Carcinoma arising in anorectal fistulas of Crohn's disease

PURPOSE: Anorectal fistulas are commonly associated with Crohn's disease. Carcinoma arising in an anal fistula in the absence of Crohn's disease occurs rarely. Carcinoma arising in an anorectal fistula of Crohn's disease is likewise rare and is the subject of this article. METHODS: We have seen eight cases in seven patients. Four of these were squamous carcinoma and three were adenocarcinoma. Details of these seven patients are presented. RESULTS: Two deaths in the four patients with squamous carcinoma and one in the two patients with adenocarcinoma with adequate follow-up suggest a poorer prognosis in both types of malignancy than when these lesions occur without Crohn's disease. CONCLUSION: Carcinoma does arise in the midst of the anorectal fistulas and abscesses of Crohn's disease. Carcinoma arising in a Crohn's disease fistula can be very difficult to diagnose. Examination may be limited by pain, stricture, or induration of the perianal and perineal tissues. Examination under anesthesia can also overlook the lesion. Diagnostic examination under anesthesia yields increases with biopsies or curettage of the fistulous tracts.     

Is Hartmann's procedure safe in Crohn's disease?

INTRODUCTION: Crohn's disease-associated colorectal cancer may occur in an area of defunctioning bowel. Some patients with Crohn's colitis undergo subtotal colectomy, ileostomy, and low Hartmann's procedure in an effort to preserve the rectum. This procedure has also been advocated for patients with severe anorectal Crohn's disease, in whom nonhealing of the perineal wound after proctectomy occurs with alarming frequency. The authors present a review of the literature and three cases of cancer developing in the defunctioning rectal stump despite surveillance proctoscopy. METHODS: Twenty-five patients underwent low Hartmann's procedure for severe anorectal Crohn's disease. Surveillance proctoscopy was performed as follow-up. Development of cancer in the rectal remnant or anus or recurrence of symptoms was managed by resection and adjuvant therapy. RESULTS: One patient developed squamous-cell carcinoma of the anal canal, underwent resection and adjuvant therapy, and was disease free at the time of this study. Two patients developed adenocarcinoma of the rectum. Both underwent resection and adjuvant therapy. One patient died and the other developed a recurrence. CONCLUSIONS: The authors recommend interval perineal proctectomy in all patients undergoing low Hartmann's procedure for severe anorectal Crohn's disease in whom rectal preservation is not possible. Regularly scheduled interim surveillance proctoscopy performed every two years, with biopsies of macroscopically normal-appearing and abnormal-appearing rectal mucosa and curetting of fistulous tracts, is also recommended to decrease the possibility of missing occult malignancies.     

Adenocarcinoma in perineal fistulas of Crohn's disease

Until recently, Crohn's disease has not been regarded as a premalignant lesion, but the increasing number of patients with Crohn's disease in whom adenocarcinoma of the gastrointestinal tract develops strongly suggests that these patients are indeed at a higher risk for carcinoma. These patients are usually young and tend to develop a malignancy in the bypassed ileum or right colon. Patients with such lesions usually have a poor prognosis. Adenocarcinoma arising in perineal fistulas secondary to Crohn's disease has not been reported in English medical literature except for one case published in 1975. In this article, the authors report a second, similar case of Crohn's disease with recurrent perineal fistulas. An infiltrating adenocarcinoma developed in these fistulas, in the anorectal region, and in the left labia. the risk of malignancy should be seriously considered in the management of Crohn's disease, especially in young patients. Because of the risk of adenocarcinoma in these patients, resection rather than bypass is recommended in the surgical management     

Conservative treatment of anorectal tumors

Our purpose was to evaluate the results of interstitial radiotherapy of anorectal tumors. From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months. Local response depended on the tumor volume treated. All 21 anal tumors showed complete response, 5 patients developed local recurrence and 4 distant metastases; 3 died from their disease. Of 12 rectal adenocarcinomas, 9 responded completely, 4 patients developed local recurrence and 4 distant metastases; 6 died from active disease. In the last group of 12 patients who were treated for recurrent tumors, 7 responded completely. One patient developed local recurrence and 9 distant metastases, only 4 are alive. A combination of external-beam and interstitial radiotherapy is a relatively simple, non-mutilating, but well-tolerated and very effective method of treatment for early carcinoma of the lower rectum and anus.     

Idiopathic Anorectal Ulceration in Patients with Human Immunodeficiency Virus Infection

Opportunistic infections and neoplasms of the anorectum have heen reported in patients with human immunodeficiency virus (HIV) infection. More recently, idiopathic alcerative lesions of the colon and rectum have been described. At our center over a 3-yr period, four patients were identified with ulcerative lesions of the rectum and/or anus that remained idiopathic despite an extensive clinical, serologic, and histopathologic evaluation. Three patients had the acquired immunodeficiency syndrome, and in one anorectal disease was the index manifestation of HIV infection. Only one of the patients had recently engaged in receptive anal intercourse. The presenting complaints were gastrointestinal hieeding in two, which was severe in one, and/or anorectal pain. Multiple colonoscopic evaluations with hiopsy of the distal colorectum documented a solitary ulcer of the rectum in one, solitary ulcer involving the anorectum in two, and multiple ulcers of the rectum and anorectnm in one. In three patients, colonoscopy to the cecum demonstrated no additional lesions. In patients with HIV infection, ulcerative lesions of the anorectum may remain unexplained despite an exhaustive evaluation. The etiology of these lesions, as well as appropriate therapy, remains to be determined.     

What is the clinicopathological characteristic of cloacogenic carcinoma outside the anorectal zone?

This study aimed to examine English-language publications on cloacogenic carcinoma which has developed outside the anorectal zone. Studies published in English literature on cloacogenic carcinoma developing in the colorectal area were accessed via Pubmed and Google scholar databases. Within these articles, studies in which there were developments in the other segments of the colon outside the anorectal zone were examined. We retrieved seven studies matching our selection criteria from the research. The studies were published between 1977 and 2009. Four of the patients were female and three were male; patient age ranged from 23 to 69 years. The anatomic tumors were in the sigmoid colon in four patients, and splenic flexure, descending colon and proximal rectum in one patient each. Four patients developed liver metastases. Basaloid carcinoma above the rectum is difficult to diagnose clinically. When suspected, the diagnosis can be made by immunohistochemical staining.     

Crohn's Disease and Colorectal Carcinoma: Rectal Cancer Complicating Longstanding Active Perianal Disease

Objectives : Reports of Crohn's disease (CD)-associated colorectal carcinoma are being cited in the medical literature with increasing frequency. Our aim was to identify subgroups of patients with risk factors that may account for this. Methods : We reviewed the medical records of 16 patients with the simultaneous diagnosis of CD and colorectal carcinoma and, in addition, reviewed previously reported cases of CD-associated colorectal carcinoma. Results : Eight male and eight female patients presented with 18 carcinomas: four right colon, four transverse, two descending colon, and eight rectal lesions. Median age at presentation was 48 yr. The mean duration of CD before presentation of carcinoma was 19.7 yr. Two lesions were discovered in strictured bowel segments. Two patients had multiple cancers. One had simultaneous cecal and left colon adenocarcinomas. The other underwent resection of a right colon lesion and 5 yr later presented with transverse colon carcinoma. Eight patients had rectal cancer; all were diagnosed preoperatively. Six of these patients had a history of severe perianal CD. Six had undergone multiple incision and drainage procedures for perirectal abscesses and fistulas. Two developed malignancies in defunctionalized rectal stumps. One of these patients presented with simultaneous squamous rectal carcinoma and papillary bile duct cholangiocarcinoma. Conclusions : Gastrointestinal malignancy in association with CD has been reported. Symptoms of chronic inflammatory disease may obscure clinical manifestations of occult malignancy and thereby delay diagnosis. Crohn's patients with longstanding anorectal or perianal disease and stricture may well warrant surveillance endoscopy and biopsy of involved areas with the hope of earlier detection and treatment of these rectal cancers.     

Colorectal carcinoma in patients with Crohn's disease

Epidemiologic studies have shown a fourfold to 20-fold increased risk of colorectal carcinoma in patients with Crohn's disease as compared with the general population, but management for this risk is controversial. This paper presents a series of 10 patients with Crohn's disease and colorectal carcinoma from one institution and a review of the literature. Compared with 118 consecutive patients having colorectal carcinoma of the usual type at the same institution, the 10 patients were younger (mean age 55 vs. 65 yr, p less than 0.05) and had a higher prevalence of mucinous carcinoma (50% vs. 9%, p less than 0.01), providing evidence in addition to the previous epidemiologic results that Crohn's disease is a predisposing (premalignant) condition for colorectal carcinoma. Eight of the 10 patients had an antecedent history of Crohn's disease, ranging from 4 to 51 yr (mean 24 yr); 2 patients presented with colorectal carcinoma and were found to have Crohn's disease. Of particular note, 9 of the 10 patients had colitis or ileocolitis, and carcinoma occurred in bypassed rectum in 2 patients. One patient had two carcinomas. Three of the 11 carcinomas were not recognized preoperatively. The anatomic sites of the cancers were not significantly different from usual colorectal carcinoma, with 7 of the 11 tumors (64%) in the sigmoid colon and rectum. Dysplasia was identified in all 10 patients, and all of the 10 resected carcinomas were found to be contiguous with high-grade dysplasia. The findings in this study support the proposals based upon epidemiologic data that surveillance should be considered for patients with clinically evident colorectal involvement by Crohn's disease or a bypassed segment of colorectum.     

Carcinoma and DNA aneuploidy in Crohn's colitis--a histological and flow cytometric study.

Twenty four patients with longstanding colonic Crohn's disease were examined prospectively with colonoscopy and multiple biopsy sampling in order to detect histological dysplasia or abnormal aneuploid DNA content, or both. Biopsy specimens were taken from 10 predetermined locations in the colon and rectum. No patient had definite dysplasia but three displayed DNA aneuploidy (12.5%), and one of these subsequently developed a carcinoma (Dukes' C at operation) in the ascending colon. No concomitant dysplasia was detected but the carcinoma as well as other parts of the mucosa were DNA aneuploid. It is concluded that dysplasia is rare in patients with Crohn's colitis, but findings of DNA aneuploidy warrant vigilance in follow up as this may indicate impending carcinoma. Further prospective studies are needed before the predictive value of DNA aneuploidy can be determined and before general recommendations of colonoscopic surveillance, as in longstanding ulcerative colitis, can be made.     

The granuloma in Crohn's disease.

The number of granulomas in sections of bowel involved by Crohn's disease has been counted and related to length of previous history, treatment with steroids, site of involvement, and the subsequent course of the disease. It was found that a high content of granulomas predicted a good prognosis in the large bowel and anus, but was of no prognostic significance in the small bowel. A large regional variation in granuloma counts was observed from an average of 1 per section in the small bowel to 6 in the colon, 18 in the rectum, and 36 in the anus. Those patients with a long clinical history showed a low granuloma content. The findings are consistent with the view that the granuloma represents an adaptive mechanism for the removal or localisation of the causative agent of Crohn's disease.     

Carcinoma complicating Crohn's disease. Report of seven cases and review of the literature.

Seven cases of adenocarcinoma complicating Crohn's disease are reviewed. In three of the patients, small bowel cancers developed in association with reginal enteritis. In four patients, carcinoma of the colon was superimposed on Crohn's colitis. In two of these, the adenocarcinoma infiltrated chronic colocutaneous fistulas. Review of the literature shows an increasing number of reports of carcinoma complicating Crohn's disease, with a total of 36 cases of small bowel cancer and 30 cases of colon cancer previously reported. The significane of these and our own cases is discussed. The possibility of carcinoma must be kept in mind by clinicians following patients with Crohn's disease. Adenocarcinoma complicating Crohn's disease occurs at a younger age, on the average, and in areas similar to the distribution of Crohn's disease rather than the usual distribution of the cancer. Preoperative diagnosis is difficult, but changes in the nature of chronic fistulas should be investigated.     

Anal Crohn's disease with carcinomain Situ

Summary A 36-year-old female with a six-year history of Crohn's disease of the anus and colon was found to havein situ cloacogenic carcinoma of the anus after having undergone total proctocolectomy for massive bleeding. This case further supports the association between Crohn's disease of the gastrointestinal tract and its potential for malignant degeneration.     

Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.

The thickness of adherent mucus gel on the surface of colonic mucosa was measured in surgically resected specimens from 46 'control' patients most of whom had carcinoma of the colon; 12 were from right colon, 17 left colon, and 21 from rectum. In addition specimens were examined from 17 patients with ulcerative colitis and 15 patients with Crohn's disease. In controls a continuous layer of mucus was readily seen on specially prepared sections viewed by phase contrast illumination. Mean values for right and left colon and rectum were 107 (48), 134 (68), and 155 (54) microns respectively with a significant difference between right colon and rectum (p = 0.015). Values in ulcerative colitis showed greater variation and in those areas with acute inflammation mucosa was denuded of the mucus layer. In contrast, values for Crohn's disease were normal or greater than normal in thickness--right colon 190 (83) microns compared with 107 48 microns, p = 0.0093. A series of validation experiments are described for the method used to measure mucus thickness. The possible role of mucus in the pathogenesis of inflammatory bowel disease is discussed.     

Crohn's disease and adenocarcinoma of the intestinal tract

Four patients with intestinal adenocarcinoma complicating Crohn's disease are reported. The youngest of the four patients was a 21-year-old female with a 9-year history of Crohn's disease of the terminal ileum as well as of the entire colon. She developed mucus-producing moderately differentiated adenocarcinoma in the cecum. Of the remaining three patients with Crohn's disease, one presented an adenocarcinoma in the ascending colon, one in the rectum and the remaining one in the duodenum. All three colorectal adenocarcinomas originated in areas of high-grade dysplasia and all four in areas with chronic transmural inflammation. The review of the literature indicates that a total of 174 small and large bowel cancers occurring in Crohn's disease have been recorded (including the four reported herein). The vast majority of the reported cases have been found in the North American subcontinent. Only in a few instances were bowel adenocarcinoma and Crohn's disease observed in the European continent. It is therefore remarkable that three of our four cases were seen within a period of 12 months. Interestingly, six patients having colorectal adenocarcinoma in association with Crohn's disease were recently reported from a single hospital in England. The question therefore arises whether our cases and those reported recently from England are unrelated and merely coincidental or whether carcinomas are now also affecting European CD patients. If the latter is the case, the surveillance policy for patients with CD should be reconsidered at this hospital.This study was supported by grants from the Karolinska Institute and Cancer Fonden.     

Carcinoma in Crohn's disease of the colon

Two cases of carcinoma in Crohn's disease of the colon are reported. One patient was a 30-year-old man who had asymptomatic Crohn's ileocolitis resulting in an acute presentation due to toxic dilatation of the colon. This was preceded by a short prodromal period of four weeks, characterized by intermittent diarrhea on the basis of a coloileal tumor fistula. A mucus-secreting adenocarcinoma was present in the sigmoid colon associated with both adjacent and one nearby focus of high-grade mucosal dysplasia. Pelvic wall and abdominal metastases were present, and the patient died two months later. The other patient was a 60-year-old woman who had a nine-year history of biopsy-proven Crohn's proctocolitis. A stricture of the sigmoid colon due to Crohn's disease also harbored an invasive adenocarcinoma. The carcinoma was not evident preoperatively or on initial gross pathologic examination. The presentation and pathology of large intestinal carcinoma in Crohn's colitis are discussed and illustrated.     

Acute toxic dilatation of the colon in Crohn's colitis

Twelve new cases of acute toxic dilatation of the colon in Crohn's colitis treated by total colectomy and ileorectal anastomosis are reported, and criteria for making the diagnosis are given.

The complication has occurred in 6% of patients diagnosed as having Crohn's disease of the colon treated at the Gordon Hospital since 1948. The patients have been predominantly young adult females, with a short preoperative history of disease. The sigmoidoscopic appearance of the rectum preoperatively has been no indication of the likelihood of recurrent disease at the anastomosis. Only four patients still have successfully functioning ileorectal anastomoses and four patients have died from the effects of the disease.

     

Adenosquamous carcinoma of the colon, rectum, and anus

PURPOSE: There have been 49 cases of adenosquamous carcinoma of the colon, rectum, and anus reported in the English literature. We have reviewed 145 cases of adenosquamous carcinoma to better define epidemiologic and survival characteristics of this extremely rare colon carcinoma. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results program public use CD-ROM file for the years 1973 through 1992 were reviewed. This represents approximately 9.5 percent of the United States population. Adenosquamous carcinomas arising in the colon, rectum, and anus were identified using the International Classification of Diseases-O codes. The Astler-Coller tumor classification was used for staging. Two-tailed Student'st-test, Mantel-Haenszel chi-squared tests, and generalized Wilcoxon's tests were used for comparisons of means, proportions, and actuarial survival rates, respectively. Survival curves were calculated by the Kaplan-Meier method. RESULTS: One hundred forty-five cases of adenosquamous carcinoma were identified, representing 0.06 percent of all colorectal malignancies. The mean age of patients was 67 years. Eighty-four percent of patients were Caucasians, 15 percent were Afro-Americans, and 1 percent were other races. Afro-Americans were diagnosed at a significantly younger age (median age, 62 years;P=0.03). Fifty-three percent of the carcinomas were located in the sigmoid colon, rectum, and anus, 28 percent in the right colon, and the rest in the middle segment. Seventy-four percent of distal cases were staged A through C, compared with 44 percent of proximal cases. Patients with adenosquamous carcinoma of the sigmoid colon, rectum, and anus survived longer than all other patients (P=0.001). Patients with adenosquamous carcinoma Stages A and B₁ had survival rates similar to patients with comparably staged adenocarcinomas. Fifty percent of the patients, including most of the patients with D stage, died in the first year. Patients with Stages B₂, C, and D adenosquamous carcinomas had a significantly shorter survival than the comparably staged adenocarcinomas (P0.02). The overall adjusted five-year survival rate was 30.7 percent. In those patients who survived more than 24 months, the five-year survival was 84 percent. CONCLUSIONS: The survival rates for patients with adenosquamous carcinoma Stages A and B₁ are similar to patients with comparably staged colorectal adenocarcinomas. However, we found that patients with colorectal and anal adenosquamous carcinomas staged B₂ through D have significantly poorer survival than patients with comparably staged adenocarcinomas, supporting the previous reports of a poor prognosis associated with adenosquamous carcinomas.     

Crohn's disease and intestinal endometriosis: an intriguing co-existence

OBJECTIVES: We present a series of eight female patients who came to surgery for complicated Crohn's disease of the terminal ileum (n = 7) or colon (n = 1). Indications for surgery were medically intractable disease in three, steroid dependence in four and ileal perforation in one. RESULTS: Histological examination using routine haematoxylin-eosin stained sections revealed the presence of intestinal endometriosis of the ileum (n = 6), colon (n = 1) or ileum and rectum (n = 1) in addition to the typical features of Crohn's disease. In particular, chronic transmural inflammation was observed in locations other than the endometriotic deposits, which were confined to the serosa in three, the muscularis propria in two, both the serosa and the muscularis propria in one and the serosa, muscularis propria and submucosa in two. In none of these patients had the diagnosis of intestinal endometriosis been suspected pre-operatively based on clinical (gynaecological) or radiological tests. CONCLUSION: Intestinal endometriosis and Crohn's disease can occur simultaneously. The diagnosis is often only made after surgical resection of the diseased segment. In Crohn's disease, endometriosis of the terminal ileum seems more common.     

Rectoanal motility in Crohn's disease patients

PURPOSE: It has been documented that Crohn's disease affects anorectal function when anorectal manifestations of the disease are present. The aim of this study was to investigate whether the presence of histologic lesions in rectal biopsy affected anorectal motility in patients with Crohn's disease but no evidence of macroscopic anorectal involvement. METHODS: Forty-one patients with documented Crohn's disease were included in the study. Twenty-one of them had no endoscopic or histologic lesions in the rectum, and 20 patients had a positive histology for Crohn's disease on rectal biopsy, with or without macroscopic or endoscopic involvement of the anorectum. All patients underwent a standard anorectal manometry, with an eight-channel, water-perfused catheter. RESULTS: Patients with positive rectal biopsy but no evidence of endoscopic rectal involvement had lower anal resting and squeeze pressures (76±16 standard deviationvs. 86±19 standard deviationP=0.002; 152±56 standard deviationvs. 192±52 standard deviationP<0.001, respectively), and a lower sphincter and high-pressure zone length (2.8±0.8 standard deviationvs. 3.2±0.8 standard deviationP=0.006; 1.7±0.6 standard deviationvs. 2±0.6 standard deviationP=0.005, respectively) compared with patients with negative rectal histology. Also, slow and ultra slow wave amplitude and ultra slow wave frequency were significantly lower (10±6 standard deviationvs. 13±7 standard deviationP=0.04; 17±16 standard deviationvs. 34±24 SDP=0.004; 0.9±0.8 standard deviationvs. 1.3±0.6 standard deviationP=0.05, respectively), rectal sensation more affected, and rectal compliance significantly reduced (7.4±1 standard deviationvs. 11.1±2.2 standard deviationP<0.001) in the former group of patients. Simultaneous presence of endoscopic and histologic lesions in the rectum was associated with further impairment of the anorectal function. CONCLUSION: Microscopic presence alone of Crohn's disease in the rectum appears to induce anorectal motility disorders. The synchronous presence of endoscopic rectal and macroscopic anal involvement is associated with further deterioration of anorectal function.     

Crohn's disease and carcinoma: Increasing justification for surveillance?

Carcinoma of the colon that arises in patients with Crohn's disease is being reported with increasing frequency. To help clarify the nature of this association, records of 25 patients with Crohn's disease and colorectal carcinoma seen from 1957 through 1989 were reviewed. One patient had leiomyosarcoma of the rectum, and two patients had the onset of Crohn's disease after the diagnosis and treatment of colorectal carcinoma. Therefore, 22 patients were available for complete retrospective analysis. The median age at diagnosis of Crohn's disease was 37 years (range, 15–67 years), and the median age at diagnosis of carcinoma was 54.5 years (range, 32–76 years). The median duration of symptoms preceding the discovery of colorectal carcinoma was 18.5 years (range, 0–32 years). Carcinoma arose in colonic segments with known Crohn's disease in 77 percent of patients, and six patients (27 percent) had associated colonic mucosal dysplasia. One lesion was classified as Dukes A, nine lesions were Dukes B, five lesions were Dukes C, and seven lesions were Dukes D. Patients with an onset of Crohn's disease before the age of 40 years had primarily Dukes C or D lesions and consequently poor survival. Most patients presented with nonspecific signs and symptoms, with nothing to distinguish the activity of the Crohn's disease from the presence of colorectal neoplasm. Younger patients with long-standing Crohn's disease should be considered for colonic surveillance to permit earlier diagnosis and treatment of potential colorectal carcinoma.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.