Management of colonic complications of type IV Ehlers-Danlos syndrome: a systematic review and evidence-based management strategy.

AIM: Type IV Ehlers Danlos Syndrome (EDS) is a connective tissue disorder affecting approximately 1 per 100,000-200,000 people. Life expectancy is reduced secondary to spontaneous vascular rupture or colonic perforation. Surgery carries significant morbidity and mortality. While strategies to manage colonic perforation include primary repair with or without a defunctioning stoma, Hartmann's procedure, total abdominal colectomy with end ileostomy and ileorectal anastomosis, evidence is contradictory and has not previously been evaluated in order to form a treatment strategy. We aim to review the published literature and identify outcome data relating to operative management of colonic perforation in type IV EDS. METHODS: Pubmed, EM-BASE, Cochrane library and Google Scholar were searched with the following details: Ehlers Danlos Syndrome AND colonic surgery. The main outcome measure was re-perforation rates following colonic surgery on patients with type IV EDS. If the nature of surgery and follow up were reported, data were recorded in a SPSS database according to PRISMA guidelines. RESULTS: One hundred and nine operations have been described in 51 patients in 44 case series. There were 26 visceral re-perforations, 2 affecting the small intestine and 24 colonic. Survival analysis favoured total abdominal colectomy compared with operations where the colon was left in situ. CONCLUSIONS: Total abdominal colectomy with end ileostomy or ileorectal anastomosis are the safest strategies after colonic perforation in type IV EDS. Anastomotic leak rates are high. End colostomy is high risk for colonic re-perforation and anastomotic leak rates are extremely high. Restoration of colonic continuity should be avoided.

Histopathological and Immunohistochemical Findings in Congenital Pouch Colon: A Prospective Study.

BACKGROUND: There is a paucity of literature on the histopathological aspects of congenital pouch colon (CPC) and immunohistochemical (IHC) assessment has not been reported. So we planned to study the histopathological and IHC findings within the spectrum of CPC and compare the findings with the normal colon. METHODS: This is a descriptive prospective study on CPC patients. There were 49 cases of CPC (42 males and 7 females) and 13 controls. Histological examination was done using hematoxylin and eosin and Masson trichrome stain. IHC analysis was done with actin, myosin, and desmin antibodies, and neuron-specific enolase and S100 markers for counting ganglionic cells. RESULTS: Histologically, congestion, edema and hemorrhage were seen in mucosa, submucosa, and serosa. Muscle layers were disrupted and divided into bands. An additional muscle coat inside of the muscularis propria was seen in CPC types 1 and 2. Mature ganglionic cells were reduced and muscle layers showed reduced and patchy positivity for smooth muscle actin, myosin, and desmin compared to a normal colon. CONCLUSIONS: Histopathological and IHC findings suggest that CPC has distinct defects in the neuromusculature.

Congenital Myenteric Hypoganglionosis.

Congenital myenteric hypoganglionosis is a rare developmental disorder characterized clinically by severe and persistent neonatal intestinal pseudoobstruction. The diagnosis is established by the prevalence of small myenteric ganglia composed of closely spaced ganglion cells with sparse surrounding neuropil. In practice, the diagnosis entails familiarity with the normal appearance of myenteric ganglia in young infants and the ability to confidently recognize significant deviations in ganglion size and morphology. We review clinical, histologic, and immunohistochemical findings from 12 patients with congenital myenteric hypoganglionosis in comparison with similar data from age-matched controls and clearly delineate the diagnostic features of the condition. Practical guidelines are provided to assist surgical pathologists, who are likely to encounter this condition only infrequently. The diagnosis typically requires full-thickness intestinal biopsy as the abnormality is confined to the myenteric plexus in many patients. Immunohistochemistry for Hu C/D may be used to confirm hypoganglionosis. Reduced staining for calretinin and NeuN implicates a selective deficiency of intrinsic primary afferent neurons in this disease.

Role of plain abdominal radiographs in predicting type of congenital pouch colon.

BACKGROUND: Congenital pouch colon (CPC) is a rare form of high ano-rectal malformation (ARM) in which part of or the entire colon is replaced by a pouch with a fistula to the genito-urinary tract. According to the Saxena-Mathur classification CPC is divided into five types. Although plain abdominal radiographs are taken in infants with suspicion of CPC to detect large dilatation of the pouch, the determination of the type of CPC is made during surgical exploration. Since large variations in the length of normal colon are present in the various types, management strategy options can be determined only at the time of surgery. OBJECTIVE: The aim of this study was to review abdominal radiographs of children with congenital pouch colon (CPC) and evaluate their value in determining the type of CPC prior to surgical exploration to assist pre-operative planning. MATERIALS AND METHODS: Over a 12-year period (1995-2007), CPC was documented in 80 children (52 boys and 28 girls, age range 1 day-9 years, median 2.4 days) and retrospective analysis of plain abdominal radiographs of 77 children at the time of presentation was performed. Radiographic findings were correlated with surgical findings. RESULTS: Of 77 children, 5 were excluded from the study since the pouch colon was perforated. The direction of the pouch apex was correlated with surgical findings to determine the CPC type (P<0.0001, Fisher exact test). Type 1 (17/18) and type 2 CPC (18/18) were characterized by a single large pouch with the apex positioned in the left hypochondrium. In type 3 CPC (2/2) the pouch apex was directed towards the right hypochondrium. In type 4 CPC the apex of the pouch was directed towards the right hypochondrium (28/33); however in 5 children it was towards the left hypochondrium. In type 5 CPC (n=1) the radiograph was inconclusive. CONCLUSION: Plain abdominal radiographs have a predictive value in determining the type of CPC and obviating the need for an invertogram.

Congenital pouch colon: an unusual histological finding.

Congenital pouch colon (CPC) is an unusual abnormality in which the colon ends in a pouch-like dilatation and there is generally an associated anorectal malformation. The condition varies from complete absence of normal colon to a nearly normal length of proximal colon with only recto-sigmoid involvement. There is a paucity of data on histological findings in cases of pouch colon. Resected specimens of five cases of CPC were taken. Microscopic sections were stained for H&E and Masson's trichrome stains. We present here an interesting histological finding, namely an unusual muscle layer, inner to the circular muscle layer, in five cases of complete or almost complete CPC and discuss the clinical significance of this finding.

Congenital colonic stenosis: a case of late-onset.

PURPOSE: Colonic atresia and stenosis are rare causes of intestinal obstruction in the infant. Only 1.8%-15% of intestinal atresias occur in the colon. Congenital colonic stenosis is even less common than colonic atresia. Only 10 cases have been reported in Literature since 1966 and only one late-onset case has been reported in Literature until now. We describe the case of a 4-month-old baby coming to our attention because of an intestinal subocclusion due to a congenital colonic stenosis of the ascending colon. CASE REPORT: A 4-month-old baby came to our attention for persistent abdominal distension, reduction of bowl function and decaying of overall clinical conditions. A plain abdominal radiograph showed distended intestinal loops with air-fluid levels and no gas in the rectum. During the barium enema the contrast medium appeared to completely fill the lumen of the colon up to the ileo-cecal valve and Cecum appearing higher than normal. Beyond the ileo-cecal valve, the contrast medium showed an abnormal hypotonic dilatation of the small intestinal loops. Suspecting an organic intestinal obstruction, an explorative laparotomy was deemed necessary and at halfway in the ascending colon a stenosis was found. RESULTS: The post-operative course was uneventful and the patient is currently in good clinical conditions, has a normal diet and is thriving. CONCLUSION: Considering both the Literature and our own experience, it is wise to reckon the congenital colonic stenosis as a rare but possible cause of complete or partial intestinal obstruction not only in the newborn but also throughout the first year of life.

Chronic bowel obstruction from colonic stenosis in early infancy-A report of two cases.

Bowel obstruction in early infancy may result from a variety of congenital anomalies involving parts of the small and large bowel. However, in infancy, chronic bowel obstructions from congenital or acquired stenosis of the colon are rare and can cause diagnostic quandary. We present two cases of an eleven-week old male and a nine-week old male with massive abdominal distension and features of chronic bowel obstruction dating from neonatal period. In the first case investigations were inconclusive and laparotomy revealed isolated stenosis of the ascending colon. In the second case colonic stenosis was suspected preoperatively and a barium enema done showed multiple colonic stenosis confirming our working diagnosis. The diagnostic dilemmas encountered in managing the first patient are discussed to highlight the need for high index of suspicion of this condition in infants with chronic constipation. The way experience in managing the first case influenced diagnosis of the second case is also highlighted.

Whole exome sequencing reveals rare variants linked to congenital pouch colon.

We demonstrate the application of whole exome sequencing to discover the rare variants for congenital pouch colon, acronymed CPC. For 18 affected individuals in a total of 64 samples, we sequenced coding regions to a mean coverage of 100×. A sufficient depth of ca. 94% of targeted exomes was achieved. Filtering against the public SNP/variant repositories, we identified a host of candidate genes, EPB41L4A and CTC1 associated with colon, neural/brain muscles and Dyskeratosis Congenita maladies. Furthermore, the stop gain mutations in the form of JAG1,OR5AR1,SLC22A24,PEX16,TSPAN32,TAF1B,MAP2K3 and SLC25A19 appears to be localized to Chromosomes 2, 11, 17 and 20 in addition to the three stop lost mutants across three genes, viz. OAS2, GBA3 and PKD1L2 affecting the colon tissue. While our results have paved way for transcendence of monogenic traits in identifying the genes underlying rare genetic disorders, it will provide helpful clues for further investigating genetic factors associated with anorectal anomalies, particularly CPC.

Tubular colonic duplication in an adult: case report and brief literature review.

Gastrointestinal tract duplication is a rare congenital anomaly that can occur anywhere along the alimentary tract. Most of the reported patients present with acute abdomen during childhood. We describe a case of tubular colonic duplication in an adult. The patient was a 25-year-old woman who presented with abdominal pain, bloating, nausea, and emesis for 3 days. The physical examination was remarkable for abdominal distension, tenderness, and rigidity. Abdominal computed tomography scan revealed abnormal intestinal dilatation. Exploratory laparotomy was performed, and tubular colonic duplication was identified intraoperatively. The diagnosis was verified by postoperative pathology results. The patient was discharged on postoperative day 14 and followed for 2 years without specific events or complications. Furthermore, we reviewed the published literature on colorectal duplication in adults for the past two decades.

Congenital duodenocolic fistula in a dog.

A one-year-old female cocker spaniel presented with a 6-month history of persistent diarrhoea. Abdominal ultrasonographic examination revealed mild diffuse thickening of the intestinal wall coupled with mesenteric lymphadenopathy. A connection between the duodenum and the colon was observed during an endoscopic procedure and confirmed by computed tomography. Surgical resection of the communication allowed remission of the diarrhoea. Histology showed a normal duodenal epithelium and muscular layer. A duodenocolic fistula is an abnormal connection within the digestive tract, which in humans is usually considered a complication of a local pathological condition. Due to the absence of a predisposing cause and, in view of the dog's age and histological results, a congenital origin was suspected.

Segmental Absence of Intestinal Musculature in a 64-Year-Old Female: Case Report and Literature Review.

BACKGROUND Segmental absence of intestinal musculature is a well described entity in premature infants. It presents with peritonitis, bowel perforation, and obstruction. The diagnosis is based on pathologic observation of absence of intestinal musculature. Researchers hypothesized that this entity is a result of a vascular accident during embryogenesis. However, segmental absence of intestinal musculature is no longer limited to the pediatric population. Recently, a few cases have been described in adults with and without significant vascular diseases. This change in the age of the affected population with segmental absence of intestinal musculature makes the understanding of the pathogenesis of this entity even more challenging. CASE REPORT Here, we report a case of segmental absence of intestinal musculature in a 64-year-old female. The patient presented to the emergency room with sudden onset of abdominal pain and signs of peritonitis. Abdominal computed tomography showed free air in the abdomen. Laparotomy was performed, and a perforation involving the descending colon was identified. Left hemicolectomy was performed. Pathologic examination of the resected colon showed segmental absence of intestinal musculature. CONCLUSIONS Although the pathologic diagnosis of segmental absence of intestinal musculature is straightforward, the assumption that this condition is limited to the pediatric population is a major player in overlooking this diagnosis in adults. Pathologists should be aware that this condition can present in adults and is segmental. Gross and microscopic examination of perforated intestine is required to reach the correct diagnosis. To our knowledge, twelve cases of this entity have been described in adults. Here we present the thirteenth case of segmental absence of intestinal musculature in an adult, and we discuss the clinical and pathologic findings of this entity as well as its pathogenesis.

Congenital segmental dilatation of colon with colonic atresia.

Congenital segmental dilatation of the colon belongs to a group of Hirschsprung's-like diseases with normal ganglion cells. The presentation is with chronic constipation affecting older children. We report a neonate with congenital segmental dilatation of the colon associated with sigmoid atresia. The child is well after a colostomy.

Congenital colonic atresia and stenosis.

Five more cases are added to the 88 reported cases of successfully treated newborns with congenital colonic atresia and stenosis. Because colonic atresia and stenosis are lethal conditions when untreated, early diagnosis and operative treatment are major requisites for survival. A two-stage procedure consisting of an emergency colostomy for decompression as the first stage and an elective resection with anastomosis a few months later is recommended. The need for thorough exploration of the abdomen is emphasized because atresias may be multiple or may be associated with additional gastrointestinal anomalies.

Meconium peritonitis.

Meconium peritonitis can have a wide range of presentations. This report discusses two cases that have recently appeared in our neonatal intensive care unit. The first report discusses the case of a meconium pseudocyst in a preterm infant. The second case reports on a newborn baby with a healed bowel perforation during the prenatal period. Finally, a brief discussion of meconium peritonitis is also included.

Congenital segmental dilatation of the colon.

Segmental dilatation of the colon with bowel wall muscle hypertrophy has been described in children 6 mo and older presenting with constipation since birth. A case of segmental dilatation of the colon without muscle hypertrophy in a newborn argues for the congenital origin of the dilatation and for the muscle hypertrophy being acquired.

Coloplasty for congenital short colon.

Seventy-two patients with complete short colon (CSC) were treated at the authors' institution between 1971 and 1994. Initially, one-stage coloplasty with abdominoperineal pull-through was performed in 10 neonates, with a 50% survival rate. The subsequent 62 patients had staged management in which a window colostomy was performed at the time of presentation. Of the 50 survivors in this group, 20 had coloplasty with a abdominoperineal or sacroabdominoperineal pull-through by June 1994. A protective ileostomy was done at the time of coloplasty in 10 patients, and was closed 6 to 12 weeks later. Two of the 20 patients who had staged reconstruction died because of complications; the others recovered well. The overall survival rate after coloplasty was 76.7%. Eighteen of the 23 survivors have had follow-up for up to 8 years. They have shown normal growth and good continence and have been free of significant long-term complications. The other 30 patients are awaiting definitive surgery. A staged management plan is advocated for complete short colon because it provides consistent results and good quality of life.

Neonatal small left colon syndrome: intramural not intraluminal obstruction.

We have described a characteristic syndrome of intestinal dysfunction in infants of diabetic mothers. This finding appears to result from a transient intramural dysfunction. Many respond to rectal irrigations alone. However, a significant number will require close observation and possible diversion for persistent partial intestinal obstruction. Failure to recognize persistent obstruction may result in intestinal perforation.

The complete spectrum of neurocristopathy in an infant with congenital hypoventilation, Hirschsprung's disease, and neuroblastoma.

Neuroblastoma, Hirschsprung's disease, and central hypoventilation (Ondine's curse) are considered aberrations of neural crest cell growth, migration, or differentiation, and as such are considered to be under the general heading of neurocristopathy. Their combined occurrence in a newborn infant presenting with total colonic aganglionosis, central hypoventilation, and multifocal neuroblastoma had not been reported previously. A 2.3-kg white full-term girl required endotracheal intubation because of persistent apnea in the first hours of life. She had progressive abdominal distension and failure to pass meconium; a barium enema was performed, which showed microcolon with meconium pellets at the distal ileum. During laparotomy the distal ileum was found to be obstructed with inspissated meconium; an ileostomy and appendectomy were performed. The resected specimens were aganglionic. An additional 20 cm of aganglionic ileum was removed, and a normally innervated ileostomy was constructed. Numerous attempts at extubation failed because of apnea. The results of an extensive apnea workup, including electroencephalogram, magnetic resonance imaging (MRI), bronchoscopy, and pH probe study, were normal. Sleep studies showed congenital central hypoventilation syndrome, and the patient underwent a tracheostomy. At 3 months, an abdominal ultrasound examination performed within a septic workup showed a right suprarenal mass extending across the midline. Thoracic and abdominal MRI scans showed large bilateral adrenal and posterior mediastinal masses. The serum catecholamines and ferritin level were markedly elevated, suggestive of neuroblastoma. In light of the child's multiple problems, the family chose to forgo further workup (including a tissue biopsy) and therapy. In the following 2 months her tumor load rapidly progressed, and she died of respiratory insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)