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Francis A Farraye

Publications and source records attributed to Francis A Farraye.

At least 37 records · Page 2Linked to original sources

Pathologic features and clinical significance of "backwash" ileitis in ulcerative colitis.

Patients with ulcerative colitis (UC) may develop inflammation in the distal ileum thought to be due to "backwash" of cecal contents ("backwash ileitis"). However, a systematic analysis of ileal changes in UC has never been performed, and the prevalence and criteria for "backwash" ileitis have not been defined. The aim of this study was to evaluate the prevalence and spectrum of inflammatory changes in the ileum in patients with UC and to correlate ileal changes with outcome after total proctocolectomy and ileal pouch-anal anastomosis. Routinely processed ileocolonic resection specimens from 200 consecutive patients with clinically and pathologically confirmed UC were evaluated for a wide variety of pathologic features in the ileum and colon. The ileal data were correlated with both the clinical features and the pathologic findings in the colon. Follow-up data were obtained to confirm absence of Crohn's disease and to evaluate outcome of ileo-anal pouches. Overall, 34 of 200 (17%) UC patients had inflammatory changes in the ileum (male/female ratio, 16/18; mean age, 42 years); 32 of 34 (94%) had pancolitis, which was significantly higher than the rate of pancolitis (39%) in patients without ileal disease (N = 166) (P < 0.001), but there were no other differences between patients with or without ileal pathology. In the colon, 22 of 34 (65%) patients had severe activity. Ileal changes included villous atrophy and crypt regeneration without increased inflammation (N = 3), increased neutrophilic and mononuclear inflammation in the lamina propria (N = 6), patchy cryptitis and crypt abscesses (N = 21) and focal superficial surface erosions (N = 4), some with pyloric metaplasia (N = 2 of 4). In general, the severity of ileal changes paralleled the severity of colonic activity. However, 2 of 4 (50%) patients with superficial erosions in the ileum had subtotal or left-sided colitis only, and had only mild colonic activity. Other cases showed only mild to moderate colonic activity and patchy or discontinuous involvement of the distal ileum. Upon follow-up of patients with erosions (mean, 48.5 months; range, 26-102 months), none developed manifestations of Crohn's disease anywhere in the gastrointestinal tract. The presence of inflammatory changes in the ileum had no effect on the prevalence of pouch complications or on the occurrence of dysplasia or cancer. Ileal changes in UC are not uncommon (prevalence, 17%), are generally mild in nature (villous atrophy, increased inflammation, scattered crypt abscesses), and are not associated with an increased rate of ileo-anal pouch complications, dysplasia, or carcinoma. In some cases, our findings are consistent with a backwash etiology. However, rarely, ileal erosions may occur in patients without cecal involvement, which may indicate that other pathogenetic mechanisms should be considered in the etiology of ileitis in UC patients.

Adult↗

Age-related vulnerabilities of older adults with colon adenomas: evidence from Project Prevent.

BACKGROUND: This report addresses the interface between cancer and aging in the context of colorectal carcinoma (CRC), the second leading cause of cancer death in the U.S. overall and the first leading cause among individuals age > or = 75 years. Because polyp risk increases with age, interventions to prevent recurrent polyps among older adults likely would reduce CRC morbidity and mortality. METHODS: Data for this study derive from Project Prevent, a multisite, randomized controlled trial designed to reduce behavioral risk factors for CRC among 1247 adults who underwent the removal of > or = 1 adenomatous colon polyps. Middle-aged and older patients were compared on key cognitive-behavioral mechanisms associated with CRC risk and established age-related factors associated with adverse health outcomes. Relations between cognitive-behavioral mechanisms and age-related vulnerability factors identified subgroups of older polyp patients that may have an enhanced risk for CRC. RESULTS: Compared with middle-aged patients, older patients were less concerned about developing CRC, less motivated to reduce their risk, and less confident that their behavior change efforts would succeed. As expected, they also reported more age-related physical, social, and economic vulnerabilities, as expected. Evidence for enhanced CRC risk was found for older patients with multiple comorbid conditions, low social support for change, and perceptions of income inadequacy. CONCLUSIONS: The presence of age-related vulnerability factors may enhance the risk of CRC among older cancer patients by creating barriers to behavioral change. Efforts to reduce the cancer burden in older populations will require attention beyond early detection and surveillance to interventions that account for the unique physical and psychosocial characteristics of older adults.

Adenomatous Polyposis Coli↗

Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis.

BACKGROUND & AIMS: A previously published study by our group suggested that adenoma-like dysplasia-associated lesions or masses (DALMs) in ulcerative colitis (UC) may be treated adequately by polypectomy and continued endoscopic surveillance. The length of follow-up evaluation in these patients averaged only 42 months. The purpose of this study was to evaluate the long-term outcome of our previously defined group of UC patients, all with adenoma-like DALMs, who were treated by polypectomy. METHODS: The clinical, endoscopic, and pathologic outcome of 34 UC patients, 24 with an adenoma-like DALM, and 10 with a coincidental sporadic adenoma, 28 of whom were treated by polypectomy and continued endoscopic surveillance, and 6 by colonic resection, were compared with the outcome of 49 non-UC patients who were treated similarly for a sporadic adenoma. The mean length of follow-up evaluation averaged 82.1 months and 71.8 months for the 2 UC subgroups, respectively, and 60.4 months for the non-UC controls. RESULTS: Overall, 20 of 34 UC patients (58.8%) developed at least one further adenoma-like DALM on follow-up evaluation. One patient had flat low-grade dysplasia present in the colon, which was resected within 6 months of the initial polypectomy, and another patient, with primary sclerosing cholangitis, developed adenocarcinoma 7.5 years after her initial polypectomy. There was no significant difference in the prevalence of polyp formation on follow-up evaluation between UC patients with an adenoma-like DALM (62.5%) and UC patients with a sporadic adenoma (50%), or between either of these 2 UC patient subgroups and the non-UC sporadic adenoma patient group (49%; P > 0.05). CONCLUSIONS: UC patients who develop an adenoma-like DALM may be treated adequately by polypectomy with complete excision and continued endoscopic surveillance.

Adenoma↗

Sequential clinical and histopathological changes in collagenous and lymphocytic colitis over time.

We conducted this retrospective study to evaluate the relationship between symptoms, histological findings, and treatment of collagenous (CC) and lymphocytic colitis (LC). We identified 19 CC and 12 LC patients having multiple colonoscopic procedures with colonic biopsies during their course of illness. A detailed histological review of all biopsies was performed. Clinical history, including symptoms and medications, was obtained in 25 of the 31 patients and was correlated with their histological findings. In all, 25% of the CC patients and 50% of the LC patients who had biopsies prior to their definitive diagnosis had the pathognomonic histological features on their prior biopsies to some extent (but were not recognized by the pathologists); however, these features were more pronounced on the biopsies from the procedure that established the diagnosis. Nonetheless, 10 of 12 such patients with clinical data available had symptoms and were being treated at the time of prior biopsies. Assessment of the relationship among histological, clinical and therapeutic data showed no association between symptoms or histological findings and treatment with any medication. In summary, in this sample of CC and LC patients, symptoms often precede fully developed histological features. No change in symptoms or histological findings was found to be associated with medication.

Abdominal Pain↗

Pediatric patients with untreated ulcerative colitis may present initially with unusual morphologic findings.

BACKGROUND: Anecdotal observations by the authors of this study, together with the results of a few previous smaller studies, suggest that children with new-onset (previously untreated) ulcerative colitis (UC) may occasionally present with discontinuous disease, relative or absolute rectal sparing, and may lack histologic features ofchronicity. Therefore, the objectives of this study were to determine the clinical and pathologic features of new-onset UC in children and to compare the initial presentation of UC in this group with a control group of adults. DESIGN: Routinely processed rectal and colonic mucosal biopsies from 73 pediatric (male/female ratio 33/40, mean age 11.5 years, range 2.5-18 years) and 38 adult patients (male/female ratio 15/23, mean age 41.5 years, range 27-64 years) who presented with new-onset UC were evaluated for a variety of clinical and pathologic features, including duration of symptoms prior to presentation, crypt architectural (e.g., atrophy, branching) and nonarchitectural (e.g., basal plasmacytosis, Paneth cell metaplasia) features of chronicity, degree of active inflammation, and distribution and extent of disease. RESULTS: A significant proportion of children with new-onset UC had patchiness of microscopic features of chronicity (21% of patients), relative (23%), or absolute (3%), rectal sparing, and had little or no crypt architectural distortion in their rectal biopsies (8%). These features were not observed in adult patients with UC. In addition, a higher proportion of children with UC initially presented with subtotal or with pancolitis compared with the adults (42% vs. 11%; P < 0.002). CONCLUSIONS: A significant proportion of children with new-onset UC may show unusual patterns of disease. Pathologists should be aware of these findings since they have significant implications for the differential diagnosis of pediatric inflammatory bowel disease.

Adolescent↗

Hyperplastic (serrated) polyps of the colorectum: relationship of CpG island methylator phenotype and K-ras mutation to location and histologic subtype.

We investigated the frequency of promoter region CpG island methylation (CIM) of hMLH1, MGMT, MINT1, MINT2, and p16 and K-ras mutations in a total of 79 hyperplastic (serrated) polyps (HPs) from 75 patients and correlated the molecular profiles to polyp location in the colorectum, histologic variation, and other factors. Methylation-specific PCR (MS-PCR) was used to assay CIM status. HPs that showed CIM of one or more or two or more of the genes assayed were classified as CpG island methylator phenotype (CIMP) and CIMP-high (CIMP-H), respectively. PCR restriction fragment length polymorphism was used to assay K-ras codon 12 and 13 mutations. Logistic regression indicated a statistically significant trend for increasing odds for CIMP (P = 0.002) and CIMP-H (P < 0.001) according to proximity to the cecum or distance from the rectum. Conversely, K-ras codon 12 mutation was present in 13 of 40 (32.5%) distally located HPs compared with 2 of 39 (5.1%) proximal HPs (P = 0.006). Histologic subtype distribution varied by proximal and distal locations. Frequency of CIMP in serrated polyps with abnormal proliferation (SPAPs), differed significantly from goblet cell serrated polyps (GCSPs) (24 of 26, 92.3% vs. 6 of 13, 46.2%) (P = 0.003) and microvesicular serrated polyps (MVSPs) (26 of 38, 68.4%) (P = 0.03). Frequency of K-ras mutation in GCSPs (7 of 13, 54%) differed from that of MVSPs (6 of 38, 16%) (P = 0.01) and SPAPs (2 of 26, 8%) (P = 0.003). Location in the colorectum and histologic subtype were major determinants of the molecular profile of HPs. The molecular findings of CIMP and K-ras mutations appear to encompass most if not all HPs; CIMP profiles suggest that SPAP is the most advanced morphologic variant. We postulate that MVSP and GCSP may be precursor lesions that, if proximally located or larger, can progress to SPAP. Frequent K-ras mutations and infrequent CIMP distinguish the distal GCSP variant.

Adult↗

The clinical significance of right-sided colonic inflammation in patients with left-sided chronic ulcerative colitis.

BACKGROUND: Rarely, patchy right colonic inflammation has been observed in patients with left sided chronic ulcerative colitis (CUC), but the clinical significance of this finding is unknown. Therefore, the aim of this study was to evaluate the clinical and pathologic features and natural history of CUC patients with left-sided colitis combined with patchy right colonic inflammation and to compare the clinical course to a control group of patients with isolated left-sided CUC. METHODS: Twelve patients with clinically and pathologically confirmed left-sided CUC, but also with patchy right colonic inflammation, were identified from a cohort of 352 consecutive patients with CUC who underwent colonoscopy at the Brigham and Women's Hospital between 1996 and 2000. In this cohort, 127 patients had left-sided colitis. As the first study to use controls in this setting, 35 consecutive patients with left-sided CUC, but without patchy right colonic inflammation, were selected and evaluated during the same time period. In all patients, the medical records were reviewed for a wide variety of clinical, endoscopic, and pathologic features. The mean follow-up time for the study and control groups was 105 +/- 128 and 112 +/- 80 months, respectively. RESULTS: Patients in the study group were significantly older than the control group at the time of diagnosis (47 +/- 17 years vs 35 +/- 14 years, p = 0.048), but the two groups had a similar gender distribution (25% male vs 40% male), prevalence of extraintestinal manifestations (25% vs 11%), frequency of nonsteroidal anti-inflammatory drug use (75% vs 50%), family history of colitis (27% vs 15%), current tobacco use (8% vs 3%), history of appendectomy (8% vs 0%), and overall severity of disease (33% vs 46%). None of the patients in the study group, and only one control patient, had disease progression to pancolitis. One study patient developed high-grade dysplasia in the rectum that required a colectomy. None of the study or control patients developed clinical or pathologic features of Crohn's disease. CONCLUSIONS: Rarely patients with left-sided CUC may have patchy right colonic inflammation. The clinical features and natural history of patients with left-sided CUC and patchy right colonic inflammation is similar to patients with isolated left-sided CUC.

Adult↗

Histologic predictors of pouchitis in patients with chronic ulcerative colitis.

Inflammation of ileal reservoir mucosa ("pouchitis") is a common sequelae in ulcerative colitis (UC) patients who have had a colectomy with ileal pouch anal-anastomosis (IPAA). Although several clinical, genetic, and laboratory parameters have been evaluated, reliable pathologic predictors for the development of pouchitis are lacking. The purpose of this case-control study was to determine whether there are any pathologic features in UC colectomy specimens that may help predict the subsequent development of pouchitis after an IPAA procedure. The study group consisted of 39 UC patients (male/female ratio: 21/18, mean age: 35 years), who had at least 1 episode of pouchitis after an IPAA procedure during the follow-up period (mean: 57 months, range: 12-121 months). There were 26 control patients (male/female ratio: 11/15, mean age: 37 years), all of whom also underwent a total colectomy and IPAA procedure for UC, but did not develop pouchitis during the follow-up period (mean: 78 months, range: 14-223 months). Routinely processed tissues from each colectomy specimen were evaluated for a variety of histologic features, such as extent of colitis, severity of colitis, extent of severe colitis, type and extent of ulceration, presence and severity of appendiceal inflammation, and the presence of active ileitis, and compared between the study and control patients. Pathologic features that were associated with the subsequent development of pouchitis included the presence of severe colitis that extended into the cecum (severe pancolitis), which was present in 7/39 (18%) pouchitis patients, but in none (0%) of the control patients (P = 0.03), early fissuring ulcers [9/39 (23%) pouchitis cases versus 1/26 (4%) controls (P = 0.04)], active inflammation of the appendix [20/32 (63%) pouchitis patients versus 7/19 (31%) controls (P = 0.03)], and appendiceal ulceration [13/32 (41%) pouchitis patients versus none (0%) of the controls (P = 0.002)]. No significant differences in patient gender or age, depth or extent of ulceration, or the presence or absence of "backwash ileitis" were identified between the 2 groups. In conclusion, there are several histologic features in colectomy specimens from UC patients who have undergone an IPAA procedure that may help predict the subsequent development of pouchitis. Of these features, appendiceal ulceration is highly associated with pouchitis.

Adolescent↗

BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status.

The aim of this study was to test the hypothesis that mutations of the oncogenes BRAF or KRAS are early events in the putative serrated polyp neoplasia pathway and more advanced pathology is associated with acquired mutator and suppressor gene inactivation by CpG island methylation of promoter regions. We assayed 79 sporadic hyperplastic polyps (HPs) classified according to the schema of Torlakovic et al and 25 serrated adenomas (SAs) for BRAF and KRAS mutations and related the findings to histologic characteristics and CpG island methylation phenotype (CIMP). Mutations at exon 15, codon 599, of BRAF were assayed using an allele-specific PCR (AS-PCR) technique and confirmed in a sample of AS-PCR- positive cases by direct sequencing of exon 15. AS-PCR-negative HPs and SAs were also sequenced on exon 15 and exon 11 to detect additional mutations. PCR-RFLP was used to assay KRAS codon 12 and 13 mutations, and these mutations were further validated by direct sequencing of the KRAS gene. BRAF599 mutations were identified in a total of 55 HPs (69.6%) and KRAS mutations in a total of 13 (16.5%). BRAF599 mutations occurred with similar frequencies among microvesicular serrated polyp (76.3%) and serrated polyp with abnormal proliferation (82.1%) subtypes but less frequently in goblet cell serrated polyps (23.1%). Conversely, KRAS mutations were most frequent in goblet cell serrated polyp (46.2%) and less frequent in microvesicular serrated polyp (13.2%) and serrated polyp with abnormal proliferation (7.1%). BRAF599 and KRAS mutations were present in 15 (60.0%) and 7 (28.0%) of SAs, respectively. BRAF 599 mutation and KRAS were mutually exclusive findings in the polyps studied and one or the other occurred in 68 of 79 (86.1%) HPs and 22 of 25 (88.0%) SAs. CpG island methylation involving 2 or more genes (CIMP-H) was present in 80.0% of SAs, 75% serrated polyp with abnormal proliferations, 47.4% of microvesicular serrated polyps, and 15.4% of goblet cell serrated polyps. SAs were significantly more likely to be CIMP-H than HPs (odds ratio 3.7; 95% confidence interval, 1.27-10.86; P = 0.017). A similar high frequency of KRAS or BRAF mutations across the histologic spectrum of the serrated polyps assayed suggests that these are early events in the serrated polyp neoplasia pathway. In contrast, the association of higher levels of CpG island methylation with more advanced histologic changes suggests that CpG island methylation plays a role in serrated polyp progression toward colorectal carcinoma.

Adenoma↗

Barriers to endoscopic colorectal cancer screening: are women different from men?

OBJECTIVES: The goals of this study were to compare women and men's understanding of screening flexible sigmoidoscopy (FS) and to identify predictors of endoscopic colorectal cancer (CRC) screening. METHODS: We mailed a 36-item questionnaire to asymptomatic patients aged 50 years or older who were scheduled for routine health assessments at a large multispecialty health-care group. Data collection included demographics, health behaviors, psychosocial factors, and CRC screening compliance. We followed participants for 1 year and assessed completion of endoscopic CRC screening. Both cross-sectional results examining previous screening and prospective results examining screening 1 year later were evaluated. RESULTS: 554 (54%) of 998 patients responded to the survey. Responses of 13 patients were excluded in the analyses due to unverifiable screening outcome. The majority of the respondents were white, and their average age was 62 years. Women reported significantly more embarrassment and fear about having FS than men. Women were more willing to consider having a FS if a female endoscopist performed the procedure. Of the 334 participants who were eligible to have endoscopic CRC screening, 53 (16%) had the procedure within a year. The odds of having the endoscopic procedures increased with the length of time the patients were under the care of their primary care providers and how strongly patients believed that one should have an FS even without symptoms. CONCLUSION: Our findings suggest some unique gender-specific attitudes and beliefs that act as potential barriers for CRC screening and further support the important role of primary care providers in facilitating timely completion of screening.

Aged↗

Screening flexible sigmoidoscopy using an upper endoscope is better tolerated by women.

BACKGROUND: Flexible sigmoidoscopy (FS) is a commonly used method for colorectal cancer screening. Women are more likely than men to have a FS with a limited depth of insertion, in part due to differences of anatomy and perception of pain. AIM: The objective of this prospective single-blinded randomized clinical study is to assess satisfaction in women undergoing screening FS using an upper endoscope (E, diameter 9.8 mm) versus a standard sigmoidoscope (S, diameter 13.3 mm) as measured by pain and discomfort and overall satisfaction using a validated survey instrument. Secondary endpoints of FS efficacy included the depth of insertion of the instrument, frequency of polyp detection, and complication rate. RESULTS: A total of 160 asymptomatic women undergoing screening FS were entered over a 4-month period (July through November 2002). All procedures were performed by two experienced physician assistants. The two groups were of similar age (E = 57.5, S = 58.2, p= 0.579) and had a similar rate of previous abdominal surgery (E = 51.2%, S = 45.0%, p= 0.428) or hysterectomy (E = 34.2%, S = 26.3%, p= 0.274). Depth of insertion of the scope was 54.5 cm (+/-9.2 cm) with the E and 51.6 cm (+/- 10.3 cm) with the S (p= 0.058). Polyps were found more frequently in the study group (18.3%) compared with the control group (p= 10.2%) though this did not reach statistical significance (p= 0.131). Overall satisfaction with FS was similar in both groups (p= 0.694) but pain and discomfort were less in the patients undergoing FS using the E (p= 0.006). Controlling for age and previous surgery the differences in pain scores remained significant (p= 0.035). Endoscopist assessment of procedure difficulty (p= 0.726) and complication rates (p= 0.614) was equivalent. Controlling for the presence of polyps, the total duration for the procedure was 7.2 min in the E group and 5.7 min in the S group (p= 0.008). There were no significant differences between women with and without hysterectomy on either overall satisfaction or pain and discomfort. CONCLUSION: Screening FS in women using an upper endoscope is a feasible approach to colorectal cancer screening. Patients screened with an upper endoscope reported less pain and discomfort compared to standard sigmoidoscope while overall satisfaction did not differ. The trend toward increased polyp detection in patients undergoing FS with an upper endoscope may be related to a more thorough examination due to less patient discomfort and/or an increased depth of insertion of the upper endoscope. Thinner, more flexible endoscopes should be considered when performing screening FS in women.

Aged↗

Endoscopic findings and their clinical correlations in patients with symptoms after gastric bypass surgery.

BACKGROUND: The aim of this study was to describe the endoscopic findings in patients with upper GI symptoms after Roux-en-Y gastric bypass surgery and to correlate clinical features with endoscopic findings. METHODS: Patients with symptoms after Roux-en-Y gastric bypass referred for endoscopy were studied. Endoscopy was performed in standard fashion with a 9.8-mm diameter endoscope. RESULTS: Forty-nine patients underwent a total of 69 upper endoscopy procedures between January 2001 and February 2003. The most common endoscopic findings were the following: normal post-surgical anatomy (21 patients, 43%), marginal ulcer (13 patients, 27%), stomal stenosis (9 patients [19%], including 5 with a concomitant marginal ulcer), and staple-line dehiscence (8 patients [16%], including one with a marginal ulcer). Abdominal pain was the most common symptom (26 patients, 53%) and was more frequent among patients with a normal endoscopy compared with those with an abnormal endoscopy (p=0.04). Stomal stenosis was present in 39% of patients with nausea, vomiting, or dysphagia; it was not present in any patient without these symptoms (p=0.001). Fifteen percent of procedures performed within the first 6 postoperative months were normal, compared with 53% of those performed beyond 6 months (p=0.02). There was no complication of endoscopy. CONCLUSIONS: Among patients with symptoms after Roux-en-Y gastric bypass presenting for endoscopy, normal post-surgical anatomy was the most common finding. Marginal ulcer was the most common abnormality. Presentation with abdominal pain and performance of endoscopy beyond the 6th post-operative month were predictive of a normal endoscopy, and lack of nausea, vomiting, and dysphagia predicted the absence of stomal stenosis.

Abdominal Pain↗