Narrow, spastic distal intestinal segment with dilated proximal segment (+ transition zone – most common at rectosigmoid region) Poor evacuation of the contrast corroborating evidence of the abnormality Contrast enema doesn’t diagnose all cases of HD (less well defined transition zone)

Classic radiographs Classic radiographs

Anorectal manometry

• absence of relaxation reflex • increased contraction of the upper anal canal • rectal distention Rectal biopsy

• the gold standard for the diagnosis of Hirschsprung disease • full-thickness or suction biopsy • typically 2 cm above dental line

Among the internal anal sphincter it is normal hypoganglionosis

Enterocolitis

• HAEC • major cause of significant morbidity and mortality • explosive diarrhea + abdominal distention + fever • Intestinal stasis → bacterial transepithelial translocation (immunological defect) → development of inflammation → sepsis Differential diagnosis

Mechanical obstructions: • meconium ileus • distal ileal or colonic atresia • small intestinal stenosis • low imperforated anus

Functional obstructions: • prematurity • small left bowel syndrome • meconium plug syndrome • sepsis or electrolyte imbalance • intestinal neuronal dysplasia

Complete obstruction (atresia) results microcolon at contrast enema studies, contrast enema could be also diagnostic as curative (child often passes meconium plug after the study)

Surgical treatment

• Primary pull-through procedure is the preferred approach • • One-stage treatment • Multi-stage treatment

Colostomy is indicated in infants who suffer from severe enterocolitis or who have markedly dilated proximal colon Intraoperative view

Intraoperative view Definitive surgical

treatment: Swenson Duhamel

Soave Rehbein

Endorectal pull-through

The operation involves removing the mucosa and submucosa of the rectum and pulling ganglionic intestine through aganglionic muscular cuff transanal vs. transabdominal Transanal endorectal pull-through (TEPT)

Polypoid diseases Gastrointestinal polyps

• isolated or syndromic • syndromes which involves polyps : Peutz-Jeghers syndrome, Gardner syndrome, Turcot syndrome • mostly benign • hamartomas of the mucosa or lymphoid hyperplasia of the submucosa • most common cause of rectal bleeding in toddlers • 80% juvenile polyps, 15% lymphoid, 3% adenomatous (!)

Jass criteria

1) >5 juvenile polyps in colon 2) polyps throughout 3) any number of polyps associated with family history of juvenile polyposis

Increased risk of cancer Juvenile polyps

• retention / inflammatory / cystic • 80% of polyps in children • smooth, spherical head (2 mm-several cm) • often ulcerated surface (bleeding!) • dilated or cystic epithelial tubules • peak incidence : 3-5yo • 40% rectosigmoid region

PANCOLONOSCOPY

Juvenile polyps

• several centimetres diameter • usually cystic spaces filled with mucus • inflammation leads to obstruction of regional colonic glands of mucosa → forming cystic structures • red streak of blood over the surface of the stool • bleeding (95%), abdominal pain • differential diagnosis : anal fissures, intussusception (worse abdominal pain), bowel hemangiomas, Schonlein-Henoch purpura Juvenile polyposis syndromes

• diffuse juvenile polyposis syndrome of infancy <6mo • diffuse juvenile polyposis 6mo-5yo • juvenile polyposis coli >5yo

Every child with >5 juvenile polyps or even on with family history is considered to have JPS

PROPHYLACTIC COLECTOMY VS REGULAR SCREENING

Juvenile polyposis syndromes

1) diarrhea, bleeding, protein-losing enteropathy 2) mild rectal bleeding and prolapse (should distinguish from FAP!) 3) bleeding, prolapse , malnutrition

• Most patients will have 50-100 colorectal polyps • High (17%) risk of carcinoma • Lobular type of polyps have higher propensity for more severe dysplasia Peutz-Jeghers syndrome

Intestinal polyps + mucocutaneous pigmentation spots

Peutz-Jeghers syndrome

• melanin spots on the buccal mucosa and lips with variable melanin pigmentation on the face and digits + polyposis of intestinal tract • polyps (from stomach to rectum) occurs most commonly in small intestine • polyps are lobulated in opposite to juvenile polyps which are non-lobulated; also type of hamartomas • autosomal dominant manner • often transient intussusception of polyp, greater risk of cancer evolution • all polyps found in endoscopy bigger than 0,5mm should be removed Lymphoid polyps

• few mm to 3 cm diameter, usually sessile • elevation of hyperplastic submucosal lymphoid aggregates • often ulcerated (volcano-like surface) • peak incidence: 4-5yo

SELF-LIMITING – SPONTANEOUS REGRESSION

FAP (familial adenomatous polyposis) • APC gene • presence of at least 100 visible adenomatous polyps in • sparse/profuse type • neoplastic transformation of the epithelial cells in proliferative portion of a crypt • probability of cancer by 25 years of age is 90% PROCTOCOLECTOMY FAP (familial adenomatous polyposis) • Gardner syndrome results from deletion 5q – mutation of APC gene (tumor suppressor product) • Colorectal polyps are hallmark of FAP • Spars / profuse • Neoplastic transformation →dysplasia • Extension of neoplastic cells into the basement membrane of the epithelium represent carcinoma in situ • Proctocolectomy and J-pouch formation at ileal part of small intestine

FAP (familial adenomatous polyposis) Other syndromes

Gardner syndrome • colonic FAP with multiple osteomas, fibromas and epidermoid cysts

Turcot syndrome • colonic FAP with intracranial brain tumors

Ulcerative colitis Ulcerative colitis

• the cause remained undetermined • 15% patients with UC have family history of IBD • rectum is involved in more than 95% • the inflammation extends proximally with continguous manner • pancolitis/ backwash ileitis • Ileostomy with one-stage proctocolectomy was considered the standard elective operation for patients with UC • Chronic inflammatory disease of the rectal and colonic mucosa and submucosa • If pancolitis occurs – most severe changes are in rectum and sigmoid colon

Pathology

• crypt abscesses leads to mucosal ulceration • mucosal bridging with pseudopolyps formation • in acute phase: distended colon, decreases peristalsis, thin muscular part of colon /hemorrhagic • flat haustral folds • the mucosa may become dysplastic Pathology

Ulcerative colitis

• the onset of UC most commonly occurs in persons in their late 20’s • male-female – up-close incidence • tenesmus, painful constipation • risk of carcinoma : 3% for patients in their first 10y of life, later it increases approximately 10-15% per decade Symptoms

• persistent diarrhea (followed by the appearance of blood, mucus or pus in the stool) • intermittent, cramping lower abdominal pain • tenesmus • anemia • many children feel tired • weight loss

Extracolonic manifestation Extracolonic manifestation

• growth retardation, arthralgias, delay of sexual maturation, skin lesions (erythema nodosum), anemia, osteoporosis, primary sclerosing cholangitis, nephrolithiasis, uveitis, stomatitis • cushingoid features from long-term steroid-therapy • , fissures, abscesses suggest Crohn’s disease

Medical treatment

5-aminosalicylic acid (5-ASA) • sulfasalazine, mesalazine Corticosteroids • prednisone Antidiarrheal medications – risk of toxic ! Immunosuppressive drugs • azathioprine, 6-mercaptopurine, cyclosporine Surgical treatment

• elective/emergency surgery • historic gold standard →proctocolectomy with permanent ileostomy • ileoanal pouch

• elective surgery – patients with persistent symptoms of UC despite medical therapy, growth retardation, severe limitations of activities and unacceptable quality of life • emergency surgery – indicated for fulminant disease ex. extensive rectal bleeding or toxic megacolon • pouch allows storage of fecal manner

Pouches

To provide sufficient length for distal ileum to reach the anus without tension, Distal 10-12 cm of ileum is doubled back on itself (at antimesenteric surfaces) Ileoanal anastomosis

Ileoanal anastomosis

• Two-stage procedure with ileostomy formation, • Second-stage: 3-month after first stage → closure of ileostomy and endoscopy • Residual fecal volume : better if it is less than 10ml • Complications : Pouchitis (most common- effect of prolonged fecal storage), obstruction of small intestine, fecal incontinence, soiling Crohn’s disease

Crohn’s disease

• multifactorial • panenteric, full thickness, aphthous ulceration • more common than UC (11 vs 2,3 per 100,000 population) • M and F are equally affected Pathology

Pathology

• extensive aphthous ulcerations of mucosa which has cobblestone appearance • the inflammation is interspersed with normal-appearing bowel (skip lesions) • transmural inflammation – fistulas (ex. to bladder, abdominal wall, perineum, ) 65% of patients with CD are 15-20-yo Symptoms

• chronic, intermittent, crampy abdominal pain • diarrhea • weight loss/ growth failure • rectal bleeding • perianal disease

Growth failure manifested by a delayed onset of puberty, sexual infantilism, short stature → malnutrition and anorexia

Extraintesinal manifestations

• arthralgia/arthritis • erythema nodosum/ pyoderma gangrenosum • Iritis / uveitis • renal stones/ gallstones Endoscopic changes

• rectal sparing • cobblestoning of mucosa • serpiginous ulcers • colonic strictures • skip lesions

Medical treatment

• corticosteroids • 5-aminosalicylic acid (5-ASA) • metronidazole • 6-mercaptopurine/azathioprine • MTX, cyclosporine • monoclonal antibodies (infliximab) • TPN Medical treatment

• Corticosteroids – prednisone/prednisolone • Use of corticosteroids may result in adverse effects of steroids : Cushing syndrome, growth suppression, cataracts, glaucoma, osteoporosis, depression • Side effects of 5-ASA: headache, nausea, fatigue, azotemia, rash, fever, hepatitis, hemolytic anemia, bone marrow suppression

Surgical treatment

Surgery should be reserved for complications of the disease or failure of medical therapy. • RLQ pain →mechanical bowel obstruction, abscess, phlegmon, formation → ileocecectomy and primary anastomosis with resection of fistulas • Heineke-Mikulicz strictureplasty

Strictureplasty – longitudinal incision across stricture and 1-2 cm to normal bowel on either side of the stricture. The bowel is then closed transversely. Surgical treatment

Surgical treatment

• Crohn’s colitis →total colectomy with end ileostomy • perianal disease →incision, drainage and debridement • Infrasphincteric fistulas → fistulotomy/ fistulectomy

High risk of recurrence! BOWEL-SPARING SURGERY INDICATED Anorectal malformations

Anorectal malformations

• 1 in 5000 live births • rectovestibular fistula – most common in females • rectourethral fistula – most common in males • 50% cases with imperforated anus have Down syndrome Classification

MALES FEMALES

Perineal fistula Perineal fistula

Rectourethral fistula Vestibular fistula

- bulbar

- prostatic <3cm common chanel

Rectovesical fistula (bladder neck) >3cm common chanel

Imperforate anus without fistula without fistula

Rectal atresia Rectal atresia

Complex defects Complex defects

Associated malformations

• cardiovascular (ASD, PDA, ToF, VSD) • gastrointestinal (esophagotracheal defects, obstruction of duodenum) • spinal and vertebral (hemivertebrae, scoliosis, butterfly vertebrae, hemisacrum) • genitourinary (VUR, renal agenesis/renal dysplasia, cryptorchidism) • gynecological (bicornuate uterus, vaginal septum) Associated malformations

CURRARINO’s TRIAD hemisacrum + imperforate anus + presacral mass

Initial management

• don’t make surgical decisions before 24 hours of age  passing of meconium through a fistula is the most valuable sign of the location of the fistula • first 24 hours : iv fluids, antibiotics, nasogastric decompression; rule out the presence of associated defects

• Anal canal allows to discriminate solids from liquids and even from gas • Patients who were born without anal canal have no sensation, but they have proprioception • Hypomotility of rectosigmoid region • Associated defects : plain radiographs, US of spine, US of abdomen Management

Newborn-male

Perineal inspection

Rectal gas below Rectal gas above coccyx coccyx Perineal fistula No assosiated Associated defects defects Flat bottom

PSARP ANOPLASTY (with/without COLOSTOMY colostomy)

Distal colostogram Management

Newborn-female

Perineal inspection

Single perineal No visible fistula orifice Perineal fistula Vestibular fistula Cross table CLOACA lateral X-ray

ANOPLASTY COLOSTOMY Rectum below COLOSTOMY OR OR PRIMARY High rectum coccyx DILATATIONS REPAIR

COLOSTOMY or COLOSTOMY PRIMARY REPAIR

PSARP

Electrical stimulation of the perineum Midline incision is created (important nerves and vessels don’t cross the midline) Patient in the prone position, midline incision is made Rectum is dissected in circumferential manner Complications

• wound infection • rectal or vaginal strictures • rectal mucosa prolapse • urethral, ureteral, vas deferens, seminal vesicles injuries • Constipation

• For anal strictures – anal dilatation program is recommended • Megarectosigmoid colon leads to constipation and constipation that is not properly managed can lead to megarectosigmoid colon

Hegar’s dilators

Thanks for your attention!