Long-standing Crohn's Disease Research Articles

Carcinoma in the residual rectum of a long-standing Crohn's disease patient following subtotal colectomy: A case report.

The development of colorectal cancer in long-standing Crohn's disease (CD) patients has become a major complication. Therapeutic guidelines for CD-associated cancer (CDAC) have already been established in Western countries; however, specific guidelines are not currently available in Japan. Surveillance of the residual intestine for cancer screening is important for long-standing CD patients. The present case report describes the occurrence of rectal carcinoma in a patient with a 25-year history of CD. A 37-year-old male with a 17-year history of CD underwent semi-emergent subtotal colectomy and ileostomy for bowel obstruction secondary to the transverse colon stenosis, and multiple severe stenosis and inflammation. Postoperatively, the patient resumed pharmacological treatment and underwent follow-up colonoscopies at ~1-2-year intervals. Despite continued pharmacological treatment, inflammation continued in the residual rectum. A total of 8 years following the primary operation, colonoscopy revealed inflammatory polyposis at the remnant rectum, which was diagnosed as adenocarcinoma. The interval between the last colonoscopy was 16 months. The patient then underwent laparoscopic abdominoperineal resection, and remained without recurrence for 12 months following resection. Thus, in long-standing CD patients, annual colonoscopy of the residual intestine may be considered for cancer screening, and specific surveillance guidelines for CDAC should be established.

Case of a 38 Year Old Male with Pulmonary Crohn's Disease

We present the case of a 38 year old male who presented with several weeks of respiratory complaints found to be the result of Crohn's Disease (CD) with Pulmonary Manifestations. His past medical history was significant for long standing CD and he was on immunosuppressive therapy with vedolizumab. Initial findings were concerning for Bronchopneumonia or a possible Metastatic Disease. Subsequent work-up eliminated infectious and cancerous etiologies. This included blood cultures, HIV, Quantiferon Gold Assay, PPD, and bronchial biopsy results. Furthermore, GMS, AFB, and Truant special stains were negative for fungal elements and mycobacteria. Eventually, the patient underwent a VATS (video-assisted thoracoscopic surgery) biopsy, which revealed noncaseating granulomas with prominent neutrophilic microabscesses. This finding led to the differential diagnosis of either a vasculitis, or a pulmonary CD. The lack of cavitation, fibrinoid necrotizing epithelioid and eosinophilic granulomas, necrotizing granulomatous vasculitis, glomerulonephritic symptoms, and a negative ANCA essentially ruled out the diagnosis of eosinophilic granulomatosis with polyangiitis. Biopsy of the lung also did not reveal the characteristic geographic necrosis and acute and chronic inflammation changes which are typical of granulomatosis with polyangiitis. These findings ultimately led to the diagnosis of Pulmonary CD with pulmonary necrobiotic nodules. This is an extremely rare manifestation of the Inflammatory Bowel Syndrome and one that clinicians should have within their differential upon treating patients with long-standing CD and pulmonary complications.

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Magnetic resonance enterography findings of a gastrocolic fistula in Crohn's disease.

Crohn’s disease (CD) is characterized by patches of inflammation, which may affect the whole gastro-intestinal tract. Internal fistulization is a common complication of CD due to the transmural nature of inflammation. However, gastrocolic fistulas are rare in CD. We present the magnetic resonance enterography (MRE) findings of a gastrocolic fistula in a patient with longstanding CD with clinical and pathologic correlation.

An index with improved diagnostic accuracy for the diagnosis of Crohn's disease derived from the Lennard-Jones criteria.

The Lennard-Jones criteria are considered the gold standard for diagnosing Crohn's disease (CD) and include the items granuloma, macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates and discontinuous inflammation on histology. The criteria have never been subjected to a formal validation process. To develop a validated and improved diagnostic index based on the items of Lennard-Jones criteria. Included were 328 adult patients with long-standing CD (median disease duration 10 years) from three centres and classified as 'established', 'probable' or 'non-CD' by Lennard-Jones criteria at time of diagnosis. Controls were patients with ulcerative colitis (n = 170). The performance of each of the six diagnostic items of Lennard-Jones criteria was modelled by logistic regression and a new index based on stepwise backward selection and cut-offs was developed. The diagnostic value of the new index was analysed by comparing sensitivity, specificity and accuracy vs. Lennard-Jones criteria. By Lennard-Jones criteria 49% (n = 162) of CD patients would have been diagnosed as 'non-CD' at time of diagnosis (sensitivity/specificity/accuracy, 'established' CD: 0.34/0.99/0.67; 'probable' CD: 0.51/0.95/0.73). A new index was derived from granuloma, fibrosis, transmural inflammation and macroscopic discontinuity, but excluded lymphoid aggregates and discontinuous inflammation on histology. Our index provided improved diagnostic accuracy for 'established' and 'probable' CD (sensitivity/specificity/accuracy, 'established' CD: 0.45/1/0.72; 'probable' CD: 0.8/0.85/0.82), including the subgroup isolated colonic CD ('probable' CD, new index: 0.73/0.85/0.79; Lennard-Jones criteria: 0.43/0.95/0.69). We developed an index based on items of Lennard-Jones criteria providing improved diagnostic accuracy for the differential diagnosis between CD and UC.

P084 An unusual case of Intradermal “Kissing” Naevus presenting as penile warts

Background/introduction We describe a case of a 38 yr old white heterosexual male with Crohns disease presenting with warty lesions of the penis which were found on histological diagnosis to be benign intradermal naevi. The differential diagnosis included papular warts, skin tags, and in this case Crohns and pyoderma gangrenosum. Aim(s)/objectives Initially presented with two smooth papular warty type lesions on the prepuce and glans adjacent to the coronal sulcus,which had been present for several months causing discomfort during sexual activity and unsightly appearance. Currently taking oral prednisolone and mesalazine for longstanding Crohns disease,with no other cutaneous manifestations, and had regular female partner. Results Initially treated with Liquid Nitrogen application but with minimal resolution and in light of his medical history to exclude “metastatic” Crohns and associated pyoderma gangrenosum a punch biopsy was carried out. Histological appearances were that of a benign intradermal naevus with characteristic nests of naevus cells within the dermis only, there was no atypia present. He was subsequently referred to the urologist for surgical excision of the lesions. Discussion/Conclusion Benign intradermal naevi or “kissing naevi” of Penis such as this are extremely rare there being only a handful previously reported. Due to the dermal location of naevus cells they usually present as skin coloured or slightly pigmented papules and may be confused with warts, skin tags or dermatofibroma. Treatment with surgical excision or laser therapy results in satisfactory functional and aesthetic outcomes.

Colonoscopy Surveillance and Management of Dysplasia in Inflammatory Bowel Disease.

Patients with long-standing ulcerative colitis (UC) and extensive Crohn's disease (CD) colitis have a high risk of colorectal cancer (CRC) and are recommended to undergo surveillance with colonoscopy. Recent data highlights their increased risk of CRC compared to the general population despite colonoscopy surveillance. The proportion of IBD patients diagnosed with interval CRC within 6 to 36months following a clearing colonoscopy was 15%. Optimizing colonoscopy surveillance methods is important. Studies have demonstrated that the best endoscopic surveillance strategy to detect dysplasia is chromoendoscopy with surface application of dyes to enhance the mucosal visualization and that visible dysplasia should be endoscopically resected. In this chapter we will summarize the optimal surveillance and management techniques for colorectal dysplasia in IBD patients.

Heterogeneity of subordination of the IL-18/IFN-γ axis to caspase-1 among patients with Crohn's disease

In Crohn's disease (CD), hierarchical architecture of the inflammatory network, including subordination of IL-18, an IFN-γ-inducing cytokine, to the inflammasome, have remained undeciphered. Heterogeneity among patients of such a subordination cannot be evaluated by animal models, monofactorial in their etiology and homogenous in disease progression. To address these issues, we set up an ex vivo model of inflamed mucosa explant cultures from patients with active long-standing CD. Th1 cytokine production, especially IFN-γ and IL-18, was assessed in relation with inflammation intensity. Subordination of the Th1 response to caspase-1, effector of the inflammasome, was determined in explant cultures subjected to pharmacological inhibition of caspase-1 by YVAD. We showed a correlation between secreted IFN-γ/IL-18 levels, and caspase-1 activation, with inflammation intensity of intestinal CD mucosa explants. Inhibition of caspase-1 activation using the specific inhibitor YVAD identified a homogenous non responder group featuring a caspase-1-independent IL-18/IFN-γ response, and a heterogenous responder group, in which both IL-18 and IFN-γ responses were caspase-1-dependent, with a 40–70% range of inhibition by YVAD. These findings bring out the concept of heterogeneity of subordination of the Th1 response to inflammasome activation among CD patients. This ex vivo model should have therapeutic relevance in allowing to determine eligibility of CD patients for new targeted therapies.

Risk of Intestinal Malignancy in Patients With Short Bowel Syndrome.

Postresection intestinal adaptation is an augmented self-renewal process that might increase the risk of malignant transformation in the intestine. Furthermore, patients with short bowel syndrome (SBS) have other characteristics that might increase this risk. Our aim was to determine the incidence of new intestinal malignancy in SBS patients. We reviewed the records of 500 adult SBS patients identified from 1982-2013. There were 199 men and 301 women ranging in age from 19-91 years. Follow-up from the time of diagnosis of SBS ranged from 12-484 months. A total of 186 (37%) patients were followed >5 years. The cause of SBS was postoperative in 35% of patients, malignancy/radiation in 19%, mesenteric vascular disease in 17%, Crohn's disease in 16%, and other in 13%. Twenty-eight (6%) patients received growth stimulatory medications. Fifteen percent of patients had a prior total colectomy. Twenty-eight (6%) patients underwent intestinal transplantation, and 115 (23%) patients had a previous abdominal malignancy, including colorectal cancer in 43 patients. Thirty-six (7%) received radiation therapy. Recurrent colon cancer was found in 2 patients, one at a stoma and the other with lung metastases. New colon cancer was found in 1 patient (0.2%), a 62-year-old woman with long-standing Crohn's disease. The incidence of colon cancer in this heterogenous group of patients with SBS was similar to that of the normal population. This suggests that the risk of developing a new colon cancer in patients with SBS is not increased.

RETRACTED: Gallstone ileus without bilioenteric fistula years after bypass surgery for Crohn's disease. Case report and clues to etiology of a neglected cause of obstruction

Gallstone ileus is a very rare cause of bowel obstruction. Patients suffering from Crohn's disease are at increased risk of developing gallstone disease, especially when terminal ileum is involved. Gallstone ileus can occur, but etiology remains controversial. We report on a case of such a rare condition, illustrating etiology and treatments. A patient with long-standing Crohn's disease, who had undergone ileotransverse bypass for ileocaecal involvement 40 years before, presented with cramp-like abdominal pain. Imaging was consistent with a gallstone ileus with no evidence of bilioenteric fistulae. At surgery, we found gallstones stuck at the site of ileotransverse anastomosis. No bilioenteric fistulae were found. Due to disease progression, many enteric fistulae were found, requiring a massive bowel resection. The diverted segment may have been responsible of gallstone formation, and etiology is discussed. Recovery after surgery was uneventful, but the patient required continued nutritional support. Physicians dealing with Crohn's disease patients with bypassed segments should keep in mind, the increased risk of gallstone formation, in order to not overlook gallstone ileus. Early suspect and diagnosis may allow for less aggressive approaches. A diverted segment should always be removed, and long-term follow-up encouraged.

Severe Back Pain in a Young Patient with Pyoderma Gangrenosum and Crohn’s Disease Controlled with Anti-tumor Necrosis Factor Therapy: Sterile Osteomyelitis

IntroductionInflammatory bowel disease has been associated with a number of cutaneous and systemic neutrophilic disorders, including pyoderma gangrenosum. In 1972, the term chronic multi-focal recurrent osteomyelitis was given to a sterile neutrophilic condition which has been associated with inflammatory bowel disease.Case ReportWe report a case of a 23-year-old man with long-standing severe Crohn’s disease which necessitated subtotal colectomy. He subsequently developed progressive, intermittent back pain that were limiting his functional movement. Numerous investigations to identify what initially was thought to be an infectious process failed to lead to the diagnosis. Biopsy of the spine identified a sterile neutrophilic infiltrate and the diagnosis of chronic recurrent multi-focal osteomyelitis was made which was successfully treated with immunosuppressive drugs.ConclusionInflammatory bowel disease can present with cutaneous and systemic neutrophilic disorders and this association is becoming increasingly recognized by gastroenterologists and dermatologists. Chronic recurrent multi-focal osteomyelitis is a sterile neutrophilic disorder which can present with bone pain and responds to immunosuppressive therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-014-0044-3) contains supplementary material, which is available to authorized users.

Possible Association of Cutaneous Rosai-Dorfman Disease and Chronic Crohn Disease

IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P<.001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease.

Epithelial-to-mesenchymal transition in a fistula-associated anal adenocarcinoma in a patient with long-standing Crohn’s disease

Anal adenocarcinomas arising from perianal fistulae represent a rare complication in Crohn's disease (CD) patients. We have previously demonstrated the involvement of an epithelial-to-mesenchymal transition (EMT) in the pathogenesis of CD-associated fistulae. Although EMT has also been implicated in the development of colorectal and anal carcinoma, the molecular link from fistula to carcinoma is unclear. We present a case of a 48-year-old White woman who developed a mucinous anal adenocarcinoma originating from a perianal, CD-associated fistula 24 years after being diagnosed with CD. To characterize the expression of EMT-associated molecules in fistula and carcinoma tissue, immunohistochemical analysis for Snail1, Slug, β-catenin and E-cadherin was performed. A mucinous anal adenocarcinoma developed on a perianal fistula in a patient with long-standing CD. After neoadjuvant radiochemotherapy, the fistula-associated tumour was resected and the patient is presently in remission. Using immunohistochemical analysis, we detected a remarkable staining of the Slug transcription factor in transitional cells lining the fistula tract. This observation is unique to this 'carcinoma'-fistula: we had previously shown Slug expression in cells surrounding the fistula tract but not in transitional cells. Expression of Snail1, β-catenin and E-cadherin in this case was comparable with our previous findings. We describe a rare case of a CD fistula-associated adenocarcinoma within an area of squamous epithelium of the perianal area and an unusual expression pattern of EMT markers in this fistula. This case seems to underline the relevance of our previous findings demonstrating that EMT plays an important role for fistula pathogenesis and likely carcinogenesis in CD patients.

Metachronous, colitis-associated rectal cancer that developed after sporadic adenocarcinoma in an adenoma in a patient with longstanding Crohn’s disease: a case report

BackgroundColorectal cancer associated with Crohn’s disease (CD) is increasing in proportion to the number of patients with CD in Japan. There are two subtypes of colorectal cancer with CD: sporadic cancer and colitis-associated cancer. Early diagnosis of colitis-associated cancer is sometimes difficult; when colorectal cancer is found in patients with CD, both colitis-associated cancer and sporadic cancer should be kept in mind. Here, we describe a case of metachronous, colitis-associated rectal cancer that developed after the complete resection of an adenoma that became a sporadic adenocarcinoma in a patient with longstanding CD. To the best of our knowledge, this is the first report of colitis-associated cancer in a patient with CD after removal of a sporadic cancer.Case presentationWe describe a 51-year old man with CD who had difficulty in defecation. A rectal polyp was detected and a transanal resection of the polyp was performed. A histopathological examination showed an adenoma with sporadic adenocarcinoma. After three years, a follow-up colonoscopy revealed a reddish, elevated lesion in the patient’s rectum. A colonoscopic biopsy showed a signet ring cell carcinoma. We performed an abdominoperineal resection of the rectum and a bilateral pelvic lymph node dissection. A histopathological examination revealed a mucinous adenocarcinoma with signet ring cell carcinoma and lymph node metastasis. The patient received adjuvant chemotherapy with oral uracil 224 mg combined with tegafur 100 mg plus leucovorin. No signs of recurrence were noted at a follow-up 18 months after the third surgery and 60 months after the second surgery.

Biopsy with Caution in the Colon Exposed to Chronic Steroids

Background: Perforation occurs in less than 1% of cases undergoing diagnostic colonoscopy. Similar perforation rate is reported in inflammatory bowel disease (IBD) patients, although there is disagreement in current literature. Severe disease on endoscopy and chronic steroid use have been associated with higher risk of perforation in IBD patients. This case describes colonic perforation after a random cecal biopsy during a surveillance colonoscopy in a well-controlled IBD patient previously exposed to years of chronic steroids. We speculate the needle in the middle of standard biopsy forceps may have punctured susceptible thin-walled cecum, resulting in perforation. Case: A 39-year-old female with long-standing ileocolonic Crohn's disease since the age of 14 without upper tract or perianal involvement maintained on asacol and imuran underwent diagnostic colonoscopy. Her colonoscopy 5 years prior was complicated by perforation due to endoscope trauma at the splenic flexure requiring diverting ileostomy and subsequent reversal. Chronic steroids resulted in right ankle bone graft approximately 15 years prior. Her Crohn's disease has been well-controlled for the last 10 years without further exposure to steroids. She was asymptomatic and inflammatory markers were normal prior to surveillance colonoscopy. Carbon dioxide was used for insufflation and the terminal ileum was intubated without difficulty. Colonoscopy revealed scattered pseudopolyps throughout the colon. A random cecal biopsy was taken using a Radial Jaw® 4 Standard Biopsy Forceps with Needle (Boston Scientific, Natick, MA). Immediately after this biopsy, perforation was recognized and three endoclips were placed. Pneumoperitoneum was confirmed on abdominal x-ray. The patient was admitted for observation with intravenous antibiotics and fluids. Twenty-four hours after the procedure, the patient was asymptomatic and discharged without the need for surgery. Biopsies showed quiescent colitis, negative for dysplasia. Conclusion: Chronic steroid use is a known risk factor for perforation during diagnostic colonoscopy in IBD patients. This case illustrates such risk from chronic steroids may linger for many years. Endoscopists should consider needleless biopsy forceps in cases of IBD patients on chronic steroids requiring multiple surveillance biopsies.

Small-bowel obstruction associated with Crohn’s enterolith

One of the lesser known clinical manifestations of Crohn's disease is the formation of small-bowel enteroliths. These concretions precipitate in the setting of small-bowel stasis within the alimentary tract and are associated with a variety of disease states causing strictures or diverticula. In the acute setting, patients typically present with signs of intestinal obstruction due to stone impaction. The case we report involves a 67-year-old female with long-standing Crohn's disease who presented with a 6-day history of worsening abdominal pain. Plain abdominal radiographs demonstrated dilated bowel loops consistent with intestinal obstruction. Computed tomography revealed a 2.5-cm calcified density at the transition point in the distal ileum, and two additional stones were present in the proximal ileum. At surgery, multiple ileal strictures were found, and ileocolic resection with primary anastomoses was performed. The accurate diagnosis of enterolithiasis in the setting of Crohn's disease has significant clinical implications for management and is a harbinger of underlying bowel stenosis.

Biodegradable stent for the treatment of a colonic stricture in Crohn’s disease

Biodegradable polydioxanone stents were developed for the treatment of refractory benign esophageal strictures but have been suggested as a new therapeutic option for intestinal strictures. The primary advantage of biodegradable stents over self-expandable metallic stents is that removal is not required. There are, however, few data available on their use in the small or large bowel. We herein describe the case of a 33-year-old patient with long-standing Crohn's disease (CD) who developed a fibrotic stricture of the sigmoid too long to be amenable to balloon dilation. The use of a biodegradable polydioxanone stent was chosen to avoid surgery. Combined endoscopic and fluoroscopic placement of the stent was technically simple, safe and clinically successful, and no recurrence of obstructive symptoms occurred during a 16-mo follow-up. Further studies are needed to evaluate the long-term efficacy and safety of biodegradable stents in the treatment of intestinal strictures, particularly in the context of CD.

Adenocarcinoma in an ano-vaginal fistula in Crohn's disease

INTRODUCTIONFistulas are a relatively common occurrence in Crohn's disease (CD), and often present early in the disease process. Additionally, patients suffering from either CD or ulcerative colitis are shown to have an increased risk of colorectal malignancies compared with the general population. PRESENTATION OF CASEWe present a case of adenocarcinoma in an ano-vaginal fistula in a patient with longstanding CD. DISCUSSIONVarious pathogenic mechanisms for the development of carcinoma in fistulas have been suggested, but there is no consensus and indeed this risk may be cumulative. In this case report, we also discuss the pathogenesis of mucinous adenocarcinoma in fistulas secondary to CD. CONCLUSIONBetter detection of adenocarcinoma in patients presenting with persistent non-resolving fistulas in the presence of CD should be undertaken with regular biopsies following examinations under anaesthetic of the anorectum.

Pulmonary Mucormycosis in a Patient with Crohn Disease on Immunosuppressive Medications including Infliximab

Case presentation A 68-year-old man presented to hospital with a two-day history of increasing shortness of breath, left-sided pleuritic chest pain and chills. His medical history was significant for longstanding Crohn disease (>55 years) requiring multiple bowel resections in the 1970s in addition to high-dose corticosteroid therapy. For the past five years, he had been maintained on infliximab with only low-dose steroids for iatrogenic adrenal insufficiency. Additional medical problems included short gut syndrome, hypothyroidism and bronchiectasis; there was no history of diabetes. He experienced two hospital admissions in the preceding six months for pneumonia, one of which was due to Pneumocystis jirovecii confirmed by open lung biopsy. His medications on this admission included budesonide 6 mg orally three times daily, azathioprine 100 mg orally twice daily, infliximab 600 mg intravenously every four weeks, levothyroxine 25 µg orally daily, atovaquone 1500 mg orally daily, and salbutamol and ipratropium inhalers as needed. His most recent dose of infliximab was one month before admission. A physical examination revealed signs of consolidation in the left lung. His complete blood count included a white blood cell

Primary Small Bowel Adenocarcinoma in the Setting of Chronic Crohnʼs Disease

Purpose: 59 Y/O Female with a history of Crohn's disease with a recent flare, complicated by small bowel obstruction treated with IV corticosteroids, infliximab and nasogastric decompression. She presents now with diffuse cramping abdominal pain, anorexia, nausea, vomiting and abdominal distention. She denied fever, chills, diarrhea, or gastrointestinal bleeding. She quit tobacco 20 years ago and denies alcohol or illicit drug use. Her family history was negligible for cancer. Exam revealed a well nourished female. Her skin had no rashes, ulcers or jaundice. Abdominal exam demonstrated a mildly distended abdomen with hyperactive bowel sounds. She had no organomegaly. No rebound or guarding tenderness was elicited. Laboratory exams were normal. CT-enterography with contrast demonstrated diffuse small bowel dilatation. There was mucosal hyper enhancement, wall thickening and mural stratification. Findings were consistent with active Crohn's disease, stricture and small bowl obstruction. She underwent laparoscopic ileocolectomy with primary anastomosis. Pathological results of resected small bowl revealed a T3 N0 adenocarcinoma of the small bowel in a background of active and chronic Crohn's disease. She was discharged and is being followed by oncology. • Small bowel adenocarcinoma in the setting of longstanding Crohn's disease is usually diagnosed on post operative pathohistological analysis. • Signet ring cells are found in 30% of specimens received from patients with Crohn's disease. • The risk of small bowel adenocarcinoma 10-25 years after the diagnosis of ileal Crohn's disease is approximately 2.2%. • Males between the ages of 30-55 are at highest risk for small bowel malignancy. • Positron emission tomography, CT- Scan and double barium enema serve a role in early preoperative detection of small bowel adenocarcioma. • Delayed diagnosis in patients with small bowel adenocarcinoma leads to poor long term prognosis. Conclusion: The diagnosis of small bowel adenocarcinoma in the setting of chronic Crohn's disease should be entertained in patients presenting with small bowl obstruction secondary to stricture formation. Studies such as positron emission tomography, computer tomography and double barium enema may serve to increase the rate of early detection and initiation of treatment.Figure: [1584]